Pseudomonas aeruginosa bloodstream infections (Pa-BSIs) are still a major cause of mortality in ICUs, posing many treatment uncertainties.

This multicentre, retrospective study analysed data from 14 Italian hospitals, including all consecutive adults developing Pa-BSI in ICU during 2021-22 and treated with antibiotics for at least 48 h. The primary aim was to identify predictors of 30 day mortality using Cox regression. Results were adjusted with inverse probability of treatment weighting (IPTW) and for immortal time bias.

Overall, 170 patients were included. High-risk BSI (source: lung, intra-abdominal, CNS) occurred in 118 (69%) patients, and 54 (32%) had septic shock. In 37 (22%), 73 (43%), 12 (7%) and 48 (28%) the definitive backbone therapy was piperacillin/tazobactam, carbapenems, colistin or new antipseudomonal cephalosporins (ceftolozane/tazobactam, n = 20; ceftazidime/avibactam, n = 22; cefiderocol, n = 6), respectively. Moreover, 58 (34%) received a second drug as combination therapy. The incidence of 30 day all-cause mortality was 27.6% (47 patients). By Cox regression, Charlson comorbidity index, neutropenia, septic shock and high-risk BSI were independent predictors of 30 day mortality, while previous colonization by P. aeruginosa, use of antipseudomonal cephalosporins as definitive treatment, and combination therapy were shown to be protective. However, after IPTW adjustment, only the protective effect of antipseudomonal cephalosporins was confirmed (adjusted HR = 0.27, 95% CI = 0.10-0.69), but not for combination therapy. Hence, the treatment effect was calculated: antipseudomonal cephalosporins significantly reduced mortality risk [-17% (95% CI = -4% to -30%)], while combination therapy was beneficial only in the case of septic shock [-66% (95% CI = -44% to -88%].

In ICU, antipseudomonal cephalosporins may be the preferred target therapy for the treatment of Pa-BSI; in addition, initial combination therapy may be protective in the case of septic shock.

Methicillin resistance in Staphylococcus aureus is conferred by the mobile genetic element, staphylococcal cassette chromosome mec (SCCmec). Methicillin-resistant Staphylococcus aureus (MRSA) can transmit among animals and humans, leading to persistence and back transmission events. The current study tested the hypothesis that companion animal and livestock-associated (LA) MRSA isolates share genomic similarity, suggesting shared ancestry with hospital-associated (HA) or community-associated (CA) MRSA. Eight S. aureus isolates from therapy dogs (n = 5) and bulk tank milk (n = 3) were genome sequenced, and 71,721 genome-wide single nucleotide polymorphism (SNP) locations were extracted and phylogenetically compared against methicillin-sensitive Staphylococcus aureus (MSSA) and MRSA genomes of isolates from a variety of species and time frames, available in the National Center for Biotechnology Information (NCBI) database. A maximum likelihood phylogenetic tree was constructed to define S. aureus lineages across isolates from animals and humans. Four isolates from companion animals and three bulk tank milk isolates clustered with human isolates, while one companion animal isolate clustered with genomes of MRSA isolated from swine. Four therapy dog isolates had CA-MRSA SCCmec types IVa, IVc, and V/VII, respectively, while one therapy dog and one bulk tank milk isolate shared SCCmec type (IIa) that is commonly seen in HA-MRSA. Two isolates from bulk tank milk were methicillin sensitive and did not carry mecA.

Methicillin-resistant Staphylococcus aureus (MRSA) infections are a major medical concern, causing a range of conditions from skin infections and invasive disease to death. MRSA was discovered as a nosocomial infection; however, it has since been isolated in communities and animals worldwide. This research was significant because canine and bulk tank milk isolates were found to have genomic relatedness to human and domestic animal S. aureus isolates. This genetic relatedness implies either a parallel evolution within hosts converging to successful genotypes or real interspecies transmission events among animals and humans.

Antimicrobial stewardship programs (ASPs) are essential for optimizing antimicrobial use, but many medium-sized hospitals lack infectious disease (ID) specialists. Ward pharmacists can contribute to ASPs, but the qualitative changes in their practice patterns after ASP implementation remains unclear. We aimed to explore the potential of text mining as a novel methodology to evaluate changes in ward pharmacist antimicrobial management practices after ASP implementation in a medium-sized hospital without ID physicians.

We conducted a retrospective observational analysis of data documented in clinical records by ward pharmacists in a 313-bed community hospital from April 2014 to March 2022. The ASP team conducted weekly reviews of targeted patients, provided feedback to physicians, and shared recommendations with ward pharmacists who then collaborated to optimize antimicrobial therapy. Using Python-based text mining with standardized technical terms and compound word extraction, we performed morphological analysis, co-occurrence network analysis, and hierarchical clustering to evaluate documentation patterns before and after ASP implementation in April 2018. Co-occurrence relationships were assessed using Dice coefficients (threshold, ≥ 0.3), and communities were detected using the Louvain algorithm. Changes in documentation patterns were compared using Fisher's exact test.

The analysis included 1,353 pre-ASP and 5,155 post-ASP clinical records containing antimicrobial-related terms, which increased from 3.12 to 7.81% of the total pharmacy records. New strong co-occurrence relationships emerged in the post-ASP period for several laboratory parameters (c-reactive protein, 0.646; estimated glomerular filtration rate, 0.594; and white blood cell count, 0.582). Network analysis revealed a shift from medication-focused communities (Medication Review, Prescription Verification, and Patient Education) to infection-focused communities (Infection Assessment, Microbiological Review, and Severe Infection Management). Although Antimicrobial Management was consistently used in both periods (odds ratio [OR]: 0.70, 95% confidence interval [CI]: 0.38-1.20), cross-tabulation analysis increased significantly in Laboratory Monitoring (OR: 1.58, 95% CI: 1.39-1.78) and Infection Assessment (OR: 2.09, 95% CI: 1.85-2.36).

This pilot application of text mining demonstrated potential as a novel methodology for objectively evaluating qualitative changes in clinical practice patterns following ASP implementation, successfully identifying shifts in pharmacists' documentation focus and providing a foundation for future multi-center validation studies across diverse healthcare settings.

In the last two decades, there has been an increase in resistance among Gram-negative bacteria in Canada. From 2007 to 2016, the proportion of ESBL-producing isolates among Escherichia coli and Klebsiella pneumoniae isolates increased from 3.5% to 11.1%. There has also been an increase in carbapenem use over this time period, which may be contributing to the increasing prevalence of carbapenemase-producing Enterobacterales (CPE) in Canada. CPE, which were historically associated with travel, are now mostly acquired domestically. The prevalence of multi-drug resistant (MDR) Pseudomonas aeruginosa has decreased slightly, possibly due to decreasing use of fluoroquinolones and aminoglycosides. Many of the most effective antimicrobials for the treatment of infections with resistant Gram-negative organisms, including many of the novel β-lactam/β-lactamase inhibitors (βL/βLIs), are not marketed in Canada. A coordinated focus on antimicrobial stewardship and infection control is necessary to slow the spread of resistance and to preserve the efficacy of our current antimicrobials for future generations.

