In Vitro Synergistic Effect of Colistin with Fosfomycin Against Carbapenem-Resistant Klebsiella pneumoniae.

BACKGROUND: The dwindling antibiotic reserve owing to augmented drug-resistant bacteria is a major handicap for treating physicians. Klebsiella pneumoniae, a gram-negative encapsulated member of the Enterobacteriaceae family, is one such pathogenic bacteria. Carbapenemase-producing Klebsiella pneumoniae is globally recognized as one of the most critical bacterial threats to public health due to its extremely limited treatment options. Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections pose therapeutic challenges due to simultaneous resistance to various other groups of antibiotics. In this study, we have evaluated the synergistic effect of fosfomycinagainst CRKP isolates when used in combination with colistin by applying the Checkerboard method. METHODS: A laboratory-based prospective study was conducted in the Department of Microbiology, JSS Hospital, Mysuru, for a period of one year after obtaining ethical clearance. Klebsiella pneumoniae isolates obtained from clinical samples were screened for carbapenem resistance by the VITEK-2 compact system (bioMérieux, Marcy-l'Étoile, France). The minimum inhibitory concentration (MIC) of colistin and fosfomycin was individually ascertained by broth microdilution (BMD). Finally, the synergistic activity of the fosfomycin-colistin combination was determined by the BMD-based Checkerboard method. RESULTS: Among the 50 CRKP isolates, 36 (72%) isolates showed synergism, eight (16%) isolates showed indifference and six (12%) isolates showed partial synergism, while none of them showed additivity and antagonism by the Checkerboard method. These results are found to be statistically significant (chi-square value of 116.204 and p-value of < 0.00001). CONCLUSION: This study showed a promising in-vitro synergy between the drugs fosfomycin and colistin by Checkerboard BMD testing protocol. Colistin being a reserve antibiotic, monotherapy comes with the limitations of higher chances of resistance as well as toxicity, which can be overcome by combination therapy, thereby decreasing CRKP-associated mortality rates and delivering holistic patient benefit.

Colonisation with multidrug-resistant organisms among dialysis patients at Universitas Academic Hospital.

Background: While most infections with multidrug-resistant organisms (MDROs) affect colonised people, there is limited evidence on MDRO colonisation in South African dialysis patients. Objectives: This study evaluated the prevalence of MDRO colonisation among dialysis patients, the resistance patterns of each MDRO and the risk factors for colonisation. Method: Rectal and nasal swabs were collected from dialysis patients who consented to participate in a 5-month study to identify selected MDROs (April 2021 - August 2021). Specimens were cultured on selected chromogenic media. Data collected included demographics, clinical information from medical records and laboratory results. Results: Multidrug-resistant organisms were isolated from 17 (23.9%) of the 71 enrolled participants. Of the 23 MDRO strains from rectal swabs (n = 71), extended-spectrum beta-lactamase-producing Enterobacterales accounted for 21.1% (15/71), vancomycin-resistant enterococci 2.8% (n = 2/71) and carbapenem-resistant Enterobacterales 4.2% (n = 3/71). Klebsiella pneumoniae (65.2%, n = 15/23) was the most prevalent MDRO. More than 80% resistance to trimethoprim and sulfamethoxazole, cefotaxine, and ciprofloxacin was noted. Significant risk factors included previous hospitalisation, proton pump inhibitor use and antibiotic exposure in the past 6 months. Conclusion: Multidrug-resistant organisms' carriage was high in our dialysis population. The infection prevention and control measures need to be revised and strengthened. Contribution: This study falls within the scope of the SAJID journal as it is the first within sub-Sahara Africa to report that approximately one-fifth of dialysis patients were colonised with MDRO, which is a significant risk for MDRO infections.

Antimicrobial resistance: use of phage therapy in the management of resistant infections.

The emergence and increase in antimicrobial resistance (AMR) is now widely recognized as a major public health challenge. Traditional antimicrobial drugs are becoming increasingly ineffective, while the development of new antibiotics is waning. As a result, alternative treatments for infections are garnering increased interest. Among these alternatives, bacteriophages, also known as phages, are gaining renewed attention and are reported to offer a promising solution to alleviate the burden of bacterial infections. This review discusses the current successes of phage therapy (PT) against multidrug-resistant organisms (MDROs), such as Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, and Enterobacter spp. The review also compares the efficacy of PT with that of chemical antibiotics, reporting on its benefits and limitations, while highlighting its impact on the human gut microbiome and immune system. Despite its potential, phage therapy is reported to face challenges such as the narrow antibacterial range, the complexity of developing phage cocktails, and the need for precise dosing and duration protocols. Nevertheless, continued research, improved regulatory frameworks, and increased public awareness are essential to realize its full potential and integration into standard medical practice, paving the way for innovative treatments that can effectively manage infections in an era of rising antimicrobial resistance.

