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Ríos Colombo NS, Paul Ross R, Hill C. Synergistic and off-target effects of bacteriocins in a simplified human intestinal microbiome: implications for Clostridioides difficile infection control. Gut Microbes 2025; 17:2451081. [PMID: 39817466 PMCID: PMC11740676 DOI: 10.1080/19490976.2025.2451081] [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: 06/28/2024] [Revised: 12/04/2024] [Accepted: 01/02/2025] [Indexed: 01/18/2025] Open
Abstract
Clostridioides difficile is a major cause of nosocomial diarrhea. As current antibiotic treatment failures and recurrence of infections are highly frequent, alternative strategies are needed for the treatment of this disease. This study explores the use of bacteriocins, specifically lacticin 3147 and pediocin PA-1, which have reported inhibitory activity against C. difficile. We engineered Lactococcus lactis strains to produce these bacteriocins individually or in combination, aiming to enhance their activity against C. difficile. Our results show that lacticin 3147 and pediocin PA-1 display synergy, resulting in higher anti-C. difficile activity. We then evaluated the effects of these L. lactis strains in a Simplified Human Intestinal Microbiome (SIHUMI-C) model, a bacterial consortium of eight diverse human gut species that includes C. difficile. After introducing the bacteriocin-producing L. lactis strains into SIHUMI-C, samples were collected over 24 hours, and the genome copies of each species were assessed using qPCR. Contrary to expectations, the combined bacteriocins increased C. difficile levels in the consortium despite showing synergy against C. difficile in agar-based screening. This can be rationally explained by antagonistic inter-species interactions within SIHUMI-C, providing new insights into how broad-spectrum antimicrobials might fail to control targeted species in complex gut microbial communities. These findings highlight the need to mitigate off-target effects in complex gut microbiomes when developing bacteriocin-based therapies with potential clinical implications for infectious disease treatment.
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Affiliation(s)
| | - R. Paul Ross
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
| | - Colin Hill
- APC Microbiome Ireland, University College Cork, Cork, Ireland
- School of Microbiology, University College Cork, Cork, Ireland
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Xia J, Liu T, Wan R, Zhang J, Fu Q. Global burden and trends of the Clostridioides difficile infection-associated diseases from 1990 to 2021: an observational trend study. Ann Med 2025; 57:2451762. [PMID: 39847395 PMCID: PMC11758798 DOI: 10.1080/07853890.2025.2451762] [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: 05/17/2024] [Revised: 09/09/2024] [Accepted: 12/09/2024] [Indexed: 01/24/2025] Open
Abstract
BACKGROUND This study was aimed to explore the global burden and trends of Clostridioides difficile infections (CDI) associated diseases. METHODS Data for this study were obtained from the Global Burden of Disease Study 2021. The burden of CDI was assessed using the age-standardized rates of disability-adjusted life years (ASR-DALYs) and deaths (ASDRs). Trends in the burden of CDI were presented using average annual percentage changes (AAPCs). RESULTS The ASR-DALYs for CDI increased from 1.83 (95% UI: 1.53-2.18) per 100,000 in 1990 to 3.46 (95% UI: 3.04-3.96) per 100,000 in 2021, with an AAPC of 2.03% (95% CI: 1.67-2.4%). The ASDRs for CDI rose from 0.10 (95% UI: 0.08-0.11) per 100,000 in 1990 to 0.19 (95% UI: 0.16-0.23) per 100,000 in 2021, with an AAPC of 2.26% (95% CI: 1.74-2.79%). In 2021, higher burdens of ASR-DALYs (10.7 per 100,000) and ASDRs (0.53 per 100,000) were observed in high socio-demographic index (SDI) areas, and among age group over 70 years (31.62/100,000 for ASR-DALYs and 2.45/100,000 for ASDRs). During the COVID-19 pandemic, the global ASR-DALYs and ASDRs slightly decreased. However, in regions with low SDI, low-middle and middle SDI, those rates slightly increased. CONCLUSION The global burden of CDI has significantly increased, particularly in regions with high SDI and among individuals aged 70 years and above. During the COVID-19 pandemic period from 2020 to 2021, the burden of CDI further increased in regions with low, low-middle, and middle SDI. These findings underscore the need for increased attention and intervention, especially in specific countries and populations.
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Affiliation(s)
- Jun Xia
- Department of Neurocritical Care, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Tan Liu
- Department of Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Rui Wan
- Department of Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Jing Zhang
- Department of Neurocritical Care, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
| | - Quanzhu Fu
- Department of Critical Care Medicine, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China
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Rhodes NG, Olinger K, Galgano SJ, Pietryga JA. Imaging of Iatrogenic Injuries to the Bowel. Radiol Clin North Am 2025; 63:387-403. [PMID: 40221182 DOI: 10.1016/j.rcl.2024.11.003] [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: 04/14/2025]
Abstract
This review discusses the ways in which the health care provider (or more broadly, the provision of medical care) can cause harm to the bowel and highlights the appearance of such untoward events on imaging. The etiologies are myriad, and as such, the radiologist must remain vigilant in identifying the presence of suspected and unsuspected injuries. Specific attention is given to complications from medication and external radiation therapy, as these interventions and their timing are often not known by the radiologist.
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Affiliation(s)
- Nicholas G Rhodes
- Musculoskeletal and Hospital Imaging, Department of Radiology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA.
| | - Kristen Olinger
- Department of Radiology, University of North Carolina, 2000 Old Clinic, 101 Manning Drive, Campus Box #7510, Chapel Hill, NC 27599, USA
| | - Samuel J Galgano
- Abdominal Imaging, Department of Radiology, University of Alabama at Birmingham, JTN 444, 619 19th Street South, Birmingham, AL 35294, USA
| | - Jason A Pietryga
- Department of Radiology, University of North Carolina, 2000 Old Clinic, 101 Manning Drive, Campus Box #7510, Chapel Hill, NC 27599, USA
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Aguilar-Zamora E, Rodríguez C, Torres J, Ortiz-Olvera N, Aparicio-Ozores G, Flores-Luna L, Quesada-Gómez C, Camorlinga-Ponce M. Predominance of FQR1 NAP1/RT027 Clostridioides difficile Among Mexican Children and Adult Patients, and its Resistance to Eleven Antibiotics. Arch Med Res 2025; 56:103171. [PMID: 39938192 DOI: 10.1016/j.arcmed.2024.103171] [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: 06/18/2024] [Revised: 11/21/2024] [Accepted: 12/20/2024] [Indexed: 02/14/2025]
Abstract
AIMS Clostridioides difficile is a major cause of antibiotic-associated diarrhea. This study investigated the diversity, clonality, and antimicrobial resistance of C. difficile isolates from Mexican children and adults with diarrhea. METHODS Between 2014 and 2016, we isolated 37 C. difficile strains in three hospitals in Mexico City. C. difficile strains were typed by PCR-ribotyping and pulsed-field gel electrophoresis (PFGE). Antimicrobial susceptibility to eleven antibiotics was determined. Whole-genome sequencing (WGS) was used to investigate the presence of antimicrobial resistance genes (ARG) and perform a pangenome analysis of 53 genomes from Mexico and 137 publicly available C. difficile genomes. RESULTS Toxigenic strains comprised six isolates from children and 31 from adults. While NAP1/RT027 isolates were found in three children, they were predominant in adults (n = 31, 90.3 %) and showed the 1058 and 008 PFGE macrorestriction patterns. All isolates were susceptible to vancomycin and metronidazole but resistant to ciprofloxacin, and over 90 % of the isolates were resistant to linezolid and carried cfr(E). The pangenome of these isolates contained 4,852 genes, of which 3,455 (81.2 %) were categorized as core genes and 801 (18.8 %) as accessory genes. In addition, our isolates demonstrated a close relationship with strains from the United States, Canada, and France. CONCLUSIONS Our work provides, for the first time, genomic insights into C. difficile strains present in Mexico. In our hospital setting, the predominant strains were primarily NAP1/RT027 and exhibited resistance to linezolid, a pattern observed in both pediatric and adult populations. This unique combination of characteristics has not been previously reported in Latin America.
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Affiliation(s)
- Emmanuel Aguilar-Zamora
- Medical Infectious Diseases Research Unit, High Specialty Medical Unit Hospital de Pediatria, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico; Escuela Nacional de Ciencias Biologicas, Instituto Politecnico National, Mexico City, Mexico
| | - Cesar Rodríguez
- Anerobic Bacteriology Research Laboratory, Centro de Investigacion de Enfermedades Tropicales and Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica
| | - Javier Torres
- Medical Infectious Diseases Research Unit, High Specialty Medical Unit Hospital de Pediatria, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Nayeli Ortiz-Olvera
- Department of Gastroenterology, High Specialty Medical Unit Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico
| | - Gerardo Aparicio-Ozores
- Department of Microbiology, Escuela Nacional de Ciencias Biologicas, Instituto Politecnico Nacional, Mexico City, Mexico
| | - Lourdes Flores-Luna
- Center for Public Health Research, National Institute of Public Health, Cuernavaca, Morelos, Mexico
| | - Carlos Quesada-Gómez
- Anerobic Bacteriology Research Laboratory, Centro de Investigacion de Enfermedades Tropicales and Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica
| | - Margarita Camorlinga-Ponce
- Medical Infectious Diseases Research Unit, High Specialty Medical Unit Hospital de Pediatria, Centro Medico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico.
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Zhang S, Ma C, Zhang H, Zhao C, Guo R, Liu J, Wang J, Yuan J, Jia K, Wu A, Chen Y, Lei J. Toxin genotypes, antibiotic resistance and their correlations in Clostridioides difficile isolated from hospitals in Xi'an, China. BMC Microbiol 2024; 24:177. [PMID: 38783194 PMCID: PMC11112860 DOI: 10.1186/s12866-024-03327-z] [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: 04/13/2023] [Accepted: 05/10/2024] [Indexed: 05/25/2024] Open
Abstract
BACKGROUND Clostridioides difficile is the main pathogen of antimicrobial-associated diarrhoea and health care facility-associated infectious diarrhoea. This study aimed to investigate the prevalence, toxin genotypes, and antibiotic resistance of C. difficile among hospitalized patients in Xi'an, China. RESULTS We isolated and cultured 156 strains of C. difficile, representing 12.67% of the 1231 inpatient stool samples collected. Among the isolates, tcdA + B + strains were predominant, accounting for 78.2% (122/156), followed by 27 tcdA-B + strains (27/156, 17.3%) and 6 binary toxin gene-positive strains. The positive rates of three regulatory genes, tcdC, tcdR, and tcdE, were 89.1% (139/156), 96.8% (151/156), and 100%, respectively. All isolates were sensitive to metronidazole, and the resistance rates to clindamycin and cephalosporins were also high. Six strains were found to be resistant to vancomycin. CONCLUSION Currently, the prevalence rate of C. difficile infection (CDI) in Xi'an is 12.67% (156/1231), with the major toxin genotype of the isolates being tcdA + tcdB + cdtA-/B-. Metronidazole and vancomycin were still effective drugs for the treatment of CDI, but we should pay attention to antibiotic management and epidemiological surveillance of CDI.
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Affiliation(s)
- Sukai Zhang
- Clinical Medicine Class of 2019, Xi'an Jiaotong University, Xi'an, China
| | - Chen Ma
- Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Haiyue Zhang
- Clinical Medicine Class of 2019, Xi'an Jiaotong University, Xi'an, China
| | - Congcong Zhao
- Clinical Medicine Class of 2019, Xi'an Jiaotong University, Xi'an, China
| | - Ruibing Guo
- Clinical Medicine Class of 2019, Xi'an Jiaotong University, Xi'an, China
| | - Jiahao Liu
- Clinical Medicine Class of 2019, Xi'an Jiaotong University, Xi'an, China
| | - Jing Wang
- Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Jing Yuan
- Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Kai Jia
- Xi'an Children's Hospital, Xi'an, China
| | | | - Yanjiong Chen
- Department of Immunology and Pathogenic Biology, College of Basic Medicine, Xi'an Jiaotong University Health Science Center, Xi'an, China
| | - Jin'e Lei
- Department of Clinical Laboratory, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
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Stallhofer J, Steube A, Katzer K, Stallmach A. Microbiota-Based Therapeutics as New Standard-of-Care Treatment for Recurrent Clostridioides difficile Infection. Visc Med 2024; 40:82-91. [PMID: 38584858 PMCID: PMC10995962 DOI: 10.1159/000535851] [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: 08/31/2023] [Accepted: 12/14/2023] [Indexed: 04/09/2024] Open
Abstract
Background Clostridioides difficile (C. difficile) is a spore-forming bacterial species that ubiquitously exists in the environment. Colonization by C. difficile is highly prevalent in infants, while fewer than 5% of adults are asymptomatic carriers. Disruption of the microbiome, such as through antibiotic treatment, triggers the germination of bacterial spores into numerous vegetative cells. These cells then produce enterotoxins that result in watery diarrhea and colonic inflammation. If left untreated, C. difficile infection (CDI) can lead to pseudomembranous colitis with the potentially life-threatening complication of toxic megacolon. Summary Over the past few decades, the incidence, morbidity, and mortality associated with CDIs have increased. They have emerged as the primary cause of nosocomial gastrointestinal infections in industrialized countries, posing a significant burden on healthcare systems. Despite antibiotics often being the cause of CDIs, they remain the standard treatment. However, a considerable number of patients treated with antibiotics will experience recurrent CDI (rCDI). Microbiota-based therapies targeting the core issue of CDI - antibiotic-induced dysbiosis - hold promise for rCDI treatment. While data for probiotics are insufficient, numerous studies have highlighted the effectiveness of fecal microbiota transplantation (FMT) as a safe and viable therapeutic option for rCDI. This approach is now endorsed by multiple guidelines. Nonetheless, regulatory prerequisites, such as comprehensive stool donor screening, restrict the widespread adoption of FMT beyond specialized centers. Recently, the US Food and Drug Administration has approved two commercial microbiota-based therapeutics to prevent CDI recurrence. These therapeutics are available by prescription in the USA. RBX2660 (REBYOTA™) comprises a diverse consortium of live microbes derived from human stool and is administered via enema. On the other hand, SER-109 (VOWST™) is an orally administered spore-based medication. In this review, we discuss the potential of microbiota-based treatments for rCDI against the background of medico-legal challenges associated with classical FMT. Key Messages FMT has emerged as a highly effective cure for rCDI. Nonetheless, regulatory prerequisites and laborious preparation procedures impede its widespread use. The establishment of ready-to-use microbiota-based therapeutics in clinical practice is necessary. In the USA, the recent approval of the first two commercial medications, including a spore-based oral preparation, marks a significant step forward.
