BACKGROUND: Antimicrobial resistance poses a significant threat to public health globally. We studied the prevalence of colonization with extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE), carbapenem-resistant Enterobacterales (CRE), and colistin-resistant Enterobacterales (Col-RE) in hospitals and the surrounding community in South India.
METHODS: Adults from 2 hospitals and the catchment community who consented to provide stool specimens were enrolled. Stools were plated on CHROMagar selective for ESCrE, CRE, and Col-RE. Bacterial identification and antibiotic susceptibility testing were done using Vitek 2 Compact and disc diffusion testing. Colistin broth microdilution was performed for a subset of isolates. Prevalence estimates were calculated with 95% confidence intervals (CIs), and differences were compared across populations using the Pearson χ  2 or Fisher exact test.
RESULTS: Between November 2020 and March 2022, 757 adults in the community and 556 hospitalized adults were enrolled. ESCrE colonization prevalence was 71.5% (95% CI, 68.1%-74.6%) in the community and 81.8% (95% CI, 78.4%-84.8%) in the hospital, whereas CRE colonization prevalence was 15.1% (95% CI, 12.7%-17.8%) in the community and 22.7% (95% CI, 19.4%-26.3%) in the hospital. Col-RE colonization prevalence was estimated to be 1.1% (95% CI, .5%-2.1%) in the community and 0.5% (95% CI, .2%-1.6%) in the hospital. ESCrE and CRE colonization in hospital participants was significantly higher compared with community participants (P < .001 for both).
CONCLUSIONS: High levels of colonization with antibiotic-resistant Enterobacterales were found in both community and hospital settings. This study highlights the importance of surveillance of colonization in these settings for understanding the burden of antimicrobial resistance.

BACKGROUND: Ceftazidime/avibactam is one of the preferred treatment options for carbapenem-resistant Enterobacterales (CRE). However, the benefit of combining ceftazidime/avibactam with another antibiotic remains unclear.
OBJECTIVE: To identify variables associated with treatment failure during the use of ceftazidime/avibactam for CRE infections and assess the effect of combining an aminoglycoside with ceftazidime/avibactam.
METHODS: This was a retrospective cohort study of patients with a positive CRE culture treated with ceftazidime/avibactam between 2015 and 2021 in 134 Veterans Affairs (VA) facilities. The primary outcome was 30-day mortality and the secondary outcome was in-hospital mortality. A subanalysis in patients who received an aminoglycoside was also performed.
RESULTS: A total of 303 patients were included. The overall 30-day and in-hospital mortality rates were 12.5% and 24.1%, respectively. Age (aOR 1.052, 95% CI 1.013-1.093), presence in the ICU (aOR 2.704, 95% CI 1.071-6.830), and receipt of an aminoglycoside prior to initiation of ceftazidime/avibactam (aOR 4.512, 95% CI 1.797-11.327) were independently associated with 30-day mortality. In the subgroup of patients that received an aminoglycoside (n=77), their use in combination with ceftazidime/avibactam had a 30-day mortality aOR of 0.321 (95% CI, 0.089-1.155).
CONCLUSIONS: In veterans treated with ceftazidime/avibactam for CRE infections, increased age, receipt of an empiric aminoglycoside, and presence in the ICU at the time of index culture were associated with higher 30-day mortality. Among patients who received an aminoglycoside, their use in combination with ceftazidime/avibactam trended toward protectiveness of 30-day mortality, suggesting a potential role for this combination to treat CRE infections in patients who are more severely ill.

This guideline aims to promote the prudent use of antibacterial agents for managing carbapenem-resistant Enterobacterales (CRE) infections in clinical practice in Korea. The general section encompasses recommendations for the management of common CRE infections and diagnostics, whereas each specific section is structured with key questions that are focused on antibacterial agents and disease-specific approaches. This guideline covers both currently available and upcoming antibacterial agents in Korea.

BACKGROUND: Patients with carbapenem-resistant Enterobacterales (CRE) in the gastrointestinal (GI) tract are at risk for subsequent infections and transmission, necessitating contact precautions. Neomycin has shown in vitro activity against CRE in 66-85% of isolates. This study evaluated the efficacy and safety of neomycin for CRE decolonization.
METHODS: In this open-label randomized controlled trial, stool/rectal swab samples from high-risk patients were collected and tested for CRE colonization in the GI tract. Patients who had CRE and met eligible criteria were divided into a neomycin group (n = 26; treated with 4.2 g/day neomycin for 5 days) and a control group (n = 26). CRE detection in stool/rectal swabs was performed on days 7 ± 2 and 14 ± 2.
RESULTS: The two groups\' baseline characteristics were similar. CRE presence on day 7 ± 2 was significantly lower in the neomycin group (46.2%) than in the control group (80.8%, p = 0.01). Efficacy of neomycin (4.2 g/day for 5 days) for CRE decolonization was 42.8-53.8% by day 7. By day 14 ± 2, the CRE rate in the neomycin group had risen to align with the control group\'s rate (73.1% vs. 61.5%, p = 0.56). The neomycin group experienced mild, temporary, gastrointestinal side-effects.
CONCLUSIONS: Neomycin effectively reduced CRE colonization on day 7 ± 2, but its impact waned by day 14 ± 2. This suggests that neomycin dosage was too low and the duration of treatment was too short for lasting CRE decolonization.

Escherichia coli KA0011 had stable minimum inhibitory concentration values around the breakpoint range of meropenem and imipenem, making it suitable for use as a quality control strain for antimicrobial susceptibility testing. Here, we report the complete genomic sequence of KA0011.