Towards evidence-based empiric antibiotic recommendations for spontaneous infections in patients with cirrhosis.

BACKGROUND: With the emergence of multidrug-resistant infections, healthcare professionals must evaluate the effectiveness of empiric antibiotic treatments. AIMS: To assess the antibiotic susceptibility patterns of microorganisms causing spontaneous infections in patients with cirrhosis and to evaluate the suitability of empiric antibiotic treatments based on major clinical guidelines. METHODS: This cross-sectional study utilized two datasets from prospective studies of patients with cirrhosis and culture-positive spontaneous bacterial infections in Argentina and Uruguay. We estimated susceptibility to commonly used antibiotics and assessed coverage following European and American recommendations. RESULTS: We analyzed 238 episodes of culture-positive spontaneous infections in 229 patients. When implementing the recommendations for empiric treatment of community-acquired spontaneous infections, ceftazidime would result in 39 % coverage, whereas ceftriaxone would reach 70 %. Cefepime, which is not included in the recommendations, would have provided coverage of 74 %. Using ertapenem for nosocomial infections would have only covered 56 % of these episodes, whereas meropenem or imipenem reached 73 % coverage. Only the combination of meropenem or imipenem plus vancomycin would achieve a coverage surpassing 85 % in healthcare-associated or nosocomial spontaneous bacterial infections. CONCLUSIONS: Our study uncovers inadequate coverage in specific clinical scenarios when adhering to recommendations, underscoring the necessity of guidelines based on local epidemiological data.

Development and validation of machine learning models to predict MDRO colonization or infection on ICU admission by using electronic health record data.

BACKGROUND: Multidrug-resistant organisms (MDRO) pose a significant threat to public health. Intensive Care Units (ICU), characterized by the extensive use of antimicrobial agents and a high prevalence of bacterial resistance, are hotspots for MDRO proliferation. Timely identification of patients at high risk for MDRO can aid in curbing transmission, enhancing patient outcomes, and maintaining the cleanliness of the ICU environment. This study focused on developing a machine learning (ML) model to identify patients at risk of MDRO during the initial phase of their ICU stay. METHODS: Utilizing patient data from the First Medical Center of the People's Liberation Army General Hospital (PLAGH-ICU) and the Medical Information Mart for Intensive Care (MIMIC-IV), the study analyzed variables within 24 h of ICU admission. Machine learning algorithms were applied to these datasets, emphasizing the early detection of MDRO colonization or infection. Model efficacy was evaluated by the area under the receiver operating characteristics curve (AUROC), alongside internal and external validation sets. RESULTS: The study evaluated 3,536 patients in PLAGH-ICU and 34,923 in MIMIC-IV, revealing MDRO prevalence of 11.96% and 8.81%, respectively. Significant differences in ICU and hospital stays, along with mortality rates, were observed between MDRO positive and negative patients. In the temporal validation, the PLAGH-ICU model achieved an AUROC of 0.786 [0.748, 0.825], while the MIMIC-IV model reached 0.744 [0.723, 0.766]. External validation demonstrated reduced model performance across different datasets. Key predictors included biochemical markers and the duration of pre-ICU hospital stay. CONCLUSIONS: The ML models developed in this study demonstrated their capability in early identification of MDRO risks in ICU patients. Continuous refinement and validation in varied clinical contexts remain essential for future applications.

Optimizing Treatment for Carbapenem-Resistant Acinetobacter baumannii Complex Infections: A Review of Current Evidence.