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Affiliation(s)
| | - Arndt Steube
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Katrin Katzer
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
| | - Andreas Stallmach
- Department of Internal Medicine IV, Jena University Hospital, Jena, Germany
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Aiman S, Farooq QUA, Han Z, Aslam M, Zhang J, Khan A, Ahmad A, Li C, Ali Y. Core-genome-mediated promising alternative drug and multi-epitope vaccine targets prioritization against infectious Clostridium difficile. PLoS One 2024; 19:e0293731. [PMID: 38241420 PMCID: PMC10798517 DOI: 10.1371/journal.pone.0293731] [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: 08/01/2023] [Accepted: 10/18/2023] [Indexed: 01/21/2024] Open
Abstract
Prevention of Clostridium difficile infection is challenging worldwide owing to its high morbidity and mortality rates. C. difficile is currently being classified as an urgent threat by the CDC. Devising a new therapeutic strategy become indispensable against C. difficile infection due to its high rates of reinfection and increasing antimicrobial resistance. The current study is based on core proteome data of C. difficile to identify promising vaccine and drug candidates. Immunoinformatics and vaccinomics approaches were employed to construct multi-epitope-based chimeric vaccine constructs from top-ranked T- and B-cell epitopes. The efficacy of the designed vaccine was assessed by immunological analysis, immune receptor binding potential and immune simulation analyses. Additionally, subtractive proteomics and druggability analyses prioritized several promising and alternative drug targets against C. difficile. These include FMN-dependent nitroreductase which was prioritized for pharmacophore-based virtual screening of druggable molecule databases to predict potent inhibitors. A MolPort-001-785-965 druggable molecule was found to exhibit significant binding affinity with the conserved residues of FMN-dependent nitroreductase. The experimental validation of the therapeutic targets prioritized in the current study may worthy to identify new strategies to combat the drug-resistant C. difficile infection.
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Affiliation(s)
- Sara Aiman
- Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing, China
| | - Qurrat ul Ain Farooq
- Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing, China
| | - Zhongjie Han
- Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing, China
| | - Muneeba Aslam
- Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan, Pakistan
| | - Jilong Zhang
- Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing, China
| | - Asifullah Khan
- Department of Biochemistry, Abdul Wali Khan University Mardan, Mardan, Pakistan
| | - Abbas Ahmad
- Department of Biotechnology, Abdul Wali Khan University Mardan, Mardan, KP, Pakistan
| | - Chunhua Li
- Faculty of Environmental and Life Sciences, Beijing University of Technology, Beijing, China
| | - Yasir Ali
- School of Biomedical Sciences, Chinese University of Hong Kong, Hong Kong, Hong Kong
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Ayada G, Atamna A, Babich T, Ben Zvi H, Elis A, Bishara J. Community versus health care-associated Clostridioides difficile infection: A comparison between clinical characteristics and outcomes in hospitalized patients. Am J Infect Control 2023; 51:1339-1343. [PMID: 37290688 DOI: 10.1016/j.ajic.2023.05.019] [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: 02/25/2023] [Revised: 05/29/2023] [Accepted: 05/31/2023] [Indexed: 06/10/2023]
Abstract
BACKGROUND Clostridioides difficile infection (CDI) can be divided according to its acquisition site, health care (HC) or community (CA) associated CDI. Studies showed severe disease, higher recurrence, and mortality among HC-CDI patients, while others reported the opposite. We aimed to compare the outcomes according to the CDI acquisition site. METHODS The study analyzed medical records and laboratory computerized system data to identify patients (≥18 years old) who were hospitalized with the first CDI from January 2013 to March 2021. Patients were divided into HC-CDI and CA-CDI groups. The primary outcome was 30-day mortality. Other outcomes: CDI severity, colectomy, intensive care unit (ICU) admission, length of hospitalization, 30 and 90-day recurrence, and 90 days all-cause mortality. RESULTS Of 867 patients, 375 were defined as CA-CDI and 492 as HC-CDI. CA-CDI patients had more underlying malignancy (26% vs 21% P = .04) and inflammatory bowel disease (7% vs 1%, P < .001). The 30 days mortality was similar (10% CA-CDI and 12% HC-CDI, P = .5), and the acquisition site was not found to be a risk factor. There was no difference in severity nor in complications, but the recurrence rate was higher among those with CA-CDI (4% vs 2%, P = .055). CONCLUSIONS There were no differences between the CA-CDI and HC-CDI groups regarding rates, in-hospital complications, short-term mortality, and 90-day recurrence rates. However, the CA-CDI patients had a higher recurrence rate at 30 days.
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Affiliation(s)
- Gida Ayada
- Internal Medicine C, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
| | - Alaa Atamna
- Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel; Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel.
| | - Tanya Babich
- Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel; Internal Medicine E, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
| | - Haim Ben Zvi
- Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel; Clinical Microbiology Laboratory, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel
| | - Avishay Elis
- Internal Medicine C, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel; Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
| | - Jihad Bishara
- Infectious Diseases Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel; Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel
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Hocking L, Ianiro G, Leong RW, Iqbal T, Kao D, Cabling M, Stockwell S, Romanelli RJ, Marjanovic S. Faecal microbiota transplantation for recurrent C. difficile infections: challenges and improvement opportunities for clinical practice and healthcare systems. Aliment Pharmacol Ther 2023; 57:549-564. [PMID: 36495561 DOI: 10.1111/apt.17309] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Revised: 09/08/2022] [Accepted: 11/03/2022] [Indexed: 02/15/2023]
Abstract
BACKGROUND There is growing interest in faecal microbiota transplantation (FMT) as a treatment for recurrent Clostridioides difficile infection (CDI), but evidence on the diverse requirements for safe, effective and accessible services is fragmented and limited. AIMS To identify key components of FMT provision relating to the patient care pathway, stool donor pathway and wider healthcare system, and to explore variation in practice METHODS: We conducted a narrative review of the literature and consultations with key clinical experts in the field. Evidence is drawn from high-income country contexts, with an emphasis on Australia, Canada, Italy and the United Kingdom as case example countries. RESULTS We identify and discuss key challenges to do with healthcare capacity (workforce, FMT and stool banking facilities), donors and donations, patient access and choice of FMT delivery routes, regulation, costs and reimbursement. We also identify improvement opportunities to increase awareness of FMT and referral processes, physician training, maintaining patient registries and outcome monitoring metrics, in-country regulatory harmonisation and tackling reimbursement challenges and discuss future research needs. CONCLUSION Effectively bringing FMT to patients in a healthcare system requires much more than just the existence of a clinically effective procedure. With FMT being a potentially effective treatment option for recurrent CDI for many patients, a well-rounded understanding of how appropriate FMT capacity can be built and nurtured is important for both healthcare providers and policymakers seeking to improve patient care.
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Affiliation(s)
| | - Gianluca Ianiro
- Gastroenterology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS and Dipartimento Universitario di Medicina e Chirurgia Traslazionale, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Rupert W Leong
- Macquarie University Hospital and Concord Hospital, Sydney, Australia
| | | | - Dina Kao
- University of Alberta, Edmonton, Alberta, Canada
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Aktories K. From signal transduction to protein toxins-a narrative review about milestones on the research route of C. difficile toxins. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2023; 396:173-190. [PMID: 36203094 PMCID: PMC9831965 DOI: 10.1007/s00210-022-02300-9] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Accepted: 09/22/2022] [Indexed: 01/29/2023]
Abstract
Selected findings about Clostridioides difficile (formerly Clostridium difficile) toxins are presented in a narrative review. Starting with a personal view on research about G proteins, adenylyl cyclase, and ADP-ribosylating toxins in the laboratory of Günter Schultz in Heidelberg, milestones of C. difficile toxin research are presented with the focus on toxin B (TcdB), covering toxin structure, receptor binding, toxin up-take and refolding, the intracellular actions of TcdB, and the treatment of C. difficile infection.
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Affiliation(s)
- Klaus Aktories
- Institute of Experimental and Clinical Pharmacology and Toxicology, Medical Faculty, University of Freiburg, Albertstr. 25, 79104, Freiburg, Germany.
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Albano GD, Midiri M, Zerbo S, Matteini E, Passavanti G, Curcio R, Curreri L, Albano S, Argo A, Cadelo M. Implementation of A Year-Long Antimicrobial Stewardship Program in A 227-Bed Community Hospital in Southern Italy. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2023; 20:996. [PMID: 36673754 PMCID: PMC9859386 DOI: 10.3390/ijerph20020996] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Revised: 12/26/2022] [Accepted: 01/01/2023] [Indexed: 06/17/2023]
Abstract
BACKGROUND Healthcare-Acquired Infections (HAIs) are serious healthcare complications affecting hospital stay, in-hospital mortality, and costs. Root cause analysis has identified the inappropriate use of antibiotics as the main causative factor in the expansion of multi-drug-resistant organisms (MDRO) in our hospital. An Antimicrobial Stewardship (AMS) program was implemented to optimize antibiotic use, limit the development of resistance, improve therapeutic efficacy and clinical outcomes, and reduce costs. METHODS The stewardship strategies were: antimicrobial oversight on "critical" antibiotics; the development of hospital guidelines on antibiotic selection with the production of a consensus document; the implementation of clinical and management control algorithms with visual impact and Business Intelligence methods; training and updating; and the monitoring of outcome measures and process indicators. RESULTS Clinical outcomes: length of stay reduced by 0.23 days, hospital readmission/first month rates decreased by 19%, and mortality for infections reduced by 8.8%. Microbiological Outcomes: Clostridium Difficile colitis incidence reduced by 9.1%.Economic Outcomes: Reduction in antimicrobial costs by 35% on average fee/discharged patient. CONCLUSIONS The systematic application of the AMS program in a small hospital led to multiple improvements in clinical, microbiological, and economic outcome measures. The analysis of the core indicators for our hospital AMS program showed a significant adherence to the model and hospital recommendations.