Escherichia coli causes >400,000 annual deaths in children aged <5 years worldwide, with morbidity and mortality exacerbated by antimicrobial-resistant strains. A high-throughput multiplexing assay called digital multiplex ligation assay (dMLA) was developed to detect simultaneously 43 priority genes in E. coli related to the following: antibiotic resistance (n = 19), virulence factors (n = 16), and phylogroup markers (n = 6) with controls (uidA, gapdh). Genes are detected via PCR amplification of adjacent probe pairs that ligate in the presence of target gene-specific DNA, followed by sequencing of amplicons on short-read sequencers. The assay was tested in technical replicates on 63 synthetic DNA controls, and applied to 58 E. coli, 2 Staphylococcus aureus, 2 Klebsiella pneumoniae, 1 Klebsiella oxytoca, 1 Vibrio cholera, 1 Pseudomonas lurida, and 1 Salmonella enterica isolates in duplicate. Whole-genome sequencing was used to assess specificity and sensitivity. dMLA showed 100% sensitivity and >99.9% specificity and balanced accuracy on synthetic DNA. Balanced accuracy, calculated as the average of sensitivity and specificity, accounts for imbalanced data sets where negative outcomes are significantly more prevalent than positive ones. dMLA achieved a balanced accuracy of 90% for bacterial isolates. The results underline dMLA's effectiveness in high-throughput characterization of E. coli libraries for antimicrobial resistance genes and virulence factors, leveraging sequencing for massively parallel multiplexing of gene regions on multiple samples simultaneously, and are extendable to targets beyond E. coli.

Assessing the burden of antimicrobial resistance is essential to determine the magnitude of this problem and to set its priority. We aimed to estimate the burden of disease caused by multidrug-resistant microorganisms (MDRO) in hospitalised patients in Spain.

Three prospective nationwide studies were conducted in 2018, 2019 and 2023. All patients with a new diagnosis of infection with any of 10 selected MDROs plus Clostridioides difficile during the study period (one week in 2018 and 2019 and two weeks in 2023) were included. Patient demographic, and clinical outcomes were analysed, including incidence, crude all-cause 30-day mortality and years of life lost (YLL). These results were used to calculate weighted and seasonally adjusted annual estimates for the whole country.

In total, 82, 133 and 130 centres participated in the study in 2018, 2019 and 2023, respectively, recording a total of 907, 1392 and 2351 MDRO infections, representing a weighted incidence density of 3.54 (95% CI 2.92-4.17), 5.01 (3.95-6.07), and 4.41 (3.55-5.27) cases/1000 stays, respectively. A total of 161, 198 and 352 patients died with an MDRO infection, representing a weighted incidence density of 0.46 (0.16-0.76), 0.43 (0.17-0.69), and 0.62 (0.52-0.72) deaths/1000 stays, respectively. Based on these data, a nationwide occurrence of 155,294 MDRO infections (95% CI 127,928-182,569) with 20,065 deaths (6938-32,958) was estimated for 2018, 210,451 MDRO infections (165,963-254,975) with 17,982 deaths (7071-28,700) for 2019, and 173,653 MDRO infections (139,814-207258) with 24,582 deaths (20,461-28,796) for 2023.

The burden of disease caused by MDRO infections among hospitalised patients in Spain is very high and remains stable over the study period. National actions to combat bacterial resistance need to be intensified.

The management costs of this study were funded by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). Researchers have participated voluntarily and none of the investigators received funding for conducting the study.

Antimicrobial stewardship supports rational antibiotic use. However, balancing access to antibiotic treatment while controlling resistance is challenging. This research used a threshold logistic modeling approach to identify targets for antibiotic usage associated with carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Klebsiella pneumonia, and extended-spectrum β-lactamases-producing Escherichia coli incidence in hospitals.

This study utilizes an ecological population-level design. Monthly pathogen cases and antibiotic use were retrospectively determined for inpatients between January 2015 and December 2023. The hospital pharmacy and microbiology information systems were used to obtain this data. Thresholds were identified by applying nonlinear modeling and logistic regression.

Incidence rates of 0.199, 0.175, and 0.146 cases/100 occupied bed-days (OBD) for carbapenem-resistant A baumannii, carbapenem-resistant K pneumonia, and extended-spectrum β-lactamases-producing E coli, respectively, were determined as the cutoff values for high (critical) incidence rates. Thresholds for aminoglycosides (0.59 defined daily dose [DDD]/100 OBD), carbapenems (6.31 DDD/100 OBD), piperacillin-tazobactam (3.71 DDD/100 OBD), third-generation cephalosporins (3.71 DDD/100 OBD), and fluoroquinolones (1.91 DDD/100 OBD), were identified. Exceeding these thresholds would accelerate the gram-negative pathogens' incidence rate above the critical incidence levels.

Threshold logistic models can help inform and implement effective antimicrobial stewardship interventions to manage resistance within hospital settings.

Infectious etiologies of deep neck space abscess (DNSA) by conventional culture tests can be challenging, which also leads to frequent irrational antibiotic usage. Metagenomic next-generation sequencing (mNGS), as a novel method for analyzing the complex microbial ecosystem from clinical samples, has been utilized in clinical research and practice of various infectious diseases but deep neck space abscess. We here aimed to explore the clinical value of mNGS for pathogen detection and treatment guidance in DNSA patients compared with conventional culture tests.

One hundred six patients diagnosed with DNSA were retrospectively enrolled and allocated into mNGS group and culture group according to whether mNGS was conducted. The pathogen detection effectiveness was of mNGS was compared with conventional culture. Effectiveness of mNGS-modified antimicrobial therapy was evaluated by comparing the treatment outcomes between two groups.

mNGS showed a significantly higher detection rate than conventional culture (p < 0.05) with faster result acquisition. Treatment success rate of patients in the mNGS group was significantly higher than in the culture group (RR: 1.22, 95%CI: 1.07-1.82, p = 0.033). Besides, patients in the mNGS group had shorter duration of irrational antimicrobial therapy, shorter hospital stay and less medical costs (p < 0.05).

mNGS is an effective technology for facilitating pathogen detection and improving treatment outcomes of DNSA patients.

Enteric infections represent a prevalent global health issue and contribute significantly to the global disease burden. This study aims to investigate the patterns and trends of enteric infections from 1990 to 2021, providing valuable insights for health policy formulation, medical resource allocation, and the optimization of patient management plans.

We analyzed the Global Burden of Disease (GBD) 2021 for 21 regions and 204 countries to understand better the health burden using prevalence, incidence, mortality, and disability-adjusted life years (DALYs), subtype, risk factors, and etiology. We tested correlations with the Socio-demographic Index (SDI), and using decomposition analysis to dissect the reasons behind changes in epidemiological indicators of the disease.