Carbapenem-resistant Acinetobacter baumannii complex (CRAB) poses a significant global health challenge owing to its resistance to multiple antibiotics and limited treatment options. Polymyxin-based therapies have been widely used to treat CRAB infections; however, they are associated with high mortality rates and common adverse events such as nephrotoxicity. Recent developments include numerous observational studies and randomized clinical trials investigating antibiotic combinations, repurposing existing antibiotics, and the development of novel agents. Consequently, recommendations for treating CRAB are undergoing significant changes. The importance of colistin is decreasing, and the role of sulbactam, which exhibits direct antibacterial activity against A. baumannii complex, is being reassessed. High-dose ampicillin-sulbactam-based combination therapies, as well as combinations of sulbactam and durlobactam, which prevent the hydrolysis of sulbactam and binds to penicillin-binding protein 2, have shown promising results. This review introduces recent advancements in CRAB infection treatment based on clinical trial data, highlighting the need for optimized treatment protocols and comprehensive clinical trials to combat the evolving threat of CRAB effectively.

Monitoring and Outcomes of Central Line-Associated Bloodstream Infections in a Tertiary Care Intensive Care Unit.

Background Central line-associated bloodstream infections (CLABSIs) are significant healthcare-associated infections that increase morbidity, mortality, and healthcare costs. This study aims to analyze the frequency, microbiology, risk factors, and outcomes of CLABSI in an adult intensive care unit. Methods We conducted a hospital-based, prospective surveillance study in the critical care unit of a tertiary care hospital. We included patients with a central line (CL) from admission until discharge or line removal. Data collection focused on patient demographics, comorbidities, CL insertion site, and CLABSI rates. The incidence of CLABSI was calculated per 1,000 CL-days, and statistical analysis was performed using the Chi-square test. Results Of the 169 patients enrolled, 123 episodes of bloodstream infections were recorded, 56 (45.5%) of which were CLABSIs. The organisms most frequently isolated were Klebsiella pneumoniae (n = 14; 24.6%), Enterobacter cloacae complex (n = 11; 19.3%), Klebsiella species (n = 7; 12.28%), and Acinetobacter baumannii (n = 7; 12.28%). The overall CLABSI rate was 24.70 per 1,000 CL-days. No significant association was found between CLABSI and patient age, gender, or the site of CL insertion. However, a significant relationship was observed between CLABSI and the presence of comorbid conditions (p = 0.001). The study also noted a high rate of antibiotic resistance among the isolated pathogens. Conclusions Our results emphasize the need for stringent infection control measures and suggest that comorbid conditions significantly increase the risk of CLABSI. Addressing antibiotic resistance and implementing effective prevention strategies are essential for reducing the burden of CLABSIs.

Impact of multidrug resistance on outcomes in hematologic cancer patients with bacterial bloodstream infections.

Despite the improved outcomes in patients with hematological malignancies, infections caused by multidrug-resistant organisms (MDROs) pose a new threat to these patients. We retrospectively reviewed the patients with hematological cancer and bacterial bloodstream infections (BSIs) at a tertiary hospital between 2003 and 2022 to assess the impact of MDROs on outcomes. Among 328 BSIs, 81 (24.7%) were caused by MDROs. MDRO rates increased from 10.3% (2003-2007) to 39.7% (2018-2022) (P < 0.001). The 30-day mortality rate was 25.0%, which was significantly higher in MDRO-infected patients than in non-MDRO-infected patients (48.1 vs. 17.4%; P < 0.001). The observed trend was more pronounced in patients with newly diagnosed diseases and relapsed/refractory disease but less prominent in patients in complete remission. Among MDROs, carbapenem-resistant Gram-negative bacteria exhibited the highest mortality, followed by vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and extended-spectrum ß-lactamase-producing Enterobacteriaceae. Multivariate analysis identified independent risk factors for 30-day mortality as age ≥ 65 years, newly diagnosed disease, relapsed/refractory disease, MDROs, polymicrobial infection, CRP ≥ 20 mg/L, and inappropriate initial antibiotic therapy. In conclusion, MDROs contribute to adverse outcomes in patients with hematological cancer and bacterial BSIs, with effects varying based on the underlying disease status and causative pathogens. Appropriate initial antibiotic therapy may improve patient outcomes.

Pharmacotherapies for multidrug-resistant gram-positive infections: current options and beyond.