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Affiliation(s)
- Giuseppe Davide Albano
- Section of Legal Medicine, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90129 Palermo, Italy
| | - Mauro Midiri
- Section of Legal Medicine, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90129 Palermo, Italy
| | - Stefania Zerbo
- Section of Legal Medicine, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90129 Palermo, Italy
| | - Emanuele Matteini
- Fondazione Istituto G. Giglio, Contrada Pietra PollastraPisciotto, 90015 Cefalù, Italy
| | - Giulia Passavanti
- Fondazione Istituto G. Giglio, Contrada Pietra PollastraPisciotto, 90015 Cefalù, Italy
| | - Rosario Curcio
- Fondazione Istituto G. Giglio, Contrada Pietra PollastraPisciotto, 90015 Cefalù, Italy
| | - Lidia Curreri
- Fondazione Istituto G. Giglio, Contrada Pietra PollastraPisciotto, 90015 Cefalù, Italy
| | - Salvatore Albano
- Fondazione Istituto G. Giglio, Contrada Pietra PollastraPisciotto, 90015 Cefalù, Italy
| | - Antonina Argo
- Section of Legal Medicine, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90129 Palermo, Italy
| | - Marcello Cadelo
- Fondazione Istituto G. Giglio, Contrada Pietra PollastraPisciotto, 90015 Cefalù, Italy
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12
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Wingen-Heimann SM, Davies K, Viprey VF, Davis G, Wilcox MH, Vehreschild MJGT, Lurienne L, Bandinelli PA, Cornely OA, Vilken T, Hopff SM, Vehreschild JJ, Webber C, Rupnik M, Wilcox M. Clostridioides difficile infection (CDI): A pan-European multi-center cost and resource utilization study, results from the Combatting Bacterial Resistance in Europe CDI (COMBACTE-CDI). Clin Microbiol Infect 2022; 29:651.e1-651.e8. [PMID: 36586512 DOI: 10.1016/j.cmi.2022.12.019] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Revised: 12/12/2022] [Accepted: 12/20/2022] [Indexed: 12/29/2022]
Abstract
OBJECTIVES Clostridioides difficile infection (CDI) is one of the leading nosocomial infections worldwide, resulting in a significantly increasing burden on the healthcare systems. However, Pan-European data about cost and resource utilization of CDI treatment do not exist. METHODS A retrospective analysis within the Combatting Bacterial Resistance in Europe CDI project was conducted based on resource costs for inpatient treatment and productivity costs. Country-specific cost values were converted to EURO referred to 1 January, 2019 values. Differences in price levels for healthcare services among the participating countries were adjusted by using an international approach of the Organisation for Economic Co-operation and Development. As the study focused on patients with recurrent CDI, the observed study population was categorized into (a) patients with CDI but without CDI recurrence (case group), (b) patients with CDI recurrence (recurrence group), and (c) patients without CDI (control group). RESULTS Overall, 430 hospitalized patients from 12 European countries were included into the analysis between July 2018 and November 2018. Distribution of mean hospital length of stay and mean overall costs per patient between the case group, recurrence group, and control group were as follows: 22 days (95% CI 17-27 days) vs. 55 days (95% CI 17-94 days) vs. 26 days (95% CI 22-31 days; p 0.008) and € 15 242 (95% CI 10 593-19 891) vs. € 52 024 (95% CI 715-103 334) vs. € 21 759 (95% CI 16 484-27 035; p 0.010), respectively. The CDI recurrence rate during the observational period was 18%. Change escalation in CDI medication (OR 3.735) and treatment in an intensive care unit (OR 5.454) were found to be the most important variables associated with increased overall costs of patients with CDI. CONCLUSIONS Treatment of patients with recurrent CDI results in a significant burden. Prevention of CDI recurrences should be in focus of daily patient care to identify the most cost-effective treatment strategy.
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Affiliation(s)
- Sebastian M Wingen-Heimann
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Cologne, Germany; University of Applied Sciences for Economics and Management (FOM), Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn-Cologne Duesseldorf, Cologne, Germany.
| | - Kerrie Davies
- Healthcare Associated Infections Research Group, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, United Kingdom; The European Study Group for C. difficile, European Society of Clinical Microbiology and Infectious Disease
| | - Virginie F Viprey
- Healthcare Associated Infections Research Group, Leeds Institute of Medical Research, University of Leeds, Leeds, United Kingdom
| | - Georgina Davis
- Healthcare Associated Infections Research Group, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, United Kingdom
| | - Mark H Wilcox
- Healthcare Associated Infections Research Group, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, United Kingdom
| | - Maria J G T Vehreschild
- Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt am Main, Germany
| | | | | | - Oliver A Cornely
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn-Cologne Duesseldorf, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Clinical Trials Centre Cologne (ZKS Köln), Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Center for Molecular Medicine Cologne, Cologne, Germany
| | - Tuba Vilken
- University of Antwerp, Vaccine & Infectious Disease Institute, Laboratory of Medical Microbiology, Antwerp, Belgium
| | - Sina M Hopff
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn-Cologne Duesseldorf, Cologne, Germany
| | - Jörg Janne Vehreschild
- University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Cologne, Germany; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; Department II of Internal Medicine, Hematology/Oncology, Goethe University Frankfurt, Frankfurt am Main, Germany
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13
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Park SO, Yeo I. Trends in Clostridioides difficile prevalence, mortality, severity, and age composition during 2003-2014, the national inpatient sample database in the US. Ann Med 2022; 54:1851-1858. [PMID: 35786103 PMCID: PMC9258430 DOI: 10.1080/07853890.2022.2092893] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Clostridioides difficile (formerly known as Clostridium difficile) infection (CDI) is one of the most prevalent healthcare-associated infections in the United States (US). In the early 2000s, CDI emerged as a great threat with increasing prevalence, mortality, and severity, especially in advanced age. We investigated the US national trends in in-hospital CDI prevalence, mortality, severity, and age composition from 2003 to 2014. METHODS We identified the patients with CDI using the national inpatient sample data from 2003 to 2014. We performed Poisson regression model and Kendall's tau-b correlation test for our analyses. RESULTS Adjusted overall CDI prevalence did not significantly change during 2003-2014. In-hospital mortality of overall CDI did not significantly change during 2003-2008, then significantly decreased during 2008-2014. Severity of overall CDI significantly increased during 2003-2008, then decreased during 2008-2014. The proportions of patients with age ≥ 65 years decreased in CDI prevalence, mortality, and severity during 2003-2014. CONCLUSIONS Compared to the earlier years 2003-2008, overall CDI outcome improved in the later years 2008-2014. Younger patients increasingly contributed to CDI prevalence, mortality, and severity during 2003-2014. More studies to understand underlying driving forces of changes in CDI trends are warranted to mitigate CDI.
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Affiliation(s)
- Sun O Park
- Division of Infectious Diseases, Department of Medicine, Albert Einstein College of Medicine and Montefiore Medical Center, Bronx, NY, USA
| | - Ilhwan Yeo
- Department of Medicine, New York Presbyterian, Queens, NY, USA
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14
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Gut Microbiota Manipulation in Irritable Bowel Syndrome. Microorganisms 2022; 10:microorganisms10071332. [PMID: 35889051 PMCID: PMC9319495 DOI: 10.3390/microorganisms10071332] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 06/24/2022] [Accepted: 06/29/2022] [Indexed: 02/05/2023] Open
Abstract
Increased knowledge suggests that disturbed gut microbiota, termed dysbiosis, might promote the development of irritable bowel syndrome (IBS) symptoms. Accordingly, gut microbiota manipulation has evolved in the last decade as a novel treatment strategy in order to improve IBS symptoms. In using different approaches, dietary management stands first in line, including dietary fiber supplements, prebiotics, and probiotics that are shown to change the composition of gut microbiota, fecal short-chain fatty acids and enteroendocrine cells densities and improve IBS symptoms. However, the exact mixture of beneficial bacteria for each individual remains to be identified. Prescribing nonabsorbable antibiotics still needs confirmation, although using rifaximin has been approved for diarrhea-predominant IBS. Fecal microbiota transplantation (FMT) has recently gained a lot of attention, and five out of seven placebo-controlled trials investigating FMT in IBS obtain promising results regarding symptom reduction and gut microbiota manipulation. However, more data, including larger cohorts and studying long-term effects, are needed before FMT can be regarded as a treatment for IBS in clinical practice.
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15
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Neumann-Schaal M, Groß U, Just I, Jahn D. Editorial: The Deadly Secrets of C. difficile-Insights Into Host-Pathogen Interaction. Front Microbiol 2022; 13:897612. [PMID: 35464954 PMCID: PMC9020219 DOI: 10.3389/fmicb.2022.897612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2022] [Accepted: 03/18/2022] [Indexed: 11/13/2022] Open
Affiliation(s)
- Meina Neumann-Schaal
- Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.,Braunschweig Integrated Centre of Systems Biology (BRICS), Braunschweig, Germany
| | - Uwe Groß
- Institute of Medical Microbiology and Virology, University Medical Center Göttingen, Göttingen, Germany
| | - Ingo Just
- Institute of Toxicology, Hannover Medical School, Hanover, Germany
| | - Dieter Jahn
- Braunschweig Integrated Centre of Systems Biology (BRICS), Braunschweig, Germany.,Institute of Microbiology, Technische Universität Braunschweig, Braunschweig, Germany
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16
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Neumann-Schaal M, Groß U, Just I, Jahn D. Editorial: The Deadly Secrets of C. Difficile-Insights Into Host-Pathogen Interaction, Volume II. Front Microbiol 2022; 13:896979. [PMID: 35464962 PMCID: PMC9019597 DOI: 10.3389/fmicb.2022.896979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2022] [Accepted: 03/16/2022] [Indexed: 11/22/2022] Open
Affiliation(s)
- Meina Neumann-Schaal
- Research Group Metabolomics, Leibniz-Institute DSMZ-German Collection of Microorganisms and Cell Cultures, Braunschweig, Germany.,Braunschweig Integrated Centre of Systems Biology (BRICS), Braunschweig, Germany
| | - Uwe Groß
- Institute of Medical Microbiology and Virology, University Medical Center Göttingen, Göttingen, Germany
| | - Ingo Just
- Institute of Toxicology, Hannover Medical School, Hannover, Germany
| | - Dieter Jahn
- Braunschweig Integrated Centre of Systems Biology (BRICS), Braunschweig, Germany.,Institute of Microbiology, Technische Universität Braunschweig, Braunschweig, Germany
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17
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Uddin R, Arif A. Potential Drug Targets Identification Against Clostridioides Difficile (CD)
and Characterization of Indispensable Proteins by a Subtractive Genomics
Approach Followed by Virtual Screening. LETT DRUG DES DISCOV 2022. [DOI: 10.2174/1570180818666210930160128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
Clostridioides difficile (CD) is an enteric multi-drug resistant pathogenic bacterium.
CD-associated infections are the leading cause of nosocomial diarrhea that can further lead to pseudomembranous
colitis, toxic mega-colon or sepsis with greater mortality and morbidity risks. CD infection
possesses higher rates of recurrence due to its greater resistance to antibiotics. Considering its higher
rates of recurrence, it has become a major burden on healthcare facilities. Therefore, there is a dire need
to identify novel drug targets to combat antibiotic resistance of Clostridioides difficile.
Objective:
To identify and propose new and novel drug targets against the Clostridioides difficile.
Methods:
In the current study, a computational subtractive genomics approach was applied to obtain a set
of potential drug targets that exist in the multi-drug resistant strain of Clostridioides difficile. Here, the
uncharacterized proteins were studied as potential drug targets. The methodology involved several bioinformatics
databases and tools. The druggable proteins sequences were retrieved based on non-homology
with host proteome and essentiality for the survival of the pathogen. The uncharacterized proteins were
functionally characterized using different computational tools, and sub-cellular localization was also predicted.
The metabolic pathways were analyzed using the KEGG database. Eventually, the druggable proteome
has been fetched using sequence similarity with the already available drug targets present in the
DrugBank database. These druggable proteins were further explored for the structural details to identify
drug candidates.
Results :
A priority list of potential drug targets was provided with the help of the applied method on the
complete proteome set of the C. difficile. Moreover, the drug-like compounds have been screened against
the potential drug targets to prioritize potential drug candidates. To facilitate the need for drug targets and
therapies, the study proposed five potential protein drug targets, out of which three proposed drug targets
were subjected to homology modeling to explore their structural and functional activities
Conclusion:
In conclusion, we proposed three unique, unexplored drug targets against C. difficile. The
structure-based methods were applied and resulted in a list of top-scoring compounds as potential inhibitors
to proposed drug targets.
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Affiliation(s)
- Reaz Uddin
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological
Sciences, University of Karachi, Karachi 75270, Pakistan
| | - Alina Arif
- Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological
Sciences, University of Karachi, Karachi 75270, Pakistan
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18
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Evaluation of a new fast in-house Real-Time PCR assay for detecting both Norovirus and toxigenic Clostridium difficile using fecal sample and rectal swab. Am J Infect Control 2022; 50:67-71. [PMID: 34461212 DOI: 10.1016/j.ajic.2021.08.026] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Revised: 08/23/2021] [Accepted: 08/23/2021] [Indexed: 12/31/2022]
Abstract
BACKGROUND Norovirus and toxigenic Clostridium difficile infections are the 2 most common causes of infectious gastroenteritis. Rapid and reliable detection of these to microorganisms is important to assess if contact precautions are indicated to prevent spreading and reduce cost of isolation. METHODS This study determines sensitivity and specificity of a new fast in-house PCR assay used on BD MAX platform to detect both norovirus and C difficile in 1 turn-over in clinical context. Furthermore, fecal samples as well as rectal swabs were used as analysis material to determine the accuracy of the new assay on a fecal samples and rectal swabs compared with standard methods. RESULTS From 227 included patients, 143 rectal swabs and 135 fecal samples obtained. The new in-house PCR showed a sensitivity of 73.3% and a specificity of 99.2% for norovirus on a fecal sample and a sensitivity of 57.1% and specificity 99.1% of for norovirus on a rectal swab. For C difficile a sensitivity of 100% and specificity of 100% on a fecal sample and a sensitivity of 90.9% and a specificity of 99.1% on a rectal swab was shown. The time consumption for detecting the 2 enteropathogens was reduced by half by using the new assay. CONCLUSIONS The new assay shows an acceptable sensitivity and specificity for C difficile and an acceptable specificity for norovirus when analysis was done on fecal samples and reduces half of the time consumption. Further research is needed to improve the accuracy of the new in-house PCR before clinical implication.