In 2021, the age-standardized rates of prevalence, incidence, deaths, and DALYs per 100,000 population for enteric infections were 879.58, 577.21, 17.83, and 1020.15, respectively. Compared to 1990, these rates exhibited -0.18, -0.12, -0.73, and -0.72 changes. Gender and age analyses revealed a higher burden among females, those under 15 years old, and the elderly. Regions with low SDI had higher epidemiological indicators. The burden of Typhoid fever declines in high-development regions. Unsafe water sources were identified as the primary risk factor globally in both 1990 and 2021. Rotavirus was the leading cause of deaths and DALYs.

This study highlights the complex epidemiological landscape of enteric infections, revealing variations in burden, risk factors, and etiological characteristics across age, gender, and geographical regions. It underscores the urgent need for healthcare professionals and policymakers to develop innovative prevention and healthcare strategies based on the current and evolving burden of enteric infections, to alleviate the global disease burden.

The increase in antimicrobial resistance presents a major challenge in treating bacterial infections, underscoring the need for innovative drug discovery approaches and novel inhibitors. Bacterial RNA polymerase (RNAP) has emerged as a crucial target for antibiotic development due to its essential role in transcription. RNAP is a molecular motor, and its function relies heavily on the dynamic shifts between multiple conformational states. While biochemical and structural experimental methods offer crucial insights into static RNAP-drug interactions, they fall short in capturing the dynamics at a molecular level. By integrating experimental data with advanced computational techniques like Markov State Models (MSMs), Generalized Master Equation (GME) Models and other machine-learning models constructed from molecular dynamics (MD) simulations, researchers can elucidate novel cryptic pockets that open transiently for antibiotic compounds and gain a more nuanced and comprehensive understanding of RNAP-drug interactions. This integrated approach not only deepens our fundamental knowledge but also enables more targeted and efficient antibiotic design strategies. In this Perspective, we highlight how this synergy between experimental and computational methods has the potential to open new pathways for innovative drug design and combination therapies that may help turn the tide in the ongoing battle against antibiotic-resistant bacteria.

This study aimed to describe the epidemiology and antimicrobial susceptibility patterns of gram-negative pathogens in Brazil from 2018 to 2020, addressing the gap in national data on healthcare-associated infections, using information from a private laboratory network.

A cross-sectional study was conducted using a database from Fleury hospital network, a private laboratory in Brazil. The analysis included blood, urine, and lower respiratory tract samples collected from January 2018 to June 2020. The study included consecutive non-duplicated isolates of Enterobacterales or P. aeruginosa from inpatients aged ≥18 years old. Bacterial identification was performed using mass spectrometry, and antimicrobial susceptibility was determined following EUCAST/BrCAST guidelines.

A total of 25,180 isolates were included in the analysis. Most of the sample consisted of female patients (57.9%), with a mean age of 70 years (SD 18.1). Enterobacterales were the most prevalent pathogens found (76.2%), while P. aeruginosa was present in the remaining 23.8%. In terms of antimicrobial susceptibility, Enterobacterales exhibited a higher susceptibility rate to ceftazidime/avibactam (97.1%) and amikacin (95.6%), while P. aeruginosa showed a higher susceptibility rate to polymyxin B (97.1%) and ceftolozane/tazobactam (86.6%). Among carbapenem-resistant P. aeruginosa isolates, 75% were susceptible to ceftolozane/tazobactam. Additionally, 24.2% of K. pneumoniae complex samples were identified.

Enterobacterales was the most frequently encountered group in Brazil. Ceftazidime/avibactam and amikacin demonstrated the highest efficacy against this group, while ceftolozane/tazobactam and polymyxin had the highest efficacy against P. aeruginosa. This highlights the importance of new β-lactam-β-lactamase inhibitor combinations for the treatment of gram-negative infections.

Background: To aid in the development of antimicrobial stewardship programs (ASPs), we analyzed the patterns and trends in antibiotic prescriptions for patients with severe acute respiratory infection (SARI), utilizing the WHO's AWaRe classification. Methods: We analyzed data from hospital-based influenza surveillance from January 2011 to December 2020 across nine Bangladeshi tertiary-level hospitals. Surveillance physicians collected WHO-defined SARI patient data, including demographics, clinical characteristics, and antibiotic prescriptions. Descriptive statistics and parametric and non-parametric tests were used for the analysis. Results: Of 21,566 SARI patients [median age 20 years (IQR: 1.33-45), 66% male], 91% were prescribed at least one antibiotic. A total of 25,133 antibiotics were prescribed, of which 47.0% were third-generation cephalosporins, 16.5% were macrolides, and 11.1% were beta-lactam/beta-lactamase inhibitors. According to the AWaRe classification, 28.7% were in the Access group, while 71.3% were in the Watch group, and none were from the Reserve group. A downward trend in Access group (30.4% to 25.1%; p = 0.010) and an upward trend in Watch group antibiotic prescription (69.6% to 74.9%; p = 0.010) were observed. We identified that patients aged < 5 years (aOR: 1.80; 95% CI: 1.44-2.25), who were treated in government hospitals (aOR: 1.45; 95% CI: 1.35-1.57), patients with the presence of lung diseases (aOR: 1.56; 95% CI: 1.35-1.80) had an increased likelihood of being prescribed Watch group antibiotics. Conclusions: This study reveals a concerning pattern of antibiotic overuse among SARI patients in Bangladesh, with a growing trend over the past decade towards increased Watch group antibiotic prescriptions. Only one-third of the prescribed antibiotics were from the Access group, falling short of the two-thirds threshold recommended by the WHO. Effective ASPs are crucial to optimize antibiotic prescriptions and mitigate the risk of antimicrobial resistance.

The filamentous temperature-sensitive protein Z (FtsZ) plays a vital role in bacterial division, making it an important antibacterial target. The inhibitor activity targeting the cleft between the H7 helix and the C-terminal substructural domain exhibited superior binding compared to the GTP binding site. This highlights the potential of the cleft as a promising target for further inhibitor discovery. In this study, we established a virtual screening (VS) pipeline using Discovery Studio software and employed FRED for molecular docking and Functional-Class Fingerprints_6 (FCFP_6) for molecular clustering, resulting in the identification of 38 potentially active compounds. These 38 compounds were then subjected to the following FtsZ inhibition assays, resulting in the four active compounds B6, B21, B26, and B31. Further experiments showed that compounds B6 and B26 exhibited antimicrobial activity with minimum inhibitory concentration (MIC) values of 8 and 32 µg/mL. Finally, molecular dynamics (MD) was used to analyze the binding modes of the protein-ligand. In addition, we predicted the physicochemical properties and toxicity of B6 and B26. In summary, our study successfully identified novel FtsZ inhibitors with antimicrobial activity through VS and in vitro biological evaluation, demonstrating their potential for further investigation.