INTRODUCTION: Infections due to multidrug-resistant organisms (MDRO) are a serious concern for public health with high morbidity and mortality. Though many antibiotics have been introduced to manage these infections, there are remaining concerns regarding the optimal management of Gram-positive MDROs. AREAS COVERED: A literature search on the PubMed/Medline database was conducted. We applied no language and time limits for the search strategy. In this narrative review, we discuss the current options for managing Gram-positive MDROs as well as non-traditional antibacterial agents in development. EXPERT OPINION: Despite their introduction more than 70 years ago, glycopeptides are still the cornerstone in treating Gram-positive infections: all registrative studies of new antibiotics have glycopeptides as control; these studies are designed as not inferior studies, therefore it is almost impossible to give recommendations other than the use of glycopeptides in the treatment of Gram-positive infections. The best evidence on treatments different from glycopeptides comes from post-hoc analysis and meta-analysis. Non-traditional antibacterial agents are being studied to aid in short and effective antibiotic therapies. The use of non-traditional antibacterial agents is not restricted to replacing traditional antibacterial agents with alternative therapies; instead, they should be used in combination with antibiotic therapies.

Effect of single-patient room design on the incidence of nosocomial infection in the intensive care unit: a systematic review and meta-analysis.

Background: Previous studies have yielded varying conclusions regarding the impact of single-patient room design on nosocomial infection in the intensive care unit (ICU). We aimed to examine the impact of ICU single-patient room design on infection control. Methods: We conducted a comprehensive search of PubMed, Embase, the Cochrane Library, Web of Science, CNKI, WanFang Data, and CBM databases from inception to October 2023, without language restrictions. We included observational cohort and quasi-experimental studies assessing the effect of single- versus multi-patient rooms on infection control in the ICU. Outcomes measured included the nosocomial infection rate, incidence density of nosocomial infection, nosocomial colonization and infection rate, acquisition rate of multidrug-resistant organisms (MDROs), and nosocomial bacteremia rate. The choice of effect model was determined by heterogeneity. Results: Our final analysis incorporated 12 studies involving 12,719 patients. Compared with multi-patient rooms in the ICU, single-patient rooms demonstrated a significant benefit in reducing the nosocomial infection rate (odds ratio [OR]: 0.68; 95% confidence interval [CI]: 0.59, 0.79; p < 0.00001). Analysis based on nosocomial infection incidence density revealed a statistically significant reduction in single-patient rooms (OR: 0.64; 95% CI: 0.44, 0.92; p = 0.02). Single-patient rooms were associated with a marked decrease in nosocomial colonization and infection rate (OR: 0.44; 95% CI: 0.32, 0.62; p < 0.00001). Furthermore, patients in single-patient rooms experienced lower nosocomial bacteremia rate (OR: 0.73; 95% CI: 0.59, 0.89; p = 0.002) and lower acquisition rate of MDROs (OR: 0.41; 95% CI: 0.23, 0.73; p = 0.002) than those in multi-patient rooms. Conclusion: Implementation of single-patient rooms represents an effective strategy for reducing nosocomial infections in the ICU. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/).

Controlling the hospital aquatic reservoir of multidrug-resistant organisms: a cross-sectional study followed by a nested randomized trial of sink decontamination.

OBJECTIVES: The hospital water environment is an important reservoir of multidrug-resistant organisms (MDROs) and presents a risk for patient safety. We assessed the effectiveness of thermal and chemical interventions on sinks contaminated with MDRO in the hospital setting. METHODS: We conducted a cross-sectional assessment of MDRO contamination of sinks and toilets in 26 clinical wards of a tertiary care hospital. MDRO-contaminated sink traps were then replaced and randomized (1:1:1) to receive chemical (sodium hypochlorite), thermal disinfection (steam), or no intervention. Interventions were repeated weekly for 4 weeks. Sinks were resampled 7 days after the last intervention. The primary outcome was the proportion of decontaminated sinks. MDROs of interest were extended spectrum beta-lactamase (ESBL) producing and carbapenemase-producing Enterobacterales, and non-fermentative Gram-negative bacilli. RESULTS: In the cross-sectional assessment, at least one MDRO was identified in 258 (36%) of the 748 samples and in 91 (47%) of the 192 water sources. In total, 57 (42%) of the 137 sinks and 34 (62%) of the 55 toilets were contaminated with 137 different MDROs. The most common MDRO were ESBL Enterobacterales (69%, 95/137), followed by Verona Integron-Borne Metallo-ß-Lactamase (VIM) carbapenemase producing Pseudomonas aeruginosa (9%, 12/137) and Citrobacter spp. (6%, 5/137). In the nested randomized trial, five of the 16 sinks (31%) in the chemical disinfection group were decontaminated, compared with 8 of 18 (44%) in the control group (OR 0.58; 95% CI, 0.14-2.32) and 9 of 17 (53%) in the thermal disinfection group (OR 1.40; 95% CI, 0.37-5.32). DISCUSSION: Our study failed to demonstrate an added benefit of repeated chemical or thermal disinfection, beyond changing sink traps, in the MDRO decontamination of sinks. Routine chlorine-based disinfection of sinks may need to be reconsidered.