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19
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Khanafer N, Vanhems P, Bennia S, Martin-Gaujard G, Juillard L, Rimmelé T, Argaud L, Martin O, Huriaux L, Marcotte G, Hernu R, Floccard B, Cassier P, Group S. Factors Associated with Clostridioides (Clostridium) Difficile Infection and Colonization: Ongoing Prospective Cohort Study in a French University Hospital. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:ijerph18147528. [PMID: 34299978 PMCID: PMC8307155 DOI: 10.3390/ijerph18147528] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/21/2021] [Accepted: 07/13/2021] [Indexed: 01/03/2023]
Abstract
Introduction: Clostridioides (Clostridium) difficile can be isolated from stool in 3% of healthy adults and in at least 10% of asymptomatic hospitalized patients. C. difficile, the most common cause of hospital-acquired infectious diarrhea in the developed world, has re-emerged in recent years with increasing incidence and severity. In an effort to reduce the spread of the pathogen, published recommendations suggest isolation and contact precautions for patients suffering from C. difficile infection (CDI). However, asymptomatic colonized patients are not targeted by infection control policies, and active surveillance for colonization is not routinely performed. Moreover, given the current changes in the epidemiology of CDI, particularly the emergence of new virulent strains either in the hospital or community settings, there is a need for identification of factors associated with colonization by C. difficile and CDI. Methods and analysis: We are carrying out a prospective, observational, cohort study in Edouard Herriot Hospital, Hospices Civils de Lyon, a 900-bed university hospital in Lyon, France. All consecutive adult patients admitted on selected units are eligible to participate in the study. Stool samples or rectal swabs for C. difficile testing are obtained on admission, every 3–5 days during hospitalization, at the onset of diarrhea (if applicable), and at discharge. Descriptive and logistic regression analyses will be completed to mainly estimate the proportion of asymptomatic colonization at admission, and to evaluate differences between factors associated with colonization and those related to CDI. Ethics: The study is conducted in accordance with the ethical principles of the Declaration of Helsinki, French law, and the Good Clinical Practice guidelines. The study protocol design was approved by the participating units, the ethics committee and the hospital institutional review board (Comité de protection des personnes et Comission Nationale de l’Informatique et des Libertés; N°: 00009118). Dissemination: The results of this study will be disseminated by presenting the findings locally at each participating ward, as well as national and international scientific meetings. Findings will be shared with interested national societies crafting guidelines in CDI.
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Affiliation(s)
- Nagham Khanafer
- International Center for Infectiology Research (CIRI), Inserm U1111, CNRS UMR5308, ENS de Lyon, Lyon 1 University, 69342 Lyon, France;
- Department of Hygiene, Epidemiology, and Prevention, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437 Lyon, France;
- European Study Group for Clostridioides Difficile (ESGCD), 4001 Basel, Switzerland
- Correspondence:
| | - Philippe Vanhems
- International Center for Infectiology Research (CIRI), Inserm U1111, CNRS UMR5308, ENS de Lyon, Lyon 1 University, 69342 Lyon, France;
- Department of Hygiene, Epidemiology, and Prevention, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437 Lyon, France;
- INSERM, F-CRIN, Réseau Innovative Clinical Research in Vaccinology (I-REIVAC), 75679 Paris, France
| | - Sabrina Bennia
- Department of Hygiene, Epidemiology, and Prevention, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437 Lyon, France;
| | | | - Laurent Juillard
- Nephrology Department, Edouard Herriot Hospital, Hospices Civils de Lyon, 69002 Lyon, France;
| | - Thomas Rimmelé
- Anesthesia and Intensive Care Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437 Lyon, France; (T.R.); (O.M.); (L.H.); (G.M.); (B.F.)
- EA 7426 PI3 (Pathophysiology of Injury-Induced Immunosuppression), Lyon 1 University, Hospices Civils de Lyon, Biomérieux, 69437 Lyon, France
| | - Laurent Argaud
- Medical Intensive Care Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437 Lyon, France; (L.A.); (R.H.)
| | - Olivier Martin
- Anesthesia and Intensive Care Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437 Lyon, France; (T.R.); (O.M.); (L.H.); (G.M.); (B.F.)
| | - Laetitia Huriaux
- Anesthesia and Intensive Care Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437 Lyon, France; (T.R.); (O.M.); (L.H.); (G.M.); (B.F.)
| | - Guillaume Marcotte
- Anesthesia and Intensive Care Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437 Lyon, France; (T.R.); (O.M.); (L.H.); (G.M.); (B.F.)
| | - Romain Hernu
- Medical Intensive Care Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437 Lyon, France; (L.A.); (R.H.)
| | - Bernard Floccard
- Anesthesia and Intensive Care Unit, Edouard Herriot Hospital, Hospices Civils de Lyon, 69437 Lyon, France; (T.R.); (O.M.); (L.H.); (G.M.); (B.F.)
| | - Pierre Cassier
- Environnemental Laboratory, Institut des Agents Infectieux, Hospices Civils de Lyon, 69317 Lyon, France;
| | - Study Group
- Edouard Herriot Hospital, Hospices Civils de Lyon, 69437 Lyon, France;
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20
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Kucharzik T, Ellul P, Greuter T, Rahier JF, Verstockt B, Abreu C, Albuquerque A, Allocca M, Esteve M, Farraye FA, Gordon H, Karmiris K, Kopylov U, Kirchgesner J, MacMahon E, Magro F, Maaser C, de Ridder L, Taxonera C, Toruner M, Tremblay L, Scharl M, Viget N, Zabana Y, Vavricka S. ECCO Guidelines on the Prevention, Diagnosis, and Management of Infections in Inflammatory Bowel Disease. J Crohns Colitis 2021; 15:879-913. [PMID: 33730753 DOI: 10.1093/ecco-jcc/jjab052] [Citation(s) in RCA: 251] [Impact Index Per Article: 62.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Affiliation(s)
- T Kucharzik
- Department of Gastroenterology, Klinikum Lüneburg, University of Hamburg, Lüneburg, Germany
| | - P Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
| | - T Greuter
- University Hospital Zürich, Department of Gastroenterology and Hepatology, Zürich, Switzerland, and Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois CHUV, University Hospital Lausanne, Lausanne, Switzerland
| | - J F Rahier
- Department of Gastroenterology and Hepatology, CHU UCL Namur, Yvoir, Belgium
| | - B Verstockt
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, KU Leuven, Leuven, Belgium, and Department of Chronic Diseases, Metabolism and Ageing, TARGID-IBD, KU Leuven, Leuven, Belgium
| | - C Abreu
- Infectious Diseases Service, Centro Hospitalar Universitário São João, Porto, Portugal
- Instituto de Inovação e Investigação em Saúde [I3s], Faculty of Medicine, Department of Medicine, University of Porto, Portugal
| | - A Albuquerque
- Gastroenterology Department, St James University Hospital, Leeds, UK
| | - M Allocca
- Humanitas Clinical and Research Center - IRCCS -, Rozzano [Mi], Italy
- Humanitas University, Department of Biomedical Sciences, Milan, Italy
| | - M Esteve
- Hospital Universitari Mútua Terrassa, Digestive Diseases Department, Terrassa, Catalonia, and Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas CIBERehd, Madrid, Spain
| | - F A Farraye
- Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, FL, USA
| | - H Gordon
- Department of Gastroenterology, Barts Health NHS Trust, Royal London Hospital, London, UK
| | - K Karmiris
- Department of Gastroenterology, Venizeleio General Hospital, Heraklion, Greece
| | - U Kopylov
- Department of Gastroenterology, Sheba Medical Center, Ramat Gan, Israel, and Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel
| | - J Kirchgesner
- Sorbonne Université, INSERM, Institut Pierre Louis d'Epidémiologie et de Santé Publique, AP-HP, Hôpital Saint-Antoine, Department of Gastroenterology, Paris, France
| | - E MacMahon
- Department of Infectious Diseases, Guy's and St Thomas' NHS Foundation Trust, London, UK
| | - F Magro
- Gastroenterology Department, Centro Hospitalar São João, Porto, Portugal
- Institute of Pharmacology and Therapeutics, Faculty of Medicine, University of Porto, Portugal
| | - C Maaser
- Outpatient Department of Gastroenterology, Department of Geriatrics, Klinikum Lüneburg, University of Hamburg, Lüneburg, Germany
| | - L de Ridder
- Department of Paediatric Gastroenterology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands
| | - C Taxonera
- IBD Unit, Department of Gastroenterology, Hospital Clínico San Carlos and Instituto de Investigación del Hospital Clínico San Carlos [IdISSC], Madrid, Spain
| | - M Toruner
- Ankara University School of Medicine, Department of Gastroenterology, Ankara, Turkey
| | - L Tremblay
- Centre Hospitalier de l'Université de Montréal [CHUM] Pharmacy Department and Faculty of Pharmacy, Université de Montréal, Montréal, QC, Canada
| | - M Scharl
- University Hospital Zürich, Department of Gastroenterology and Hepatology, Zürich, Switzerland
| | - N Viget
- Department of Infectious Diseases, Tourcoing Hospital, Tourcoing, France
| | - Y Zabana
- Hospital Universitari Mútua Terrassa, Digestive Diseases Department, Terrassa, Catalonia, and Centro de Investigación Biomédica en red de Enfermedades Hepáticas y Digestivas CIBERehd, Madrid, Spain
| | - S Vavricka
- University Hospital Zürich, Department of Gastroenterology and Hepatology, Zürich, Switzerland
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21
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Lin FJ, Huang YC, Huang YC, Huang LM, Liu CC, Chi H, Lin HC, Ho YH, Wu FT, Mu JJ, Hsiung CA, Huang CY, Shih SM. Clinical and epidemiological features in hospitalized young children with acute gastroenteritis in Taiwan: A multicentered surveillance through 2014-2017. J Formos Med Assoc 2021; 121:519-528. [PMID: 34167879 DOI: 10.1016/j.jfma.2021.06.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/20/2021] [Accepted: 06/01/2021] [Indexed: 01/05/2023] Open
Abstract
BACKGROUND/PURPOSE Acute gastroenteritis (AGE) remains a significant health issue in children. The worldwide evolution of pediatric AGE pathogens had been recorded since the introduction of rotavirus vaccine. Ten years after the rotavirus vaccine was introduced to the private sectors in Taiwan, a nationwide study was conducted to elucidate the epidemiological changes among major AGE pathogens. METHODS From January 2014 to December 2017, children younger than 5 years old, hospitalized with AGE at 10 hospitals across Taiwan were enrolled. Stool specimens were tested for Salmonella spp., Campylobacter spp., Clostridiodes difficile, norovirus, and rotavirus by polymerase chain reaction (PCR). The epidemiological and clinical information was collected. RESULTS Enteric pathogen were detected in 1983 (42.2%) of 4700 subjects, with Salmonella spp. (12.5%) being the leading cause of AGE, followed by norovirus (11.2%), rotavirus (8.7%), C. difficile (4.2%), Campylobacter spp. (1.0%), and a mixture of at least 2 of 5 above-mentioned pathogens (4.6%). The case distributions varied across different regions. In eastern Taiwan, rotavirus (21/131, 16.0%) remained the most common pathogen detected. The rotavirus vaccine uptake rate is significantly lower in patients with rotavirus AGE. Besides, rotavirus AGE frequently occurred in children with foreign parent(s), Taiwanese indigenous people, and those with the household monthly income < NT$ 60,000. CONCLUSION Salmonella spp. and norovirus were two major pathogens of pediatric AGE in Taiwan during 2014-17. Providing low-to middle-income households with free rotavirus vaccine nationwide and an industry-led act to reduce salmonellosis should be considered by the authorities.
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Affiliation(s)
- Fang-Ju Lin
- Division of Infectious Diseases, Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Yi-Chuan Huang
- Division of Infectious Diseases, Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
| | - Yhu-Chering Huang
- Department of Pediatrics, Chang Gung Children's Hospital and Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Li-Min Huang
- Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan
| | - Ching-Chuan Liu
- Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hsin Chi
- Department of Pediatrics, Mackay Children's Hospital, Mackay Medical College, Taipei, Taiwan
| | - Hsiao-Chuan Lin
- Department of Pediatrics, China Medical University Hospital, Taichung, Taiwan
| | - Yu-Huai Ho
- Division of Infectious Disease, Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Fang-Tzy Wu
- Center for Diagnostics and Vaccine Development, Centers for Disease Control, Taiwan
| | - Jung-Jung Mu
- Center for Diagnostics and Vaccine Development, Centers for Disease Control, Taiwan
| | - Chao A Hsiung
- Institute of Population Health Sciences, National Health Research Institutes, Taiwan
| | - Ching-Yi Huang
- Institute of Population Health Sciences, National Health Research Institutes, Taiwan
| | - Shu-Man Shih
- Institute of Population Health Sciences, National Health Research Institutes, Taiwan
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22
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Luz MRMPD, Waizbort RF. [Fecal microbiota transplants in the treatment of pseudomembranous colitis (1958-2013): priority of discovery and thought styles in the academic literature]. ACTA ACUST UNITED AC 2021; 27:859-878. [PMID: 33111793 DOI: 10.1590/s0104-59702020000400009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Accepted: 06/04/2019] [Indexed: 01/05/2023]
Abstract
In 1958, Eiseman and contributors published the first scientific paper reporting the use of fecal microbiota transplant for treating pseudomembranous colitis. The relevance of this innovative paper was only acknowledged in 1990. The academic literature on the theme is characterized by a narrative that has undergone successive revisions. We suggest that such revisions were based on claims of priority of scientific discoveries, as described by Merton. The revival of fecal microbiota transplants is interpreted as a process of genesis of a scientific fact, as defined by Fleck: there is a switch from a thought style based on the use of antibiotics to treat infectious diseases to another that accepts the ecological relations between hosts, vectors and parasites.