Bacterial respiratory infections pose significant health risks to children, particularly infants susceptible to upper respiratory tract infections (URTIs). The COVID-19 pandemic has further exacerbated the prevalence of these infections, with pathogens such as Mycoplasma pneumoniae, Streptococcus pneumoniae, Legionella pneumophila, Staphylococcus aureus, Haemophilus influenzae, and Klebsiella species commonly implicated in pediatric cases. The critical need for accurate and timely detection of these bacterial agents has highlighted the importance of advanced diagnostic techniques, including multiplex real-time PCR, in clinical practice. Multiplex real-time polymerase chain reaction (PCR) offers several advantages, including rapid results, high sensitivity, and specificity. By accelerating the diagnostic process, this approach enables early intervention and targeted treatment, ultimately improving patient outcomes. In addition to PCR technologies, rapid and point-of-care testing (POCT) play a crucial role in the prompt diagnosis of bacterial respiratory infections. These tests are designed to be user-friendly, sensitive, and deliver quick results, making them particularly valuable in urgent clinical settings. POCT tests are often categorized into two main groups: those aimed at determining the cause of infection and those focused on confirming the presence of specific pathogens. By utilizing POCT, healthcare providers can make rapid and informed treatment decisions, leading to more effective management of bacterial respiratory infections in children. As the medical community continues to explore innovative diagnostic approaches, the integration of molecular and rapid testing methods offers significant promise in the realm of bacterial respiratory infections. By adopting these cutting-edge technologies, healthcare professionals can enhance their ability to accurately diagnose these infections, tailor treatment strategies, and ultimately improve patient care.

Sepsis, a life-threatening condition with a high mortality rate, requires intensive care unit (ICU) admission. The increasing hospitalization rate for patients with sepsis has escalated medical costs due to the strain on ICU resources. Efficient management of ICU resources is critical to addressing this challenge.

This study utilized the dataset collected from 521 patients with sepsis at Chungbuk National University Hospital between July 2020 and August 2023. A transformer-based deep learning model was developed to predict ICU length of stay (LOS). The model incorporated global and local input data analysis through classification and feature-wise tokens, based on sequential organ failure assessment (SOFA) criteria. Model performance was evaluated using four-fold cross-validation.

The proposed model achieved a mean absolute error (MAE) of 2.05 days for predicting ICU LOS. The result demonstrates the ability of the proposed model to provide accurate and reliable predictions.

The proposed model offers valuable insights for healthcare resource management by optimizing ICU resource allocation and potentially reducing medical expenses. These findings highlight the applicability of the proposed model to efficient healthcare cost management.

Daptomycin is a lipopeptide antibiotic with a broad spectrum of activity against gram-positive bacteria. Although information on daptomycin-induced adverse events can be found in clinical trials, data regarding the impact of age on these events are insufficient. Therefore, we evaluated whether age affects the occurrence of daptomycin-induced adverse events using adverse drug event reports in post-marketing stages provided by the U.S. Food and Drug Administration (FDA).

A total dataset of 7307 reports of patients treated with daptomycin in the FDA's Adverse Event Reporting System were analyzed. The patients were divided into seven age groups: 0-28 days, >28 days-23 months, 2-11 years, 12-17 years, 18-64 years, 65-80 years, and >80 years. A disproportionality analysis was conducted to calculate the reporting odds ratio, with a 95 % confidence interval. The univariate regression analysis was conducted using the percentage of each adverse event and age groups.

Compared with the number of reports aged 18-64 years, there were significantly increased reports of eosinophilic pneumonia in patients aged 65-80 years and >80 years, anaphylactic reaction and pseudomembranous colitis in patients aged 12-17 years, and acute renal failure in patients aged 65-80 years. The regression coefficient for the reporting proportion of eosinophilic pneumonia was significantly positive.

Our findings revealed age-related trends in daptomycin-induced adverse events, supporting the idea that implementing age-dependent follow-up and supportive care helps in the continuation of daptomycin therapy.

New Delhi metallo-β-lactamase (NDM)-producing carbapenem-resistant Enterobacterales (CRE) is a globally growing threat. We sought to describe the microbiology, management and outcomes of patients with this infection at our facility.

This is a descriptive case series of patients with NDM-producing Escherichia coli isolated from culture in Detroit between July 2021 and February 2023. Demographics, risk factors, clinical characteristics, management and outcomes were described.

Nine patients were included in the study. Most patients were female with a median age of 67 years. Hepatobiliary disease accounted for 90% of underlying conditions. Nearly all patients had prior antibiotic exposure and the most common specimen source was intra-abdominal fluid. Three patients were not treated due to colonisation; among those treated, the majority received trimethoprim-sulfamethoxazole. The median treatment duration and length of stay were 7 and 15.5 days, respectively. Six (67%) patients survived.

This report describes a large case series of NDM-producing E. coli infection. Patients with significant comorbidities remain at high risk for CRE infection. Antibiotic options for the treatment of NDM organisms are very limited; new and effective therapies are urgently needed.

Multidrug-resistant organisms (MDROs) are transmitted through the hands of healthcare workers who touch the environments of patients with MDROs. Patients identified as being infected with MDROs are subjected to contact precautions and isolated in a single room. Nurses need to have the correct knowledge of infection prevention and be interested in the psychological conditions of isolated patients with MDROs.

To develop and evaluation of an education program for nurses to emphasize the psychological care of isolated patients with MDROs.

To evaluate the effectiveness of the educational program, this study employed a quasi-experimental design.

Seventy-eight nurses working in inpatient wards at four medical facilities were assigned to the program participant group (N = 25) and the non-participant group (N = 53).

This experimental study utilized the five steps of the ADDIE instructional model (analysis, design, development, implementation, and evaluation) to design an educational program. The first step was to identify educational needs. The next steps were to design the program and develop educational materials. In the fourth step, training on infection control measures for MDROs and psychological care for patients with MDROs in isolation was conducted. Finally, in the fifth step, the effectiveness of the educational program was evaluated by scoring on expected behaviors to improve the psychological state of patients in isolation.

The program participants group exhibited behavioral changes and attitudes that observed physiological and psychological responses related to patient anxiety and depression (p < .05).

The education program increased the understanding of the psychological state of patients with MDROs and the observation of physiological and psychological reactions. This suggests that an education program based on ID is likely to have the potential to change nurses' behavior to improve the quality of care for patients with isolated infections.

Accurate estimates of incremental cost (IC) attributable to antimicrobial resistance (AMR) provide information of immense public health importance to the policy makers. Here, we present the IC from patient perspective for treating antimicrobial-resistant pathogens in India.

This cohort study was conducted in eight hospitals including government (GH), private (PH) and trust hospitals (TH), considering their ownership, geographical location and categories of cities. This study had a retrospective component, which calculated the direct cost of treating resistant and susceptible blood stream infections caused by selected WHO priority pathogens. The prospective component estimated indirect cost and financial coping strategies for the treatment of AMR. In the retrospective component, 1723 records were included and 170 patients were recruited in the prospective component.

The median total cost for management of antimicrobial-resistant infections was US$199 (IQR 89, 377) as opposed to US$109 (IQR 55, 229) for susceptible infection in GH. Our study has revealed that the ICs for Enterobacteriaceae (53.9%), Acinetobacter (43.8%) and Staphylococcus (49.7%) at GHs were higher for resistant pathogens. Pharmaceutical cost was the major contributor to IC at GHs (61.5%) and PHs (27.1%). In the prospective component, 46.5% of patients resorted to borrowing money for hospitalisation expenses and the per day median total cost for resistant and sensitive infection was estimated to be US$65 and US$35, respectively.

