Explore the vast range of titles available.

Background Colistin-carbapenem combination therapy is frequently used for carbapenem-resistant Gram-negative infections, but its impact on subsequent acquisition of carbapenem-resistant Enterobacterales (CRE) requires further investigation. We evaluated the incidence of CRE acquisition and performed molecular characterization of recovered isolates following treatment with colistin–meropenem versus colistin monotherapy. Methods This analysis addressed a pre-specified secondary aim of the AIDA multicenter randomized controlled trial, which compared colistin monotherapy to colistin–meropenem combination therapy for carbapenem-resistant Gram-negative infections at six hospitals in Israel, Greece, and Italy. Rectal swabs were obtained at enrollment and weekly until day 28 or discharge. Swabs were processed centrally by plating onto MacConkey agar supplemented with imipenem to selectively isolate CRE. Recovered colonies were identified using MALDI-TOF mass spectrometry, and meropenem minimum inhibitory concentrations (MICs) were determined by broth microdilution. Clinical cultures were obtained as indicated and processed locally, and CRE isolates were sent to the central laboratory for confirmation and characterization. Whole-genome sequencing was used to determine sequence types and resistance genes. Patients were excluded if they had CRE detected at baseline, either by rectal culture or as the index clinical isolate, or if no follow-up rectal cultures were available. Results Among 197 eligible patients (99 colistin; 98 colistin–meropenem), CRE acquisition occurred in 6 (3.0%): 1/99 (1.0%, 95% CI 0.03–5.5%) in the monotherapy arm and 5/98 (5.1%, 95% CI 1.7–11.5%) in the combination arm ( p  = 0.12). Two patients in the combination arm developed clinical infections caused by CRE (bacteremia and pneumonia); none occurred in the monotherapy arm. Carbapenemase genes were detected in four of the six acquired CRE isolates: one in the monotherapy arm ( bla VIM ) and three in the combination arm (all bla KPC ). Identified species included Klebsiella pneumoniae and Escherichia coli belonging to established and emerging high-risk, multidrug-resistant clones. Conclusions Patients treated with colistin-meropenem had a higher, though not statistically significant, rate of CRE acquisition. Early detection of high-risk CRE clones highlights the need to weigh potential unintended consequences when selecting combination regimens for multidrug-resistant infections. Trial Registration AIDA trial was registered with ClinicalTrials.gov, number NCT01732250 (submitted 19-11-2012).

The development of novel antibiotics is mandatory to curb the growing antibiotic resistance problem resulting in difficult-to-treat bacterial infections. Here, we have determined the spectrum of activity of cystobactamids and chelocardins, two novel and promising classes of molecules with different modes of action. A panel of 297 clinically relevant Gram-negative and Gram-positive isolates with different antibiotic susceptibility profiles, going from wild type to multi- or even extremely drug resistant (MDR, XDR) and including carbapenem-resistant isolates, were tested using broth microdilution assays to determine the minimal inhibitory concentrations (MICs), MIC50s and MIC90s of two cystobactamids derivatives (CN-861-2 and CN-DM-861) and two chelocardin derivatives (CHD and CDCHD). Cystobactamids revealed potent activities on the majority of tested Enterobacterales (MIC50s ranging from 0.25 to 4 µg/mL), except for Klebsiella pneumoniae isolates (MIC50s is 128 µg/mL). Pseudomonas aeruginosa and Acinetobacter baumannii showed slightly higher MIC50s (4 µg/mL and 8 µg/mL, respectively) for cystobactamids. Chelocardins inhibited the growth of Enterobacterales and Stenotrophomas maltophilia at low to moderate MICs (0.25–16 µg/mL) and the chemically modified CDCHD was active at lower MICs. A. baumannii and P. aeruginosa were less susceptible to these molecules with MICs ranging from 0.5 to 32 µg/mL. These molecules show also interesting in vitro efficacies on clinically relevant Gram-positive bacteria with MICs of 0.125–8 µg/mL for cystobactamids and 0.5–8 µg/mL for chelocardins. Taken together, the cystobactamid CN-DM-861 and chelocardin CDCHD showed interesting antibiotic activities on MDR or XDR bacteria, without cross-resistance to clinically relevant antibiotics such as carbapenems, fluoroquinolones, and colistin.