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23
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Allegretti JR, Nije C, McClure E, Redd WD, Wong D, Zhou JC, Bazarbashi AN, McCarty TR, Hathorn KE, Shen L, Jajoo K, Chan WW. Prevalence and impact of Clostridioides difficile infection among hospitalized patients with coranavirus disease 2019. JGH Open 2021; 5:622-625. [PMID: 34013064 PMCID: PMC8114993 DOI: 10.1002/jgh3.12497] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2020] [Revised: 01/10/2021] [Accepted: 01/13/2021] [Indexed: 12/23/2022]
Affiliation(s)
- Jessica R Allegretti
- Division of Gastroenterology, Hepatology and EndoscopyBrigham and Women's HospitalBostonMassachusettsUSA
- Harvard Medical SchoolBostonMassachusettsUSA
| | - Cheikh Nije
- Harvard Medical SchoolBostonMassachusettsUSA
- Department of MedicineBrigham and Women's HospitalBostonMassachusettsUSA
| | - Emma McClure
- Division of Gastroenterology, Hepatology and EndoscopyBrigham and Women's HospitalBostonMassachusettsUSA
| | - Walker D Redd
- Harvard Medical SchoolBostonMassachusettsUSA
- Department of MedicineBrigham and Women's HospitalBostonMassachusettsUSA
| | - Danny Wong
- Harvard Medical SchoolBostonMassachusettsUSA
- Department of MedicineBrigham and Women's HospitalBostonMassachusettsUSA
| | | | - Ahmad N Bazarbashi
- Division of Gastroenterology, Hepatology and EndoscopyBrigham and Women's HospitalBostonMassachusettsUSA
- Harvard Medical SchoolBostonMassachusettsUSA
| | - Thomas R McCarty
- Division of Gastroenterology, Hepatology and EndoscopyBrigham and Women's HospitalBostonMassachusettsUSA
- Harvard Medical SchoolBostonMassachusettsUSA
| | - Kelly E Hathorn
- Division of Gastroenterology, Hepatology and EndoscopyBrigham and Women's HospitalBostonMassachusettsUSA
- Harvard Medical SchoolBostonMassachusettsUSA
| | - Lin Shen
- Division of Gastroenterology, Hepatology and EndoscopyBrigham and Women's HospitalBostonMassachusettsUSA
- Harvard Medical SchoolBostonMassachusettsUSA
| | - Kunal Jajoo
- Division of Gastroenterology, Hepatology and EndoscopyBrigham and Women's HospitalBostonMassachusettsUSA
- Harvard Medical SchoolBostonMassachusettsUSA
| | - Walter W Chan
- Division of Gastroenterology, Hepatology and EndoscopyBrigham and Women's HospitalBostonMassachusettsUSA
- Harvard Medical SchoolBostonMassachusettsUSA
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24
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Risk factors of Clostridium difficile-associated diarrhea in hospitalized adults: Vary by hospitalized duration. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2021; 54:276-283. [PMID: 31522990 DOI: 10.1016/j.jmii.2019.07.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 07/17/2019] [Accepted: 07/29/2019] [Indexed: 02/06/2023]
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25
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Mizusawa M, Carroll KC. Advances and required improvements in methods to diagnosing Clostridioides difficile infections in the healthcare setting. Expert Rev Mol Diagn 2021; 21:311-321. [PMID: 33682564 DOI: 10.1080/14737159.2021.1900737] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
INTRODUCTION Clostrididioides difficile is associated with adverse clinical outcomes and increased morbidity, mortality, length of hospital stay, and health-care costs.Areas Covered: We searched relevant papers in PubMed for the last 10 years. In major papers, we scanned the bibliographies to ensure that important articles were included. This review addresses the evolving epidemiology of Clostridioides difficile infection (CDI) and discusses novel methods/approaches for improving the diagnosis of this important disease. EXPERT OPINION No single diagnostic test to date has demonstrated optimum sensitivity and specificity for detection of CDI. Many institutions have developed multi-step algorithms consistent with guidelines established by various professional societies. Some institutions have successfully tried to improve the pretest probability of molecular assays by implementing appropriate sample rejection criteria and establishing best practice alerts at the time of electronic order entry. Others have established PCR cycle threshold cutoffs to attempt to differentiate symptomatic patients from asymptomatic carriers or to make predictions about severity of disease with variable success. As research advances our understanding of C. difficile pathogenesis and pathophysiology, more information on CDI specific biomarkers is emerging. Finally, assessments of the microbiome and metabolome may expand the diagnostic armamentarium with advances in mass spectrometry and sequencing technologies.
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Affiliation(s)
- Masako Mizusawa
- Section of Infectious Diseases, Department of Internal Medicine, University of Missouri, Kansas City, Missouri, Kansas City, MO, USA
| | - Karen C Carroll
- Director Division of Medical Microbiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA
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26
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Clostridioides Difficile Infection : A comprehensive review for primary providers. ACTA ACUST UNITED AC 2021; 59:262-269. [PMID: 33713592 DOI: 10.2478/rjim-2021-0010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Indexed: 11/20/2022]
Abstract
Clostridioides Difficile infection (CDI) is an issue of great concern due to its rising incidence, recurrence, morbidity and impact on healthcare spending. Treatment guidelines have changed in the last few years, and new therapies are being considered. This is a practical review for the primary care practitioner of the latest guidelines for CDI diagnosis, treatment and emerging therapies.
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27
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Haider A, Alavi F, Siddiqa A, Abbas H, Patel H. Fulminant Pseudomembranous Colitis Leading to Clostridium Paraputrificum Bacteremia. Cureus 2021; 13:e13763. [PMID: 33842139 PMCID: PMC8022762 DOI: 10.7759/cureus.13763] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023] Open
Abstract
Clostridium species are spore-forming gram-positive anaerobic rod bacteria that cause a broad range of infections in humans, including intra-abdominal infections, myonecrosis, and bacteremia. Pseudomembranous colitis (PMC) is a severe form of infection caused by Clostridioides difficile. Clostridial bacteremia usually occurs in the settings of neutropenia, alcohol abuse, diabetes mellitus, sickle cell anemia, malignancy, hemodialysis, inflammatory bowel disease, and AIDS. We report a case of fulminant PMC leading to C. paraputrificum bacteremia in an otherwise immunocompetent patient. To our knowledge, this is the first case report of such an occurrence.
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Affiliation(s)
- Asim Haider
- Internal Medicine, BronxCare Health System, Bronx, USA
| | - Fareeha Alavi
- Internal Medicine, BronxCare Health System, Bronx, USA
| | | | - Hafsa Abbas
- Gastroenterology, BronxCare Health System, Bronx, USA
| | - Harish Patel
- Gastroenterology, BronxCare Health System, Bronx, USA
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28
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Hung YP, Tsai CS, Tsai BY, Tsai PJ, Lee YT, Lee JC, Liu HC, Hsueh PR, Lee CC, Ko WC. Clostridioides difficile infection in patients with hematological malignancy: A multicenter study in Taiwan. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2021; 54:1101-1110. [PMID: 33678554 DOI: 10.1016/j.jmii.2021.02.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/09/2020] [Revised: 01/26/2021] [Accepted: 02/05/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND Among the individuals with hematological malignancy (HM) complicated with Clostridioides difficile infection (CDI), the variables associated with in-hospital mortality and recurrence of CDI were investigated. MATERIAL AND METHODS Including adults with HM and those without malignancy suffering from CDI from January 2015 to December 2016 in three hospitals in Taiwan. RESULTS Totally 314 patients including 77 with HM and 237 patients without malignancy were included. HM patients more often had low leukocyte counts (<500 cells/mL: 28.6% vs. 2.1%) than those without malignancy and more patients without malignancy had severe CDI than patients with HM (31.6% vs. 14.3%, P = .003), according to the severity score of IDSA/SHEA. Patients with HM had a higher recurrence rate of CDI (14.3%, 11/77 vs. 7.2%, 17/237; P = .07) and longer hospital stay (47.2 ± 40.8 days vs. 33.3 ± 37.3 days; P = .006) than those without malignancy. In the multivariate analyses for those with HM and CDI, the in-hospital mortality was associated with vancomycin-resistant Enterococcus (VRE) colonization or infection (odds ratio [OR] 7.72; P = .01), and C. difficile ribotype 078 complex infection (OR 9.22; P = .03). Moreover underlying hematological malignancy (OR 2.74; P = .04) and VRE colonization/infection (OR 2.71; P = .02) were independently associated with CDI recurrence. CONCLUSION Patients with HM complicated with CDI were often regarded as non-severe infection, but had a similar in-hospital mortality rate as those without malignancy. CDI due to ribotype 078 complex isolates heralded a poor prognosis among HM patients.
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Affiliation(s)
- Yuan-Pin Hung
- Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Executive Yuan, Tainan, Taiwan; Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chin-Shiang Tsai
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Bo-Yang Tsai
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Pei-Jane Tsai
- Department of Medical Laboratory Science and Biotechnology, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yuan-Ti Lee
- Department of Internal Medicine and Division of Infectious Diseases, Chung Shan Medical University Hospital, and School of Medicine, Chung Shan Medical University Taichung, Taiwan
| | - Jen-Chieh Lee
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Hsiu-Chuan Liu
- Department of Experiment and Diagnosis, Tainan Hospital, Ministry of Health and Welfare, Executive Yuan, Tainan, Taiwan
| | - Po-Ren Hsueh
- Department of Laboratory Medicine and Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Ching-Chi Lee
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Clinical Medicine Research Center, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
| | - Wen-Chien Ko
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
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29
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Proteomic Adaptation of Clostridioides difficile to Treatment with the Antimicrobial Peptide Nisin. Cells 2021; 10:cells10020372. [PMID: 33670309 PMCID: PMC7918085 DOI: 10.3390/cells10020372] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 02/04/2021] [Accepted: 02/08/2021] [Indexed: 01/05/2023] Open
Abstract
Clostridioides difficile is the leading cause of antibiotic-associated diarrhea but can also result in more serious, life-threatening conditions. The incidence of C. difficile infections in hospitals is increasing, both in frequency and severity, and antibiotic-resistant C. difficile strains are advancing. Against this background antimicrobial peptides (AMPs) are an interesting alternative to classic antibiotics. Information on the effects of AMPs on C. difficile will not only enhance the knowledge for possible biomedical application but may also provide insights into mechanisms of C. difficile to adapt or counteract AMPs. This study applies state-of-the-art mass spectrometry methods to quantitatively investigate the proteomic response of C. difficile 630∆erm to sublethal concentrations of the AMP nisin allowing to follow the cellular stress adaptation in a time-resolved manner. The results do not only point at a heavy reorganization of the cellular envelope but also resulted in pronounced changes in central cellular processes such as carbohydrate metabolism. Further, the number of flagella per cell was increased during the adaptation process. The potential involvement of flagella in nisin adaptation was supported by a more resistant phenotype exhibited by a non-motile but hyper-flagellated mutant.
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30
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Pereira RFC, Theizen TH, Machado D, Guarnieri JPDO, Gomide GP, Hollanda LMD, Lancellotti M. Analysis of potential virulence genes and competence to transformation in Haemophilus influenzae biotype aegyptius associated with Brazilian Purpuric Fever. Genet Mol Biol 2021; 44:e20200029. [PMID: 33395458 PMCID: PMC7816109 DOI: 10.1590/1678-4685-gmb-2020-0029] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Accepted: 11/18/2020] [Indexed: 11/21/2022] Open
Abstract
Brazilian Purpuric Fever (BPF) is a hemorrhagic pediatric illness caused by Haemophilus influenzae biogroup aegyptius (Hae), a bacterium that was formerly associated with self-limited purulent conjunctivitis. BPF is assumed to be eradicated. However, the virulence mechanisms inherent to Hae strains associated with BPF is still a mystery and deficient in studies. Here, we aim to analyze the role of the autotransporter genes related to adherence and colonization las, tabA1, and hadA genes through RT-qPCR expression profiling and knockout mutants. Relative quantification by real-time PCR after infection in human cells and infant rat model suggests that las was initially downregulated probably duo to immune evasion, tabA1, and hadA were overexpressed in general, suggesting an active role of TabA1 and HadA1 adhesins in Hae in vitro and in vivo. Transformation attempts were unsuccessful despite the use of multiple technical approaches and in silico analysis revealed that Hae lacks genes related to competence in Haemophilus, which could be part of the elucidation of the difficulty of genetically manipulating Hae strains.