The current study concluded that the presence of any critical or high priority pathogens led to an increase in the direct and indirect medical costs. The IC varied with hospital type, length of stay, pathogen, comorbidities and diagnosis. Prospective studies are needed for precise understanding of variations in the costs of treating AMR infections.

Antimicrobial resistance (AMR) represents a major threat to medical practice, complicating infection management, and increasing mortality and healthcare costs. Macro estimations of this health issue remain underexplored because data are currently limited to hospital systems. This study aims to estimate the economic and human burden of AMR in Spain at a macro level. An economic model was constructed based on prevalence rates, premature deaths and published literature to assess costs. Methodology was based on several techniques depending on the type of cost to be estimated: hospital inpatient care costs (based on extra hospital days); outpatient care costs (employing reimbursement rates from regional health services); productivity losses due to premature deaths (using the Human Capital Approach) and morbidity (based on days absent from work). Using data from EARS-NET, ESAC-NET and GBD, a total of 30 bacteria-drug resistance combinations were analysed. The results showed that 77,870 infections, 6,199 premature deaths, and 426,495 extra hospital days were attributable to AMR in Spain, mostly due to Gram-negative bacteria. AMR was also responsible for 3,112 years of working life lost. The costs reached EUR 338.6 million (0.03% of GDP), costing each Spaniard EUR 7.15 per year. Direct costs accounted for 72% of total costs, while indirect costs represented 28%. To date, this is the first study that evaluates the cost of AMR across such a wide range of bacteria and infection sites. These estimates are useful for approximating the problem and for planning containment and action strategies.

Recognition of carbapenem-resistant gram-negative bacteria (CR-GNB) carriage is frequently delayed, which increases the risk of subsequent infection and transmission. Previously, we developed a scoring system to identify CR-GNB carriage upon intensive care unit (ICU) admission. Although the ICU-CARB score showed satisfactory performance, it has not been externally validated. In this study, therefore, we externally validated the ICU-CARB score.

In the previous article, we introduced a risk-scoring system that incorporated seven key variables: neurological disease, high-risk department history, length of stay ≥ 14 days, ICU history, invasive mechanical ventilation, gastrointestinal tube placement, and carbapenem usage. To externally validate the ICU-CARB score, we conducted a study involving patients admitted to the ICUs of four tertiary hospitals between January 2021 and December 2023. Patients from three hospitals were grouped into Cohort I (n = 815) and those from the fourth hospital into Cohort II (n = 1602). Model calibration, discrimination, and performance were then assessed.

A total of 2417 patients were included, among which 289 (12%) carried CR-GNB upon ICU admission. Neurological disease, high-risk department history and length of stay ≥ 14 days were still 3 most important contributing factors in the scoring system. The ICU-CARB score exhibited high calibration, with an area under the receiver operating characteristic curve of 0.825 (95% confidence interval [CI], 0.778-0.873) for Cohort I and 0.823 (95% CI, 0.791-0.855) for Cohort II. The ICU-CARB score showed a highly positive association with CR-GNB carriage in both cohort I (C = 0.315; P < 0.001) and Cohort II (C = 0.381; P < 0.001).

Despite differences in patient population characteristics, the ICU-CARB score for CR-GNB carriage upon ICU admission exhibited good discrimination in external validation, supporting its potential generalizability to other ICU settings.

The escalating antimicrobial resistance (AMR) in highly virulent Vibrio vulnificus poses a significant public health concern in Asia. Profiling the antibiogram of this pathogen is crucial for revealing its complex AMR patterns and guiding the selection of appropriate medications. Although previous studies have provided valuable insights regarding V. vulnificus AMR, they are constrained by limited sample diversity, inconsistent methodologies, and insufficient regional data. Moreover, no systematic attempt has been made to synthesize V. vulnificus AMR data across various sources and regions in Asia. A systematic review and meta-analysis are thus conducted in this study to assess the current AMR status of V. vulnificus isolated from clinical, environmental, and seafood samples. By synthesizing data from 32 articles across 13 Asian countries, a broader antibiogram has been provided, covering 13 major antimicrobial groups against V. vulnificus. Subgroup and regression analyses were also performed using study-level and country-specific covariates to explore the associated risk factors. The findings revealed low AMR rates for tetracyclines (4.89 %), quinolones (1.85 %), nitrofurans (0.86 %), and phenicols (0.61 %), highlighting their potential as primary treatment options. Conversely, high AMR rates were detected for lincosamides (80.32 %), polypeptides (64.42 %), and glycopeptides (56.14 %), necessitating careful consideration for their clinical use. For study-level covariates, subgroup and meta-regression analyses revealed that variations in the type of antimicrobial (R 2  = 26.5 %, p < 0.0001), country (R 2  = 18.33 %, p < 0.0001), and pathogen source (R 2  = 10.46 %, p = 0.0007) significantly contributed to between-study heterogeneity in the detected AMR rates across studies. Moreover, the analyses of country-specific covariates indicated that antimicrobial consumption (AMC) in healthcare systems (R 2  = 29.3, p = 0.06) and the country's gross domestic product (GDP) (R 2  = 28.59, p = 0.06) affected the variations in AMR rates across countries to some extent. Consideration of study-level and country-specific covariates is thus recommended for future research to effectively mitigate the threat of V. vulnificus AMR across Asia and reduce its pervasive impact on public health.

Antimicrobial compounds play a critical role in combating microbial infections. However, the emergence of antibiotic and antifungal resistance and the scarcity of new antibiotic developments pose a significant threat and demand the discovery of new antimicrobials for both bacterial and fungal pathogens. Our previous work described the first generation (G1) of organoantimony-based compounds that showed antimicrobial activity against several bacterial and fungal pathogens. Here, we present our efforts in modifying these compounds by replacing the tetraphenyl backbone in G1 compounds with a trimethyl group, thereby generating a new series of compounds we refer to as "generation 2", G2. In addition to the novel backbone structure, we introduced three new anionic chloro-cyanoxime ligand groups, namely 2,4-diCl-PhCO-, 2,6-diCl-PhCO- and 2Cl-PhCO-, which were found to be biologically active in the past. Nine new compounds of SbMe3L2 composition were obtained in high yields and characterized by NMR, IR spectroscopies, thermogravimetric TG/DSC and X-ray single crystal analyses. The antibacterial activity of the cyanoximates was tested against three bacterial (Pseudomonas aeruginosa PAO1, Escherichia coli S17 and methicillin-resistant Staphylococcus aureus (MRSA) NRS70) and two fungal (Candida albicans strain SC5314 and Cryptococcus neoformans strain H99) pathogens. Two compounds, SbMe3(MCO)2 and SbMe3(2,4-diClPhCO)2, were active against bacterial strains and inhibited the growth of PAO1 and MRSA with MICs of 50 and 100 µg/mL, respectively. Three compounds, SbMe3(MCO)2, SbMe3(ECO)2 and SbMe3(TCO)2, were active against fungal strains and inhibited either one of or both C. albicans and C. neoformans at MICs of 2.6-66.67 μg/mL. In addition, SbMe3(TCO)2 and SbMe3(MCO)2 were fungicidal at MFC 33.33-66.67 μg/mL. Ultra-thin-layer TEM imaging suggested that SbMe3(MCO)2 targets the integrity of bacterial membranes. Overall, four of the studied G2 series compounds possess antimicrobial activity against a broad range of microbial pathogens, with particular potential against fungal pathogens, which will be explored in further studies.

