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Shan Y, Liu L, Wang F, Yu L, Liu D, Zheng C, He Q, Li C, Li S, Yu Z. Association between inequalities in mental health resources and burdens of mental health disorders in 146 countries and territories: An observational study. J Affect Disord 2025; 379:812-821. [PMID: 40113180 DOI: 10.1016/j.jad.2025.03.094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Revised: 03/06/2025] [Accepted: 03/17/2025] [Indexed: 03/22/2025]
Abstract
BACKGROUND Mental health disorders impose a substantial social and economic burden. We conducted a comprehensive assessment of global mental health resource allocation and the associated burdens of mental health disorders, examining the relationship between these two factors. METHODS We utilized data from the WHO Global Health Observatory and GBD 2021 to encompass 146 countries. We employed spatial autocorrelation analysis and Lorenz curves to characterize the spatial distribution. Additionally, we examined the association between mental health resources and the burdens of mental disorders using a generalized linear regression model (GLM). RESULTS Countries and territories with higher income levels were more likely to have greater mental health resources (p < 0.05). Globally, the average mental health resource allocation index (IMRA) was 18.14, and Moran's I was 0.509 (p < 0.001). The Lorenz curve of mental health resources lay below the equality line, suggesting that these resources were more concentrated in countries and territories with higher HDI values. Between 2011 and 2021, the age-standardized incidence rate of all mental health disorders increased significantly (EAPC: 1.41 %, 95 % CI: 0.40 % to 2.53 %, p = 0.011). In multivariable GLM, a negative association was observed between the Index of IMRA and total mental health incidence. CONCLUSION Inequalities in mental health resources persist, and the burdens of mental disorders are increasing globally. Our findings underscore the critical need to reduce the overall burden of mental health disorders through enhanced allocation of prevention-oriented resources. Countries at different levels of human development face distinct challenges and priorities in mental health resource allocation.
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Affiliation(s)
- Ying Shan
- Breast Center, The Second Hospital of Shandong University, Jinan 250033, Shandong, China; Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong, China
| | - Liyuan Liu
- Breast Center, The Second Hospital of Shandong University, Jinan 250033, Shandong, China; Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong, China
| | - Fei Wang
- Breast Center, The Second Hospital of Shandong University, Jinan 250033, Shandong, China; Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong, China
| | - Lixiang Yu
- Breast Center, The Second Hospital of Shandong University, Jinan 250033, Shandong, China; Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong, China
| | - Dongxu Liu
- Breast Center, The Second Hospital of Shandong University, Jinan 250033, Shandong, China; Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong, China
| | - Chao Zheng
- Breast Center, The Second Hospital of Shandong University, Jinan 250033, Shandong, China; Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong, China
| | - Qiufeng He
- Department of Quality Control, Shandong Mental Health Center, Shandong University, Jinan, Shandong 250014, China
| | - Cheng Li
- Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China
| | - Shixue Li
- Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; National Health Commission of China (NHC) Key Laboratory of Health Economics and Policy Research, Shandong University, Jinan, Shandong, China.
| | - Zhigang Yu
- Breast Center, The Second Hospital of Shandong University, Jinan 250033, Shandong, China; Institute of Translational Medicine of Breast Disease Prevention and Treatment, Shandong University, Jinan, Shandong, China.
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Trang VAV, Truyen TTTT, Nguyen MT, Mai HP, Phan TC, Phan SH, Le Nguyen HM, Nguyen HDT, Le NHD, Tu MN, Huynh VTV, Nguyen HTA, Ho DBH, Tran NTU, Tran NHU, Le BNT, Doan DT, Pham HD, Phan TB, Pham PP, Nguyen TV, Nguyen PCH. Development of a novel risk score for diagnosing urinary tract infections: Integrating Sysmex UF-5000i urine fluorescence flow cytometry with urinalysis. PLoS One 2025; 20:e0323664. [PMID: 40367086 PMCID: PMC12077719 DOI: 10.1371/journal.pone.0323664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Accepted: 04/13/2025] [Indexed: 05/16/2025] Open
Abstract
BACKGROUND Urinary tract infections (UTIs) are common globally, and are developing increased antibiotic resistance. Despite being the diagnostic "gold standard," urine culture is limited by slow results and a high rate of false negative findings, leading to treatment delays, higher costs, and overuse of empirical antibiotics. Our study aims to develop a rapid and reliable model to predict clinical outcomes. METHODS From January 1st to October 31st, 2023, we enrolled patients with symptoms suggesting UTI from the Outpatient Department of our hospital. Inclusion criteria were patients aged ≥18, initially diagnosed with UTI, available urinalysis, flow cytometry, and urinary culture. Exclusion criteria included failed sample collection and cultures, and pregnant women. A case-control study was conducted, with UTI cases defined as ≥ 10^5 CFU/ µ L and controls as < 10^5 CFU/ µ L, matched for age and sex in a 1:1 ratio. For validation, retrospective cases from July to December 2022 were selected with matching controls. Using urine culture as the gold standard, the predictive model was developed with backward stepwise logistic regression. Model discrimination was assessed using area under the curve (AUC). RESULTS In our discovery cohort, we included 1,335 UTI cases and 1,282 non-UTI controls, with mean ages of 52.9 ± 17.1 years and 51.9 ± 16.4 years, and females of 76.9% and 77.7%. Using 100 cells/uL as a threshold, bacterial counts demonstrated a sensitivity of 91.0% and specificity of 45.7%. Our novel UTIRisk score, developed from urinalysis and flow cytometry parameters, showed strong discrimination for UTI, with a AUC of 0.82 (95% CI: 0.81-0.84). In the validation cohort, the AUC was 0.77 (95% CI: 0.74-0.80). The UTIRisk score exhibited excellent specificity (96.5%) and high positive predictive value (92.6%). The score performed strongly across subgroups, particularly in males and patients aged ≥65. CONCLUSIONS Our UTIRisk score can improve diagnosis, reduce unnecessary urine cultures, optimize antibiotic use, and help control antibiotic resistance in LMICs. Multicenter, and intervention-based studies are warranted before clinical implementation.
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Affiliation(s)
- Vo Anh Vinh Trang
- Binh Dan Hospital, Ho Chi Minh, Vietnam
- Faculty of Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh, Vietnam
| | - Thien Tan Tri Tai Truyen
- School of Medicine, Tan Tao University, Long An, Vietnam
- Faculty of Medicine, Nam Can Tho University, Can Tho, Vietnam
| | | | - Huu Phong Mai
- Faculty of Medicine, Nam Can Tho University, Can Tho, Vietnam
| | - Tri Cuong Phan
- Faculty of Medicine, Nam Can Tho University, Can Tho, Vietnam
| | - Son Hoang Phan
- Faculty of Medicine, Nam Can Tho University, Can Tho, Vietnam
| | | | | | - Nguyen Hai Dang Le
- Binh Dan Hospital, Ho Chi Minh, Vietnam
- Faculty of Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh, Vietnam
| | | | | | | | | | | | | | | | | | - Huu Doan Pham
- Binh Dan Hospital, Ho Chi Minh, Vietnam
- Faculty of Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh, Vietnam
| | | | | | - Tuan Vinh Nguyen
- Binh Dan Hospital, Ho Chi Minh, Vietnam
- University of Health Sciences, Vietnam National University Ho Chi Minh City, Ho Chi Minh, Vietnam
| | - Phuc Cam Hoang Nguyen
- Binh Dan Hospital, Ho Chi Minh, Vietnam
- Faculty of Medicine, Pham Ngoc Thach University of Medicine, Ho Chi Minh, Vietnam
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Tang K, Feng J, Lai H, Zhao Z, Zou Y, Lv Q, Dai F, Qiu X, Lai W. Global Burden and Trends of UTI in Premenopausal and Postmenopausal Women from 1990 to 2021 and Projections to 2044. Int J Womens Health 2025; 17:1375-1392. [PMID: 40390759 PMCID: PMC12086863 DOI: 10.2147/ijwh.s517387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2025] [Accepted: 04/25/2025] [Indexed: 05/21/2025] Open
Abstract
Objective Urinary tract infection (UTI) are an important health issue for women, and this study aimed to assess the different disease burdens in premenopausal and postmenopausal women. Methods In this cross-sectional study, secondary analysis was conducted using Global Burden of Disease (GBD) 2021 data to assess the burden of urinary tract infections in women. Our study applied a joinpoint regression model to assess temporal trends and factors, an age-period-cohort (APC) analysis to evaluate age, period, and cohort effects, and a health inequality analysis to examine regional disparities based on the socio-demographic index (SDI), along with a predictive model for future trend forecasting. Results From 1990 to 2021, UTI incidence grew faster in premenopausal women (average annual percentage change [AAPC] 0.17 [95% CI 0.15-0.18]) than in postmenopausal women (AAPC 0.04 [95% CI 0.02-0.07]), while mortality increased more for postmenopausal women (AAPC 1.08 [95% CI 0.81-1.36]) than premenopausal women (AAPC 0.45 [95% CI 0.33-0.56]). The COVID-19 pandemic saw a surge in premenopausal UTI incidence (AAPC 0.64 [95% CI 0.62-0.66]). Age, period, and cohort analyses revealed an age-related risk increase in premenopausal women, especially in early birth cohorts. Global health inequalities escalated, with a heavier UTI burden in lower SDI countries. By 2044, projections predict 253.33 million cases in premenopausal and 164.72 million in postmenopausal women, with the biggest increases in the 30-34 and 50-54 age brackets. Conclusion The study underscores global UTI burden disparities between pre- and postmenopausal women, worsened by COVID-19, urging future policies to enhance healthcare access, antibiotic stewardship, and high-risk group targeting.
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Affiliation(s)
- Ke Tang
- Department of Urology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, 510317, People’s Republic of China
| | - Jiayao Feng
- Department of Urology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, 510317, People’s Republic of China
| | - Hongshen Lai
- Department of Urology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, 510317, People’s Republic of China
| | - Zhongxiang Zhao
- Department of Urology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, 510317, People’s Republic of China
| | - Yeson Zou
- Department of Urology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, 510317, People’s Republic of China
| | - Qian Lv
- Department of Urology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, 510317, People’s Republic of China
| | - Fazhong Dai
- Department of Urology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, 510317, People’s Republic of China
| | - Xiaofu Qiu
- Department of Urology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, 510317, People’s Republic of China
| | - Wenjie Lai
- Department of Urology, The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, Guangdong, 510317, People’s Republic of China
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Bhuiya S, Kaushik S, Logheeswaran J, Karthika P, Prathiviraj R, Selvin J, Kiran GS. Emergence of Recurrent Urinary Tract Infection: Dissecting the mechanism of Antimicrobial Resistance, Host-Pathogen Interaction, and Hormonal Imbalance. Microb Pathog 2025:107698. [PMID: 40373943 DOI: 10.1016/j.micpath.2025.107698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2024] [Revised: 04/19/2025] [Accepted: 05/12/2025] [Indexed: 05/17/2025]
Abstract
Urinary tract infection is one of the most common infections worldwide, causing numerous deaths every year. The gut-bladder axis has been recently found to be a key factor in initiating UTI pathogenesis, along with the imbalance in the gut microbiome, which is associated with advanced susceptibility to rUTI. The patients who suffer from UTIs are, more often than not, the ones who have the lowest levels of butyrate-producing gut bacteria. Antibiotics cause dysbiosis in the gut and increase the growth of uropathogenic strains. Moreover, the gut-vagina and vagina-bladder axes are involved in UTIs by transferring microbial species, modulating the immune response, and developing intracellular bacterial reservoirs in the bladder. The rising usage of antibiotics has raised antimicrobial resistance (AMR) worldwide and recently worsened the treatment of UTIs. Resistance mechanisms include enzymatic hydrolysis of antibiotics, efflux systems, biofilm formation, horizontal gene transfer, and a weakened host's immune system, allowing bacteria to escape from the treatments. Besides, in pregnant women and adolescents, the alterations in sex hormone levels increase the risk of rUTIs. Knowledge of microbiota that harbor in the gut-vagina and vagina-bladder axes might lead to the invention of nonantibiotic preventive and therapeutic techniques in the future. In conclusion, this review emphasizes the need for a study to understand the host-microbe interactions, gut health, and AMR to effectively deal with and prevent recurrent UTIs. Also, the review explores a comprehensive analysis of the epigenetic network between host UTIs and marker genes in E. coli.
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Affiliation(s)
- Shraddha Bhuiya
- Department of Food Science and Technology, Pondicherry University, Puducherry 605014, India
| | - Saumya Kaushik
- Department of Food Science and Technology, Pondicherry University, Puducherry 605014, India
| | - Jwalaa Logheeswaran
- Department of Food Science and Technology, Pondicherry University, Puducherry 605014, India
| | - P Karthika
- Department of Food Science and Technology, Pondicherry University, Puducherry 605014, India
| | | | - Joseph Selvin
- Department of Microbiology, Pondicherry University, Puducherry 605014, India
| | - George Seghal Kiran
- Department of Food Science and Technology, Pondicherry University, Puducherry 605014, India.
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Liyanarachi KV, Flatby H, Hallan S, Åsvold BO, Damås JK, Rogne T. Uromodulin and Risk of Upper Urinary Tract Infections: A Mendelian Randomization Study. Am J Kidney Dis 2025; 85:570-576.e1. [PMID: 39805364 DOI: 10.1053/j.ajkd.2024.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2024] [Revised: 11/15/2024] [Accepted: 11/27/2024] [Indexed: 01/16/2025]
Abstract
RATIONALE & OBJECTIVE Observational studies suggest that uromodulin, produced by the kidneys, is associated with a reduced risk of upper urinary tract infections (UTIs), but inferences are limited by potential confounding factors. This study sought to explore further the validity of this association using Mendelian randomization (MR). STUDY DESIGN Two-sample MR study. SETTING & PARTICIPANTS The study included 29,315 and 13,956 participants from 18 cohorts of mainly European ancestry with measured urinary and serum uromodulin levels, respectively, and 3,873 and 512,608 participants from the UK Biobank, the Trøndelag Health Study, or the Michigan Genomic Initiative with and without upper UTIs. EXPOSURES We identified uncorrelated (r2 < 0.01) single nucleotide variations that were strongly associated (P < 5 × 10-6) with urinary and serum uromodulin levels from the aforementioned two genome-wide association studies. Both studies accounted for kidney function. OUTCOMES Genetic associations for the risk of upper UTIs extracted from the aforementioned independent genome-wide association study. ANALYTICAL APPROACH Inverse variance-weighted and sensitivity analyses were performed. The strength of each genetic instrument was estimated using the F statistic. RESULTS A 1-standard deviation increase in genetically predicted urinary uromodulin level was associated with an odds ratio (OR) for upper UTIs of 0.80 (95% CI, 0.67-0.95; P = 0.01). A 1-standard deviation increase in serum uromodulin was not statistically associated with elevated odds of upper UTIs, OR = 0.95 (95% CI, 0.89-1.01; P = 0.12). These findings were consistent across the sensitivity analyses. LIMITATIONS Analyses could be performed on only participants of predominantly European ancestry, potentially decreasing the generalizability of our findings. CONCLUSIONS This two-sample MR study found that increased levels of genetically predicted urinary uromodulin were associated with a reduced risk of upper UTIs. These findings support the hypothesis that uromodulin may have a protective role against upper UTIs. PLAIN-LANGUAGE SUMMARY Traditional studies have suggested that uromodulin, a protein produced by the kidneys, may reduce the risk of urinary tract infections (UTIs). The certainty of these findings is limited by the potential influence of unmeasured confounding factors. Therefore, we decided to address this concern by using genetic data to perform a two-sample Mendelian randomization analysis, a technique known to limit the influence of such factors. Our findings support the hypothesis that uromodulin in urine may have a protective role against upper UTIs. The findings were consistent across sensitivity and sex-specific analyses. Further research into the implications of these findings for the treatment of UTIs as well as the possible utility of urinary uromodulin as a diagnostic marker is warranted.
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Affiliation(s)
- Kristin Vardheim Liyanarachi
- Mid-Norway Center for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; Department of Infectious Diseases, Clinic of Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway.
| | - Helene Flatby
- Mid-Norway Center for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Stein Hallan
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Nephrology, Clinic of Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Bjørn Olav Åsvold
- HUNT Center for Molecular and Clinical Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology, Trondheim, Norway; HUNT Research Center, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger, Norway; Department of Endocrinology, Clinic of Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Jan Kristian Damås
- Mid-Norway Center for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Infectious Diseases, Clinic of Medicine, St. Olav's Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Tormod Rogne
- Mid-Norway Center for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway; Yale Department of Chronic Disease Epidemiology and Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, Connecticut
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Kongsomboonchoke P, Mongkolkarvin P, Khunti P, Vijitphichiankul J, Nonejuie P, Thiennimitr P, Chaikeeratisak V. Rapid formulation of a genetically diverse phage cocktail targeting uropathogenic Escherichia coli infections using the UTI89 model. Sci Rep 2025; 15:12832. [PMID: 40229393 PMCID: PMC11997193 DOI: 10.1038/s41598-025-96561-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Accepted: 03/28/2025] [Indexed: 04/16/2025] Open
Abstract
Urinary tract infections are commonly caused by uropathogenic Escherichia coli (UPEC). Due to the emergence of multidrug-resistant UPEC, rendering antibiotic treatment ineffective, phage combination-based therapy has been proposed as a potential alternative. Here, we present a formulation of a genetically diverse phage-derived cocktail that is rapidly customized for UPEC using E. coli UTI89 as a model strain. Through our rapid selection and combination of four phages against UPEC strain UTI89 (SR01, SR02, SR04, and Zappy) from our library, the combination of two lytic phages, SR02 and SR04, exhibits the strongest suppression of bacterial growth for at least 16 h, with no emergence of phage resistance observed in vitro. Phage SR02 undergoes subcellular activity for 25 min, producing approximately 106 progeny particles per cell, while SR04 completes its replication cycle in 20 min, generating around 564 progeny particles per cell. These two novel phages are genetically diverse, and their cocktail exhibited potent suppression of bacterial growth, independent of multiplicities of infection (MOIs), significantly reducing the viable bacterial counts after treatment in vitro. The phage cocktail has low immunogenicity and does not induce any proinflammatory gene responses in human bladder uroepithelial cells. Moreover, the cocktail effectively eradicates the invading UPEC strain UTI89 in the uroepithelial cells at a comparable level to that of phage SR04 alone, likely releasing some immunostimulatory agents that, in turn, trigger upregulation of MIP-3 and IL-8 genes. Altogether, this study offers an alternative pipeline for rapidly formulating genetically diverse phage-derived cocktails, which is specifically customized for targeted bacteria.