Antimicrobial resistance (AMR) presents a growing threat to global healthcare. This descriptive epidemiological study investigates the prevalence and characteristics of Enterobacterales with AMR factors in a tertiary teaching hospital in Italy over the course of the year 2021. In 2021, the prevalence of colonisation by Enterobacterales with AMR factors in patients was 1.08%. During the observation period, a total of 8834 rectal swabs were performed, with 1453 testing positive. A total of 5639 rectal swabs were performed according to a hospital procedure for the active screening of MDRO colonisation at the time of admission. Of these, 679 were positive for microorganisms under surveillance, and 74 patients were colonised with Enterobacterales, predominantly Klebsiella pneumoniae and Escherichia coli. Antibiotic resistance factors were observed in 61 of these 74 patients (82.43%) of these patients, with NDM and KPC being the most frequent resistance factors. A statistically significant trend in positive swabs was observed across different ward categories (surgery, ICUs, and medical wards). Regarding specific trends, the rate of positive admission screening in medical and surgical wards was higher than in ICU wards. The results highlight the ease with which Enterobacterales develops resistance across different ward categories. The findings underscore the need for adjusted screening protocols and tailored infection prevention strategies in various care settings.

Infections due to Klebsiella pneumoniae have been increasing in intensive care units (ICUs) in the last decade. Such infections pose a serious problem, especially when antimicrobial resistance is present. We created a task force of experts, including specialists in intensive care medicine, anaesthesia, microbiology and infectious diseases, selected on the basis of their varied experience in the field of nosocomial infections, who conducted a comprehensive review of the recently published literature on the management of carbapenemase-producing Enterobacterales (CPE) infections in the intensive care setting from 2012 to 2022 to summarize the best available treatment. The group established priorities regarding management, based on both the risk of developing infections caused by K. pneumoniae and the risk of poor outcome. Moreover, we reviewed and updated the most important clinical entities and the new antibiotic treatments recently developed. After analysis of the priorities outlined, this group of experts established a series of recommendations and designed a management algorithm.

Background Accumulating evidence shows a role of the hospital wastewater system in the spread of multidrug-resistant organisms, such as carbapenemase producing Enterobacterales (CPE). Several sequential outbreaks of CPE on the geriatric ward of the Ghent University hospital have led to an outbreak investigation. Focusing on OXA-48 producing Citrobacter freundii , the most prevalent species, we aimed to track clonal relatedness using whole genome sequencing (WGS). By exploring transmission routes we wanted to improve understanding and (re)introduce targeted preventive measures. Methods Environmental screening (toilet water, sink and shower drains) was performed between 2017 and 2021. A retrospective selection was made of 53 Citrobacter freundii screening isolates (30 patients and 23 environmental samples). DNA from frozen bacterial isolates was extracted and prepped for shotgun WGS. Core genome multilocus sequence typing was performed with an in-house developed scheme using 3,004 loci. Results The CPE positivity rate of environmental screening samples was 19.0% (73/385). Highest percentages were found in the shower drain samples (38.2%) and the toilet water samples (25.0%). Sink drain samples showed least CPE positivity (3.3%). The WGS data revealed long-term co-existence of three patient sample derived C. freundii clusters. The biggest cluster (ST22) connects 12 patients and 8 environmental isolates taken between 2018 and 2021 spread across the ward. In an overlapping period, another cluster (ST170) links eight patients and four toilet water isolates connected to the same room. The third C. freundii cluster (ST421) connects two patients hospitalised in the same room but over a period of one and a half year. Additional sampling in 2022 revealed clonal isolates linked to the two largest clusters (ST22, ST170) in the wastewater collection pipes connecting the rooms. Conclusions Our findings suggest long-term circulation and transmission of carbapenemase producing C. freundii clones in hospital sanitary installations despite surveillance, daily cleaning and intermittent disinfection protocols. We propose a role for the wastewater drainage system in the spread within and between rooms and for the sanitary installations in the indirect transmission via bioaerosol plumes. To tackle this problem, a multidisciplinary approach is necessary including careful design and maintenance of the plumbing system.