This work aims to screen the major species of bacteria distributed in the filling area in one of the new pharmaceutical facilities in the 6th of October city in Egypt and their phylogenic relationship. One hundred percent of collected Gram-positive and Gram-negative isolates of bacteria were sensitive to Levofloxacin. There were five Gram-positive multidrug-resistant (MDR) bacterial isolates and one Gram-negative (MDR) bacterial isolate (three (from personnel), two (from surface), and one (from air)). The five Gram-positive MDR bacterial isolates were resistant to Tobramycin, Gentamicin, Piperacillin, Cefaclor, and Amikacin while the one Gram-negative MDR bacterial isolate was resistant to Ceftazidime, Cefotaxime, Tobramycin, Gentamicin, Piperacillin, Cefoperazone/Sulbactam, Ofloxacin, and Polymixin b. The existence of multidrug-resistant bacteria inside cleanrooms of pharmaceutical plants signifies a life-threatening danger on human through generating contaminated drugs and/or vaccines that undoubtedly harm the consumer's healthiness. The technique of 16SrRNA gene sequencing was used to identify multidrug-resistant bacterial isolates. All tested disinfectants were bactericidal except Dettol that was found to be a bacteriostatic agent and had an anti-biofilm effect. Clorox was the most potent disinfectant that had the least MIC and MBC of 0.0002% and 0.0004%, respectively. Ethanol and Klericide were excellent sanitizing agents. The strongest biofilm formed by Staphylococcus gallinarum strain MN1812 was disrupted by Clorox with a concentration of 0.000098%. Only Dettol with a concentration of 6.3% achieved the highest disruption for the biofilm of Staphylococcus gallinarum strain NM2009. Staphylococcus gallinarum strain MN1812 followed by Bacillus amyloliquefaciens showed the highest adhesion and invasion efficiencies to Caco-cells among the investigated bacterial strains. Klericide and Dettol mixture showed more anti adhesion and invasion effects against Staphylococcus gallinarum strain NM2009 and strain MN1812 and Pseudomonas putida compared to using Klericide alone. Ethanol and Klericide had the least contact time (30 s) against most of the tested bacteria.

Aged care staff and doctors frequently highlight consumers' role in antibiotic treatment decisions. However, few studies include consumers. This study aimed to investigate consumer perspectives on antibiotic use in residential aged care.

A search across 6 online databases yielded 3,373 studies, with 5 meeting inclusion criteria. Participant quotes, themes, statistical analyses, and authors' interpretive summaries in the included studies were inductively coded and refined to generate themes.

Three themes emerged: perception of benefits and risks of antibiotics, perceived role in antibiotic treatment decision-making, and information-communication needs. Consumers held positive attitudes toward antibiotics, did not associate antibiotics with the exclusive treatment of bacterial infections, and had limited awareness of potential risks, such as antibiotic resistance. Studies showed diverse perceptions regarding residents' and their families' involvement in antibiotic treatment decision-making with some residents actively seeking antibiotics and others trusting doctors to decide. Studies also described consumer need for effective provider-consumer communication and information sharing that was affected by contextual barriers such as motivation, preferences, available information resources, and provider attitudes.

Limited literature is available on consumer perspectives on antibiotic use in aged care. The review highlights that consumer needs are more complex than simply wanting an antibiotic. Antimicrobial stewardship programs should target consumer awareness, beliefs, and provider-consumer communication to enhance antibiotic use in aged care.

Predicting the length of stay in advance will not only benefit the hospitals both clinically and financially but enable healthcare providers to better decision-making for improved quality of care. More importantly, understanding the length of stay of severe patients who require general anesthesia is key to enhancing health outcomes.

Here, we aim to discover how machine learning can support resource allocation management and decision-making resulting from the length of stay prediction.

A retrospective cohort study was conducted from January 2018 to October 2020. A total cohort of 240,000 patients' medical records was collected. The data were collected exclusively for preoperative variables to accurately analyze the predictive factors impacting the postoperative length of stay. The main outcome of this study is an analysis of the length of stay (in days) after surgery until discharge. The prediction was performed with ridge regression, random forest, XGBoost, and multi-layer perceptron neural network models.

The XGBoost resulted in the best performance with an average error within 3 days. Moreover, we explain each feature's contribution over the XGBoost model and further display distinct predictors affecting the overall prediction outcome at the patient level. The risk factors that most importantly contributed to the stay after surgery were as follows: a direct bilirubin laboratory test, department change, calcium chloride medication, gender, and diagnosis with the removal of other organs. Our results suggest that healthcare providers take into account the risk factors such as the laboratory blood test, distributing patients, and the medication prescribed prior to the surgery.

We successfully predicted the length of stay after surgery and provide explainable models with supporting analyses. In summary, we demonstrate the interpretation with the XGBoost model presenting insights on preoperative features and defining higher risk predictors to the length of stay outcome. Our development in explainable models supports the current in-depth knowledge for the future length of stay prediction on electronic medical records that aids the decision-making and facilitation of the operation department.

The swift rise of antibiotic resistance, coupled with limited new antibiotic discovery, presents a significant hurdle to global public health, demanding innovative therapeutic solutions. Recently, collateral sensitivity (CS), the phenomenon in which resistance to one antibiotic increases vulnerability to another, has come to light as a potential path forward in this attempt. Targeting either unidirectional or reciprocal CS holds promise for constraining the emergence of drug resistance and notably enhancing treatment outcomes. Typically, the alteration of bacterial physiology, such as bacterial membrane potential, expression of efflux pumps, cell wall structures, and endogenous enzymatic actions, are involved in evolved collateral sensitivity. In this review, we present a thorough overview of CS in antibiotic therapy, including its definition, importance, and underlying mechanisms. We describe how CS can be exploited to prevent the emergence of resistance and enhance the results of treatment, but we also discuss the challenges and restrictions that come with implementing this practice. Our review underscores the importance of continued exploration of CS mechanisms in the broad spectrum and clinical validation of therapeutic approaches, offering insights into its role as a valuable tool in combating antibiotic resistance.

Extending a consistent pharmacy antimicrobial stewardship weekend service was a newly implemented initiative. We sought to evaluate the impact of incorporating an Infectious Diseases (ID)-trained clinical pharmacist into an antimicrobial stewardship program (AMS) during weekends.