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Affiliation(s)
| | - Panupon Mongkolkarvin
- Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | - Patiphan Khunti
- Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand
| | | | - Poochit Nonejuie
- Center for Advanced Therapeutics, Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, Thailand
| | - Parameth Thiennimitr
- Department of Microbiology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
- Center of Excellence in Microbial Diversity and Sustainable Utilization, Chiang Mai University, Chiang Mai, 50200, Thailand
| | - Vorrapon Chaikeeratisak
- Department of Biochemistry, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
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Fekadu S, Weldegebreal F, Shumie T, Mekonnen GK. A comparative study on nosocomial and community-acquired bacterial urinary tract infections: prevalence, antimicrobial susceptibility pattern, and associated risk factors among symptomatic patients attending Hiwot Fana Comprehensive Specialized University Hospital, Eastern Ethiopia. FRONTIERS IN EPIDEMIOLOGY 2025; 5:1517476. [PMID: 40259954 PMCID: PMC12009891 DOI: 10.3389/fepid.2025.1517476] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Accepted: 03/05/2025] [Indexed: 04/23/2025]
Abstract
Background Urinary tract infections (UTIs) remain one of the most common diseases worldwide that occur both in the community and in healthcare settings. Thus, this study aimed to compare the burden of nosocomial and community-acquired bacterial UTIs among patients attending Hiwot Fana Comprehensive Specialized University Hospital, Eastern Ethiopia. Method A hospital-based cross-sectional study was conducted using a convenient sampling technique from January 2024 to April 2024. Descriptive statistics were employed, and bivariate and multivariable logistic regression analyses were used to identify associated factors at p < 0.05 with a 95% confidence interval (CI) considered statistically significant. Results The rate of hospital-acquired UTIs was 42% (95% CI: 35-50), while the rate of community-acquired UTIs was 28% (95% CI: 22-36). The predominant bacterial isolates were Escherichia coli (37%), Staphylococcus aureus (7.8%), and Klebsiella pneumoniae (7.8%). The overall multidrug resistance rate was 91 (77.8%). Lack of formal education [adjusted odds ratio (AOR), 0.02; 95% CI: 0.001-0.6], surgery during admission (AOR, 0.02; 95% CI: 0.002-0.3), delay in voiding urine (AOR, 0.01; 95% CI: 0.005-0.1), previous UTIs (AOR, 0.04; 95% CI: 0.004-0.4), and previous admission (AOR, 0.07; 95% CI: 0.01-0.5) were the main factors significantly associated with bacterial UTIs. Conclusions A significantly higher prevalence of hospital-acquired bacterial UTIs was observed compared to community-acquired bacterial UTIs. The commonest isolates were E.coli, S. aureus, and K. pneumoniae. The drug resistance rate was very high. Modifiable individual-level factors were the major significant factors of UTIs. Thus, health workers and other stakeholders should tackle UTIs by increasing community awareness, promoting personal hygiene, and improving healthcare service quality.
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Affiliation(s)
- Sisay Fekadu
- School of Medical Laboratory Sciences, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
- Department of Clinical Laboratory, Hiwot Fana Specialized University Hospital, Harar, Ethiopia
| | - Fitsum Weldegebreal
- School of Medical Laboratory Sciences, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
- Laboratory Bacteriology Research, Department of Diagnostic Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium
| | - Tadesse Shumie
- School of Medical Laboratory Sciences, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
| | - Getachew Kabew Mekonnen
- School of Medical Laboratory Sciences, College of Health and Medical Sciences, Haramaya University, Harar, Ethiopia
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Afeke I, Adu-Amankwaah J, Hamid AWM, Kwadzokpui PK, Aninagyei E, Emmanuel G, Deku JG. Urinary tract infections and antimicrobial susceptibility: A retrospective trend analysis of uropathogens in women in Accra, Ghana (2019-2022). PLoS One 2025; 20:e0321293. [PMID: 40184369 PMCID: PMC11970639 DOI: 10.1371/journal.pone.0321293] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Accepted: 03/04/2025] [Indexed: 04/06/2025] Open
Abstract
Urinary tract infections (UTIs) remain a significant public health concern, with evolving patterns in prevalence and antimicrobial resistance. This retrospective study, conducted at the Greater Accra Regional Hospital in Accra, Ghana, analyzed 11,280 urine cultures obtained exclusively from female patients from 2019 to 2022 to assess trends in UTI burden, prevalence stratified by age and month, and antimicrobial susceptibility patterns. In all, urine pathogens were isolated in 4475 (39.67%) of the samples tested. Of the total number of uropathogens isolated, majority of them were bacterial pathogens (94.21%), with an increasing proportion of fungal infections, specifically candida species (5.79%). Irrespective of the year, the highest prevalence of uropathogens were consistently recorded in the month of May, while individuals aged ≥ 90 years exhibited the greatest odds of infection in 2020 (aOR: 1.88, p = 0.039). Escherichia coli (30.51%) and Staphylococcus aureus (15.16%) were the most prevalent Gram-negative and Gram-positive pathogens, respectively. Antimicrobial susceptibility testing revealed declining antibiotic effectiveness over time, with notable exceptions for gentamicin (97.4% effectiveness against Enterococcus spp.) and ofloxacin (82.9% against Enterococcus spp.). Alarmingly, most antibiotics exhibited effectiveness rates below 20% by 2022, underscoring the growing resistance challenge. These findings, drawn from a key healthcare facility in Ghana's capital, highlight the dynamic nature of UTIs and the urgent need for targeted interventions, optimized antimicrobial stewardship, and continuous monitoring of resistance patterns to improve patient outcomes.
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Affiliation(s)
- Innocent Afeke
- Department of Medical Laboratory Sciences, School of Allied Health Sciences, University of Health and Allied Sciences, Ho, Ghana
| | | | - Abdul-Wahab Mawuko Hamid
- Department of Medical Laboratory Sciences, School of Allied Health Sciences, University of Health and Allied Sciences, Ho, Ghana
| | | | - Enoch Aninagyei
- Department of Biomedical Sciences, School of Basic and Biomedical Sciences, University of Health and Allied Sciences, Ho, Ghana
| | - Glona Emmanuel
- Department of Medical Laboratory Sciences, School of Allied Health Sciences, University of Health and Allied Sciences, Ho, Ghana
| | - John Gameli Deku
- Department of Medical Laboratory Sciences, School of Allied Health Sciences, University of Health and Allied Sciences, Ho, Ghana
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Bhise M, Chauhan K, Anandani G, Agarwal A. Etiological Profile and Antibiotic Susceptibility of Urinary Isolates Causing Urinary Tract Infections in Patients Attending a Tertiary Care Hospital in Rajkot, Gujarat. Cureus 2025; 17:e81633. [PMID: 40322354 PMCID: PMC12048744 DOI: 10.7759/cureus.81633] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/02/2025] [Indexed: 05/08/2025] Open
Abstract
OBJECTIVES This study aims to determine the occurrence of urinary tract infections (UTIs) and the bacteriological spectrum in urine samples, as well as to assess the antibiotic susceptibility patterns of the isolates. MATERIALS AND METHODS A retrospective study (October 2022 to October 2024) was conducted in the microbiology department, analyzing urine sample records using biochemical techniques and antimicrobial susceptibility testing guided by the Clinical and Laboratory Standards Institute. Data analysis was performed using SPSS Statistics version 23 (IBM Corp., 2015). RESULTS Among 1,027 samples, 13.43% yielded positive cultures. Most infections occurred in females (64.49%), particularly those aged 51-70 (56%). Gram-negative bacteria (89.13%), predominantly Escherichia coli and Klebsiella pneumoniae, were more common than Gram-positive bacteria (9.42%). Effective antibiotics included fosfomycin (85.97%), gentamicin (90%), and nitrofurantoin (77.6%). CONCLUSIONS UTIs in this region are largely caused by Gram-negative bacteria, primarily Escherichia coli. Nitrofurantoin and fosfomycin are recommended for initial treatment. These findings support the development of empirical treatment protocols for the region.
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Affiliation(s)
- Mayuri Bhise
- Microbiology, All India Institute of Medical Sciences, Rajkot, Rajkot, IND
| | - Kinjal Chauhan
- Microbiology, All India Institute of Medical Sciences, Rajkot, Rajkot, IND
| | - Garima Anandani
- Pathology, All India Institute of Medical Sciences, Rajkot, Rajkot, IND
| | - Ashwini Agarwal
- Microbiology, All India Institute of Medical Sciences, Rajkot, Rajkot, IND
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10
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Heida A, Hamilton MT, Gambino J, Sanderson K, Schoen ME, Jahne MA, Garland J, Ramirez L, Quon H, Lopatkin AJ, Hamilton KA. Population Ecology-Quantitative Microbial Risk Assessment (QMRA) Model for Antibiotic-Resistant and Susceptible E. coli in Recreational Water. ENVIRONMENTAL SCIENCE & TECHNOLOGY 2025; 59:4266-4281. [PMID: 40008406 PMCID: PMC12070308 DOI: 10.1021/acs.est.4c07248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/27/2025]
Abstract
Understanding and predicting the role of waterborne environments in transmitting antimicrobial-resistant (AMR) infections are critical for public health. A population ecology-quantitative microbial risk assessment (QMRA) model is proposed to evaluate urinary tract infection (UTI) development due to recreational waterborne exposures to Escherichia coli (E. coli) and antibiotic-resistant extended-spectrum β-lactamase-producing (ESBL) E. coli. The horizontal gene transfer (HGT) mechanism of conjugation and other evolutionary factors were modeled separately in the environment and the gut. Persistence/dilution dominated HGT in the environment; however, HGT highly impacted predicted ESBL populations in the body. Predicted disability life year (DALY) risks from exposure to ESBL E. coli at concentrations consistent with US recreational water criteria were less than the 10-6 pppy benchmark value but greater than the susceptible E. coli DALY risks associated with a UTI health outcome. However, the prevailing susceptible dose-response relationship may underestimate ESBL risk if HGT rates in vivo approach those reported in vitro. A sensitivity analysis demonstrated that DALY values, E. coli/ESBL concentrations, and exposure parameters were influential on predicted risks. The model is a preliminary tool to begin the expansion of the QMRA paradigm to explore the impacts of evolutionary changes in AMR risk assessment.
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Affiliation(s)
- Ashley Heida
- School for Engineering of Matter, Transport and Energy, Arizona State University, Tempe, Arizona 85287, United States; The Biodesign Institute Center for Environmental Health Engineering, Arizona State University, Tempe, Arizona 85281, United States
| | - Mark T. Hamilton
- Computer Science & Artificial Intelligence Lab, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States; New England Research and Development Center, Cambridge, Massachusetts 02139, United States
| | - Julia Gambino
- Duke University, Durham, North Carolina 27708, United States
| | | | - Mary E. Schoen
- Soller Environmental, Berkeley, California 94703, United States
| | - Michael A. Jahne
- Office of Research and Development, U.S. Environmental Protection Agency, 26 W. Martin Luther King Jr. Dr., Cincinnati, Ohio 45268, United States
| | - Jay Garland
- Office of Research and Development, U.S. Environmental Protection Agency, 26 W. Martin Luther King Jr. Dr., Cincinnati, Ohio 45268, United States
| | - Lucia Ramirez
- The Biodesign Institute Center for Environmental Health Engineering, Arizona State University, Tempe, Arizona 85281, United States
| | - Hunter Quon
- The Biodesign Institute Center for Environmental Health Engineering, Arizona State University, Tempe, Arizona 85281, United States; School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, Arizona 85281, United States
| | - Allison J. Lopatkin
- Department of Chemical Engineering and Department of Microbiology and Immunology, University of Rochester, Rochester, New York 14627, United States
| | - Kerry A. Hamilton
- The Biodesign Institute Center for Environmental Health Engineering, Arizona State University, Tempe, Arizona 85281, United States; School of Sustainable Engineering and the Built Environment, Arizona State University, Tempe, Arizona 85281, United States
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11
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Saraiva A, Raheem D, Roy PR, BinMowyna MN, Romão B, Alarifi SN, Albaridi NA, Alsharari ZD, Raposo A. Probiotics and Plant-Based Foods as Preventive Agents of Urinary Tract Infection: A Narrative Review of Possible Mechanisms Related to Health. Nutrients 2025; 17:986. [PMID: 40290034 PMCID: PMC11944753 DOI: 10.3390/nu17060986] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Revised: 03/05/2025] [Accepted: 03/10/2025] [Indexed: 04/30/2025] Open
Abstract
Urinary tract infections (UTIs) are a prevalent global health issue, often requiring antibiotic treatment, which contributes to antimicrobial resistance. This narrative review explores the potential of probiotics and plant-based foods as alternative or complementary preventive strategies against UTIs. Fermented foods, such as yogurt, kefir, and kombucha, contain probiotic strains that can modulate the gut and urogenital microbiota, enhancing resistance to uropathogens. Likewise, plant-based foods, including cranberry, garlic, bearberry, juniper, and nettle, possess bioactive compounds with antimicrobial, anti-inflammatory, and diuretic properties. Laboratory and clinical studies suggest that these natural interventions may reduce the incidence of UTIs by inhibiting pathogen adhesion, modulating immune responses, and promoting urinary tract health. However, despite promising findings, inconsistencies in study methodologies, dosage standardization, and long-term efficacy warrant further investigation. Future research should focus on optimizing probiotic formulations, standardizing plant-based supplement dosages, and assessing potential food-drug interactions to establish evidence-based guidelines for UTI prevention.
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Affiliation(s)
- Ariana Saraiva
- Research in Veterinary Medicine (I-MVET), Faculty of Veterinary Medicine, Lisbon University Centre, Lusófona University, Campo Grande 376, 1749-024 Lisboa, Portugal;
| | - Dele Raheem
- Global Change Research, Arctic Centre, University of Lapland, 96101 Rovaniemi, Finland;
| | - Poly Rani Roy
- Department of Chemistry, Jagannath University, Dhaka 1100, Bangladesh;
| | - Mona N. BinMowyna
- College of Education, Shaqra University, Shaqra 11911, Saudi Arabia;
| | - Bernardo Romão
- Faculty of Health Sciences, Department of Nutrition, University of Brasília, Brasília 70910-900, Brazil;
| | - Sehad N. Alarifi
- Department of Food and Nutrition Science, Al-Quwayiyah College of Sciences and Humanities, Shaqra University, Shaqraa 11971, Saudi Arabia;
| | - Najla A. Albaridi
- Department of Health Science, College of Health and Rehabilitation, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia;
| | - Zayed D. Alsharari
- Department of Clinical Nutrition, Faculty of Applied Medical Sciences, University of Tabuk, P.O. Box 741, Tabuk 71491, Saudi Arabia;
| | - António Raposo
- CBIOS (Research Center for Biosciences and Health Technologies), Universidade Lusófona de Humanidades e Tecnologias, Campo Grande 376, 1749-024 Lisboa, Portugal
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12
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Kebede D, Shiferaw Y, Kebede E, Demsiss W. Antimicrobial susceptibility and risk factors of uropathogens in symptomatic urinary tract infection cases at Dessie Referral Hospital, Ethiopia. BMC Microbiol 2025; 25:126. [PMID: 40057723 PMCID: PMC11889879 DOI: 10.1186/s12866-025-03842-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2024] [Accepted: 02/24/2025] [Indexed: 05/13/2025] Open
Abstract
BACKGROUND Urinary tract infection (UTI) is one of the most common bacterial infections encountered by clinicians in developing countries, affecting the urethra, bladder, and kidneys. It is a prevalent infectious disease among outpatients and hospitalized patients, leading to morbidity and mortality. Antibiotic resistance among uropathogens varies geographically, but empirical treatment is common in our study area. Therefore, this study aimed to evaluate antimicrobial susceptibility and risk factors of uropathogens in symptomatic UTI cases at Dessie Referral Hospital in northeast Ethiopia. METHODS A hospital-based cross-sectional study design was utilized to examine 256 participants with urinary tract complaints from February 1, 2024, to May 30, 2024. Consecutive convenience sampling was used to select participants. Midstream urine samples were collected, and bacteriological tests, including culture, Gram stain, biochemical tests, and antimicrobial susceptibility tests, were conducted following standard procedures. The data were entered into EpiData version 3.1 and analyzed using SPSS version 20 software. Bivariate and multivariate logistic regressions were carried out to identify potential risk factors associated with urinary tract infection. RESULTS The overall prevalence of bacteriuria was 22.7%. Escherichia coli (E. coli) accounted for the highest proportion 21(30.4%), followed by Coagulase-negative Staphylococcus (CoNS) at 15(21.7%) and Klebsiella spp 12(17.4%). Most Gram-positive bacteria were susceptible to gentamicin 19(90.5%) but less sensitive to trimethoprim-sulfamethoxazole 16(76.2%) and nitrofurantoin 18(85.7%). High resistance rates were observed for penicillin 9(60%) and cefoxitin 14(66.7%). On the other hand, amikacin (83.3%), gentamicin (81.3%), and nitrofurantoin (89.7%) were effective against Gram-negative bacteria. Resistance to tetracycline and ampicillin was reported at 53.8% against both groups of bacteria. Female sex (AOR = 4.21; 95% CI = 1.43-8.29, P = 0.002), diabetes mellitus (AOR = 14.786; 95% CI = 3.91-70.72, P = 0.001), and human immunodeficiency virus positivity (AOR = 5.273; 95% CI = 2.596-17.410, P = 0.002) were identified as significant risk factors for bacteriuria. CONCLUSION The prevalence of UTI among syptomatic patients was 22.7%. E. coli and coagulase negative Staphylococcus were the predominant isolates. The identified bacteria were resistant to commonly use antimicrobials. Therefore, there should be continuous surveillance of UTI and antimicrobial susceptibility testing to minimize urinary tract infection and antibiotic resistance in our study setting.