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Affiliation(s)
| | - Thais Holtz Theizen
- Universidade Estadual de Campinas, Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Campinas, SP, Brazil
| | - Daisy Machado
- Universidade Estadual de Campinas, Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Campinas, SP, Brazil
| | | | - Gabriel Piccirillo Gomide
- Universidade Estadual de Campinas - UNICAMP, Faculdade de Ciências Farmacêuticas - FCF, Campinas, SP, Brazil
| | - Luciana Maria de Hollanda
- Universidade Estadual de Campinas, Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Campinas, SP, Brazil
| | - Marcelo Lancellotti
- Universidade Estadual de Campinas, Departamento de Bioquímica e Biologia Tecidual, Instituto de Biologia, Campinas, SP, Brazil.,Universidade Estadual de Campinas - UNICAMP, Faculdade de Ciências Farmacêuticas - FCF, Campinas, SP, Brazil
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Inatomi T, Otomaru K. Effects of heat-killed Enterococcus faecalis T-110 supplementation on gut immunity, gut flora, and intestinal infection in naturally aged hamsters. PLoS One 2020; 15:e0240773. [PMID: 33378402 PMCID: PMC7773277 DOI: 10.1371/journal.pone.0240773] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2020] [Accepted: 12/14/2020] [Indexed: 12/25/2022] Open
Abstract
Infectious diseases are a threat to elderly individuals, whose immune systems weaken with age. Among the various infectious diseases, Clostridium difficile infection is associated with a high rate of mortality in elderly individuals and is a serious health problem worldwide, owing to the increasing infection rates. Probiotic use has been proposed as an effective countermeasure for C. difficile infection. The aim of this study was to evaluate the effects of heat-killed Enterococcus faecalis T-110 on intestinal immunity, intestinal flora, and intestinal infections, especially C. difficile infections, in naturally ageing animals, for extrapolating the results to elderly human subjects. Twenty female hamsters were randomly distributed into two groups. Group 1 was fed a basal diet and group 2 was fed a basal diet supplemented with heat-killed E. faecalis for 7 days. Heat-killed E. faecalis T-110 improved the gut immunity and microflora, especially Clostridium perfringens and C. difficile, in naturally aged hamsters. Therefore, heat-killed E. faecalis T-110 use may be a countermeasure against age-related immune dysfunction and intestinal infections, especially C. difficile infection, in elderly humans. However, further investigation in this regard is needed in humans.
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Affiliation(s)
| | - Konosuke Otomaru
- Joint Faculty of Veterinary Medicine, Kagoshima University, Korimoto, Kagoshima, Japan
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32
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Dhruv S, Polavarapu A, Gumaste V. Fidaxomicin Use for Clostridium Difficile Infection Probably Decreases the Effect of Coumadin® in Elderly. Cureus 2020; 12:e11915. [PMID: 33425501 PMCID: PMC7785468 DOI: 10.7759/cureus.11915] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022] Open
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Bilgin H, Sayın E, Gürün HP, Tükenmez-Tigen E, Ülger Toprak N, Korten V. Hospital acquired Clostridioides difficile infection and risk factors for severity in a university hospital: A prospective study. Am J Infect Control 2020; 48:1426-1430. [PMID: 32522607 DOI: 10.1016/j.ajic.2020.05.042] [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: 03/03/2020] [Revised: 05/29/2020] [Accepted: 05/30/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND Clostridioides difficile infection (CDI) is a well-known cause of health care-associated diarrhea. Data about CDI epidemiology of Turkey is limited. This study investigates CDI incidence, clinical characteristics, and factors associated with severe CDI in a tertiary care center university hospital. METHODS This is a case control study was conducted between 2012 and 2016. We included all patients, 18 years of age or more, with CDI diagnosis. For each patient diagnosed with CDI, information was collected concerning the severity of disease, treatment regimen, treatment response, disease recurrence, 30-day case fatality. Cases defined as severe hospital acquired CDI (HA-CDI) and controls defined as non-severe CDI patients. RESULTS We identified 100 cases of HA-CDI out of 111 patients. Total CDI incidence was 1.19/10,000 patient-days. The incidence decreased 32.5% during the study period. We identified severe CDI in 24% of patients. Age and admission to intensive care unit were independent risk factors for severe CDI. CONCLUSION This study reports a 5-year prospective epidemiology of CDI in a tertiary care center in Istanbul, Turkey. The findings of this study suggest that HA-CDI incidence and proportion of severe CDI is low compared to European and US literature. We believe that CDI is underreported, neglected but still an important health care associated infection in Turkey.
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Analysis of predisposing factors for the development of Clostridioides difficile infection recurrence. Eur J Clin Microbiol Infect Dis 2020; 39:2161-2168. [DOI: 10.1007/s10096-020-03982-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2020] [Accepted: 07/03/2020] [Indexed: 10/23/2022]
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Stephenson B, Lanzas C, Lenhart S, Ponce E, Bintz J, Dubberke ER, Day J. Comparing intervention strategies for reducing Clostridioides difficile transmission in acute healthcare settings: an agent-based modeling study. BMC Infect Dis 2020; 20:799. [PMID: 33115427 PMCID: PMC7594474 DOI: 10.1186/s12879-020-05501-w] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 10/12/2020] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Clostridioides difficile infection (CDI) is one of the most common healthcare infections. Common strategies aiming at controlling CDI include antibiotic stewardship, environmental decontamination, and improved hand hygiene and contact precautions. Mathematical models provide a framework to evaluate control strategies. Our objective is to evaluate the effectiveness of control strategies in decreasing C. difficile colonization and infection using an agent-based model in an acute healthcare setting. METHODS We developed an agent-based model that simulates the transmission of C. difficile in medical wards. This model explicitly incorporates healthcare workers (HCWs) as vectors of transmission, tracks individual patient antibiotic histories, incorporates varying risk levels of antibiotics with respect to CDI susceptibility, and tracks contamination levels of ward rooms by C. difficile. Interventions include two forms of antimicrobial stewardship, increased environmental decontamination through room cleaning, improved HCW compliance, and a preliminary assessment of vaccination. RESULTS Increased HCW compliance with CDI patients was ranked as the most effective intervention in decreasing colonizations, with reductions up to 56%. Antibiotic stewardship practices were highly ranked after contact precaution compliance. Vaccination and reduction of high-risk antibiotics were the most effective intervention in decreasing CDI. Vaccination reduced CDI cases to up to 90%, and the reduction of high-risk antibiotics decreased CDI cases up to 23%. CONCLUSIONS Overall, interventions that decrease patient susceptibility to colonization by C. difficile, such as antibiotic stewardship, were the most effective interventions in reducing both colonizations and CDI cases.
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Affiliation(s)
- Brittany Stephenson
- Department of Engineering, Computing, and Mathematical Sciences, Lewis University, 1 University Parkway, Romeoville, 60446 IL USA
| | - Cristina Lanzas
- Department of Population Health and Pathobiology, North Carolina State University, 1052 William Moore Drive, Raleigh, 27606 NC USA
| | - Suzanne Lenhart
- Department of Mathematics, University of Tennessee, 1403 Circle Drive, Knoxville, 37996 TN USA
| | - Eduardo Ponce
- Department of Electrical Engineering and Computer Science, University of Tennessee, 1520 Middle Drive, Knoxville, 37996 TN USA
| | - Jason Bintz
- School of Arts and Sciences, Johnson University, Knoxville, 37998 TN USA
| | - Erik R. Dubberke
- Division of Infectious Disease, Washington University School of Medicine, 660 S Euclid Ave, St. Louis, 63110 MO USA
| | - Judy Day
- Department of Mathematics, University of Tennessee, 1403 Circle Drive, Knoxville, 37996 TN USA
- Department of Electrical Engineering and Computer Science, University of Tennessee, 1520 Middle Drive, Knoxville, 37996 TN USA
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Liu JY, Dickter JK. Nosocomial Infections: A History of Hospital-Acquired Infections. Gastrointest Endosc Clin N Am 2020; 30:637-652. [PMID: 32891222 DOI: 10.1016/j.giec.2020.06.001] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
In the United States, healthcare acquired infections (HAIs) or nosocomial infections are the sixth leading cause of death. This article reviews the history, prevalence, economic costs, morbidity and mortality, and risk factors associated with HAIs. Types of infections described include bacterial, fungal, viral, and multidrug resistant infections that contribute to the most common causes of HAIs, which include catheter- associated urinary tract infections, hospital-acquired pneumonias, bloodstream infections, and surgical site infections. Most nosocomial infections are preventable and monitoring and prevention strategies are described.
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Affiliation(s)
- Jia-Yia Liu
- American Medical Physicians and Surgeons Advancement Alliance; Department of Medicine, Loma Linda University, Loma Linda, CA, USA; Division of Infectious Diseases, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
| | - Jana K Dickter
- Division of Infectious Diseases, City of Hope, 1500 East Duarte Road, Duarte, CA 91010, USA
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Mahatanan R, Tantisattamo E, Charoenpong P, Ferrey A. Outcomes of C difficile infection in solid-organ transplant recipients: The National Inpatient Sample (NIS) 2015-2016. Transpl Infect Dis 2020; 23:e13459. [PMID: 32894617 DOI: 10.1111/tid.13459] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Revised: 08/04/2020] [Accepted: 08/20/2020] [Indexed: 01/07/2023]
Abstract
BACKGROUND Clostridioides (formerly Clostridium) difficile infection (CDI) is one of the leading causes of morbidity and mortality worldwide. Solid organ transplant (SOT) recipients are at an increased risk for CDI. A recent study showed an overall improvement in mortality amongst hospitalized individuals with CDI, but it is unclear if this benefit extends to SOT recipients. METHODS We scrutinized the 2015 and 2016 National Inpatient Sample (NIS), the largest all-payer inpatient database in the United States for CDI data in patients with SOT. SOT was defined as any recipient who had received a heart, lung, liver, intestinal, kidney, pancreas, or combined thoracic and/or abdominal organ transplantation. Baseline characteristics, comorbidities, and concomitant diagnosis of pneumonia or urinary tract infection were adjusted for in our analysis. Primary outcomes included inpatient mortality, hospital length of stay and total hospital charges. RESULTS A total of 105 780 hospital discharges of SOT recipients were included. The incidence of CDI was 3554 (3.36%) among SOTs. CDI was associated with a higher inpatient mortality (OR 1.85, 95% CI 1.56-2.20, P < .01), longer length of hospital stay (mean difference 5.07 days, 95% CI 4.43-5.71, P < .01) and higher total hospital charges (mean difference 43 958 US dollars, P < .01). CONCLUSION Our study found that CDI is associated with poorer overall outcomes among hospitalized SOT recipients. However, there was a possible improving trend of the outcomes when compare to previous studies.
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Affiliation(s)
- Rattanaporn Mahatanan
- Department of Internal Medicine, Redington-Fairview General Hospital, Skowhegan, ME, USA.,Division of Infectious Disease, Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, NH, USA
| | - Ekamol Tantisattamo
- Harold Simmons Center for Kidney Disease Research and Epidemiology, Division of Nephrology, Hypertension and Kidney Transplantation, Department of Medicine, University of California Irvine School of Medicine, Orange, CA, USA.,Nephrology Section, Department of Medicine, Tibor Rubin Veterans Affairs Medical Center, VA Long Beach Healthcare System, Long Beach, CA, USA.,Multi-Organ Transplant Center, Section of Nephrology, Department of Internal Medicine, William Beaumont Hospital, Oakland University William Beaumont School of Medicine, Royal Oak, MI, USA
| | - Prangthip Charoenpong
- Division of Pulmonary and Critical Care Medicine, Louisiana State University Health Sciences Center - Shreveport, Shreveport, LA, USA
| | - Antoney Ferrey
- Nephrology Section, Department of Medicine, Tibor Rubin Veterans Affairs Medical Center, VA Long Beach Healthcare System, Long Beach, CA, USA
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Stallmach A, Katzer K, Reuken P. [Non-severe Clostridioides difficile Infection: Are the data adequate to give up metronidazole?]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2020; 58:778-784. [PMID: 32785914 DOI: 10.1055/a-1190-5735] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
Clostridioides difficile infections (CDI) are typical antibiotic therapy associated complications. Notwithstanding the fact that the clinical picture of CDI may extend to the development of a toxic megacolon with potentially life-threatening sequelae, mild infectious forms associated with uncomplicated diarrhoea are by far the most prevalent and should also be treated according to clear clinical practice guidelines. However, there are currently conflicting international guidelines governing metronidazole-based treatment of mild infections. In light of this shortcoming, we performed a selective literature search of guidelines and clinical studies relating to the use of metronidazole for mild CDIs. The evaluation of randomised controlled trials demonstrates that, in statistical terms, vancomycin is significantly superior to metronidazole (NNT 16). When large cohort studies are included, this difference in effectiveness is reduced to 2,5 % (NNT 40). Inconsistent criteria for defining a mild CDI, different doses, applications and time intervals (e. g. additional IV administration of metronidazole) and the retrospective nature of some studies make it difficult to identify the influence of possible interference variables in this evaluation. Nevertheless, a mild CDI can be successfully treated with metronidazole; other recommendations, particularly those of American associations, should be evaluated critically. It is important to note that this therapy recommendation does not apply to patients with chronic inflammatory bowel diseases or other patients with pertinent comorbidities.