Background In 2018, Singapore’s National Infection Prevention & Control Committee (NIPC) recommended standard precautions and unrestricted movements for CPE carriers in nursing homes. Objective This study investigates the short-term impact of this intervention on CPE transmission in a nursing home in Singapore. Methods We conducted a prospective cohort study between 1st April and 11th July 2019 in a 255-bedded nursing home in Singapore. Stool samples from residents and environmental samples from sink strainers in the residents’ bedrooms, bathrooms, and lavatories, and shower drain traps in bathrooms were collected at baseline, week 2, week 8, and week 12 and tested for CPE. We performed whole genomic sequencing (WGS) to find out if there was any bacterial or plasmid linkage among the residents and between the residents and environment. Results A total of 32 residents, including six known CPE carriers, were recruited and completed the three-month follow-up visits. Of the six known CPE carriers, five tested negative for CPE, while one consistently tested positive for CPE throughout the study. Of the 28 sink strainers, six (21.43%) were positive for CPE. CPE was not detected in any shower drain trap throughout the study. Only one resident acquired CPE at week 12. WGS analysis of available CPE isolates showed no bacterial or plasmid linkage between residents or between residents and the environment. Conclusions Standard precautions and unrestricted movement of CPE carriers may be sufficient to control CPE transmission in the nursing home setting. Larger studies with more extensive environmental sampling and longer follow-up periods are needed to confirm this.

Introduction Despite a scarcity of data, before 2022 Ukraine was already considered a high-prevalence country for carbapenemase-producing Enterobacterales (CPE), and the situation has dramatically worsened during the full-scale war with Russia. The aim of this study was to analyse CPEs isolated in Poland from victims of war in Ukraine. Methods The study included 65 CPE isolates from March 2022 till February 2023, recovered in 36 Polish medical centres from 57 patients arriving from Ukraine, differing largely by age and reason for hospitalisation. All isolates were sequenced by MiSeq and ten Klebsiella pneumoniae isolates also by MinION. Taxonomy, clonality and resistomes were analysed for all CPEs, whereas phylogeny, serotypes, virulomes and plasmids were characterised for K. pneumoniae , and partially for Escherichia coli ST131, using various bioinformatic tools. Results Multifactorial diversity of the isolates reflected the patients’ clinical-epidemiological heterogeneity. The CPEs represented six species. Klebsiella pneumoniae was the most prevalent with 50 isolates and 15 sequence types (STs), mainly ST395, ST307, ST11, ST147 and ST23, producing NDM (-1/-5), OXA-48 (-48/-1242) or KPC (-2/-3)-like carbapenemases. Each of the STs produced groups of loosely related isolates, clusters of close relatives and/or unique isolates, correlating with K serotypes and carbapenemases. Many of these, especially NDM-1- and/or OXA-48-producing ST395 and ST307, were related to Russian organisms. Others, for example, NDM-1-producing ST11, clustered with those from Poland. Numerous K. pneumoniae isolates had specific virulence genes, including aerobactin iuc , largely due to spread of pNDM-MAR plasmids, showing both resistance and virulence. Two E. coli ST131 isolates belonged to clades B or C1 and produced KPC-3 or NDM-1, respectively. Conclusions Together with similar studies from Germany and The Netherlands, this work has documented broad dissemination of CPE in Ukraine, driven by a number of specific K. pneumoniae lineages circulating over a large territory of Eastern Europe.