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Affiliation(s)
- Destaw Kebede
- Department of Medical Laboratory Science, Medical Microbiology Unit, Amhara Public Health Institute (APHI), Debre Markos City, Amhara Regional State, Ethiopia.
| | - Yeromnesh Shiferaw
- Department of Medical Laboratory Science, Metema General Hospital, Metema City, Amhara Regional State, Ethiopia
- Department of Medical Laboratory Sciences, College of Medicine and Health Science, Wollo University, Dessie City, Amhara Regional State, Ethiopia
| | - Edosa Kebede
- Department of Medical Laboratory Sciences, College of Medicine and Health Science, Wollo University, Dessie City, Amhara Regional State, Ethiopia
| | - Wondmagegn Demsiss
- Department of Medical Laboratory Sciences, College of Medicine and Health Science, Wollo University, Dessie City, Amhara Regional State, Ethiopia
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13
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Karlsson PA, Bolin C, Spång L, Frithiof R, Hultström M, Lipcsey M, Wang H, Järhult JD. Bacteriuria and antibiotic use during the third wave of COVID-19 intensive care in Sweden. Infect Dis (Lond) 2025; 57:284-293. [PMID: 39509144 DOI: 10.1080/23744235.2024.2423884] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 10/24/2024] [Accepted: 10/27/2024] [Indexed: 11/15/2024] Open
Abstract
BACKGROUND Urinary tract infections (UTIs) are prevalent among patients carrying indwelling catheters in the intensive care unit (ICU). This study investigates antibiotic use and bacterial colonisation among ICU patients during the third wave of the COVID-19 pandemic, building on our prior discovery of increased Enterococcus colonisation associated with increased cephalosporin use in early COVID-19. METHODS Longitudinal urine samples from COVID-19 patients (n = 109) with transurethral catheterisation were analysed for bacterial prevalence, further identified via MALDI-TOF. Microbiological results were combined with clinical data obtained daily, assessed and compared with COVID-19 waves 1 and 2. RESULTS Patients in wave 3 exhibited improved outcomes compared to those in waves 1 and 2, alongside a decrease in antibiotic use. Staphylococcus emerged as the primary bacterium and early colonizer of the urinary tract, potentially due to the absence of antibiotic treatment. Our results imply that length of stay (LOS) correlates solely with enteric pathogens and that antibiotic treatment correlates with colonisation by certain uropathogens, whereas the absence of antimicrobial therapy is associated with rapid colonisation of skin flora. Polymicrobial colonisation was common, predominantly involving Gram-positive bacteria. CONCLUSION Our findings underscore the complexity of bacteriuria in ICU patients, advocating for targeted surveillance and tailored antibiotic approaches to mitigate UTI risk. Insights into antibiotic use and bacterial colonisation are vital for optimising stewardship practices, combating antimicrobial resistance, and enhancing ICU patient outcomes.
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Affiliation(s)
- Philip A Karlsson
- Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
| | - Christian Bolin
- Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
| | - Labolina Spång
- Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, Sweden
| | - Robert Frithiof
- Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, Sweden
| | - Michael Hultström
- Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, Sweden
- Department of Medical Cell Biology, Integrative Physiology, Uppsala University, Uppsala, Sweden
| | - Miklos Lipcsey
- Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, Sweden
- Hedenstierna Laboratory, Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Helen Wang
- Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden
| | - Josef D Järhult
- Department of Medical Sciences, Zoonosis Science Center, Uppsala University, Uppsala, Sweden
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14
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Fritzenwanker M, Grabitz MO, Negwer V, Schwengers O, Arneth B, Chakraborty T, Imirzalioglu C, Wagenlehner F. Genome-based development and clinical evaluation of a customized LAMP panel to rapidly detect, quantify, and determine antibiotic sensitivity of Escherichia coli in native urine samples from urological patients. Eur J Clin Microbiol Infect Dis 2025; 44:703-715. [PMID: 39775368 PMCID: PMC11880174 DOI: 10.1007/s10096-024-05030-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 12/19/2024] [Indexed: 01/11/2025]
Abstract
PURPOSE We designed and tested a point of care test panel to detect E.coli and antibiotic susceptibility in urine samples from patients at the point of care in the urological department. The aim of this approach is to facilitate choosing an appropriate antibiotic for urinary tract infections (UTI) at first presentation in the context of increasing antibiotic resistance in uropathogens worldwide. METHODS We analyzed 162 E.coli isolates from samples from a university urological department to determine phenotypic and genotypic resistance data. With this data we created customized LAMP (loop-mediated isothermal amplification) panels for a commercial machine with which to detect and possibly quantify E.coli and six antibiotic resistance determinants. In a second step we tested these panel(s) for diagnostic accuracy on 1596 urine samples and compared with routine microbiological culture. RESULTS E.coli was detected with 95.4% sensitivity and 96.1% specificity. Dynamics of the LAMP amplification could be used to gauge bacterial loads in the samples. Antibiotic sensitivity was detected with good negative (sensitive) predictive values: ampicillin 92.8%, ampicillin/sulbactam 96.4%, cefuroxime 92.8%, cefotaxime 97.8%, trimethoprim/sulfamethoxazole 96.5%, ciprofloxacin 96.8%. CONCLUSION The LAMP panel provided E.coli detection and sensitivity information within one hour and thus could principally guide initial antibiotic therapy upon patients presenting with UTI. The panel helps to select initial adequate antibiotic therapy as well as providing diagnostic stewardship. Follow up investigations will expand the test system to other uropathogens.
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Affiliation(s)
- Moritz Fritzenwanker
- Institute of Medical Microbiology, Justus Liebig University Giessen, Giessen, Germany
- Clinic for Urology, Pediatric Urology and Andrology, Justus-Liebig-University, Giessen, Germany
- German Center for Infection Research (DZIF), partner site Giessen-Marburg-Langen, Giessen, Germany
| | - Marcel O Grabitz
- Institute of Medical Microbiology, Justus Liebig University Giessen, Giessen, Germany
- Clinic for Urology, Pediatric Urology and Andrology, Justus-Liebig-University, Giessen, Germany
- German Center for Infection Research (DZIF), partner site Giessen-Marburg-Langen, Giessen, Germany
| | - Vera Negwer
- Institute of Medical Microbiology, Justus Liebig University Giessen, Giessen, Germany
- Clinic for Urology, Pediatric Urology and Andrology, Justus-Liebig-University, Giessen, Germany
- German Center for Infection Research (DZIF), partner site Giessen-Marburg-Langen, Giessen, Germany
| | - Oliver Schwengers
- Bioinformatics and Systems Biology, Justus Liebig University Giessen, Giessen, Germany
| | - Borros Arneth
- Institute of Laboratory Medicine and Pathobiochemistry, Phillips University, Marburg, Germany
| | - Trinad Chakraborty
- Institute of Medical Microbiology, Justus Liebig University Giessen, Giessen, Germany
- German Center for Infection Research (DZIF), partner site Giessen-Marburg-Langen, Giessen, Germany
| | - Can Imirzalioglu
- Institute of Medical Microbiology, Justus Liebig University Giessen, Giessen, Germany.
- German Center for Infection Research (DZIF), partner site Giessen-Marburg-Langen, Giessen, Germany.
| | - Florian Wagenlehner
- Clinic for Urology, Pediatric Urology and Andrology, Justus-Liebig-University, Giessen, Germany
- German Center for Infection Research (DZIF), partner site Giessen-Marburg-Langen, Giessen, Germany
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15
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Jangid H, Shidiki A, Kumar G. Cranberry-derived bioactives for the prevention and treatment of urinary tract infections: antimicrobial mechanisms and global research trends in nutraceutical applications. Front Nutr 2025; 12:1502720. [PMID: 40078413 PMCID: PMC11896822 DOI: 10.3389/fnut.2025.1502720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2024] [Accepted: 02/03/2025] [Indexed: 03/14/2025] Open
Abstract
Introduction Urinary tract infections (UTIs) are a global health concern, increasingly complicated by antibiotic resistance. Cranberry-derived bioactive compounds, particularly proanthocyanidins (PACs), have emerged as a promising non-antibiotic strategy for UTI prevention. This review examines their efficacy, mechanisms of action, and the evolving research landscape through bibliometric analysis. Methods A comprehensive literature review was conducted to assess the role of cranberry metabolites in UTI prevention, focusing on anti-adhesive and antimicrobial mechanisms. Additionally, a bibliometric analysis of publications from 1962 to 2024 was performed to evaluate research trends, collaboration networks, and thematic developments. Results Cranberry metabolites, particularly A-type PACs, flavonoids, and phenolic acids, inhibit Escherichia coli adhesion to urothelial cells, reducing UTI recurrence. Gut microbiota-driven transformation of PACs into bioactive metabolites enhances their efficacy, while cranberry oligosaccharides disrupt biofilm formation in high-risk populations. Bibliometric analysis reveals a surge in research interest post-2000, with increasing global collaborations and a focus on clinical applications. Discussion and conclusion Cranberry bioactives demonstrate significant potential in UTI management, yet variations in formulation, dosage, and metabolic bioavailability present challenges. The growing research interest underscores the need for standardized clinical studies to optimize therapeutic efficacy and establish evidence-based guidelines for their use.
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Affiliation(s)
- Himanshu Jangid
- Department of Microbiology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India
| | - Amrullah Shidiki
- Department of Microbiology, National Medical College and Teaching Hospital, Birgunj, Nepal
| | - Gaurav Kumar
- Department of Microbiology, School of Bioengineering and Biosciences, Lovely Professional University, Phagwara, Punjab, India
- Amity Institute of Microbial Technology (AIMT), Jaipur, Rajasthan, India
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16
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Bermudez T, Schmitz JE, Boswell M, Humphries R. Novel technologies for the diagnosis of urinary tract infections. J Clin Microbiol 2025; 63:e0030624. [PMID: 39760497 PMCID: PMC11837515 DOI: 10.1128/jcm.00306-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2025] Open
Abstract
Urinary tract infections (UTIs) impose a substantial burden on patient quality of life and urine testing accounts for the majority of workload in many clinical microbiology laboratories. Traditional UTI diagnosis relies on symptoms, urinalysis, and culture which are interpreted based on historical guidelines. This approach, while foundational, presents limitations, particularly in complex cases. Low-level bacteriuria and the presence of fastidious organisms are often overlooked or entirely missed in standard urine culture, stressing the need for novel diagnostic methods and technologies. This mini-review summarizes the existing state of UTI diagnostics in 2024 and covers current and upcoming technologies including rapid molecular-based pathogen identification, next-generation sequencing, and advanced antimicrobial susceptibility testing. However, these methods represent unique challenges, and as they are implemented, they will require the field to adapt to new concepts to avoid misdiagnosis and overtreatment.
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Affiliation(s)
- Tomas Bermudez
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Jonathan E. Schmitz
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Malcolm Boswell
- Independent MicroDx Consultancy Services, Tuson, Arizona, USA
| | - Romney Humphries
- Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA
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17
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Baimakhanova B, Sadanov A, Trenozhnikova L, Balgimbaeva A, Baimakhanova G, Orasymbet S, Tleubekova D, Amangeldi A, Turlybaeva Z, Nurgaliyeva Z, Seisebayeva R, Kozhekenova Z, Sairankyzy S, Shynykul Z, Yerkenova S, Turgumbayeva A. Understanding the Burden and Management of Urinary Tract Infections in Women. Diseases 2025; 13:59. [PMID: 39997066 PMCID: PMC11854091 DOI: 10.3390/diseases13020059] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2024] [Revised: 02/10/2025] [Accepted: 02/14/2025] [Indexed: 02/26/2025] Open
Abstract
Urinary tract infections (UTIs) represent a prevalent health concern among the female population, with anatomical and physiological determinants such as a shorter urethra and its proximity to the rectum augmenting vulnerability. The presence of Escherichia coli and various other pathogens plays a significant role in the etiology of these infections, which can be aggravated by sexual intercourse and disturbances to the vaginal microbiome. The physiological alterations associated with pregnancy further elevate the likelihood of UTIs, with untreated cases potentially leading to severe complications such as pyelonephritis, preterm labor, and stillbirth. Furthermore, postmenopausal women encounter an augmented risk of UTIs attributable to estrogen deficiency and vaginal atrophy, as well as conditions including pelvic organ prolapse (POP) and urinary incontinence (UI), which hinder optimal bladder functionality. The aforementioned factors, in conjunction with the rising prevalence of cesarean deliveries and catheterization, complicate the management of UTIs. While precise diagnosis is paramount, it remains a formidable challenge, notwithstanding advancements in molecular diagnostic techniques. Management strategies encompass antibiotic-sparing therapies; however, the increasing incidence of multidrug resistance represents an alarming trend. Diverse guidelines from various medical specialties endeavor to standardize treatment approaches, yet significant inconsistencies continue to exist. This study systematically appraises the extant guidelines, evaluating the quality of evidence while identifying areas of agreement and discord to supply practitioners with effective strategies for UTI management.
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Affiliation(s)
- Baiken Baimakhanova
- LLP "Research and Production Center for Microbiology and Virology", 105 Bogenbay Batyr Str., Almaty 050010, Kazakhstan
| | - Amankeldi Sadanov
- LLP "Research and Production Center for Microbiology and Virology", 105 Bogenbay Batyr Str., Almaty 050010, Kazakhstan
| | - Lyudmila Trenozhnikova
- LLP "Research and Production Center for Microbiology and Virology", 105 Bogenbay Batyr Str., Almaty 050010, Kazakhstan
| | - Assya Balgimbaeva
- LLP "Research and Production Center for Microbiology and Virology", 105 Bogenbay Batyr Str., Almaty 050010, Kazakhstan
| | - Gul Baimakhanova
- LLP "Research and Production Center for Microbiology and Virology", 105 Bogenbay Batyr Str., Almaty 050010, Kazakhstan
| | - Saltanat Orasymbet
- LLP "Research and Production Center for Microbiology and Virology", 105 Bogenbay Batyr Str., Almaty 050010, Kazakhstan
| | - Diana Tleubekova
- LLP "Research and Production Center for Microbiology and Virology", 105 Bogenbay Batyr Str., Almaty 050010, Kazakhstan
| | - Alma Amangeldi
- LLP "Research and Production Center for Microbiology and Virology", 105 Bogenbay Batyr Str., Almaty 050010, Kazakhstan
| | - Zere Turlybaeva
- LLP "Research and Production Center for Microbiology and Virology", 105 Bogenbay Batyr Str., Almaty 050010, Kazakhstan
| | - Zhanar Nurgaliyeva
- Department of Outpatient Pediatrics, School of Pediatrics, S.D. Asfendiyarov Kazakh National Medical University, 96 Tolebi Str., Almaty 050010, Kazakhstan
| | - Roza Seisebayeva
- Department of Outpatient Pediatrics, School of Pediatrics, S.D. Asfendiyarov Kazakh National Medical University, 96 Tolebi Str., Almaty 050010, Kazakhstan
| | - Zhanat Kozhekenova
- Department of Public Health, S.D. Asfendiyarov Kazakh National Medical University, 96 Tolebi Str., Almaty 050010, Kazakhstan
| | - Saltanat Sairankyzy
- Department of Propaedeutics of Childhood Diseases, School of Pediatrics, S.D. Asfendiyarov Kazakh National Medical University, 96 Tolebi Str., Almaty 050010, Kazakhstan
| | - Zhanserik Shynykul
- Higher School of Medicine, Al-Farabi Kazakh National University, Almaty 050040, Kazakhstan
| | - Sandugash Yerkenova
- Department of Public Health, S.D. Asfendiyarov Kazakh National Medical University, 96 Tolebi Str., Almaty 050010, Kazakhstan
| | - Aknur Turgumbayeva
- Higher School of Medicine, Al-Farabi Kazakh National University, Almaty 050040, Kazakhstan
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18
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Gómez-Quiroz A, Avila-Cardenas BB, De Arcos-Jiménez JC, Perales-Guerrero L, Martínez-Ayala P, Briseno-Ramirez J. The Clinical Implications of Inappropriate Therapy in Community-Onset Urinary Tract Infections and the Development of a Bayesian Hierarchical Weighted-Incidence Syndromic Combination Antibiogram. Antibiotics (Basel) 2025; 14:187. [PMID: 40001430 PMCID: PMC11851549 DOI: 10.3390/antibiotics14020187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2025] [Revised: 02/05/2025] [Accepted: 02/11/2025] [Indexed: 02/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES The rise in multidrug-resistant pathogens complicates UTI management, particularly in empirical therapy. This study aimed to develop and describe a Bayesian hierarchical weighted-incidence syndromic combination antibiogram (WISCA) model to optimize antibiotic selection for adult patients with community-onset UTIs. METHODS A retrospective study was conducted using a Bayesian hierarchical model. Data from microbiology laboratory records and medical databases were analyzed, focusing on age, prior antibiotic exposure, and clinical characteristics. Clinical outcomes, including extended hospital stays and in-hospital mortality, were evaluated before WISCA model development. Unlike traditional antibiograms, a WISCA integrates patient-specific factors to improve antimicrobial coverage estimations. A total of 11 monotherapies and 18 combination therapies were tested against 15 pathogens, with posterior coverage probabilities and 95% highest density intervals (HDIs) used to assess coverage. RESULTS Inappropriate final antibiotic treatment was associated with worse outcomes. The Bayesian framework improved estimations, particularly for rare pathogen-antibiotic interactions, increasing model applicability in high-resistance settings. Combination regimens showed superior coverage, especially in MDR cases and older adults. CONCLUSIONS This study employed a comprehensive methodological approach for WISCA development, enhancing empirical antibiotic selection by incorporating local resistance data and patient-specific factors in a middle-income Latin American country with a high antimicrobial resistance profile. These findings provide a foundation for future clinical applications and antimicrobial stewardship strategies in high-resistance environments.
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Affiliation(s)
- Adolfo Gómez-Quiroz
- Microbiology Laboratory, Hospital Civil de Guadalajara “Fray Antonio Alcalde”, Guadalajara 44280, Mexico; (A.G.-Q.); (B.B.A.-C.)
| | - Brenda Berenice Avila-Cardenas
- Microbiology Laboratory, Hospital Civil de Guadalajara “Fray Antonio Alcalde”, Guadalajara 44280, Mexico; (A.G.-Q.); (B.B.A.-C.)
| | - Judith Carolina De Arcos-Jiménez
- Laboratory of Microbiological, Molecular and Biochemical Diagnostics (LaDiMMB), Tlajomulco University Center, University of Guadalajara, Tlajomulco de Zuñiga 45641, Mexico;
| | - Leonardo Perales-Guerrero
- Department of Internal Medicine, Hospital Civil de Guadalajara “Fray Antonio Alcalde”, Guadalajara 44280, Mexico;
| | - Pedro Martínez-Ayala
- HIV Unit, Hospital Civil de Guadalajara “Fray Antonio Alcalde”, Guadalajara 44280, Mexico;
| | - Jaime Briseno-Ramirez
- Department of Internal Medicine, Hospital Civil de Guadalajara “Fray Antonio Alcalde”, Guadalajara 44280, Mexico;
- Health Division, Tlajomulco University Center, University of Guadalajara, Tlajomulco de Zuñiga 45641, Mexico
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19
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He Y, Zhao J, Wang L, Han C, Yan R, Zhu P, Qian T, Yu S, Zhu X, He W. Epidemiological trends and predictions of urinary tract infections in the global burden of disease study 2021. Sci Rep 2025; 15:4702. [PMID: 39922870 PMCID: PMC11807111 DOI: 10.1038/s41598-025-89240-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2024] [Accepted: 02/04/2025] [Indexed: 02/10/2025] Open
Abstract
Urinary tract infections (UTIs) are prevalent; however, comprehensive and current epidemiological data remain scarce. This study examined the global, national, and regional burden of UTIs by sex, age, and socio-demographic index (SDI) from 1990 to 2021. The 2021 Global Burden of Disease study included age-standardised incidence rate (ASIR), age-standardised prevalence rate (ASPR), age-standardised death rate (ASDR), and age-standardised disability-adjusted life years rate (ASDAR). The estimated annual percentage change was used to depict temporal trends, whereas Pearson correlation analysis explore its correlation with the human development index (HDI), the SDI, and age-standardised rates (ASRs). An autoregressive integrated moving average model forecasted the UTI burden trends. From 1990 to 2021, the number of UTI cases increased by 66.45%, reaching 4.49 billion cases, with an ASIR of 5,531.88 per 100,000 population. The greatest incidence of UTIs was seen in women and older adult men. Tropical Latin America and low-middle SDI regions exhibited the highest ASIR, ASPR, ASDR, and ASDAR, while East Asia showed the lowest. ASDR and ASDAR decreased with higher SDI levels. ASR and HDI were weakly positively correlated with ASDR and ASDAR. ASIR, ASPR, and ASDAR are projected to increase until 2050. The global burden of UTIs is rising and is influenced by geographical location, age, sex, and economic development, crucial for guiding medical practices and forming relevant policies.