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Affiliation(s)
- Andreas Stallmach
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Friedrich-Schiller-Universität Jena, Deutschland
| | - Katrin Katzer
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Friedrich-Schiller-Universität Jena, Deutschland
| | - Philipp Reuken
- Klinik für Innere Medizin IV (Gastroenterologie, Hepatologie und Infektiologie), Universitätsklinikum Jena, Friedrich-Schiller-Universität Jena, Deutschland
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Oral vancomycin prophylaxis for the prevention of Clostridium difficile infection: A systematic review and meta-analysis. Infect Control Hosp Epidemiol 2020; 41:1302-1309. [PMID: 32594929 DOI: 10.1017/ice.2020.277] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Recently, oral vancomycin prophylaxis (OVP) has been suggested for the prevention of Clostridium difficile infection (CDI). We conducted a systematic review and meta-analysis to investigate the efficacy and safety of this approach. DESIGN Systematic review and meta-analysis. METHODS We conducted a computerized search of MEDLINE, EMBASE, and Cochrane databases from inception to March 2019 for publications investigating OVP for CDI prevention. Results were screened for eligibility. Relevant data were extracted and analyzed. Publication bias was assessed using the Egger test. RESULTS Ultimately, 8 retrospective studies and 1 prospective study examining 2174 patients, published between 2016 and 2019 were included in the review. OVP was associated with decreased CDI (odds ratio, 0.263; 95% confidence interval, 0.13-0.52) with considerable heterogeneity (I2 = 61%). Meta-regression showed that total daily dose of OVP correlated with CDI, explaining 100% of heterogeneity between studies. Furthermore, 3 studies evaluated the risk of vancomycin-resistant enterococci (VRE) infection after OVP and found no significant increase. CONCLUSION Our results suggest that OVP might decrease CDI rates in at-risk populations, although this conclusion should be interpreted with caution. Higher daily doses of OVP might increase CDI. Although the use of OVP in high-risk patients may reduce CDI, this suggestion has yet to be validated by prospective blinded randomized controlled trials.
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Impact of a Multiplex Polymerase Chain Reaction Assay on the Clinical Management of Adults Undergoing a Lumbar Puncture for Suspected Community-Onset Central Nervous System Infections. Antibiotics (Basel) 2020; 9:antibiotics9060282. [PMID: 32466378 PMCID: PMC7344633 DOI: 10.3390/antibiotics9060282] [Citation(s) in RCA: 17] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2020] [Revised: 05/20/2020] [Accepted: 05/22/2020] [Indexed: 12/03/2022] Open
Abstract
Patients admitted from the community with a suspected central nervous system (CNS) infection require prompt diagnostic evaluation and correct antimicrobial treatment. A retrospective, multicenter, pre/post intervention study was performed to evaluate the impact that the BioFire® FilmArray® meningitis/encephalitis (ME) panel run in-house had on the clinical management of adult patients admitted from the community with a lumbar puncture (LP) performed for a suspected CNS infection. The primary outcome was the effect that this intervention had on herpes simplex virus (HSV) polymerase chain reaction (PCR) turnaround time (TAT). Secondary outcomes included the effect that this intervention had on antiviral days of therapy (DOT), total antimicrobial DOT, and hospital length of stay (LOS). A total of 81 and 79 patients were included in the pre-intervention and post-intervention cohorts, respectively. The median HSV PCR TAT was significantly longer in the pre-intervention group (85 vs. 4.1 h, p < 0.001). Total antiviral DOT was significantly greater in the pre-intervention group (3 vs. 1, p < 0.001), as was total antimicrobial DOT (7 vs. 5, p < 0.001). Pre-intervention hospital LOS was also significantly longer (6.6 vs. 4.4 days, p = 0.02). Implementing the ME panel in-house for adults undergoing an LP for a suspected community-onset CNS infection significantly reduced the HSV PCR TAT, antiviral DOT, total antimicrobial DOT, and hospital LOS.
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Wijarnpreecha K, Panjawatanan P, Thongprayoon C, Ungprasert P. Statins & risk of Clostridium difficile infection: A meta-analysis. Indian J Med Res 2020; 150:359-364. [PMID: 31823917 PMCID: PMC6902370 DOI: 10.4103/ijmr.ijmr_1973_17] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Background & objectives: Clostridium difficile infection is one of the most common healthcare-associated infections worldwide. Recent epidemiologic studies have suggested that statin users may have a lower risk of C. difficile infection, although the results are inconsistent. This meta-analysis was conducted with the aim of summarizing all available data to assess the risk of C. difficile infection among statin users versus non-users. Methods: A literature review was performed using the MEDLINE and EMBASE databases from inception to October 2017. Cohort, case-control and cross-sectional studies that compared the risk of C. difficile infection among statin users versus non-users were included. Pooled odds ratio (OR) and 95 per cent confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Results: Six case-control studies and two cross-sectional studies met the eligibility criteria and were included in this meta-analysis. The risk of C. difficile infection among statin users was significantly lower than non-users with the pooled OR of 0.74 (95% CI, 0.61-0.89). The statistical heterogeneity of this study was high (I2=90%). Interpretation & conclusions: This meta-analysis demonstrated a decreased risk of C. difficile infection among statin users versus non-users. Further studies are required to clarify the role of statins for prevention of C. difficile infection in clinical practice.
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Affiliation(s)
- Karn Wijarnpreecha
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, New York, USA
| | | | - Charat Thongprayoon
- Department of Internal Medicine, Bassett Medical Center, Cooperstown, New York, USA
| | - Patompong Ungprasert
- Department of Internal Medicine, Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA; Department of Research & Development, Clinical Epidemiology Unit, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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Frisbee AL, Petri WA. Considering the Immune System during Fecal Microbiota Transplantation for Clostridioides difficile Infection. Trends Mol Med 2020; 26:496-507. [PMID: 32359480 PMCID: PMC7198612 DOI: 10.1016/j.molmed.2020.01.009] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Revised: 01/05/2020] [Accepted: 01/21/2020] [Indexed: 12/15/2022]
Abstract
Our understanding and utilization of fecal microbiota transplantation (FMT) has jump-started over the past two decades. Recent technological advancements in sequencing and metabolomics have allowed for better characterization of our intestinal microbial counterparts, triggering a surge of excitement in the fields of mucosal immunology and microbiology. This excitement is well founded, as demonstrated by 90% relapse-free cure rates in FMT treatment for recurrent Clostridioides difficile infections. Growing evidence suggests that in addition to bacterial factors, the host immune response during C. difficile infection greatly influences disease severity. In this review, we discuss recent advancements in understanding the interplay between immune cells and the microbiota and how they may relate to recovery from C. difficile through FMT therapy.
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Affiliation(s)
- Alyse L Frisbee
- Department of Microbiology, Immunology, and Cancer Biology, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
| | - William A Petri
- Department of Microbiology, Immunology, and Cancer Biology, University of Virginia Health System, Charlottesville, Virginia 22908, USA; Department of Medicine, University of Virginia Health System, Charlottesville, Virginia 22908, USA; Department of Pathology, University of Virginia Health System, Charlottesville, Virginia 22908, USA
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Luo Y, Lucas AL, Grinspan AM. Fecal Transplants by Colonoscopy and Capsules Are Cost-Effective Strategies for Treating Recurrent Clostridioides difficile Infection. Dig Dis Sci 2020; 65:1125-1133. [PMID: 31493042 DOI: 10.1007/s10620-019-05821-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 08/28/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Recurrent Clostridioides difficile infections (CDIs) occur frequently and pose a substantial economic burden on the US healthcare system. The landscape for the treatment of CDI is evolving. AIM To elucidate the most cost-effective strategy for managing recurrent CDI. METHODS A decision tree analysis was created from a modified third-party payer's perspective to compare the cost-effectiveness of five strategies for patients experiencing their first CDI recurrence: oral vancomycin, fidaxomicin, fecal microbiota transplant (FMT) via colonoscopy, FMT via oral capsules, and a one-time infusion of bezlotoxumab with vancomycin. Effectiveness measures were quality-adjusted life years (QALY). A willingness-to-pay (WTP) threshold of $100,000 per QALY was set. One-way and probabilistic sensitivity analyses were performed. RESULTS Base-case analysis showed that FMT via colonoscopy was associated with the lowest cost at $5250 and that FMT via capsules was also a cost-effective strategy with an incremental cost-effectiveness ratio (ICER) of $31205/QALY. Sensitivity analyses demonstrated that FMT delivered by oral capsules and colonoscopy was comparable cost-effective modalities. At its current cost and effectiveness, bezlotoxumab was not a cost-effective strategy. CONCLUSIONS FMT via oral capsules and colonoscopy is both cost-effective strategies to treat the first recurrence of CDI. Further real-world economic studies are needed to understand the cost-effectiveness of all available strategies.
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Affiliation(s)
- Yuying Luo
- Department of Medicine, The Icahn School of Medicine at Mount Sinai, One Gustave Levy Place, New York, NY, 10029, USA.
| | - Aimee L Lucas
- The Henry D. Janowitz Division of Gastroenterology, The Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY, 10029, USA
| | - Ari M Grinspan
- The Henry D. Janowitz Division of Gastroenterology, The Icahn School of Medicine at Mount Sinai, 1468 Madison Avenue, New York, NY, 10029, USA
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Schwartz R, Guichard A, Franc NC, Roy S, Bier E. A Drosophila Model for Clostridium difficile Toxin CDT Reveals Interactions with Multiple Effector Pathways. iScience 2020; 23:100865. [PMID: 32058973 PMCID: PMC7011083 DOI: 10.1016/j.isci.2020.100865] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2019] [Revised: 12/05/2019] [Accepted: 01/17/2020] [Indexed: 12/11/2022] Open
Abstract
Clostridium difficile infections (CDIs) cause severe and occasionally life-threatening diarrhea. Hyper-virulent strains produce CDT, a toxin that ADP-ribosylates actin monomers and inhibits actin polymerization. We created transgenic Drosophila lines expressing the catalytic subunit CDTa to investigate its interaction with host signaling pathways in vivo. When expressed in the midgut, CDTa reduces body weight and fecal output and compromises survival, suggesting severe impairment of digestive functions. At the cellular level, CDTa induces F-actin network collapse, elimination of the intestinal brush border, and disruption of intercellular junctions. We confirm toxin-dependent re-distribution of Rab11 to enterocytes' apical surface and observe suppression of CDTa phenotypes by a Dominant-Negative form of Rab11 or RNAi of the dedicated Rab11GEF Crag (DENND4). We also report that Calmodulin (Cam) is required to mediate CDTa activity. In parallel, chemical inhibition of the Cam/Calcineurin pathway by Cyclosporin A or FK506 also reduces CDTa phenotypes, potentially opening new avenues for treating CDIs.
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Affiliation(s)
- Ruth Schwartz
- Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093-0335, USA
| | - Annabel Guichard
- Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093-0335, USA; Tata Institute for Genetics and Society-UCSD, La Jolla, CA 92093-0335, USA
| | - Nathalie C Franc
- Franc Consulting, San Diego, CA 92117-3314, USA; The Scripps Research Institute, La Jolla, CA 92037, USA
| | - Sitara Roy
- Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093-0335, USA
| | - Ethan Bier
- Section of Cell and Developmental Biology, University of California, San Diego, La Jolla, CA 92093-0335, USA; Tata Institute for Genetics and Society-UCSD, La Jolla, CA 92093-0335, USA.