The number of documented interventions was 451 on 362 patients compared to 115 interventions on 108 patients during the pre-implementation period (p = 0.04), with interventions primarily targeting Watch antibiotics, as classified by the WHO AWaRe classification. A reduction in the LOS was observed, with a median of 16 days (8-34) during the post-implementation period compared to 27.5 days (10-56) during the pre-implementation period (p = 0.001). The median DOT increased during the post-implementation period to 8 (6-11), versus the increase to 7 (4-11) during the pre-implementation period (p ≤ 0.001). Finally, there was no significant difference observed in healthcare-associated CDI and infection-related readmission.

This is a retrospective single-center, pre-post quasi-experimental study. Data including the documented pharmacist interventions were collected from the electronic medical record (EMR), the pre-implementation phase was in 2020, and post-implementation was in 2021. The primary outcome was to identify the number of AMS interventions through prospective audit and feedback review analysis. Secondary outcomes included antibiotic days of therapy (DOT), length of hospital stay (LOS), healthcare-associated Clostridioides difficile infection (CDI), and infection-related readmission.

The pharmacist-driven weekend AMS is an opportunity for pharmacists to intervene and optimize patients' care plans. This initiative demonstrated significant increased AMS-related interventions, promoted judicious antimicrobial use, and contributed to a reduced length of hospital stay. Our findings need to be replicated in a larger prospective study.

Methicillin-resistant Staphylococcus aureus (MRSA) colonization in neonatal intensive care units (NICUs) is a significant global health concern, leading to severe infections, extended hospital stays, and substantial economic burdens on health-care systems. To develop effective infection control strategies, we need to fill existing gaps in our understanding of MRSA epidemiology in neonates. The aim of this systematic review is to provide an extensive analysis of the proportion of MRSA colonizations in NICUs.

We used a comprehensive search strategy across databases such as Medline, Embase, Global Health, Web of Science, and Global Index Medicus, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles were independently reviewed and selected based on a variety of criteria, including the inclusion of neonates tested for MRSA colonization during NICU stay, and the reporting of community-acquired and hospital-acquired MRSA (CA-MRSA and HA-MRSA) incidence levels. Exclusion criteria included studies outside NICUs, those focused on specific MRSA outbreaks or clinical infections, review studies, and those lacking abstracts or full texts. Five authors independently extracted data, which was summarized and checked for quality. Statistical analysis included a random-effects model to compute pooled proportions, stratification by geographical location, evaluation of heterogeneity, and examination of publication bias.

Our systematic review evaluated 62 studies out of an initial 536 records identified. The majority of the selected studies were conducted in high-income countries, primarily in the United States. From these studies, we estimated a cumulative incidence rate of 7.2% for MRSA colonization in NICUs. When the source of MRSA was considered, CA-MRSA incidence was 2.7%, while HA-MRSA incidence was notably higher at 11%. A subgroup analysis showed geographical differences in the cumulative incidence of MRSA colonization in NICUs, with Brazil having the lowest incidence and Taiwan the highest. The proportion of HA-MRSA colonization also varied significantly by country, with South Korea reporting higher incidence rates than the United States. However, the differences in CA-MRSA colonization rates between countries and WHO regions were not statistically significant.

Our systematic review found a cumulative incidence of 7.2% for MRSA colonization in NICUs, with HA-MRSA (11%) being more prevalent than CA-MRSA (2.7%). Regional variations were detected, with Taiwan exhibiting the highest cumulative incidence and South Korea having both the highest CA-MRSA and HA-MRSA. These findings underline the substantial public health impact of MRSA, especially in NICUs, necessitating context-specific prevention and control strategies. Future research should strive to address these regional disparities and aspire to attain a more globally representative understanding of MRSA colonization rates.

Antimicrobial resistance is a global public health threat. Antimicrobial-resistant infections are on the rise and are associated with increased morbidity, mortality, and health care costs. Infants and children are affected by transmission of antimicrobial-resistant zoonotic pathogens through the food supply, direct contact with animals, environmental pathways, and contact with infected or colonized humans. Although the judicious use of antimicrobial agents is necessary for maintaining the health and welfare of humans and animals, it must be recognized that all use of antimicrobial agents exerts selective pressure that increases the risk of development of resistance. This report describes historical and recent use of antibiotics in animal agriculture, reviews the mechanisms of how such use contributes to development of resistance and can adversely affect child health, and discusses US initiatives to curb unnecessary use of antimicrobial agents in agriculture.

Antimicrobial resistance (AMR) is a global health challenge that threatens humans, animals and the environment. Evidence is emerging for a role of healthcare infrastructure, environments and patient pathways in promoting and maintaining AMR via direct and indirect mechanisms. Advances in vaccination and monoclonal antibody therapies together with integrated surveillance, rapid diagnostics, targeted antimicrobial therapy and infection control measures offer opportunities to address healthcare-associated AMR risks more effectively. Additionally, innovations in artificial intelligence, data linkage and intelligent systems can be used to better predict and reduce AMR and improve healthcare resilience. In this Review, we examine the mechanisms by which healthcare functions as a driver, reservoir and amplifier of AMR, contextualized within a One Health framework. We also explore the opportunities and innovative solutions that can be used to combat AMR throughout the patient journey. We provide a perspective on the current evidence for the effectiveness of interventions designed to mitigate healthcare-associated AMR and promote healthcare resilience within high-income and resource-limited settings, as well as the challenges associated with their implementation.

Antimicrobial resistance (AMR), frequently considered a major global public health threat, requires a comprehensive understanding of its emergence, mechanisms, advances, and implications. AMR's epidemiological landscape is characterized by its widespread prevalence and constantly evolving patterns, with multidrug-resistant organisms (MDROs) creating new challenges every day. The most common mechanisms underlying AMR (i.e., genetic mutations, horizontal gene transfer, and selective pressure) contribute to the emergence and dissemination of new resistant strains. Therefore, mitigation strategies (e.g., antibiotic stewardship programs-ASPs-and infection prevention and control strategies-IPCs) emphasize the importance of responsible antimicrobial use and surveillance. A One Health approach (i.e., the interconnectedness of human, animal, and environmental health) highlights the necessity for interdisciplinary collaboration and holistic strategies in combating AMR. Advancements in novel therapeutics (e.g., alternative antimicrobial agents and vaccines) offer promising avenues in addressing AMR challenges. Policy interventions at the international and national levels also promote ASPs aiming to regulate antimicrobial use. Despite all of the observed progress, AMR remains a pressing concern, demanding sustained efforts to address emerging threats and promote antimicrobial sustainability. Future research must prioritize innovative approaches and address the complex socioecological dynamics underlying AMR. This manuscript is a comprehensive resource for researchers, policymakers, and healthcare professionals seeking to navigate the complex AMR landscape and develop effective strategies for its mitigation.

To outline the procedural implementation and optimization of rapid diagnostic test (RDT) results for bloodstream infections (BSIs) and to evaluate the combination of RDTs with real-time antimicrobial stewardship team (AST) support plus clinical surveillance platform (CSP) software on time to appropriate therapy in BSIs at a single health system.