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Affiliation(s)
- Yining He
- Division of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China
| | - Jing Zhao
- Division of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China
| | - Lanhui Wang
- Division of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China
| | - Chao Han
- Division of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China
- Yancheng Dafeng Hospital of Chinese Medicine, Teaching Hospital of Nanjing University of Chinese Medicine, Yancheng, 224199, China
| | - Ruxue Yan
- Division of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China
| | - Peiqi Zhu
- Division of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China
| | - Tianyang Qian
- Division of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China
| | - Siyao Yu
- Division of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China
| | - Xiaolin Zhu
- Department of Nephrology, the Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, 210017, China.
| | - Weiming He
- Division of Nephrology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing, 210029, China.
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20
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Amiri F, Safiri S, Aletaha R, Sullman MJM, Hassanzadeh K, Kolahi AA, Arshi S. Epidemiology of urinary tract infections in the Middle East and North Africa, 1990-2021. Trop Med Health 2025; 53:16. [PMID: 39910666 DOI: 10.1186/s41182-025-00692-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2024] [Accepted: 01/19/2025] [Indexed: 02/07/2025] Open
Abstract
OBJECTIVE This research reports the incidence, mortality, and disability-adjusted life years (DALYs) associated with urinary tract infections (UTIs) in the Middle East and North Africa (MENA) region, stratified by sex, age, and Socio-demographic Index (SDI) from 1990 to 2021. METHODS Data were sourced from the Global Burden of Disease 2021 study, encompassing all 21 countries in the region. Metrics such as absolute counts, age-standardised rates, and percentage changes from 1990 to 2021 are presented with 95% uncertainty intervals (UIs). RESULTS In 2019, the MENA region recorded an incidence rate of 4,033.4 per 100,000 (95% UIs: 3,553.7-4,548.7) and 7,687 deaths (95% UIs: 6,663-8,969). The DALY rate was 41.3 per 100,000 (95% UIs: 36.1-47.2), which was highest among older adults, reaching a peak in the 80-89 age range, and increasing with age, particularly from the 50 + age groups. A non-linear relationship was identified between the burden of UTIs and the SDI, with higher-than-expected rates in lower SDI countries such as Syria and Lebanon. CONCLUSION Despite a substantial increase in the total number of UTI cases and DALYs in the region from 1990 to 2021, the age-standardised rates remained stable. The larger burden in lower SDI countries highlights the urgent need for targeted public health interventions. Improving healthcare access and antibiotic stewardship is crucial to mitigating the growing burden of UTIs, particularly among older populations in the region.
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Affiliation(s)
- Fatemeh Amiri
- Social Determinants of Health Research Center, Department of Community Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Saeid Safiri
- Social Determinants of Health Research Center, Department of Community Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
- Clinical Research Development Unit of Tabriz Valiasr Hospital, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Reza Aletaha
- Neurosciences Research Center, Aging Research Institute, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Mark J M Sullman
- Department of Life and Health Sciences, University of Nicosia, Nicosia, Cyprus
- Department of Social Sciences, University of Nicosia, Nicosia, Cyprus
| | - Kamaleddin Hassanzadeh
- Department of Urology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ali-Asghar Kolahi
- Social Determinants of Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shahnam Arshi
- Social Determinants of Health Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
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21
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Alhaj SS, Allami S, Mohamadiyeh A, Agha A, Ali AKA, Habbal JMB, Saeed BQ. Knowledge, attitudes, and practices regarding urinary tract infections among women in the United Arab Emirates. PLoS One 2025; 20:e0298993. [PMID: 39792816 PMCID: PMC11723537 DOI: 10.1371/journal.pone.0298993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2024] [Accepted: 10/22/2024] [Indexed: 01/12/2025] Open
Abstract
BACKGROUND Urinary tract infections (UTIs), which are infections of the kidneys, ureters, bladder, or urethra, are a worldwide public health concern. As compared to men, women are more prone to UTIs. There have been several studies that explore the knowledge, attitudes, and practices of women regarding UTIs in different countries, but no such study has been conducted in the UAE; therefore, we conducted this study in the UAE setting. METHODS This study was conducted using an online survey created on Microsoft Forms. The minimum sample size required for our study was 385. This study was conducted after obtaining ethical approval from the Research Ethics Committee at the University of Sharjah. A personally designed questionnaire consisting of 21 items, derived from previous research was used to record data. The data was analyzed using SPSS. RESULTS A total of 475 females were included in the study. Most respondents were aged 18-30 years (47.4%). Our study found that a majority of the participants (69.7%) correctly identified bacteria as the most common cause of UTIs. With regards to practices undertaken during UTIs, among the participants with a history of UTI episodes, 32.6% waited 24-48 hours before seeking medical attention at a hospital or clinic, while 10% did not visit a hospital at all. Distinct trends were found when comparing demographic factors with knowledge levels. Most notably, the age group of 18-30 years showed the highest percentage of high-knowledge individuals (49%) compared to other age groups (p < 0.05). Education level was significantly (p = 0.003) associated with UTI knowledge. Going to the hospital/clinic was reported by 41% with high knowledge but only by 20% of those with poor knowledge. Moreover, a higher proportion of individuals with high knowledge sought medical attention immediately within 24 hours (47%). CONCLUSION Most of the participants possessed adequate knowledge regarding UTIs. Higher knowledge levels were associated with more proactive and appropriate health behaviors, such as seeking medical attention promptly and drinking more water.
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Affiliation(s)
| | - Sajad Allami
- College of Medicine, University of Sharjah, Sharjah, UAE
| | | | - Ammar Agha
- College of Medicine, University of Sharjah, Sharjah, UAE
| | | | | | - Balsam Qubais Saeed
- Clinical Sciences Department, College of Medicine, University of Sharjah, Sharjah, UAE
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22
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Milosevic M, Magnutzki A, Braun T, Hussain S, Jakschitz T, Kragl M, Soeberdt M, Nausch B, Bonn GK, Huber LA, Valovka T. Anti-inflammatory and cytoprotective polypharmacology of Canephron N reveals targeting of the IKK-NF-κB and p38-MK2-RIPK1 axes. Biomed Pharmacother 2025; 182:117747. [PMID: 39671726 DOI: 10.1016/j.biopha.2024.117747] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2024] [Revised: 12/06/2024] [Accepted: 12/08/2024] [Indexed: 12/15/2024] Open
Abstract
Urinary tract infections are among the most frequently occurring forms of infection, and inflammation and tissue damage contribute significantly to symptoms, e.g., dysuria and urge. Canephron N is an orally bioavailable herbal medicine with anti-inflammatory, spasmolytic, anti-adhesive, and anti-nociceptive therapeutic effects that is approved for the treatment of uncomplicated urinary tract infections. Here, we used renal tubular epithelial HK-2 cells to study the anti-inflammatory and cytoprotective effects and molecular mechanisms of its active component, BNO 2103. BNO 2103 suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation by lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα) and prevented inhibitory κB kinase (IKK)-dependent phosphorylation and degradation of inhibitor of nuclear factor kappa B alpha (IκBα). BNO 2103 also suppressed the inflammation-specific S536 phosphorylation of the NF-κB subunit p65 and the production of a specific set of inflammatory cytokines. Unlike other NF-κB inhibitors, BNO 2103 demonstrated cytoprotection against TNFα-induced cytotoxicity. Our data suggest that BNO 2103 acts primarily through the mitogen-activated protein kinase p38 (p38 MAPK)-MAPK-activated protein kinase 2 (MK2) axis by promoting receptor-interacting serine/threonine protein kinase 1 (RIPK1) phosphorylation at S320. Simultaneously, it suppresses S166 autophosphorylation and subsequent activation of RIPK1, which is required for apoptotic and necroptotic responses to TNFα. This study confirms Canephron N as an effective alternative to traditional anti-inflammatory drugs and provides initial evidence of its ability to inhibit apoptosis and necroptosis in the urogenital system. It also presents a detailed pathway investigation that identifies the specific targets of Canephron N within the NF-κB signaling cascade.
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Affiliation(s)
- Marija Milosevic
- ADSI-Austrian Drug Screening Institute, Leopold-Franzens University of Innsbruck, Innsbruck 6020, Austria
| | - Alexander Magnutzki
- ADSI-Austrian Drug Screening Institute, Leopold-Franzens University of Innsbruck, Innsbruck 6020, Austria
| | - Theodor Braun
- ADSI-Austrian Drug Screening Institute, Leopold-Franzens University of Innsbruck, Innsbruck 6020, Austria
| | - Shah Hussain
- ADSI-Austrian Drug Screening Institute, Leopold-Franzens University of Innsbruck, Innsbruck 6020, Austria
| | - Thomas Jakschitz
- ADSI-Austrian Drug Screening Institute, Leopold-Franzens University of Innsbruck, Innsbruck 6020, Austria
| | | | | | | | - Günther K Bonn
- ADSI-Austrian Drug Screening Institute, Leopold-Franzens University of Innsbruck, Innsbruck 6020, Austria.
| | - Lukas A Huber
- Institute of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria; ADSI-Austrian Drug Screening Institute, Leopold-Franzens University of Innsbruck, Innsbruck 6020, Austria.
| | - Taras Valovka
- Institute of Cell Biology, Biocenter, Medical University of Innsbruck, Innsbruck 6020, Austria; Department of Pediatrics I, Medical University of Innsbruck, Innsbruck 6020, Austria.
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23
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Wang YC, Jiesisibieke ZL, Yang YP, Wang BL, Hsiung MC, Tung TH. Disparities in the Prevalence of Urinary Diseases Among Prisoners in Taiwan: Population-Based Cross-Sectional Study. JMIR Public Health Surveill 2024; 10:e60136. [PMID: 39727265 PMCID: PMC11693784 DOI: 10.2196/60136] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2024] [Revised: 10/02/2024] [Accepted: 10/09/2024] [Indexed: 12/28/2024] Open
Abstract
BACKGROUND Prisoner health is a major global concern, with prisoners often facing limited access to health care and enduring chronic diseases, infectious diseases, and poor mental health due to unsafe prison environments, unhygienic living conditions, and inadequate medical resources. In Taiwan, prison health is increasingly an issue, particularly concerning urinary diseases such as urinary tract infections. Limited access to health care and unsanitary conditions exacerbate these problems. Urinary disease epidemiology varies by sex and age, yet studies in Asia are scarce, and comprehensive data on urinary diseases in Taiwanese prisons remain limited. OBJECTIVE This study aimed to investigate the prevalence of urinary diseases among Taiwanese prisoners and explore the differences in disease prevalence between men and women, as well as across different age groups. METHODS This study used data on prisoners from the National Health Insurance Research Database covering the period from January 1 to December 31, 2013. Prisoners covered by National Health Insurance who were diagnosed with urinary diseases, identified by ICD-9-CM (International Classification of Diseases, Ninth Revision, Clinical Modification) codes 580-599 based on their medical records, and had more than one medical visit to ambulatory care or inpatient services were included. Sex- and age-stratified analyses were conducted to determine the differences in the prevalence of urinary diseases. RESULTS We examined 83,048 prisoners, including 2998 with urinary diseases. The overall prevalence of urinary system diseases among prisoners was 3.61% (n=2998; n=574, 6.64% in men and n=2424, 3.26% in women). The prevalence rate in men was significantly lower than that in women (prevalence ratio: 0.46, P<.001). In age-stratified analysis, the prevalence rate among prisoners aged >40 years was 4.5% (n=1815), compared to 2.77% (n=1183) in prisoners aged ≤40 years. Prisoners aged >40 years had a higher prevalence (prevalence ratio: 1.69, P<.001). Other disorders of the urethra and urinary tract (ICD-9-CM: 599), including urinary tract infection, urinary obstruction, and hematuria, were the most prevalent diseases of the urethra and urinary tract across age and sex groups. Women and older prisoners had a higher prevalence of most urinary tract diseases. There were no significant sex-specific differences in adjusted prevalence ratios for acute glomerulonephritis, nephrotic syndrome, kidney infections, urethritis (nonsexually transmitted), or urethral syndrome. However, based on the age-specific adjusted prevalence ratio analysis, cystitis was more prevalent among younger prisoners (prevalence ratio: 0.69, P=.004). CONCLUSIONS Urinary system infections and inflammation are common in prisons. Our findings advocate for policy reforms aimed at improving health care accessibility in prisons, with a particular focus on the needs of high-risk groups such as women and older prisoners. Further research linking claims data with prisoner information is crucial to providing more comprehensive medical services and achieving health equity.
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Affiliation(s)
- Yen-Chun Wang
- Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
- Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Zhu Liduzi Jiesisibieke
- Evidence-Based Medicine Center, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, 150 Ximen Street, Gucheng Street, Linhai, Zhejiang, 317000, China, 86 13666801279
| | - Yu-Pei Yang
- Evidence-Based Medicine Center, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, 150 Ximen Street, Gucheng Street, Linhai, Zhejiang, 317000, China, 86 13666801279
- Department of Hematology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, Zhejiang, China
| | - Bing-Long Wang
- School of Health Policy and Management, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China
| | - Ming-Chon Hsiung
- Department of Occupational Safety and Health, Cheng-Hsin General Hospital, Taipei, Taiwan
| | - Tao-Hsin Tung
- Evidence-Based Medicine Center, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, 150 Ximen Street, Gucheng Street, Linhai, Zhejiang, 317000, China, 86 13666801279
- Department of Urology, Enze Medical Center (Group), Affiliated to Hangzhou Medical College, Linhai, Zhejiang, China
- Key Laboratory of Evidence-based Radiology of Taizhou, Linhai, Zhejiang, China
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24
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Flatby HM, Ravi A, Liyanarachi KV, Afset JE, Rasheed H, Brumpton BM, Hveem K, Åsvold BO, DeWan AT, Solligård E, Damås JK, Rogne T. A Genome-wide Association Study of Susceptibility to Upper Urinary Tract Infections. J Infect Dis 2024; 230:e1334-e1343. [PMID: 38713594 PMCID: PMC11646603 DOI: 10.1093/infdis/jiae231] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Revised: 03/21/2024] [Accepted: 05/06/2024] [Indexed: 05/09/2024] Open
Abstract
BACKGROUND Our goal was to identify genetic and modifiable risk factors for upper urinary tract infections (UTIs). METHODS We used data from UK Biobank, the Trøndelag Health Study, and the Michigan Genomics Initiative to conduct genome-wide association studies and sex-stratified analyses on upper UTI. Mendelian randomization (MR) analyses were conducted to examine potential causal relationships between cardiometabolic risk factors and upper UTIs. RESULTS One genome-wide significant (P ≤ 5E-08) locus was associated with the susceptibility to upper UTI, located near TSN in the female-only analysis. Additionally, we identified suggestive (P ≤ 5E-06) loci near DNAI3 for females, SCAMP1-AS1 for males, and near TSN, LINC00603, and HLA-DQA2 for both sexes. In MR analyses, higher genetically predicted lifetime smoking scores were associated with an increased risk of developing upper UTI for females and both sexes (odds ratio [OR], 4.84, P = 4.50E-06 and OR, 2.79, P = 3.02E-05, respectively). CONCLUSIONS We found that genetic variants near TSN was associated with the risk of upper UTIs among females. In addition, we found several genetic loci with suggestive associations with the risk of upper UTIs. Finally, MR analyses found smoking to be a potential causal risk factor for upper UTIs.
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Affiliation(s)
- Helene M Flatby
- Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology
- Clinic of Anaesthesia and Intensive Care
| | - Anuradha Ravi
- Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology
- Department of Medical Genetics
| | - Kristin V Liyanarachi
- Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology
- Department of Infectious Diseases, St Olavs Hospital, Trondheim University Hospital
| | - Jan E Afset
- Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology
- Department of Medical Microbiology, St Olavs Hospital, Trondheim University Hospital
| | - Humaira Rasheed
- K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology
- Clinic of Medicine, St Olavs Hospital, Trondheim University Hospital, Trondheim
| | - Ben M Brumpton
- K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology
- Clinic of Medicine, St Olavs Hospital, Trondheim University Hospital, Trondheim
- The Trøndelag Health Study Research Center, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger
| | - Kristian Hveem
- K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology
- Department of Research, Innovation, and Education
| | - Bjørn O Åsvold
- K. G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, Norwegian University of Science and Technology
- The Trøndelag Health Study Research Center, Department of Public Health and Nursing, Norwegian University of Science and Technology, Levanger
- Department of Endocrinology, Clinic of Medicine, St Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Andrew T DeWan
- Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology
- Department of Chronic Disease Epidemiology and Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, Connecticut
| | - Erik Solligård
- Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology
- Department of Innovation, Education and Health Sciences, Helse Møre og Romsdal Hospital Trust, Ålesund, Norway
| | - Jan K Damås
- Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology
- Department of Infectious Diseases, St Olavs Hospital, Trondheim University Hospital
- Centre of Molecular Inflammation Research, Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Tormod Rogne
- Mid-Norway Centre for Sepsis Research, Department of Circulation and Medical Imaging, Norwegian University of Science and Technology
- Department of Chronic Disease Epidemiology and Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, Connecticut
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25
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Lopatto EDB, Santiago-Borges JM, Sanick DA, Malladi SK, Azimzadeh PN, Timm MW, Fox IF, Schmitz AJ, Turner JS, Ahmed SS, Ortinau L, Gualberto NC, Pinkner JS, Dodson KW, Ellebedy AH, Kau AL, Hultgren SJ. Monoclonal antibodies targeting the FimH adhesin protect against uropathogenic E. coli UTI. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.12.10.627638. [PMID: 39713358 PMCID: PMC11661314 DOI: 10.1101/2024.12.10.627638] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/24/2024]
Abstract
As antimicrobial resistance increases, urinary tract infections (UTIs) are expected to pose an increased burden in morbidity and expense on the healthcare system, increasing the need for alternative antibiotic-sparing treatments. Most UTIs are caused by uropathogenic Escherichia coli (UPEC), while Klebsiella pneumoniae causes a significant portion of non-UPEC UTIs. Both bacteria express type 1 pili tipped with the mannose-binding FimH adhesin critical for UTI pathogenesis. We generated and biochemically characterized 33 murine monoclonal antibodies (mAbs) to FimH. Two mAbs protected mice from E. coli UTI. Mechanistically, we show that this protection is Fc-independent and mediated by the ability of these mAbs to sterically block FimH function. Our data reveals that FimH mAbs hold promise as an antibiotic-sparing treatment strategy.