Global antimicrobial resistance and antibiotic use in COVID-19 patients within health facilities: A systematic review and meta-analysis of aggregated participant data.

OBJECTIVES: The COVID-19 pandemic has posed a significant threat to the global healthcare system, presenting a major challenge to antimicrobial stewardship worldwide. This study aimed to provide a comprehensive and up-to-date picture of global antimicrobial resistance (AMR) and antibiotic use in COVID-19 patients. METHODS: We conducted a systematic review to determine the prevalence of AMR and antibiotic usage among COVID-19 patients receiving treatment in healthcare facilities. Our search encompassed the PubMed, Web of Science, Embase, and Scopus databases, spanning studies published from December 2019 to May 2023. We utilized random-effects meta-analysis to assess the prevalence of multidrug-resistant organisms (MDROs) and antibiotic use in COVID-19 patients, aligning with both the WHO's priority list of MDROs and the AWaRe list of antibiotic products. Estimates were stratified by region, country, and country income. Meta-regression models were established to identify predictors of MDRO prevalence and antibiotic use in COVID-19 patients. The study protocol was registered with PROSPERO (CRD 42023449396). RESULTS: Among the 11,050 studies screened, 173 were included in the review, encompassing a total of 892,312 COVID-19 patients. MDROs were observed in 42.9% (95% CI 31.1-54.5%, I2 = 99.90%) of COVID-19 patients: 41.0% (95% CI 35.5-46.6%) for carbapenem-resistant organisms (CRO), 19.9% (95% CI 13.4-27.2%) for methicillin-resistant Staphylococcus aureus (MRSA), 24.9% (95% CI 16.7-34.1%) for extended-spectrum beta-lactamase-producing organisms (ESBL), and 22.9% (95% CI 13.0-34.5%) for vancomycin-resistant Enterococcus species (VRE), respectively. Overall, 76.2% (95% CI 69.5-82.9%, I2 = 99.99%) of COVID-19 patients were treated with antibiotics: 29.6% (95% CI 26.0-33.4%) with "Watch" antibiotics, 22.4% (95% CI 18.0-26.7%) with "Reserve" antibiotics, and 16.5% (95% CI 13.3-19.7%) with "Access" antibiotics. The MDRO prevalence and antibiotic use were significantly higher in low- and middle-income countries than in high-income countries, with the lowest proportion of antibiotic use (60.1% (95% CI 52.1-68.0%)) and MDRO prevalence (29.1% (95% CI 21.8-36.4%)) in North America, the highest MDRO prevalence in the Middle East and North Africa (63.9% (95% CI 46.6-81.2%)), and the highest proportion of antibiotic use in South Asia (92.7% (95% CI 90.4-95.0%)). The meta-regression identified antibiotic use and ICU admission as a significant predictor of higher prevalence of MDROs in COVID-19 patients. CONCLUSIONS: This systematic review offers a comprehensive and current assessment of MDRO prevalence and antibiotic use among COVID-19 patients in healthcare facilities. It underscores the formidable challenge facing global efforts to prevent and control AMR amidst the backdrop of the COVID-19 pandemic. These findings serve as a crucial warning to policymakers, highlighting the urgent need to enhance antimicrobial stewardship strategies to mitigate the risks associated with future pandemics.

Multidrug-Resistant Organisms: The Silent Plight of Burn Patients.

The global increasing spread of multidrug-resistant organisms (MDROs) is threatening the control of various infections in vulnerable populations and patient groups. One of the most affected groups is patients with burns, who are prone to hyperinfection as they suffer from a hypermetabolic state and weaken immune barriers. Those patients also share the infection risk of patients hospitalized for a long time, including ventilator-associated pneumonia and urinary tract infections. While some preventative and therapeutic management styles are still controversial, we discuss consensuses here. In this review, we aim to present the current knowledge on multidrug resistance with a special focus on patients with burns, discuss various causative organisms and their treatment options, and highlight the importance of antibiotic stewardship and teamwork in responding to an outbreak of MDROs.