Blood culture reporting and communication were reported for four time periods: (i) a pre-BCID [BioFire® FilmArray® Blood Culture Identification (BCID) Panel] implementation period that consisted of literature review and blood culture notification procedure revision; (ii) a BCID implementation period that consisted of BCID implementation, real-time results notification via CSP, and creation of a treatment algorithm; (iii) a post-BCID implementation period; and (iv) a BCID2 implementation period. Time to appropriate therapy metrics was reported for the BCID2 time period.

The mean time from BCID2 result to administration of effective antibiotics was 1.2 h (range 0-7.9 h) and time to optimal therapy was 7.6 h (range 0-113.8 h) during the BCID2 Panel implementation period. When comparing time to optimal antibiotic administration among patients growing ceftriaxone-resistant Enterobacterales, the BCID2 Panel group (mean 2.8 h) was significantly faster than the post-BCID Panel group (17.7 h; P = 0.0041).

Challenges exist in communicating results to the appropriate personnel on the healthcare team who have the knowledge to act on these data and prescribe targeted therapy against the pathogen(s) identified. In this report, we outline the procedures for telephonic communication and CSP support that were implemented at our health system to distribute RDT data to individuals capable of assessing results, enabling timely optimization of antimicrobial therapy.

Antimicrobials, such as antibiotics or antivirals are medications employed to prevent and treat infectious diseases in humans, animals, and plants. Antimicrobial Resistance occurs when bacteria, viruses, and parasites no longer respond to these medicines. This resistance renders antibiotics and other antimicrobial drugs ineffective, making infections challenging or impossible to treat. This escalation in drug resistance heightens the risk of disease spread, severe illness, disability, and mortality. With datasets now containing hundreds or even thousands of pathogen genomes, machine learning techniques are on the rise for predicting antibiotic resistance in pathogens, prediction based on gene content and genome composition. Aim of this work is to combine and incorporate machine learning methods on bacterial genomic data to predict antimicrobial resistance, we will focus on the case of Klebsiella pneumoniae in order to support clinicians in selecting appropriate therapy.

The emergence of antibiotic resistance (AR) poses a significant threat to both public health and aquatic ecosystems. Wastewater treatment plants (WWTPs) have been identified as potential hotspots for disseminating AR in the environment. However, only a limited number of studies have been conducted on AR dissemination through WWTPs in Sri Lanka. To address this knowledge gap in AR dissemination through WWTP operations in Sri Lanka, we critically examined the global situation of WWTPs as hotspots for transmitting antibiotic-resistant bacteria (ARB) and antibiotic-resistant genes (ARGs) by evaluating more than a hundred peer-reviewed international publications and available national publications. Our findings discuss the current state of operating WWTPs in the country and highlight the research needed in controlling AR dissemination. The results revealed that the impact of different wastewater types, such as clinical, veterinary, domestic, and industrial, on the dissemination of AR has not been extensively studied in Sri Lanka; furthermore, the effectiveness of various wastewater treatment techniques in removing ARGs requires further investigation to improve the technologies. Furthermore, existing studies have not explored deeply enough the potential public health and ecological risks posed by AR dissemination through WWTPs.

The successful evolution of KPC-2 in bacteria has limited the clinical practice of carbapenems. This dilemma deteriorated the prognosis of associated infections and hence attracted increasing attention from researchers to explore alternative therapeutic options. Here, the enzyme inhibition assay was first performed to screen for a potent KPC-2 inhibitor. The synergistic effect of the candidate with carbapenems was further confirmed by checkboard minimum inhibitory concentration (MIC) assay, time-killing assay, disk diffusion method, and live/dead bacteria staining analysis. The mechanisms by which the candidate acts were subsequently explored through molecular dynamics (MD) simulations, etc. Our study found that Ginkgolic Acid (C13:0) (GA) exhibited effective KPC-2 inhibitory activity in both laboratory strain and clinical strain containing KPC-2. It could potentiate the killing effect of carbapenems on KPC-2-positive Klebsiella pnenmoniae (K. pnenmoniae). Further explorations revealed that GA could competitively bind to the active pocket of KPC-2 with meropenem (MEM) via residues Trp104, Gly235, and Leu166. The secondary structure and functional groups of KPC-2 were subsequently altered, which may be the main mechanism by which GA exerted its KPC-2 inhibitory effect. In addition, GA was also found to synergize with MEM to disrupt membrane integrity and increase membrane permeability, which may be another mechanism by which GA reinforced the bactericidal ability of carbapenems. Our study indicated that GA was a significant KPC-2 inhibitor that could prolong the lifespan of carbapenems and improve the prognosis of patients.

Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae are associated with most nosocomial infections worldwide. Although gaps remain in the knowledge of their susceptibility patterns, these are in antimicrobial stewardship. This study aimed to describe antimicrobial susceptibility profiles of the above organisms isolated from postmortem blood from stillbirths and under-five children enrolled in the Child Health and Mortality Prevention Surveillance (CHAMPS) program in Sierra Leone. This was a surveillance study of bacteria isolates from postmortem blood cultures taken within 24 h of death from stillbirths and children aged 0-59 months between March 2019 and February 2022. This was followed by identification and antibiotic sensitivity testing using Becton Dickinson Phoenix M50 (USA). Descriptive analysis was used to characterize the isolates and their antimicrobial susceptibility patterns. Of 367 isolates, K. pneumoniae was the most frequently isolated organism (n = 152; 41.4%), followed by E. coli (n = 40; 10.9%) and E. cloacae (n = 35; 9.5%). Using BACTEC™ FX 40 (Franklin Lakes, NJ, USA), 367 isolates were identified from blood using bacteriological methods. Extended spectrum beta-lactamase (ESBL) was observed in 143 (94.1%) of K. pneumoniae isolates and 27 (65.5%) of E. coli isolates. Carbapenem-resistant organisms (CRO) were seen in 31 (20.4%) of K. pneumoniae and 5 (12.5%) of E. coli isolates. A multidrug resistance (MDR) pattern was most prevalent in E.cloacae (33/35; 94.3%), followed by K. pneumoniae (138/152; 90.8%). Our study showed a high prevalence of multidrug resistance among bacterial isolates in the catchment areas under surveillance by the CHAMPS sites in Sierra Leone.

Pseudomonas aeruginosa is one of the most common nosocomial pathogens and part of the top emergent species associated with antimicrobial resistance that has become one of the greatest threat to public health in the twenty-first century. This bacterium is provided with a wide set of virulence factors that contribute to pathogenesis in acute and chronic infections. This review aims to summarize the impact of multidrug resistance on the virulence and fitness of P. aeruginosa. Although it is generally assumed that acquisition of resistant determinants is associated with a fitness cost, several studies support that resistance mutations may not be associated with a decrease in virulence and/or that certain compensatory mutations may allow multidrug resistance strains to recover their initial fitness. We discuss the interplay between resistance profiles and virulence from a microbiological perspective but also the clinical consequences in outcomes and the economic impact.