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Affiliation(s)
- Edward D. B. Lopatto
- Department of Molecular Microbiology, Washington University in St Louis, St Louis, MO, U.S.A
- Center for Women’s Infectious Disease Research, Washington University in St Louis, St Louis, MO, U.S.A
| | - Jesús M. Santiago-Borges
- Department of Molecular Microbiology, Washington University in St Louis, St Louis, MO, U.S.A
- Center for Women’s Infectious Disease Research, Washington University in St Louis, St Louis, MO, U.S.A
- Division of Allergy and Immunology, Department of Medicine, Washington University in St Louis, St Louis, MO, U.S.A
| | - Denise A. Sanick
- Department of Molecular Microbiology, Washington University in St Louis, St Louis, MO, U.S.A
- Center for Women’s Infectious Disease Research, Washington University in St Louis, St Louis, MO, U.S.A
| | - Sameer Kumar Malladi
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, U.S.A
| | - Philippe N. Azimzadeh
- Department of Molecular Microbiology, Washington University in St Louis, St Louis, MO, U.S.A
- Center for Women’s Infectious Disease Research, Washington University in St Louis, St Louis, MO, U.S.A
| | - Morgan W. Timm
- Department of Molecular Microbiology, Washington University in St Louis, St Louis, MO, U.S.A
- Center for Women’s Infectious Disease Research, Washington University in St Louis, St Louis, MO, U.S.A
| | - Isabella F. Fox
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, U.S.A
| | - Aaron J. Schmitz
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, U.S.A
| | - Jackson S. Turner
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, U.S.A
| | - Shaza Sayed Ahmed
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, U.S.A
| | - Lillian Ortinau
- Department of Molecular Microbiology, Washington University in St Louis, St Louis, MO, U.S.A
- Center for Women’s Infectious Disease Research, Washington University in St Louis, St Louis, MO, U.S.A
- Division of Allergy and Immunology, Department of Medicine, Washington University in St Louis, St Louis, MO, U.S.A
| | - Nathaniel C. Gualberto
- Department of Molecular Microbiology, Washington University in St Louis, St Louis, MO, U.S.A
- Center for Women’s Infectious Disease Research, Washington University in St Louis, St Louis, MO, U.S.A
| | - Jerome S. Pinkner
- Department of Molecular Microbiology, Washington University in St Louis, St Louis, MO, U.S.A
- Center for Women’s Infectious Disease Research, Washington University in St Louis, St Louis, MO, U.S.A
| | - Karen W. Dodson
- Department of Molecular Microbiology, Washington University in St Louis, St Louis, MO, U.S.A
- Center for Women’s Infectious Disease Research, Washington University in St Louis, St Louis, MO, U.S.A
| | - Ali H. Ellebedy
- Department of Molecular Microbiology, Washington University in St Louis, St Louis, MO, U.S.A
- Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, U.S.A
- Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO, U.S.A
| | - Andrew L. Kau
- Department of Molecular Microbiology, Washington University in St Louis, St Louis, MO, U.S.A
- Center for Women’s Infectious Disease Research, Washington University in St Louis, St Louis, MO, U.S.A
- Division of Allergy and Immunology, Department of Medicine, Washington University in St Louis, St Louis, MO, U.S.A
| | - Scott J. Hultgren
- Department of Molecular Microbiology, Washington University in St Louis, St Louis, MO, U.S.A
- Center for Women’s Infectious Disease Research, Washington University in St Louis, St Louis, MO, U.S.A
- Center for Vaccines and Immunity to Microbial Pathogens, Washington University School of Medicine, St. Louis, MO, U.S.A
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Gilboa M, Boatwright R, Salazar V, Simon JC, North B, Vu C, Vega A, Jennings Deronde K, Rosa R, Abbo LM. Development and validation of an antimicrobial stewardship clinical decision-support tool to improve the management of urinary tract infections versus asymptomatic bacteriuria in hospitalized patients. ANTIMICROBIAL STEWARDSHIP & HEALTHCARE EPIDEMIOLOGY : ASHE 2024; 4:e210. [PMID: 39563917 PMCID: PMC11574593 DOI: 10.1017/ash.2024.433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/25/2024] [Revised: 08/27/2024] [Accepted: 08/27/2024] [Indexed: 11/21/2024]
Abstract
Objective To assess the effectiveness of a 3-question decision-support tool to guide the diagnosis and treatment of urinary tract infections (UTIs) in acute care hospitalized patients as an antibiotic and diagnostic stewardship initiative. Design Retrospective cohort study. Setting Four acute care hospitals within the same health system in Miami, FL. Patients 124, admitted from the emergency department and hospitalized adult patients, treated with antibiotics for the indication of a UTI between March and April 2023. Intervention We developed a 3-step clinical decision-support tool (CDST) to evaluate the appropriateness of urine cultures and antibiotic treatment. The tool's recommendations when deciding to prescribe antibiotics were compared with the actual need for treatment throughout the hospitalization, up to the time of patient discharge. Results Overall, 31% of antibiotics prescribed for UTIs were inappropriate and met the criteria for asymptomatic bacteriuria (ASB) based on the CDST. Prospective implementation of the decision-support tool could potentially reduce antibiotic use by 33.6%, corresponding to 265 days of unnecessary therapy. The sensitivity and specificity of the tool were calculated to be 98.6% and 100%, respectively, indicating high accuracy in identifying the need for antibiotic treatment. Urinalysis alone was insufficient to differentiate between symptomatic UTIs and ASB, with leukocyturia present in 95.3% of UTI cases and 94.6% of ASB cases (P = 0.87). Conclusions Implementing a 3-question CDST may reduce unnecessary laboratory work-up and treatment for ASB improving the diagnostic and antimicrobial stewardship of UTIs.
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Affiliation(s)
- Mayan Gilboa
- Faculty of Medicine, Tel Aviv University, Tel Aviv-Yafo, Israel
- Department of Infection prevention and control, Jackson Health System, Miami, FL, USA
- Infection Prevention and Control Unit, Sheba Medical Center, Ramat Gan, Israel
| | | | | | - Julio C Simon
- Department of Pharmacy, Jackson Health System, Miami, FL, USA
| | - Brianna North
- Department of Pharmacy, Jackson Health System, Miami, FL, USA
| | - Christine Vu
- Department of Pharmacy, Jackson Health System, Miami, FL, USA
| | - Ana Vega
- Department of Pharmacy, Jackson Health System, Miami, FL, USA
| | | | - Rossana Rosa
- Department of Infection prevention and control, Jackson Health System, Miami, FL, USA
| | - Lilian M Abbo
- Department of Infection prevention and control, Jackson Health System, Miami, FL, USA
- Department of Medicine, Division of Infectious Diseases, University of Miami Miller School of Medicine, Miami, FL, USA
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Newlands AF, Kramer ML, Maxwell K, Price JL, Finlay KA. The mediating role of coping in the relationship between perceived health and psychological wellbeing in recurrent urinary tract infection: the rUTI Illness Process Model. Health Psychol Behav Med 2024; 12:2420806. [PMID: 39502339 PMCID: PMC11536654 DOI: 10.1080/21642850.2024.2420806] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 10/15/2024] [Indexed: 11/08/2024] Open
Abstract
Background: Recurrent urinary tract infection (rUTI) is associated with significant symptom and quality of life burden. Given the unique challenges in diagnostics and management, healthcare disillusionment and stigmatisation which distinguish rUTI from other urological conditions, specific identification of the key illness processes experienced by this patient population is required. This study aimed to identify the unique illness processes and perceptions that contribute to quality of life in rUTI, through perceived health status, psychological wellbeing, and coping. Methods: An international sample of adults living with rUTI (N = 389, 96.9% female) completed a cross-sectional survey comprising the following standardised questionnaires: the EuroQoL EQ-5D-5L, Patient Health Questionnaire 9 (PHQ-9), Generalised Anxiety Disorder 7 (GAD-7), Connor-Davidson Resilience Scale-10 (CD-RISC-10), Pain Catastrophising Scale (PCS). Sociodemographic characteristics were also assessed. Structural equation modelling was conducted to identify the underlying constructs which contributed to psychological wellbeing in rUTI, establishing the 'rUTI Illness Process Model'. Results: The positive relationship between 'perceived health status' and 'psychological wellbeing' was partially mediated by 'rUTI coping', after controlling for the impact of household income and age (p < .001). The model demonstrated a large effect size (R 2 = .81) and good local and global fit. Overall, rUTI coping skills, boosted by resilience and weakened by pain catastrophising, contribute to a significant proportion of the positive relationship between perceived health status and psychological wellbeing in rUTI. A uniquely vulnerable patient phenotype emerges from this new research, with patients who are younger and/or of lower socioeconomic status at greater risk of poorer rUTI health outcomes and psychological wellbeing, potentially requiring further support. Conclusions: The rUTI Illness Process Model establishes the crucial need to clinically characterise the individualised illness perceptions and metacognitive strategies held by people living with rUTI, revealing that patient-centred interventions targeting illness perceptions and coping strategies require prioritisation to enhance patient outcomes and the patient experience of living with rUTI.
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Affiliation(s)
- Abigail F. Newlands
- School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK
| | - Melissa L. Kramer
- School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK
- Live UTI Free Ltd, Dublin, Ireland
| | - Kayleigh Maxwell
- Department of Psychology, Faculty of Natural Sciences, University of Stirling, Stirling, UK
| | | | - Katherine A. Finlay
- School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK
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Dutta R, Stothers L, Ackerman AL. Manipulating the Gut Microbiome in Urinary Tract Infection-Prone Patients. Urol Clin North Am 2024; 51:525-536. [PMID: 39349020 DOI: 10.1016/j.ucl.2024.07.016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/02/2024]
Abstract
Although antibiotics remain the mainstay of urinary tract infection treatment, many affected women can be caught in a vicious cycle in which antibiotics given to eradicate one infection predispose them to develop another. This effect is primarily mediated by disturbances in the gut microbiome that both directly enrich for uropathogenic overgrowth and induce systemic alterations in inflammation, tissue permeability, and metabolism that also decrease host resistance to infection recurrences. Here, we discuss nonantibiotic approaches to manipulating the gut microbiome to reverse the systemic consequences of antibiotics, including cranberry supplementation and other dietary approaches, probiotic administration, and fecal microbiota transplantation.
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Affiliation(s)
- Rahul Dutta
- Division of Urogynecology and Reconstructive Pelvic Surgery, David Geffen School of Medicine at UCLA, Box 951738, Los Angeles, CA 90095-1738, USA
| | - Lynn Stothers
- Division of Urogynecology and Reconstructive Pelvic Surgery, David Geffen School of Medicine at UCLA, Box 951738, Los Angeles, CA 90095-1738, USA
| | - A Lenore Ackerman
- Division of Urogynecology and Reconstructive Pelvic Surgery, David Geffen School of Medicine at UCLA, Box 951738, Los Angeles, CA 90095-1738, USA.
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Bellankimath AB, Chapagain C, Branders S, Ali J, Wilson RC, Johansen TEB, Ahmad R. Culture and amplification-free nanopore sequencing for rapid detection of pathogens and antimicrobial resistance genes from urine. Eur J Clin Microbiol Infect Dis 2024; 43:2177-2190. [PMID: 39283495 PMCID: PMC11534888 DOI: 10.1007/s10096-024-04929-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2024] [Accepted: 08/23/2024] [Indexed: 11/05/2024]
Abstract
PURPOSE Urinary Tract Infections (UTIs) are among the most prevalent infections globally. Every year, approximately 150 million people are diagnosed with UTIs worldwide. The current state-of-the-art diagnostic methods are culture-based and have a turnaround time of 2-4 days for pathogen identification and susceptibility testing. METHODS This study first establishes an optical density culture-based method for spiking healthy urine samples with the six most prevalent uropathogens. Urine samples were spiked at clinically significant concentrations of 103-105 CFU/ml. Three DNA extraction kits (BioStic, PowerFood, and Blood and Tissue) were investigated based on the DNA yield, average processing time, elution volume, and the average cost incurred per extraction. After DNA extraction, the samples were sequenced using MinION and Flongle flow cells. RESULTS The Blood and Tissue kit outperformed the other kits based on the investigated parameters. Using nanopore sequencing, all the pathogens and corresponding genes were only identified at a spike concentration of 105 CFU/ml, achieved after 10 min and 3 hours of sequencing, respectively. However, some pathogens and antibiotic-resistance genes (ARG) could be identified from spikes at 103 colony formation units (CFU/mL). The overall turnaround time was five hours, from sample preparation to sequencing-based identification of pathogen ID and antimicrobial resistance genes. CONCLUSION This study demonstrates excellent promise in reducing the time required for informed antibiotic administration from 48 to 72 h to five hours, thereby reducing the number of empirical doses and increasing the chance of saving lives.
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Affiliation(s)
| | - Crystal Chapagain
- Department of Biotechnology, Inland Norway University of Applied Sciences, Holsetgata 22, Hamar, 2317, Norway
| | - Sverre Branders
- Department of Biotechnology, Inland Norway University of Applied Sciences, Holsetgata 22, Hamar, 2317, Norway
| | - Jawad Ali
- Department of Biotechnology, Inland Norway University of Applied Sciences, Holsetgata 22, Hamar, 2317, Norway
| | - Robert C Wilson
- Department of Biotechnology, Inland Norway University of Applied Sciences, Holsetgata 22, Hamar, 2317, Norway
| | - Truls E Bjerklund Johansen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Institute of Clinical Medicine, University of Aarhus, Aarhus, Denmark
| | - Rafi Ahmad
- Department of Biotechnology, Inland Norway University of Applied Sciences, Holsetgata 22, Hamar, 2317, Norway.
- Institute of Clinical Medicine, Faculty of Health Sciences, UiT - The Arctic University of Norway, Hansine Hansens veg 18, Tromsø, 9019, Norway.
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Luu AP, Rao SS, Malik HY, Shi RB, Toubian AA, Kamei DT. Investigating bottom phase extraction from aqueous two-phase systems for detecting bacteria using the lateral-flow immunoassay. Anal Biochem 2024; 694:115634. [PMID: 39094782 DOI: 10.1016/j.ab.2024.115634] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/29/2024] [Accepted: 07/30/2024] [Indexed: 08/04/2024]
Abstract
Lateral-flow immunoassays (LFAs) can be used to diagnose urinary tract infections caused by Escherichia coli (E. coli) at the point of care. Unfortunately, urine samples containing dilute concentrations of E. coli can yield false negative results on LFAs. Our laboratory was first to implement aqueous two-phase systems (ATPSs) to preconcentrate samples into smaller volumes prior to their application on LFAs. This is achieved by manipulating the ratio of the volume of the top phase to that of the bottom phase (volume ratio; VR) and concentrating biomarkers in the bottom phase which, when applied to LFAs in fixed volumes, leads to corresponding improvements in sensitivity. This work is the first demonstration that the same LOD can be achieved irrespective of the VR when the entire bottom phase is added to LFAs. A custom 3D-printed device was also developed to decrease liquid handling steps. Across different VRs expected from patient urine variability, this diagnostic workflow successfully detected E. coli concentrations down to 2 × 105 colony-forming units (cfu) mL-1 in synthetic urine, demonstrating consistent 10-fold improvements in sensitivity compared to trials conducted without ATPS preconcentration. This method successfully addresses the variability of patient samples while remaining easy to use at the point of care.
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Affiliation(s)
- Audrey P Luu
- Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA
| | - Shreedevi S Rao
- Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA
| | - Humza Y Malik
- Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA
| | - Robin B Shi
- Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA
| | - Adam A Toubian
- Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA
| | - Daniel T Kamei
- Department of Bioengineering, University of California, Los Angeles, CA, 90095, USA.
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Diggle J, Van Der Goes Van Naters A, Roula MA, Mitchell S, Whiffen D, Nieuwland J, Hayhurst E. Lodestar DX, an evaluation: loop-mediated isothermal amplification (LAMP) for the diagnosis of urinary tract infection in symptomatic adult females. JAC Antimicrob Resist 2024; 6:dlae148. [PMID: 39291181 PMCID: PMC11406545 DOI: 10.1093/jacamr/dlae148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Accepted: 08/12/2024] [Indexed: 09/19/2024] Open
Abstract
Background Over 404.6 million people are affected worldwide each year by urinary tract infections (UTIs), with ∼237 000 associated deaths globally in 2019. Much more common in women than men, acute UTI occurs in up to 50% of the female population. Despite this, there is a lack of good diagnostic tools for use at the point-of-care, and over- and under-diagnosis are common, leading to long-term complications and patient suffering, and driving the spread of antimicrobial resistance through insufficient appropriate antibiotic stewardship. Objectives To evaluate the performance of a novel point-of-care testing platform, Lodestar DX, in comparison with standard laboratory processing of urine specimens. Methods A total of 199 fresh urine samples from symptomatic adult females suspected of having an acute UTI were tested using Lodestar DX and the results compared with standard laboratory methods performed at a local microbiology laboratory. Results Using standard laboratory methods, 129/199 samples produced a result and could be compared. Overall sensitivity and specificity of Lodestar DX were 88.1% (95% CI: 77.8%-94.7%) and 83.9% (95% CI: 72.3%-92.0%), respectively (n = 129), with a positive predictive value of 85.5% (95% CI: 76.9%-91.3%), a negative predictive value of 86.7% (95% CI: 77.1%-92.6%) and an overall accuracy of 86.1% (95% CI: 78.9%-91.5%). Conclusions The results show good correlation between Lodestar DX results and those of the standard laboratory method for this patient group. However, the platform would benefit from further testing to establish its true point-of-care compatibility and a direct comparison between this and other testing methods, such as urine dipstick testing.