Molecular characterization of Staphylococcus aureus isolated from hospital-acquired infections in Ilam, Iran.

OBJECTIVE: This research study was undertaken to investigate antimicrobial resistance patterns and the prevalence of hospital-acquired infections (HAIs). The study focuses on common microorganisms responsible for HAIs and explores emerging challenges posed by antimicrobial drug-resistant isolates. METHODS: A comprehensive analysis of 123 patients with HAIs, hospitalized in surgical department and intensive care unit (ICU) at Imam Khomeini Hospital, Ilam, Iran, was conducted over a six-month period. Pathogenic bacterial isolates, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA), were isolated and subjected to antibiotic susceptibility testing. RESULTS: The study findings revealed a significant prevalence of multidrug-resistant (MDR) isolates, of which 73.3% were MRSA. Notably, 6.7% of S. aureus isolates exhibited resistance to vancomycin, indicating the emergence of VRSA. Respiratory infections were identified as the most prevalent HAI, constituting 34.67% of cases, often arising from extended ICU stays and invasive surgical procedures. Furthermore, patients aged 60 and above, particularly those associated with MDR, exhibited higher vulnerability to HAI. CONCLUSIONS: This research sheds light on the intricate interplay between drug resistance and HAI, highlighting the imperative role of rational antibiotic use and infection control in addressing this critical healthcare challenge.

Fecal Carriage of Multidrug-Resistant Organisms Increases the Risk of Hepatic Encephalopathy in Cirrhotic Patients: Insights from Gut Microbiota and Metabolite Features.

Background: Impact of fecal colonization by multidrug-resistant organisms (MDROs) on changes in gut microbiota and associated metabolites, as well as its role in cirrhosis-associated outcomes, has not been thoroughly investigated. Methods: Eighty-eight cirrhotic patients and 22 healthy volunteers were prospectively enrolled with analysis conducted on plasma metabolites, fecal MDROs, and microbiota. Patients were followed for a minimum of one year. Predictive factors for cirrhosis-associated outcomes were identified using Cox proportional hazards regression models, and risk factors for fecal MDRO carriage were assessed using logistic regression model. Correlations between microbiota and metabolic profiles were evaluated through Spearman's rank test. Results: Twenty-nine (33%) cirrhotic patients exhibited MDRO carriage, with a notably higher rate of hepatic encephalopathy (HE) in MDRO carriers (20.7% vs. 3.2%, p = 0.008). Cox regression analysis identified higher serum lipopolysaccharide levels and fecal MDRO carriage as predictors for HE development. Logistic regression analysis showed that MDRO carriage is an independent risk factor for developing HE. Microbiota analysis showed a significant dissimilarity of fecal microbiota between cirrhotic patients with and without MDRO carriage (p = 0.033). Thirty-two metabolites exhibiting significantly different expression levels among healthy controls, cirrhotic patients with and without MDRO carriage were identified. Six of the metabolites showed correlation with specific bacterial taxa expression in MDRO carriers, with isoaustin showing significantly higher levels in MDRO carriers experiencing HE compared to those who did not. Conclusion: Fecal MDRO carriage is associated with altered gut microbiota, metabolite modulation, and an elevated risk of HE occurrence within a year.

Clinical features and risk factors for pyogenic liver abscess caused by multidrug-resistant organisms: A retrospective study.

The incidence rate of pyogenic liver abscess caused by multidrug-resistant bacteria has increased in recent years. This study aimed to identify the clinical characteristics and risk factors for pyogenic liver abscess caused by multidrug-resistant bacteria. We conducted a retrospective analysis of the clinical features, laboratory test results, and causes of pyogenic liver abscesses in 239 patients admitted to a tertiary hospital. Multivariable logistic regression was used to identify risk factors for multidrug resistance. Among patients with pyogenic liver abscesses, the rate of infection caused by multidrug-resistant organisms was observed to be 23.0% (55/239), with a polymicrobial infection rate of 14.6% (35/239). Additionally, 71 cases (29.7%) were associated with biliary tract disease. Patients with pyogenic liver abscesses caused by multidrug-resistant organisms had a significantly higher likelihood of polymicrobial infection and increased mortality (7/44 [15.9%] vs. 3/131 [2.3%]; p = .003). The Charlson Comorbidity Index (adjusted odds ratio [aOR]: 1.32, 95% confidence interval [CI]: 1.06-1.68), hospitalization (aOR: 10.34, 95% CI: 1.86-60.3) or an invasive procedure (aOR: 9.62; 95% CI: 1.66-71.7) within the past 6 months, and gas in the liver on imaging (aOR: 26.0; 95% CI: 3.29-261.3) were independent risk factors for pyogenic liver abscess caused by multidrug-resistant bacteria. A nomogram was constructed based on the risk factors identified. The nomogram showed high diagnostic accuracy (specificity, 0.878; sensitivity 0.940). Multidrug-resistant organisms causing pyogenic liver abscesses have specific characteristics. Early identification of patients at high risk of infection with multidrug-resistant organisms could help improve their management and enable personalized treatment.