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Kwah JH, Somani SN, Stevens WW, Kern RC, Smith SS, Welch KC, Conley DB, Tan BK, Grammer LC, Yang A, Schleimer RP, Peters AT. Clinical factors associated with acute exacerbations of chronic rhinosinusitis. J Allergy Clin Immunol 2020; 145:1598-1605. [PMID: 32004523 DOI: 10.1016/j.jaci.2020.01.023] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2019] [Revised: 11/20/2019] [Accepted: 01/06/2020] [Indexed: 12/27/2022]
Abstract
BACKGROUND Chronic rhinosinusitis (CRS) is complicated by frequent acute exacerbations leading to significant health care burden and impaired quality of life. OBJECTIVE The objective of this study was to identify clinical factors associated with frequent acute exacerbation of CRS (AECRS). METHODS This is a retrospective cohort study of patients with CRS from January 1, 2014, to May 31, 2016. Frequent AECRS was defined as at least 4 episodes over a 12-month period in which an antibiotic was prescribed for worsening sinus symptoms, and infrequent AECRS was defined as 0 to 3 episodes. Clinical factors, including asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, and autoimmune disease, were evaluated for associations between the 2 groups. RESULTS Of the 3109 patients with CRS who were identified, 600 (19.3%) were classified as having frequent exacerbation. Asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, and autoimmune disease were associated with frequent AECRS with statistically significant adjusted odds ratios (aORs) after controlling for age, race, and sex in multivariate analysis (asthma aOR = 2.61 [95% CI = 2.14-3.18]; allergic rhinitis aOR = 1.96 [95% CI = 1.58-2.42]; eosinophil count of at least 150 cells per microliter aOR = 1.54 [95% CI = 1.21-1.97]; and autoimmune disease aOR = 1.68 [95% CI = 1.36-2.07]). Antibody deficiency, antibiotic allergy, lower FEV1, radiographic sinus disease severity, nasal polyposis, and systemic corticosteroid use were also associated with frequent AECRS. CONCLUSION Patients with frequent episodes of AECRS were characterized by a higher prevalence of asthma, allergic rhinitis, eosinophil count of at least 150 cells per microliter, autoimmune disease, and other allergic and immunologic diseases. These findings identify a high-risk phenotype of patients with CRS for preventive interventions to reduce exacerbation frequency.
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Affiliation(s)
- Jason H Kwah
- Department of Medicine, Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Ill
| | - Shaan N Somani
- Department of Medicine, Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Ill
| | - Whitney W Stevens
- Department of Medicine, Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Ill; Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Ill
| | - Robert C Kern
- Department of Medicine, Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Ill; Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Ill
| | - Stephanie S Smith
- Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Ill
| | - Kevin C Welch
- Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Ill
| | - David B Conley
- Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Ill
| | - Bruce K Tan
- Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Ill
| | - Leslie C Grammer
- Department of Medicine, Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Ill
| | - Amy Yang
- Biostatistics Collaboration Center, Feinberg School of Medicine, Northwestern University, Chicago, Ill
| | - Robert P Schleimer
- Department of Medicine, Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Ill; Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Ill
| | - Anju T Peters
- Department of Medicine, Division of Allergy and Immunology, Feinberg School of Medicine, Northwestern University, Chicago, Ill; Department of Otolaryngology-Head and Neck Surgery, Feinberg School of Medicine, Northwestern University, Chicago, Ill.
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Todorov SD, Kang HJ, Ivanova IV, Holzapfel WH. Bacteriocins From LAB and Other Alternative Approaches for the Control of Clostridium and Clostridiodes Related Gastrointestinal Colitis. Front Bioeng Biotechnol 2020; 8:581778. [PMID: 33042979 PMCID: PMC7517946 DOI: 10.3389/fbioe.2020.581778] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Accepted: 08/25/2020] [Indexed: 12/14/2022] Open
Abstract
The gut microbiome is considered as a promising target for future non-conventional therapeutic treatment of inflammatory and infectious diseases. The search for appropriate safe and beneficial (lactic acid bacterial and other) putative probiotic strains and/or their antimicrobial metabolites represents a challenging approach for combating several problematic and emerging infections. The process of selecting suitable strains, especially of lactic acid bacteria (LAB) with superior properties, has been accelerated and intensified during the past two decades, also thanks to recent developments in lab techniques. Currently, special focus is on the potential of antimicrobial metabolites produced by some LAB strains and their application as active therapeutic agents. The vision is to develop a scientific basis for 'biotherapeutics' as alternative to conventional approaches in both human and veterinary medicine. Consequently, innovative and promising applications of LAB to the therapeutic practice are presently emerging. An overview of the existing literature indicates that some antimicrobial metabolites such as bacteriocins, widely produced by different bacterial species including LAB, are promising biotherapeutic agents for controlling infections caused by potential pathogens, such as Clostridium and Clostridiodes. Non-conventional, safe and well designed therapeutic treatments may contribute to the improvement of gut dysbiotic conditions. Thereby gut homeostasis can be restored and inflammatory conditions such as gastrointestinal colitis ameliorated. Combining the knowledge on the production, characterization and application of bacteriocins from probiotic LAB, together with their antibacterial properties, appears to be a promising and novel approach in biotherapy. In this overview, different scenarios for the control of Clostridium spp. by application of bacteriocins as therapeutic agents, also in synergistic combination with antibiotics, will be discussed.
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Affiliation(s)
- Svetoslav D. Todorov
- Advanced Green Energy and Environment Institute (AGEE), Handong Global University, Pohang, South Korea
| | - Hye-Ji Kang
- Advanced Green Energy and Environment Institute (AGEE), Handong Global University, Pohang, South Korea
- HEM Inc., Handong Global University, Pohang, South Korea
| | - Iskra V. Ivanova
- Department of General and Applied Microbiology, Faculty of Biology, Sofia University “St. Kliment Ohridski”, Sofia, Bulgaria
| | - Wilhelm H. Holzapfel
- Advanced Green Energy and Environment Institute (AGEE), Handong Global University, Pohang, South Korea
- HEM Inc., Handong Global University, Pohang, South Korea
- *Correspondence: Wilhelm H. Holzapfel,
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Vent-Schmidt J, Attara GP, Lisko D, Steiner TS. Patient Experiences with Clostridioides difficile Infection: Results of a Canada-Wide Survey. Patient Prefer Adherence 2020; 14:33-43. [PMID: 32021115 PMCID: PMC6954101 DOI: 10.2147/ppa.s229539] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2019] [Accepted: 12/17/2019] [Indexed: 11/23/2022] Open
Abstract
PURPOSE Clostridioides difficile infection (CDI) is the most prevalent cause of nosocomial infectious diarrhea in Canada and is highly correlated with antibiotic use and contact with health care facilitates. The often-severe symptoms of CDI include diarrhea, dehydration, and abdominal pain. Patients often relapse following symptom resolution, resulting in increased morbidity. Previous research on the impact of CDI centered around the health-care system, clinician perspectives and economic burden, but not on patient experiences. The purpose of this study was to understand the impact of CDI on patients in Canada. METHODS The Gastrointestinal Society conducted online surveys and gathered data from 167 qualifying participants, who were either patients or their non-treating caregivers. Quantitative parameters were analyzed by descriptive and comparative statistics and contextualized with qualitative insights derived from thematic analysis of open-ended questions. RESULTS Our findings, which focused on clinical parameters such as prior exposure to health-care settings, antibiotic use, and patients' symptoms, mirrored findings from previous research. Interestingly, most surveyed respondents experienced delays in diagnosis and treatment; 29% waited 6-30 days and 10% over 30 days. This delayed diagnosis was further complicated by the report that 62% of respondents did not experience symptom resolution within 7 days of initiating treatment. Importantly, our results suggest a lasting impact after the resolution of CDI and we saw a reduction of self-assessed quality of life from prior to post CDI. Patients' priorities regarding their experience with CDI focused around concerns about the health-care system, particularly time to diagnosis and treatment, concerns about antibiotic usage and needs from health-care providers. CONCLUSION This is the first Canadian report on patients' experience with CDI. Our data highlight the symptom-related impact on patients and the long-lasting effect on the quality of life including emotional impact. Reducing time to diagnosis and improving patient education are important priorities to attenuate the impact on patients.
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Affiliation(s)
- Jens Vent-Schmidt
- Department of Medicine, University of British Columbia, Vancouver, BCV6T 1Z3, Canada
- Department of Biology, Kwantlen Polytechnic University, Langley, BCV3A 8G9, Canada
| | - Gail P Attara
- Gastrointestinal Society, Canadian Society of Intestinal Research, Vancouver, BCV5R 5W2, Canada
| | - Daniel Lisko
- Department of Medicine, University of British Columbia, Vancouver, BCV6T 1Z3, Canada
| | - Theodore S Steiner
- Department of Medicine, University of British Columbia, Vancouver, BCV6T 1Z3, Canada
- Correspondence: Theodore S Steiner Department of Medicine, University of British Columbia, 950 West 28 Ave, Vancouver, BCV5Z 4H4, CanadaTel +1 604 845 2000 ext. 4910 Email
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Birhanu Y, Amogne W, Mohammed A, Asefa M, Teferra F, Yasin M. Pseudomembranous Colitis in Four Ethiopian Patients: A Case Series. Int Med Case Rep J 2020; 13:409-414. [PMID: 32982480 PMCID: PMC7490089 DOI: 10.2147/imcrj.s266619] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2020] [Accepted: 09/01/2020] [Indexed: 01/05/2023] Open
Abstract
We present a series of four patients who had been admitted to two hospitals in Addis Ababa after presenting with persistent and chronic diarrhoea. All patients were subsequently diagnosed to have Clostridioides difficile-associated pseudomembranous colitis, a disease that has long been regarded as a rare diagnosis in sub-Saharan Africa, and which has not yet been reported in Ethiopia. This case series is believed to create a much-needed awareness among physicians on the existence of this treatable but potentially fatal disease.
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Affiliation(s)
- Yohannes Birhanu
- College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
- Correspondence: Yohannes Birhanu Email
| | - Wondwossen Amogne
- College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia
| | | | - Mesfin Asefa
- St. Paul’s Hospital, Millennium Medical College, Addis Ababa, Ethiopia
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Febrile Neutropenia in Acute Leukemia. Epidemiology, Etiology, Pathophysiology and Treatment. Mediterr J Hematol Infect Dis 2020; 12:e2020009. [PMID: 31934319 PMCID: PMC6951355 DOI: 10.4084/mjhid.2020.009] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2019] [Accepted: 12/17/2019] [Indexed: 12/11/2022] Open
Abstract
Acute leukemias are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. An important cause of both the latter is infectious complications. Patients with acute leukemia are highly susceptible to infectious diseases due to factors related to the disease itself, factors attributed to treatment, and specific individual risk factors in each patient. Patients with chemotherapy-induced neutropenia are at particularly high risk, and microbiological agents include viral, bacterial, and fungal agents. The etiology is often unknown in infectious complications, although adequate patient evaluation and sampling have diagnostic, prognostic and treatment-related consequences. Bacterial infections include a wide range of potential microbes, both Gram-negative and Gram-positive species, while fungal infections include both mold and yeast. A recurring problem is increasing resistance to antimicrobial agents, and in particular, this applies to extended-spectrum beta-lactamase resistance (ESBL), Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and even carbapenemase-producing Enterobacteriaceae (CPE). International guidelines for the treatment of sepsis in leukemia patients include the use of broad-spectrum Pseudomonas-acting antibiotics. However, one should implant the knowledge of local microbiological epidemiology and resistance conditions in treatment decisions. In this review, we discuss infectious diseases in acute leukemia with a major focus on febrile neutropenia and sepsis, and we problematize the diagnostic, prognostic, and therapeutic aspects of infectious complications in this patient group. Meticulously and thorough clinical and radiological examination combined with adequate microbiology samples are cornerstones of the examination. Diagnostic and prognostic evaluation includes patient review according to the multinational association for supportive care in cancer (MASCC) and sequential organ failure assessment (SOFA) scoring system. Antimicrobial treatments for important etiological agents are presented. The main challenge for reducing the spread of resistant microbes is to avoid unnecessary antibiotic treatment, but without giving to narrow treatment to the febrile neutropenic patient that reduce the prognosis.
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In vitro and in vivo anti-clostridial activity of newly isolated Pediococcus acidilactici SPM138 against Clostridium difficile. Anaerobe 2019; 61:102146. [PMID: 31887433 DOI: 10.1016/j.anaerobe.2019.102146] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Revised: 12/03/2019] [Accepted: 12/23/2019] [Indexed: 11/23/2022]
Abstract
Clostridium difficile infection (CDI) has become a growing health concern, as evident from the increase in the mortality rate among elderly or hospitalized patients. Treatment of CDI is usually based on antibiotics (metronidazole and vancomycin), but it has some limitations, including cost and antibiotic resistance. Probiotics could offer an effective remedy to prevent CDI and could be an auxiliary agent in treatment CDI. Here, the anti-clostridial activity of a newly isolated probiotic strain, Pediococcus acidilactici SPM138 (SPM138) was evaluated. The cultivation of C. difficile (CD) with SPM138, inhibited the growth of CD and significantly reduced CD toxins level. The result of MTT assay showed that, incubation with 25% CD culture supernatant decreased the survival rate of HT-29 cells to less than 20%. However, the survival rate of these cells increased to 98% in the presence of the 25% CD + SPM138 supernatant. The mRNA expression of IL-6, IL-8 and PTGS2 in HT-29 cells decreased by more than 60% upon incubation with CD + SPM138 co-cultures as compared to the levels observed after treatment with CD supernatant only. The concentration of IL-8 also decreased by more than 60% upon treatment with CD + SPM138 co-culture supernatant. In a C. difficile PCR ribotype 027-infected mouse model, the concentration of CD toxin in stool samples of SPM138-fed mice was only 37% of that reported in C. difficile 027-infected group. These findings show that P. acidilactici SPM138 may be a promising probiotic in CDI.
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