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Affiliation(s)
- Joanna Diggle
- Public Health Wales Microbiology, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, Wales
- University of South Wales, Faculty of Computing, Engineering and Science, Pontypridd CF37 1DL, Wales
- Llusern Scientific Limited, Cardiff Edge Business Park, Longwood Drive, Cardiff CF14 7YU, Wales
| | | | - Mohammed Ali Roula
- University of South Wales, Faculty of Computing, Engineering and Science, Pontypridd CF37 1DL, Wales
- Llusern Scientific Limited, Cardiff Edge Business Park, Longwood Drive, Cardiff CF14 7YU, Wales
| | - Shanine Mitchell
- Public Health Wales Microbiology, University Hospital of Wales, Heath Park, Cardiff CF14 4XW, Wales
| | - Dewi Whiffen
- Llusern Scientific Limited, Cardiff Edge Business Park, Longwood Drive, Cardiff CF14 7YU, Wales
| | - Jeroen Nieuwland
- University of South Wales, Faculty of Computing, Engineering and Science, Pontypridd CF37 1DL, Wales
- Llusern Scientific Limited, Cardiff Edge Business Park, Longwood Drive, Cardiff CF14 7YU, Wales
| | - Emma Hayhurst
- Llusern Scientific Limited, Cardiff Edge Business Park, Longwood Drive, Cardiff CF14 7YU, Wales
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Silago V, Oravcova K, Matthews L, Mshana SE, Claus H, Seni J. Epidemiology and antimicrobial resistance trends of pathogens causing urinary tract infections in Mwanza, Tanzania: A comparative study during and after the implementation of the National Action Plan on Antimicrobial Resistance (2017-2022). Int J Infect Dis 2024; 147:107208. [PMID: 39128601 PMCID: PMC11442316 DOI: 10.1016/j.ijid.2024.107208] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2024] [Revised: 07/30/2024] [Accepted: 08/06/2024] [Indexed: 08/13/2024] Open
Abstract
OBJECTIVES To delineate the epidemiology and antimicrobial resistance (AMR) trends of pathogens causing urinary tract infections (UTIs) during (June 2019-June 2020) and after (March-July 2023) the implementation of the National Action Plan on AMR 2017-2022 in Mwanza, Tanzania. METHODS This cross-sectional study was conducted among 2097 patients with clinical symptoms of UTIs during (n = 1144) and after (n = 953) the National Action Plan on AMR 2017-2022. Quantitative urine culture was done to isolate significant bacteria causing UTI, which were then identified to the species level and tested for antimicrobial susceptibility. Tabulations, descriptive, and logistic regression analyses were used to analyze categorical and continuous variables, as well as the association between outcome and independent variables. Statistical significance was defined as P ≤0.05 at a 95% confidence interval (CI). RESULTS The overall prevalence of culture-positive UTIs was 22.8% (479 of 2097; 95% CI: 21.1-24.7%), with no significant difference between the study periods (21.8% [249 of 1144; 95% CI: 19.5-24.3%]) vs 24.1% (230 of 953; 95% CI: 21.5-26.9%), P = 0.274). We observed a significant increase in resistance to ciprofloxacin (32.0% vs 45.8%, P = 0.0481) and third-generation cephalosporins (marked by extended-spectrum β-lactamase-producing Enterobacterales [ESBL-PE], 38.7% vs 56.9%, P = 0.0307). Additionally, UTIs caused by ESBL-PE is significantly common among patients in higher-tier hospitals (58.4% vs 34.0%; OR [95% CI]: 2.51 [1.41-4.48], P = 0.002). CONCLUSIONS There was a significant increase in bacterial resistance to ciprofloxacin and third-generation cephalosporins, as well as ESBL-PE. These results emphasize the critical need to enhance AMR surveillance, improve infection prevention and control measures, and strengthen antimicrobial stewardship programs.
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Affiliation(s)
- Vitus Silago
- Department of Microbiology and Immunology, Weill Bugando School of Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; Institute for Hygiene and Microbiology, University of Würzburg, Würzburg, Germany.
| | - Katarina Oravcova
- Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow, UK
| | - Louise Matthews
- Institute of Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow, UK
| | - Stephen E Mshana
- Department of Microbiology and Immunology, Weill Bugando School of Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania
| | - Heike Claus
- Institute for Hygiene and Microbiology, University of Würzburg, Würzburg, Germany
| | - Jeremiah Seni
- Department of Microbiology and Immunology, Weill Bugando School of Medicine, Catholic University of Health and Allied Sciences, Mwanza, Tanzania
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Hernandez R, Meisenbach RJ. Exploring Stigma Communication About Urinary Tract Infections in the United States. HEALTH COMMUNICATION 2024:1-9. [PMID: 39348233 DOI: 10.1080/10410236.2024.2407209] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/02/2024]
Abstract
Urinary tract infections (UTIs) have steadily increased in prevalence and severity among women in the United States and can lead to serious complications if left untreated. Yet, women are often reluctant to discuss such infections due to potential stigmatization. Indeed, UTI treatment and prevention often involves communication with intimate partners and physicians, and this communication can require stigma management. Further, stigma communication can influence women's experiences with UTI symptoms and treatment. The theory of stigma management communication is well-suited to explore how stigma-related communication unfolds about the experience, diagnosis, and treatment of UTIs. The current study uses in-depth interviews conducted in 2022 to learn about experiences with stigma communication surrounding UTIs. Findings reveal that participants perceived UTIs as stigmatized due to associations between UTIs and female gender, sexual behavior, genital health, and hygiene. Participants described using stigma management strategies to accept, ignore, avoid, reduce responsibility for, and challenge stigmas related to UTIs. This analysis has implications for theorizing choice in stigma management research and for provider-patient interactions surrounding UTIs.
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Affiliation(s)
- Rachael Hernandez
- Department of Communication, Department of Public Health, University of Missouri
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Sujith S, Solomon AP, Rayappan JBB. Comprehensive insights into UTIs: from pathophysiology to precision diagnosis and management. Front Cell Infect Microbiol 2024; 14:1402941. [PMID: 39380727 PMCID: PMC11458535 DOI: 10.3389/fcimb.2024.1402941] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 09/02/2024] [Indexed: 10/10/2024] Open
Abstract
Urinary tract infections (UTIs) are the second most common infectious disease, predominantly impacting women with 150 million individuals affected globally. It increases the socio-economic burden of society and is mainly caused by Escherichia coli, Proteus mirabilis, Klebsiella pneumoniae, Enterobacter spp., and Staphylococcus spp. The severity of the infection correlates with the host factors varying from acute to chronic infections. Even with a high incidence rate, the diagnosis is mainly based on the symptoms, dipstick analysis, and culture analysis, which are time-consuming, labour-intensive, and lacking sensitivity and specificity. During this period, medical professionals prescribe empirical antibiotics, which may increase the antimicrobial resistance rate. Timely and precise UTI diagnosis is essential for addressing antibiotic resistance and improving overall quality of life. In response to these challenges, new techniques are emerging. The review provides a comprehensive overview of the global burden of UTIs, associated risk factors, implicated organisms, traditional and innovative diagnostic methods, and approaches to UTI treatment and prevention.
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Affiliation(s)
- Swathi Sujith
- Quorum Sensing Laboratory, Centre for Research in Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur, India
| | - Adline Princy Solomon
- Quorum Sensing Laboratory, Centre for Research in Infectious Diseases (CRID), School of Chemical and Biotechnology, SASTRA Deemed to be University, Thanjavur, India
| | - John Bosco Balaguru Rayappan
- Nanosensors Laboratory, School of Electrical & Electronics Engineering, Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), SASTRA Deemed to be University, Thanjavur, India
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Çelik H, Caf BB, Çebi G. Innovative Biosensor Technologies in the Diagnosis of Urinary Tract Infections: A Comprehensive Literature Review. Indian J Microbiol 2024; 64:894-909. [PMID: 39282176 PMCID: PMC11399381 DOI: 10.1007/s12088-024-01359-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2024] [Accepted: 07/21/2024] [Indexed: 09/18/2024] Open
Abstract
Urinary tract infections (UTIs) are prevalent bacterial infections globally, posing significant challenges due to their frequency, recurrence, and antibiotic resistance. This review delves into the advancements in UTI diagnostics over the past decade, particularly focusing on the development of biosensor technologies. The emergence of biosensors, including microfluidic, optical, electrochemical, immunosensors, and nanotechnology-based sensors, offers enhanced diagnostic accuracy, reduced healthcare costs. Despite these advancements, challenges such as technical limitations, the need for cross-population validation, and economic barriers for widespread implementation persist. The integration of artificial intelligence and smart devices in UTI diagnostics, highlighting the innovative approaches and their implications for patient care. The article envisions a future where multidisciplinary research and innovation overcome current obstacles, fully leveraging the potential of biosensor technologies to transform biosensor-based UTIs diagnosis. The ultimate goal is to achieve rapid, accurate, and non-invasive diagnostics, making healthcare more accessible and effective.
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Affiliation(s)
- Haluk Çelik
- Vivosens, Inc., 44 Tehama Street, Suite 409, San Francisco, CA 94105 USA
- Program of Stem Cell and Tissue Engineering, Institute of Graduate Education, Istinye University, 34010 Istanbul, Turkey
| | - Balım Bengisu Caf
- Vivosens, Inc., 44 Tehama Street, Suite 409, San Francisco, CA 94105 USA
- Program of Bioengineering, Graduate School of Science and Engineering, Yıldız Technical University, 34220 Esenler, Istanbul, Turkey
| | - Gizem Çebi
- Vivosens, Inc., 44 Tehama Street, Suite 409, San Francisco, CA 94105 USA
- Program of Chemical Engineering, Institute of Graduate School, Istanbul Technical University, ITU Ayazaga Kampusu, 34469 Maslak, Istanbul, Turkey
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Ahmed S, Shree N, Narula AS, Nirala PK, Majid H, Garg A, Nayeem U, Khan MA. The prevalence of multidrug resistance in uropathogens of patients admitted in the intensive care unit of a tertiary care hospital. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:7117-7127. [PMID: 38643454 DOI: 10.1007/s00210-024-03108-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 04/14/2024] [Indexed: 04/22/2024]
Abstract
Urinary tract infections (UTIs) are among the most common bacterial infections, posing significant public health challenges due to increasing antimicrobial resistance (AMR). This study aims to assess the prevalence, demographic characteristics, microbial profile, and antimicrobial resistance patterns in Indian patients with UTIs admitted to intensive care unit. A total of 154 patients with positive UTIs were included in this cross-sectional study. The prevalence data including demographics, microbial isolates, and antimicrobial susceptibility patterns were collected. Additionally, risk factors for multidrug resistance uropathogens were assessed using multivariate analyses. The patient cohort had diverse demographic, with a slight male predominance of 52.6% (n = 81). The most common comorbidities were hypertension 59.1% (n = 91) and diabetes mellitus 54.5% (n = 84). The microbial profile was dominated by gram-negative bacteria, particularly Escherichia coli 26.62% (n = 41) and Klebsiella pneumoniae 17.53% (n = 27). The predominant gram-positive and fungal isolate was Enterococcus faecium 7.14% (n = 11) and Candida spp. 18.83% (n = 29), respectively. Substantial resistance was noted against common antimicrobials, with variations across different pathogens. Gram-negative bacteria, particularly Escherichia coli and Klebsiella pneumoniae, exhibited high MDR rates, emphasizing the challenge of antimicrobial resistance. Multivariate logistic regression identified age groups 50-65 and over 65, and prolonged catheterization as significant risk factors for MDR infections. A significantly high resistance rate among pathogens emphasizes the need for judicious antimicrobial use. Our findings emphasize the necessity of ongoing surveillance and tailored interventions based on local pathogen prevalence and antibiogram data to effectively address the threat of AMR threat for better management of UTI management in ICU settings.
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Affiliation(s)
- Shaista Ahmed
- Department of Translational and Clinical Research, School of Chemical and Life Science, Jamia Hamdard, New Delhi, 110062, India
| | - Neetu Shree
- Department of Microbiology, Hamdard Institute of Medical Sciences & Research, New Delhi, 110062, India
| | - Ajit Singh Narula
- Department of Nephrology, Fortis Escort Heart Institute and Research Centre, New Delhi, 110025, India
| | - Purushottam Kr Nirala
- Department of Nephrology, Fortis Escort Heart Institute and Research Centre, New Delhi, 110025, India
| | - Haya Majid
- Department of Translational and Clinical Research, School of Chemical and Life Science, Jamia Hamdard, New Delhi, 110062, India
| | - Aakriti Garg
- Department of Translational and Clinical Research, School of Chemical and Life Science, Jamia Hamdard, New Delhi, 110062, India
- Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi, 110062, India
| | - Uzma Nayeem
- Department of Translational and Clinical Research, School of Chemical and Life Science, Jamia Hamdard, New Delhi, 110062, India
| | - Mohd Ashif Khan
- Department of Translational and Clinical Research, School of Chemical and Life Science, Jamia Hamdard, New Delhi, 110062, India.
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Namusoosa R, Mugerwa I, Kasozi KI, Muruta A, Najjuka G, Atuhaire WD, Nabadda S, Mwebesa H, Olaro C, Ssewanyana I, Ssemaganda A, Muwonge A. The epidemiology of antibiotic-resistant clinical pathogens in Uganda. J Glob Health 2024; 14:04184. [PMID: 39212655 PMCID: PMC11364088 DOI: 10.7189/jogh.14.04184] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/04/2024] Open
Abstract
Background Antibiotic resistance (ABR) is a global challenge, and its control depends on robust evidence primarily derived from surveillance systems. Methods We utilised a national surveillance data set to demonstrate how such evidence can be systematically generated. In doing so, we characterised the ABR profiles of priority clinical pathogens, identified associated factors, and drew inferences on antibiotic usage in Uganda. Results Of the 12 262 samples collected between 2019-21, we analysed 9033 with complete metadata. ABR was steadily increasing at a rate of 0.5% per year, with a surge in 2021 and the highest and lowest levels of penicillin and carbapenems detected in the northern (odds ratio (OR) = 2.26; P < 0.001) and the northeast (OR = 0.28; P < 0.001) regions of Uganda respectively. ABR was commonly observed with Escherichia coli (OR = 1.18; P < 0.001) and Klebsiella pneumoniae (OR = 1.25; P < 0.001) among older and male patients (61-70 years old) (OR = 1.88; P = 0.005). Multi-drug resistance (MDR) and ABR were disproportionately higher among bloodstream infections than respiratory tract infections and urinary tract infections, often caused by Acinetobacter baumannii. Co-occurrence of ABR suggests that cephalosporins such as ceftriaxone are in high use all over Uganda. Conclusions ABR is indeed a silent pandemic, and our results suggest it is increasing at 0.5% per year, with a notable surge in 2021 likely due to coronavirus disease 2019 (COVID-19). Of concern, ABR and MDR are mainly associated with bloodstream and surgical wound infections, with a gender and age dimension. However, it is encouraging that carbapenem resistance remains relatively low. Such evidence is critical for contextualising the implementation and evaluation of national action plans.
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Affiliation(s)
- Ritah Namusoosa
- Department of National Health Laboratories and Diagnostic Services, National Microbiology Reference Laboratory, Ministry of Health, Kampala, Uganda
| | - Ibrahim Mugerwa
- Department of National Health Laboratories and Diagnostic Services, Ministry of Health, Kampala, Uganda
| | - Keneth Iceland Kasozi
- Infection Medicine, College of Medicine and Veterinary Medicine, Deanery of Biomedical Sciences, The University of Edinburgh, Edinburgh, UK
- School of Medicine, Kabale University, Kabale, Uganda
| | - Allan Muruta
- Department of National Disease Control, Ministry of Health, Kampala, Uganda
| | - Grace Najjuka
- Department of National Health Laboratories and Diagnostic Services, National Microbiology Reference Laboratory, Ministry of Health, Kampala, Uganda
| | - Winifred D Atuhaire
- Department of National Health Laboratories and Diagnostic Services, National Microbiology Reference Laboratory, Ministry of Health, Kampala, Uganda
| | - Susan Nabadda
- Department of National Health Laboratories and Diagnostic Services, Ministry of Health, Kampala, Uganda
| | - Henry Mwebesa
- Directorate of Curative Services, Ministry of Health, Kampala, Uganda
| | - Charles Olaro
- Directorate of Curative Services, Ministry of Health, Kampala, Uganda
| | - Isaac Ssewanyana
- Department of National Health Laboratories and Diagnostic Services, Ministry of Health, Kampala, Uganda
| | - Aloysious Ssemaganda
- Department of National Health Laboratories and Diagnostic Services, Ministry of Health, Kampala, Uganda
| | - Adrian Muwonge
- The Digital One Health Laboratory, Division of Epidemiology, Roslin Institute, The University of Edinburgh, Edinburgh, UK
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Alonso-Tarrés C, Benjumea Moreno C, Navarro F, Habison AC, Gonzàlez-Bertran E, Blanco F, Borràs J, Garrigó M, Saker J. Bacteriuria and phenotypic antimicrobial susceptibility testing in 45 min by point-of-care Sysmex PA-100 System: first clinical evaluation. Eur J Clin Microbiol Infect Dis 2024; 43:1533-1543. [PMID: 38825624 PMCID: PMC11271345 DOI: 10.1007/s10096-024-04862-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 05/23/2024] [Indexed: 06/04/2024]
Abstract
PURPOSE This study compared the results of the new Sysmex PA-100 AST System, a point-of-care analyser, with routine microbiology for the detection of urinary tract infections (UTI) and performance of antimicrobial susceptibility tests (AST) directly from urine. METHODS Native urine samples from 278 female patients with suspected uncomplicated UTI were tested in the Sysmex PA-100 and with reference methods of routine microbiology: urine culture for bacteriuria and disc diffusion for AST. RESULTS The analyser delivered bacteriuria results in 15 min and AST results within 45 min. Sensitivity and specificity for detection of microbiologically confirmed bacteriuria were 84.0% (89/106; 95% CI: 75.6-90.4%) and 99.4% (155/156; 95% CI: 96.5-100%), respectively, for bacterial species within the analyser specifications. These are Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis and Staphylococcus saprophyticus, which are common species causing uncomplicated UTI. Overall categorical agreement (OCA) for AST results for the five antimicrobials tested in the Sysmex PA-100 (amoxicillin/clavulanic acid, ciprofloxacin, fosfomycin, nitrofurantoin and trimethoprim) ranged from 85.4% (70/82; 95%CI: 75.9-92.2%) for ciprofloxacin to 96.4% (81/84; 95% CI: 89.9-99.3%) for trimethoprim. The Sysmex PA-100 provided an optimal treatment recommendation in 218/278 cases (78.4%), against 162/278 (58.3%) of clinical decisions. CONCLUSION This first clinical evaluation of the Sysmex PA-100 in a near-patient setting demonstrated that the analyser delivers phenotypic AST results within 45 min, which could enable rapid initiation of the correct targeted treatment with no further adjustment needed. The Sysmex PA-100 has the potential to significantly reduce ineffective or unnecessary antibiotic prescription in patients with UTI symptoms.