Multidrug-resistant pathogens and ventilator-associated pneumonia in critically ill COVID-19 and non-COVID-19 patients: a prospective observational monocentric comparative study.

BACKGROUND: The COVID-19 pandemic has increased the incidence of ventilator-associated pneumonia (VAP) among critically ill patients. However, a comparison of VAP incidence in COVID-19 and non-COVID-19 cohorts, particularly in a context with a high prevalence of multidrug-resistant (MDR) organisms, is lacking. MATERIAL AND METHODS: We conducted a single-center, mixed prospective and retrospective cohort study comparing COVID-19 patients admitted to the intensive care unit (ICU) of the "Città della Salute e della Scienza" University Hospital in Turin, Italy, between March 2020 and December 2021 (COVID-19 group), with a historical cohort of ICU patients admitted between June 2016 and March 2018 (NON-COVID-19 group). The primary objective was to define the incidence of VAP in both cohorts. Secondary objectives were to evaluate the microbial cause, resistance patters, risk factors and impact on 28 days, ICU and in-hospital mortality, duration of ICU stay, and duration of hospitalization). RESULTS: We found a significantly higher incidence of VAP (51.9% - n = 125) among the 241 COVID-19 patients compared to that observed (31.2% - n = 78) among the 252 NON-COVID-19 patients. The median SOFA score was significantly lower in the COVID-19 group (9, Interquartile range, IQR: 7-11 vs. 10, IQR: 8-13, p < 0.001). The COVID-19 group had a higher prevalence of Gram-positive bacteria-related VAP (30% vs. 9%, p < 0.001), but no significant difference was observed in the prevalence of difficult-to-treat (DTR) or MDR bacteria. ICU and in-hospital mortality in the COVID-19 and NON-COVID-19 groups were 71% and 74%, vs. 33% and 43%, respectively. The presence of COVID-19 was significantly associated with an increased risk of 28-day all-cause hospital mortality (Hazard ratio, HR: 7.95, 95% Confidence Intervals, 95% CI: 3.10-20.36, p < 0.001). Tracheostomy and a shorter duration of mechanical ventilation were protective against 28-day mortality, while dialysis and a high SOFA score were associated with a higher risk of 28-day mortality. CONCLUSION: COVID-19 patients with VAP appear to have a significantly higher ICU and in-hospital mortality risk regardless of the presence of MDR and DTR pathogens. Tracheostomy and a shorter duration of mechanical ventilation appear to be associated with better outcomes.

Novel preventive bundle for multidrug-resistant organisms in intensive care setting; tertiary care experience.

Background: A widely-accepted standardized preventive bundle targeting multidrug-resistant organisms (MDROs) is lacking. The objective was to describe the components, implementation, compliance, and impact of a novel MDROs bundle in intensive care units (ICUs). Methods: Cohort study of surveillance activities on the components of MDROs bundle (July 2019 to June 2022) and the incidence of MDROs (April 2016 to June 2022). The implementation of MDROs bundle were preceded by ICPs-led education of the staff working in target ICUs about the importance and components of the MDROs bundle. These included the overall use of antimicrobials, appropriate environmental cleaning, appropriate contact precautions, and hand hygiene compliance. Results: During implementation, the overall use of antimicrobials was 57.8 days of therapy per 100 patient-days (44,492/76,933). It was higher in adult compared with pediatric/neonatal ICUs (p < 0.001). Appropriate environmental cleaning was 74.8% (12,409/16,582), appropriate contact precautions was 83.8% (10,467/12,497), and hand hygiene compliance was 86.9% (27,023/31,096). The three components were significantly higher in pediatric/neonatal compared with adult ICUs (p = 0.027, p < 0.001, p = 0.006, respectively). The MDROs rates per 10,000 patient-days were 71.8 before (April 2016 to June 2019) and 62.0 during (July 2019 to June 2022) the bundle implementation (858/119,565 versus 891/143,649 p = 0.002). The reduction in MDROs rates were replicated in adult (p = 0.001) but not pediatric/neonatal ICUs (p = 0.530). Conclusions: The finding of this study indicate that the implementation of the current bundle was associated with a modest decrease in MDROs rates in adult ICUs. The provided detailed definitions and methodology will facilitate its use by other healthcare facilities.