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Affiliation(s)
- Carles Alonso-Tarrés
- Microbiology Laboratory, Fundació Puigvert, C/Cartagena 340-350, Barcelona, Spain.
- Departament de Genètica i Microbiologia, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain.
| | | | - Ferran Navarro
- Departament de Genètica i Microbiologia, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain
- Microbiology Laboratory, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Aline C Habison
- New Business Development Department, Sysmex Europe SE, Norderstedt, Germany
| | | | | | - Jaume Borràs
- Emergency Unit, Fundació Puigvert, Barcelona, Spain
| | - Montserrat Garrigó
- Departament de Genètica i Microbiologia, Universitat Autònoma de Barcelona, Cerdanyola del Vallès, Barcelona, Spain
- Microbiology Laboratory, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
| | - Jarob Saker
- Medical Scientific Department, Sysmex Europe SE, Norderstedt, Germany
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James B, Reesaul H, Kashif S, Behruznia M, Meehan CJ, Domingo-Sananes MR, Hubbard ATM. The effect of antibiotic selection on collateral effects and evolvability of uropathogenic Escherichia coli. NPJ ANTIMICROBIALS AND RESISTANCE 2024; 2:19. [PMID: 39036800 PMCID: PMC11254750 DOI: 10.1038/s44259-024-00037-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 06/28/2024] [Indexed: 07/23/2024]
Abstract
Trimethoprim is recommended as a first-line treatment of urinary tract infections (UTIs) in the UK. In 2018, 31.4% of Escherichia coli isolated from UTIs in England were trimethoprim-resistant, leading to overreliance on other first and second-line antibiotics. Here, we assessed whether, in principle, prior selection with trimethoprim results in collateral effects to other antibiotics recommended for the treatment of UTIs. As collateral effects, we considered changes in susceptibility, mutation-selection window and population establishment probability. We selected 10 trimethoprim-resistant derivatives from three clinical isolates of uropathogenic Escherichia coli. We found that mutations conferring trimethoprim resistance did not have any collateral effects on fosfomycin. In contrast, resistance to trimethoprim resulted in decreased susceptibility (collateral resistance) to nitrofurantoin, below the clinical breakpoint and narrowed the mutation-selection window, thereby reducing the maximum concentration for selection of nitrofurantoin resistance mutations. Our analyses demonstrate that multiple collateral responses should be accounted for when predicting and optimising antibiotic use, limiting future antimicrobial resistance emergence.
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Affiliation(s)
- Beth James
- Department of Biosciences, Nottingham Trent University, Clifton Campus, College Drive, Clifton, Nottingham NG11 8NS UK
| | - Hishikha Reesaul
- Department of Biosciences, Nottingham Trent University, Clifton Campus, College Drive, Clifton, Nottingham NG11 8NS UK
| | - Sidra Kashif
- Department of Biosciences, Nottingham Trent University, Clifton Campus, College Drive, Clifton, Nottingham NG11 8NS UK
| | - Mahboobeh Behruznia
- Department of Biosciences, Nottingham Trent University, Clifton Campus, College Drive, Clifton, Nottingham NG11 8NS UK
| | - Conor J. Meehan
- Department of Biosciences, Nottingham Trent University, Clifton Campus, College Drive, Clifton, Nottingham NG11 8NS UK
| | - Maria Rosa Domingo-Sananes
- Department of Biosciences, Nottingham Trent University, Clifton Campus, College Drive, Clifton, Nottingham NG11 8NS UK
| | - Alasdair T. M. Hubbard
- Department of Biosciences, Nottingham Trent University, Clifton Campus, College Drive, Clifton, Nottingham NG11 8NS UK
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Behere MJ, Haldar S. Market-ready U-AST kit: simple, fast, cost-effective solution for concurrently detecting urinary tract infection and antibiotic resistance. ANALYTICAL METHODS : ADVANCING METHODS AND APPLICATIONS 2024; 16:4516-4523. [PMID: 38881391 DOI: 10.1039/d4ay00632a] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/18/2024]
Abstract
There is an increasing demand for an inexpensive, quick, accessible, and simple method for the detection of urinary tract infection (UTI) together with the antibiotic-resistance profile of the infection-causing bacteria. Our primary goal is to assist doctors in prescribing antibiotics that will quickly treat infections and reduce the likelihood of antibiotic resistance spreading throughout the community. To this end, a urinary tract infection antibiotic-sensitivity test (U-AST) kit was developed for the validation of bacterial infection in the urinary tract and determination of the antibiotic-resistance profile of the bacteria in a short time. The U-AST kit was standardized using standard strains of bacteria, specifically Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Vibrio cholerae, and Pseudomonas species. Further, the kit was validated using 50 clinical urine samples with variation in their physical and chemical parameters, and the resistance pattern against five therapeutically important antibiotics were tested. The results acquired using the U-AST kit showed a 100% similarity to those acquired using the laboratory-based gold standard method. Interestingly, the U-AST kit required a maximum of 9 h to understand the bacterial contamination and resistance profile of the bacterial community, which was observed by a simple color change. The same result can be obtained using the gold standard method but requires 36-72 h, a sophisticated microbiology method, and skilled microbiologists. Other methods can also predict infection quickly with the aid of sophisticated instrumentation; however, understanding the antibiotic-resistance pattern is not possible. To the best of our understanding, this is a unique technique for the quick, easy, and inexpensive detection of UTI with antibiotic sensitivity testing and does not require a special laboratory set-up or expert personnel. The commercialization of the developed clinically validated U-AST kit is currently underway.
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Affiliation(s)
- Maheshawari J Behere
- Analytical and Environmental Science Division & Centralized Instrument Facility, CSIR-Central Salt & Marine Chemicals Research Institute, G.B. Marg, Bhavnagar 364002, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
| | - Soumya Haldar
- Analytical and Environmental Science Division & Centralized Instrument Facility, CSIR-Central Salt & Marine Chemicals Research Institute, G.B. Marg, Bhavnagar 364002, India.
- Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India
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Kaye KS, Gupta V, Mulgirigama A, Joshi AV, Scangarella-Oman NE, Yu K, Watts J, Mitrani-Gold FS. Co-resistance Among Escherichia coli and Klebsiella pneumoniae Urine Isolates from Female Outpatients with Presumed UTI: A Retrospective US Cohort Study. Infect Dis Ther 2024; 13:1715-1722. [PMID: 38842759 PMCID: PMC11219620 DOI: 10.1007/s40121-024-00995-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2024] [Accepted: 05/14/2024] [Indexed: 06/07/2024] Open
Abstract
INTRODUCTION Urinary tract infections (UTIs) caused by antimicrobial-resistant Enterobacterales are a global health threat. There are limited surveillance data available to characterize the prevalence of antimicrobial resistance among outpatients in the United States (US). METHODS This retrospective cohort (database) study investigated co-resistance among Escherichia coli and Klebsiella pneumoniae urinary isolates from US female outpatients aged ≥ 12 years with presumed uncomplicated UTI (uUTI), ≥ 3 months of data (2011-2019), and antimicrobial susceptibility testing results. Eligible isolates were the first urinary E. coli or K. pneumoniae isolate per patient collected within 30 days; classified as not susceptible (NS) if antimicrobial susceptibility testing results were intermediate or resistant to each antibiotic tested. Four resistance phenotypes were identified: NS to fluoroquinolones (FQ), trimethoprim/sulfamethoxazole (SXT), nitrofurantoin (NTF), and extended-spectrum β-lactamase+/third-generation cephalosporin (ESBL+/3GC NS). Co-resistance phenotypes included all possible combinations of resistance to ≥ 2 drug classes. RESULTS Of 1,513,882 E. coli isolates and 250,719 K. pneumoniae isolates, 856,918 and 187,459 isolates with ≥ 1 resistance phenotype were included in the analysis, respectively. The most common resistance phenotypes were SXT NS for the E. coli isolates (44.8%) and NTF NS for the K. pneumoniae isolates (75.5%), while ESBL+/3GC NS comprised 11.2 and 5.9%, respectively. Among ESBL+/3GC NS E. coli isolates, 72.4, 56.7, and 46.6% were co-resistant to FQ, SXT, and FQ + SXT, respectively. For ESBL+/3GC NS K. pneumoniae isolates, 65.7 and 45.7% were co-resistant to SXT and FQ + SXT. CONCLUSION Both species exhibited high rates of co-resistance, emphasizing the need to raise awareness of co-resistance and of the unmet need for effective treatment options for uUTI.
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Affiliation(s)
- Keith S Kaye
- Division of Allergy, Immunology and Infectious Diseases, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ, USA
| | - Vikas Gupta
- MMS Medical Affairs, Becton, Dickinson and Company, Franklin Lakes, NJ, USA
| | | | | | | | - Kalvin Yu
- Medical and Scientific Affairs, Becton, Dickinson and Company, Franklin Lakes, NJ, USA
| | - Janet Watts
- Data Science and Analytics, Becton, Dickinson and Company, Franklin Lakes, NJ, USA
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Hayward G, Mort S, Hay AD, Moore M, Thomas NPB, Cook J, Robinson J, Williams N, Maeder N, Edeson R, Franssen M, Grabey J, Glogowska M, Yang Y, Allen J, Butler CC. d-Mannose for Prevention of Recurrent Urinary Tract Infection Among Women: A Randomized Clinical Trial. JAMA Intern Med 2024; 184:619-628. [PMID: 38587819 PMCID: PMC11002776 DOI: 10.1001/jamainternmed.2024.0264] [Citation(s) in RCA: 20] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2023] [Accepted: 12/12/2023] [Indexed: 04/09/2024]
Abstract
Importance Recurrent urinary tract infection (UTI) is a common debilitating condition in women, with limited prophylactic options. d-Mannose has shown promise in trials based in secondary care, but effectiveness in placebo-controlled studies and community settings has not been established. Objective To determine whether d-mannose taken for 6 months reduces the proportion of women with recurrent UTI experiencing a medically attended UTI. Design, Setting, and Participants This 2-group, double-blind randomized placebo-controlled trial took place across 99 primary care centers in the UK. Participants were recruited between March 28, 2019, and January 31, 2020, with 6 months of follow-up. Participants were female, 18 years or older, living in the community, and had evidence in their primary care record of consultations for at least 2 UTIs in the preceding 6 months or 3 UTIs in 12 months. Invitation to participate was made by their primary care center. A total of 7591 participants were approached, 830 responded, and 232 were ineligible or did not proceed to randomization. Statistical analysis was reported in December 2022. Intervention Two grams daily of d-mannose powder or matched volume of placebo powder. Main Outcomes and Measures The primary outcome measure was the proportion of women experiencing at least 1 further episode of clinically suspected UTI for which they contacted ambulatory care within 6 months of study entry. Secondary outcomes included symptom duration, antibiotic use, time to next medically attended UTI, number of suspected UTIs, and UTI-related hospital admissions. Results Of 598 women eligible (mean [range] age, 58 [18-93] years), 303 were randomized to d-mannose (50.7%) and 295 to placebo (49.3%). Primary outcome data were available for 583 participants (97.5%). The proportion contacting ambulatory care with a clinically suspected UTI was 150 of 294 (51.0%) in the d-mannose group and 161 of 289 (55.7%) in the placebo group (risk difference, -5%; 95% CI, -13% to 3%; P = .26). Estimates were similar in per protocol analyses, imputation analyses, and preplanned subgroups. There were no statistically significant differences in any secondary outcome measures. Conclusions and Relevance In this randomized clinical trial, daily d-mannose did not reduce the proportion of women with recurrent UTI in primary care who experienced a subsequent clinically suspected UTI. d-Mannose should not be recommended for prophylaxis in this patient group. Trial Registration isrctn.org Identifier: ISRCTN13283516.
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Affiliation(s)
- Gail Hayward
- Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, England, United Kingdom
| | - Sam Mort
- Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, England, United Kingdom
| | - Alastair D. Hay
- Centre for Academic Primary Care, NIHR School for Primary Care Research, Bristol Medical School: Population Health Sciences, University of Bristol, Bristol, England, United Kingdom
| | - Michael Moore
- Primary Care Research Centre, Primary Care, Population Sciences and Medical Education, Faculty of Medicine, University of Southampton, Southampton, England, United Kingdom
| | - Nicholas P. B. Thomas
- Windrush Medical Practice, Witney, England, United Kingdom
- NIHR Clinical Research Network Thames Valley and South Midlands, Oxford, England, United Kingdom
| | - Johanna Cook
- Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, England, United Kingdom
| | - Jared Robinson
- Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, England, United Kingdom
| | - Nicola Williams
- Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, England, United Kingdom
| | - Nicola Maeder
- Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, England, United Kingdom
| | - Rebecca Edeson
- Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, England, United Kingdom
| | - Marloes Franssen
- Oxford Trauma and Emergency Care, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, Oxford University, England, United Kingdom
| | - Jenna Grabey
- Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, England, United Kingdom
| | - Margaret Glogowska
- Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, England, United Kingdom
| | - Yaling Yang
- Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, England, United Kingdom
| | - Julie Allen
- Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, England, United Kingdom
| | - Christopher C. Butler
- Nuffield Department of Primary Care Health Sciences, Oxford University, Oxford, England, United Kingdom
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Tuo Z, Wu R, Wang J, Li D, Ke M, Feng D. Temporal trends in the prevalence of urinary tract infections among women of childbearing age in global (1990-2019). World J Urol 2024; 42:346. [PMID: 38780809 DOI: 10.1007/s00345-024-05058-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Accepted: 05/12/2024] [Indexed: 05/25/2024] Open
Affiliation(s)
- Zhouting Tuo
- Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, 230601, China
| | - Ruicheng Wu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Jie Wang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Dengxiong Li
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China
| | - Mang Ke
- Department of Urology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, China
| | - Dechao Feng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, China.
- Department of Urology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, China.
- Division of Surgery and Interventional Science, University College London, London, W1W 7TS, UK.
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Razack SA, Lee Y, Bose S, Shin H, Jung WK, Kang HW. Photo-triggered caffeic acid delivery via psyllium polysaccharide- gellan gum-based injectable bionanogel for epidermoid carcinoma treatment. Int J Biol Macromol 2024; 267:131166. [PMID: 38582464 DOI: 10.1016/j.ijbiomac.2024.131166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Revised: 03/16/2024] [Accepted: 03/25/2024] [Indexed: 04/08/2024]
Abstract
Here, the simultaneous effect of chemo- and photothermal therapy against epidermoid carcinoma (EC) was investigated. A novel hydrogel, termed bionanogel (BNG), was designed using psyllium mucilage polysaccharide and bacterial gellan gum, incorporated with nanocomplex carrying caffeic acid (CA) and IR-820, and further characterized. The dual effect of BNG and 808 nm laser (BNG + L) on EC was investigated. Staining and scratch assays were performed to analyze their therapeutic effect on EC. In vivo evaluations of BNG + L in xenograft models were performed. Rapid transition, limited swelling, degradability and high tensile strength indicated BNG stability and sustained drug release. Irradiation with 808 nm laser light at 1.25 W /cm2 for 4 min resulted in a temperature increase of 53 °C and facilitated cell ablation. The in vitro studies showed that BNG + L suppressed cancer progression via a late apoptotic effect. The in vivo study showed that the slow release of CA from BNG + L significantly attenuated EC with low mitotic index and downregulation of proteins involved in cancer proliferation such as EGFR, AKT, PI3K, ERK, mTOR and HIF-1α. Thus, BNG could be a novel medium for targeted and controlled drug delivery for the treatment of epidermoid cancer when triggered by NIR light.
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Affiliation(s)
- Sirajunnisa Abdul Razack
- Marine Integrated Biomedical Technology Center, The National Key Research Institutes in Universities, Pukyong National University, Busan, Republic of Korea
| | - Yeachan Lee
- Center for Advanced Models for Translational Sciences and Therapeutics and Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Sivakumar Bose
- Marine Integrated Biomedical Technology Center, The National Key Research Institutes in Universities, Pukyong National University, Busan, Republic of Korea
| | - Hwarang Shin
- Marine Integrated Biomedical Technology Center, The National Key Research Institutes in Universities, Pukyong National University, Busan, Republic of Korea; Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan, Republic of Korea
| | - Won-Kyo Jung
- Marine Integrated Biomedical Technology Center, The National Key Research Institutes in Universities, Pukyong National University, Busan, Republic of Korea; Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan, Republic of Korea; Major of Biomedical Engineering, Division of Smart Healthcare, College of Information, Pukyong National University, Busan, Republic of Korea
| | - Hyun Wook Kang
- Marine Integrated Biomedical Technology Center, The National Key Research Institutes in Universities, Pukyong National University, Busan, Republic of Korea; Industry 4.0 Convergence Bionics Engineering, Pukyong National University, Busan, Republic of Korea; Major of Biomedical Engineering, Division of Smart Healthcare, College of Information, Pukyong National University, Busan, Republic of Korea.