Antibacterial activity of ibezapolstat against antimicrobial-resistant clinical strains of Clostridioides difficile.

Antimicrobial resistance is emerging in clinical strains of Clostridioides difficile. Ibezapolstat (IBZ) is a DNA polymerase IIIC inhibitor that has completed phase II clinical trials. IBZ has potent in vitro activity against wild-type, susceptible strains but its effect on C. difficile strains with reduced susceptibility to metronidazole (MTZ), vancomycin (VAN), or fidaxomicin (FDX) has not been tested. The primary objective of this study was to test the antibacterial properties of IBZ against multidrug-resistant C. difficile strains. The in vitro activity, bactericidal, and time-kill activity of IBZ versus comparators were evaluated against 100 clinical strains of which 59 had reduced susceptibility to other C. difficile antibiotics. Morphologic changes against a multidrug resistance strain were visualized by light and scanning electron microscopy. The overall IBZ MIC50/90 values (µg/mL) for evaluated C. difficile strains were 4/8, compared with 2/4 for VAN, 0.5/1 for FDX, and 0.25/4 for MTZ. IBZ MIC50/90 values did not differ based on non-susceptibility to antibiotic class or number of classes to which strains were non-susceptible. IBZ bactericidal activity was similar to the minimum inhibitory concentration (MIC) and maintained in wild-type and non-susceptible strains. Time-kill assays against two laboratory wild-type and two clinical non-susceptible strains demonstrated sustained IBZ activity despite reduced killing by comparator antibiotics for IBZ and VAN non-susceptible strains. Microscopy visualized increased cell lengthening and cellular damage in multidrug-resistant strains exposed to IBZ sub-MIC concentrations. This study demonstrated the potent antibacterial activity of IBZ against a large collection of C. difficile strains including multidrug-resistant strains. This study highlights the therapeutic potential of IBZ against multidrug-resistant strains of C. difficile.

Discontinuation of Contact Precautions for Methicillin-resistant Staphylococcus aureus in a Pediatric Healthcare System.

BACKGROUND: Many hospitals caring for adult patients have discontinued the requirement for contact precautions (CP) for patients with methicillin-resistant Staphylococcus aureus (MRSA) infection or colonization without reported negative effects. It is not clear whether this experience can be extrapolated to pediatric facilities. METHODS: CP for MRSA were discontinued in all locations except the neonatal intensive care unit at a 3-hospital pediatric healthcare system in September 2019. All hospitalized patients underwent surveillance for LabID healthcare facility-onset MRSA infections. Analysis was done using interrupted time series (ITS) from September 2017 through August 2023 and aggregate before-and-after rate ratios. RESULTS: There were 234 incident healthcare facility-onset MRSA infections during 766 020 patient days of surveillance. After discontinuation of CP for MRSA there was no change in the ITS slope (0.06, 95% CI: -0.35 to 0.47, P = .78) or intercept (0.21, 95% CI: -0.36 to 0.78, P = .47) of the LabID healthcare facility-onset MRSA infection incidence density rate. Additionally, there was no change in the aggregate incidence density rate of these MRSA LabID events (aggregate rate ratio = 0.98, 95% CI: 0.74 to 1.28). MRSA nasal colonization among patients being screened before cardiac surgery did not change (aggregate rate ratio = 0.94, 95% CI: 0.60 to 1.48). The prevalence rate of contact isolation days decreased by 14.0%. CONCLUSIONS: Discontinuation of CP for pediatric patients with MRSA was not associated with increased MRSA infection over 4 years. Our experience supports considering discontinuation of CP for MRSA in similar pediatric healthcare settings in the context of good adherence to horizontal infection prevention measures.