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King W, Homer T, Harding C, Mossop H, Chadwick T, Abouhajar A, Vale L. Cost-effectiveness of methenamine hippurate compared with antibiotic prophylaxis for the management of recurrent urinary tract infections in secondary care: a multicentre, open-label, randomised, non-inferiority trial. BMJ Open 2024; 14:e074445. [PMID: 38684270 PMCID: PMC11086477 DOI: 10.1136/bmjopen-2023-074445] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Accepted: 04/05/2024] [Indexed: 05/02/2024] Open
Abstract
OBJECTIVES To estimate the cost-effectiveness of methenamine hippurate compared with antibiotic prophylaxis in the management of recurrent urinary tract infections. DESIGN Multicentre, open-label, randomised, non-inferiority trial. SETTING Eight centres in the UK, recruiting from June 2016 to June 2018. PARTICIPANTS Women aged ≥18 years with recurrent urinary tract infections, requiring prophylactic treatment. INTERVENTIONS Women were randomised to receive once-daily antibiotic prophylaxis or twice-daily methenamine hippurate for 12 months. Treatment allocation was not masked and crossover between arms was allowed. PRIMARY AND SECONDARY OUTCOME MEASURES The primary economic outcome was the incremental cost per quality-adjusted life year (QALY) gained at 18 months. All costs were collected from a UK National Health Service perspective. QALYs were estimated based on responses to the EQ-5D-5L administered at baseline, 3, 6, 9, 12 and 18 months. Incremental costs and QALYs were estimated using an adjusted analysis which controlled for observed and unobserved characteristics. Stochastic sensitivity analysis was used to illustrate uncertainty on a cost-effectiveness plane and a cost-effectiveness acceptability curve. A sensitivity analysis, not specified in the protocol, considered the costs associated with antibiotic resistance. RESULTS Data on 205 participants were included in the economic analysis. On average, methenamine hippurate was less costly (-£40; 95% CI: -684 to 603) and more effective (0.014 QALYs; 95% CI: -0.05 to 0.07) than antibiotic prophylaxis. Over the range of values considered for an additional QALY, the probability of methenamine hippurate being considered cost-effective ranged from 51% to 67%. CONCLUSIONS On average, methenamine hippurate was less costly and more effective than antibiotic prophylaxis but these results are subject to uncertainty. Methenamine hippurate is more likely to be considered cost-effective when the benefits of reduced antibiotic use were included in the analysis. TRIAL REGISTRATION NUMBER ISRCTN70219762.
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Affiliation(s)
- William King
- Health Economics Group, Newcastle University Population Health Sciences Institute, Newcastle upon Tyne, UK
| | - Tara Homer
- Health Economics Group, Newcastle University Population Health Sciences Institute, Newcastle upon Tyne, UK
| | - Chris Harding
- Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Helen Mossop
- Newcastle University Population Health Sciences Institute, Newcastle upon Tyne, UK
| | - Thomas Chadwick
- Newcastle University Population Health Sciences Institute, Newcastle upon Tyne, UK
| | - Alaa Abouhajar
- Newcastle Clinical Trials Unit, Newcastle University, Newcastle upon Tyne, UK
| | - Luke Vale
- Health Economics Group, Newcastle University Population Health Sciences Institute, Newcastle upon Tyne, UK
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Newlands AF, Kramer M, Roberts L, Maxwell K, Price JL, Finlay KA. Evaluating the quality of life impact of recurrent urinary tract infection: Validation and refinement of the Recurrent UTI Impact Questionnaire (RUTIIQ). Neurourol Urodyn 2024; 43:902-914. [PMID: 38385648 DOI: 10.1002/nau.25426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2023] [Revised: 12/08/2023] [Accepted: 02/05/2024] [Indexed: 02/23/2024]
Abstract
BACKGROUND AND AIMS Recurrent urinary tract infection (rUTI) has significant negative consequences for a wide variety of quality of life (QoL) domains. Without adequate validation and assessment of the unique insights of people living with rUTI, clinical results cannot be fully understood. The Recurrent UTI Impact Questionnaire (RUTIIQ), a novel patient-reported outcome measure of rUTI psychosocial impact, has been robustly developed with extensive patient and clinician input to facilitate enhanced rUTI management and research. This study aimed to confirm the structural validity of the RUTIIQ, assessing its strength and bifactor model fit. METHODS A sample of 389 adults experiencing rUTI (96.9% female, aged 18-87 years) completed an online cross-sectional survey comprising a demographic questionnaire and the RUTIIQ. A bifactor graded response model was fitted to the data, optimizing the questionnaire structure based on item fit, discrimination capability, local dependence, and differential item functioning. RESULTS The final RUTIIQ demonstrated excellent bifactor model fit (RMSEA = 0.054, CFI = 0.99, SRMSR = 0.052), and mean-square fit indices indicated that all included items were productive for measurement (MNSQ = 0.52-1.41). The final questionnaire comprised an 18-item general "rUTI QoL impact" factor, and five subfactor domains measuring "personal wellbeing" (three items), "social wellbeing" (four items), "work and activity interference" (four items), "patient satisfaction" (four items), and "sexual wellbeing" (three items). Together, the general factor and five subfactors explained 81.6% of the common model variance. All factor loadings were greater than 0.30 and communalities greater than 0.60, indicating good model fit and structural validity. CONCLUSIONS The 18-item RUTIIQ is a robust, patient-tested questionnaire with excellent psychometric properties, which capably assesses the patient experience of rUTI-related impact to QoL and healthcare satisfaction. Facilitating standardized patient monitoring and improved shared decision-making, the RUTIIQ delivers the unique opportunity to improve patient-centered care.
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Affiliation(s)
- Abigail F Newlands
- School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK
| | | | - Lindsey Roberts
- School of Psychology, University of Buckingham, Buckingham, UK
| | - Kayleigh Maxwell
- Department of Psychology, Faculty of Natural Sciences, University of Stirling, Stirling, UK
| | | | - Katherine A Finlay
- School of Psychology and Clinical Language Sciences, University of Reading, Reading, UK
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Ali H, Vikash F, Moond V, Khalid F, Jamil AR, Dahiya DS, Sohail AH, Gangwani MK, Patel P, Satapathy SK. Global trends in hepatitis C-related hepatocellular carcinoma mortality: A public database analysis (1999-2019). World J Virol 2024; 13:89469. [PMID: 38616850 PMCID: PMC11008397 DOI: 10.5501/wjv.v13.i1.89469] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2023] [Revised: 12/19/2023] [Accepted: 01/18/2024] [Indexed: 03/11/2024] Open
Abstract
BACKGROUND Hepatitis C is the leading cause of chronic liver disease worldwide and it significantly contributes to the burden of hepatocellular carcinoma (HCC). However, there are marked variations in the incidence and mortality rates of HCC across different geographical regions. With the advent of new widely available treatment modalities, such as direct-acting antivirals, it is becoming increasingly imperative to understand the temporal and geographical trends in HCC mortality associated with Hepatitis C. Furthermore, gender disparities in HCC mortality related to Hepatitis C are a crucial, yet underexplored aspect that adds to the disease's global impact. While some studies shed light on gender-specific trends, there is a lack of comprehensive data on global and regional mortality rates, particularly those highlighting gender disparities. This gap in knowledge hinders the development of targeted interventions and resource allocation strategies. AIM To understand the global and regional trends in Hepatitis C-related HCC mortality rates from 1990 to 2019, along with gender disparities. METHODS We utilized the Global Burden of Disease database, a comprehensive repository for global health metrics to age-standardized mortality rates due to Hepatitis C-related HCC from 1999 to 2019. Rates were evaluated per 100000 population and assessed by World Bank-defined regions. Temporal trends were determined using Joinpoint software and the Average Annual Percent Change (AAPC) method, and results were reported with 95% confidence intervals (CI). RESULTS From 1990 to 2019, overall, there was a significant decline in HCC-related mortality rates with an AAPC of -0.80% (95%CI: -0.83 to -0.77). Females demonstrated a marked decrease in mortality with an AAPC of -1.06% (95%CI: -1.09 to -1.03), whereas the male cohort had a lower AAPC of -0.52% (95%CI: -0.55 to -0.48). Regionally, East Asia and the Pacific demonstrated a significant decline with an AAPC of -2.05% (95%CI: -2.10 to -2.00), whereas Europe and Central Asia observed an uptrend with an AAPC of 0.72% (95%CI: 0.69 to 0.74). Latin America and the Caribbean also showed an uptrend with an AAPC of 0.06% (95%CI: 0.02 to 0.11). In the Middle East and North Africa, the AAPC was non-significant at 0.02% (95%CI: -0.09 to 0.12). North America, in contrast, displayed a significant upward trend with an AAPC of 2.63% (95%CI: 2.57 to 2.67). South Asia (AAPC -0.22%, 95%CI: -0.26 to -0.16) and Sub-Saharan Africa (AAPC -0.14%, 95%CI: -0.15 to -0.12) trends significantly declined over the study period. CONCLUSION Our study reports disparities in Hepatitis C-related HCC mortality between 1999 to 2019, both regionally and between genders. While East Asia and the Pacific regions showed a promising decline in mortality, North America has experienced a concerning rise in mortality. These regional variations highlight the need for healthcare policymakers and practitioners to tailor public health strategies and interventions. The data serves as a call to action, particularly for regions where mortality rates are not improving, emphasizing the necessity for a nuanced, region-specific approach to combat the global challenge of HCC secondary to Hepatitis C.
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Affiliation(s)
- Hassam Ali
- Department of Internal Medicine/Gastroenterology, East Carolina University Brody School of Medicine, Greenville, NC 27834, United States
| | - Fnu Vikash
- Department of Internal Medicine, Jacobi Medical Center/Albert Einstein College of Medicine, Bronx, NY 10461, United States
| | - Vishali Moond
- Department of Internal Medicine, Saint Peter's University Hospital/Robert Wood Johnson Medical School, New Brunswick, NJ 08901, United States
| | - Fatima Khalid
- Department of Internal Medicine, Quaid-e-Azam Medical College, Bahawalpur 63100, Punjab, Pakistan
| | - Abdur Rehman Jamil
- Department of Internal Medicine, Samaritan Medical Centre, Watertown, MA 13601, United States
| | - Dushyant Singh Dahiya
- Division of Gastroenterology, Hepatology & Motility, The University of Kansas School of Medicine, Kansas City, KS 66160, United States
| | - Amir Humza Sohail
- Department of Surgery, New York University Winthrop Hospital, New York, Mineloa, NY 11501, United States
| | - Manesh Kumar Gangwani
- Department of Internal Medicine, The University of Toledo, Toledo, OH 43606, United States
| | - Pratik Patel
- Department of Gastroenterology, Mather Hospital/Hofstra University Zucker School of Medicine, NY 11777, United States
| | - Sanjaya K Satapathy
- Division of Hepatology, Department of Medicine, North Shore University Hospital, Manhasset, NY 11030, United States
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Nawaz A, Zafar S, Alessa AH, Khalid NA, Shahzadi M, Majid A, Badshah M, Shah AA, Khan S. Characterization of ES10 lytic bacteriophage isolated from hospital waste against multidrug-resistant uropathogenic E. coli. Front Microbiol 2024; 15:1320974. [PMID: 38525078 PMCID: PMC10957765 DOI: 10.3389/fmicb.2024.1320974] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 01/29/2024] [Indexed: 03/26/2024] Open
Abstract
Escherichia coli is the major causative agent of urinary tract infections worldwide and the emergence of multi-drug resistant determinants among clinical isolates necessitates the development of novel therapeutic agents. Lytic bacteriophages efficiently kill specific bacteria and seems promising approach in controlling infections caused by multi-drug resistant pathogens. This study aimed the isolation and detailed characterization of lytic bacteriophage designated as ES10 capable of lysing multidrug-resistant uropathogenic E. coli. ES10 had icosahedral head and non-contractile tail and genome size was 48,315 base pairs long encoding 74 proteins. Antibiotics resistance, virulence and lysogenic cycle associated genes were not found in ES10 phage genome. Morphological and whole genome analysis of ES10 phage showed that ES10 is the member of Drexlerviridae. Latent time of ES10 was 30 min, burst size was 90, and optimal multiplicity of infection was 1. ES10 was stable in human blood and subsequently caused 99.34% reduction of host bacteria. Calcium chloride shortened the adsorption time and latency period of ES10 and significantly inhibited biofilm formation of host bacteria. ES10 caused 99.84% reduction of host bacteria from contaminated fomites. ES10 phage possesses potential to be utilized in standard phage therapy.
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Affiliation(s)
- Aneela Nawaz
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Sabeena Zafar
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | | | - Nauman Ahmed Khalid
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Muqaddas Shahzadi
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Alina Majid
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Malik Badshah
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Aamer Ali Shah
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
| | - Samiullah Khan
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad, Pakistan
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Korsten K, de Gier A, Leenders A, Wever PC, Kolwijck E. Using the Sysmex UF-4000 urine flow cytometer for rapid diagnosis of urinary tract infection in the clinical microbiological laboratory. J Clin Lab Anal 2024; 38:e25004. [PMID: 38454622 PMCID: PMC10959182 DOI: 10.1002/jcla.25004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2023] [Revised: 12/21/2023] [Accepted: 12/31/2023] [Indexed: 03/09/2024] Open
Abstract
BACKGROUND Urinary tract infections are responsible for a significant worldwide disease burden. Performing urine culture is time consuming and labor intensive. Urine flow cytometry might provide a quick and reliable method to screen for urinary tract infection. METHODS We analyzed routinely collected urine samples received between 2020 and 2022 from both inpatients and outpatients. The UF-4000 urine flow cytometer was implemented with an optimal threshold for positivity of ≥100 bacteria/μL. We thereafter validated the prognostic value to detect the presence of urinary tract infection (UTI) based on bacterial (BACT), leukocyte (WBC), and yeast-like cell (YLC) counts combined with the bacterial morphology (UF gram-flag). RESULTS In the first phase, in 2019, the UF-4000 was implemented using 970 urine samples. In the second phase, between 2020 and 2022, the validation was performed in 42,958 midstream urine samples. The UF-4000 screen resulted in a 37% (n = 15,895) decrease in performed urine cultures. Uropathogens were identified in 18,673 (69%) positively flagged urine samples. BACT > 10.000/μL combined with a gram-negative flag had a >90% positive predictive value for the presence of gram-negative uropathogens. The absence of gram-positive flag or YLC had high negative predictive values (99% and >99%, respectively) and are, therefore, best used to rule out the presence of gram-positive bacteria or yeast. WBC counts did not add to the prediction of uropathogens. CONCLUSION Implementation of the UF-4000 in routine practice decreased the number of cultured urine samples by 37%. Bacterial cell counts were highly predictive for the presence of UTI, especially when combined with the presence of a gram-negative flag.
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Affiliation(s)
- Koos Korsten
- Department of Medical Microbiology and Infection ControlAmsterdam UMC, location AMCAmsterdamThe Netherlands
- Department of Medical MicrobiologyJeroen Bosch Hospital's HertogenboschThe Netherlands
| | - Astrid de Gier
- Department of Medical MicrobiologyJeroen Bosch Hospital's HertogenboschThe Netherlands
| | - Alexander Leenders
- Department of Medical MicrobiologyJeroen Bosch Hospital's HertogenboschThe Netherlands
| | - Peter C. Wever
- Department of Medical MicrobiologyJeroen Bosch Hospital's HertogenboschThe Netherlands
| | - Eva Kolwijck
- Department of Medical MicrobiologyJeroen Bosch Hospital's HertogenboschThe Netherlands
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50
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Mititelu M, Olteanu G, Neacșu SM, Stoicescu I, Dumitrescu DE, Gheorghe E, Tarcea M, Busnatu ȘS, Ioniță-Mîndrican CB, Tafuni O, Belu I, Popescu A, Lupu S, Lupu CE. Incidence of Urinary Infections and Behavioral Risk Factors. Nutrients 2024; 16:446. [PMID: 38337730 PMCID: PMC10856807 DOI: 10.3390/nu16030446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 01/29/2024] [Accepted: 01/30/2024] [Indexed: 02/12/2024] Open
Abstract
This evaluation of the impact of behavioral risk factors on the incidence of urinary infections was based on a questionnaire in which 1103 respondents, predominantly women (883), participated. From the statistical processing of the data, it was observed that 598 of the respondents were of normal weight; the rest, more than half, were underweight or overweight (χ2 = 32.46, p < 0.001), with male respondents being predominantly overweight or obese (169 out of a total of 220). Most of the respondents were young (χ2 = 15.45, p < 0.001), under the age of 45 (840). According to the processed data, it was found that respondents in the age group of 26-35 years showed the greatest vulnerability to recurrent urinary infections, while the age group of 18-25 years recorded the highest number of responses related to the rare presence or even absence of episodes of urinary infections. A body weight-related vulnerability was also noted among the respondents; the majority of obese people declared that they face frequent episodes of urinary infections. Regarding diet quality, 210 respondents reported an adherence to an unhealthy diet, 620 to a moderately healthy diet, and 273 to a healthy diet. Of the respondents who adhered to a healthy diet, 223 were women (χ2 = 2.55, p = 0.279). There was a close connection between diet quality and the frequency of urinary infections: from the statistical processing of the data, it was observed that the highest percentage of respondents who rarely (57.14%) or never got urinary infections (29.30%) were among those who adhered to a healthy diet, and the highest percentage of those who declared that they often got urinary infections were among those with increased adherence to an unhealthy diet (χ2 = 13.46, p = 0.036). The results of this study highlight a strong impact of obesity, reduced consumption of fruit and vegetables, and sedentary lifestyle on the risk of recurring urinary infections.
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Affiliation(s)
- Magdalena Mititelu
- Department of Clinical Laboratory and Food Safety, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 020956 Bucharest, Romania; (M.M.); (G.O.)
| | - Gabriel Olteanu
- Department of Clinical Laboratory and Food Safety, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 020956 Bucharest, Romania; (M.M.); (G.O.)
| | - Sorinel Marius Neacșu
- Department of Pharmaceutical Technology and Bio-Pharmacy, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 020945 Bucharest, Romania
| | - Iuliana Stoicescu
- Department of Chemistry and Quality Control of Drugs, Faculty of Pharmacy, Ovidius University of Constanta, 900470 Constanta, Romania;
| | - Denisa-Elena Dumitrescu
- Department of Organic Chemistry, Faculty of Pharmacy, Ovidius University of Constanta, 900470 Constanta, Romania;
| | - Emma Gheorghe
- Department of Preclinical Sciences I—Histology, Faculty of Medicine, Ovidius University of Constanta, 900470 Constanta, Romania
| | - Monica Tarcea
- Department of Community Nutrition and Food Safety, G.E. Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, 540142 Mures, Romania;
| | - Ștefan Sebastian Busnatu
- Department of Cardio-Thoracic Pathology, Faculty of Medicine, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Corina-Bianca Ioniță-Mîndrican
- Department of Toxicology, Faculty of Pharmacy, Carol Davila University of Medicine and Pharmacy, 020945 Bucharest, Romania;
| | - Ovidiu Tafuni
- Department of Preventive Medicine, Nicolae Testemițanu State University of Medicine and Pharmacy from the Republic of Moldova, MD-2004 Chisinau, Moldova;
| | - Ionela Belu
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania;
| | - Antoanela Popescu
- Department of Pharmacognosy, Faculty of Pharmacy, Ovidius University of Constanta, 900470 Constanta, Romania;
| | - Sergiu Lupu
- Department of Navigation and Naval Transport, Faculty of Navigation and Naval Management, Mircea cel Batran Naval Academy, 900218 Constanta, Romania;
| | - Carmen Elena Lupu
- Department of Mathematics and Informatics, Faculty of Pharmacy, Ovidius University of Constanta, 900001 Constanta, Romania;
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