UNASSIGNED: Carbapenem-resistant Enterobacterales (CRE) infection is an urgent threat to human health. This study aimed to develop and validate a novel multiplex real-time PCR (multi-qPCR) assay for the detection of the blaKPC, blaNDM, blaIMP, blaOXA-48-like, and blaVIM genes in CRE isolates and clinical samples, as well as to compare it with three phenotypic methods.
UNASSIGNED: The reliability and limit of detection (LOD) of the multi-qPCR assay were evaluated. PCR and DNA sequencing were used as the reference methods to identify carbapenemase genes in CRE isolates and clinical samples. The accuracy of the multi-qPCR assay, modified carbapenem inactivation and EDTA-modified carbapenem inactivation method (mCIMandeCIM), carbapenemase inhibitor-based combined disk test (CDT), and colloidal gold-based immunochromatographic test was compared with the reference methods with 182 isolates of CRE. Furthermore, 112 clinical samples were collected to validate the efficacy of this multi-qPCR assay.
UNASSIGNED: The standard deviations (CVs) of intra-assay and inter-assay of the multi-qPCR assay were ≤ 0.53% and ≤ 2.04% for detecting the five major carbapenemase genes, respectively; while the LOD ranged from 2×102 copies/mL to 8×102 copies/mL. PCR and DNA sequencing confirmed 168 out of 182 CRE isolates producing carbapenemase(s): KPC (n = 93), NDM (n = 46), IMP (n = 8), OXA-48-like (n = 14), VIM (n = 1), KPC&NDM (n = 5), and KPC&NDM&IMP (n = 1). The accuracy of mCIMandeCIM, CDT, Colloidal Gold, and the multi-qPCR assay was 96.2%, 89.6%, 100%, and 100% respectively for detecting carbapenemase(s) producers. Moreover, the sensitivity and specificity of the multi-qPCR assay were all 100% for the detection of each carbapenemase gene in clinical samples, compared with PCR and sequencing.
UNASSIGNED: For clinical isolate detection, the multi-qPCR assay is comparable to Colloidal Gold, and superior to mCIMandeCIM and CDT; while for clinical samples detection, it also shows excellent performance. Therefore, the multi-qPCR assay has great potential for clinical diagnosis.

BACKGROUND: The Infectious Diseases Society of America (IDSA) is committed to providing up-to-date guidance on the treatment of antimicrobial-resistant (AMR) infections. This guidance document focuses on infections caused by extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E), AmpC β- lactamase-producing Enterobacterales (AmpC-E), carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa with difficult-to-treat resistance (DTR P. aeruginosa), carbapenem-resistant Acinetobacter baumannii (CRAB), and Stenotrophomonas maltophilia. This updated document replaces previous versions of the guidance document.
METHODS: A panel of six infectious diseases specialists with expertise in managing antimicrobial- resistant infections formulated questions about the treatment of infections caused by ESBL-E, AmpC-E, CRE, DTR P. aeruginosa, CRAB, and S. maltophilia. Because of differences in the epidemiology of AMR and availability of specific anti-infectives internationally, this document focuses on the treatment of AMR infections in the United States.
RESULTS: Preferred and alternative suggested treatment approaches are provided with accompanying rationales, assuming the causative organism has been identified and antibiotic susceptibility results are known. Approaches to empiric treatment, transitioning to oral therapy, duration of therapy, and other management considerations are discussed briefly. Suggested approaches apply for both adult and pediatric populations, although suggested antibiotic dosages are provided only for adults.
CONCLUSIONS: The field of AMR is highly dynamic. Consultation with an infectious diseases specialist is recommended for the treatment of AMR infections. This document is current as of December 31, 2023 and will be updated periodically. The most current version of this document, including date of publication, is available at www.idsociety.org/practice-guideline/amr-guidance/.

Carbapenem-resistant Enterobacterales are being reported increasingly and cause nosocomial infections, which may include postoperative mediastinitis. This paper reports a case of postoperative mediastinitis caused by an Escherichia coli NDM-1 carbapenemase producer in a 13-month-old boy with DiGeorge syndrome. The infection was managed with surgical debridement and antibiotherapy with aztreonam, ceftazidime-avibactam and IV fosfomycin for 6 weeks. The evolution was favourable, without relapse over 10 weeks of follow-up.

Background/Objectives: Among various carbapenemases, New Delhi metallo-beta-lactamases (NDMs) are recognized as the most powerful type capable of hydrolyzing all beta-lactam antibiotics, often conferring multi-drug resistance to the microorganism. The objective of this review is to synthesize current scientific data on NDM inhibitors to facilitate the development of future therapeutics for challenging-to-treat pathogens. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Extension for Scoping Reviews, we conducted a MEDLINE search for articles with relevant keywords from the beginning of 2009 to December 2022. We employed various generic terms to encompass all the literature ever published on potential NDM inhibitors. Results: Out of the 1760 articles identified through the database search, 91 met the eligibility criteria and were included in our analysis. The fractional inhibitory concentration index was assessed using the checkerboard assay for 47 compounds in 37 articles, which included 8 compounds already approved by the Food and Drug Administration (FDA) of the United States. Time-killing curve assays (14 studies, 25%), kinetic assays (15 studies, 40.5%), molecular investigations (25 studies, 67.6%), in vivo studies (14 studies, 37.8%), and toxicity assays (13 studies, 35.1%) were also conducted to strengthen the laboratory-level evidence of the potential inhibitors. None of them appeared to have been applied to human infections. Conclusions: Ongoing research efforts have identified several potential NDM inhibitors; however, there are currently no clinically applicable drugs. To address this, we must foster interdisciplinary and multifaceted collaborations by broadening our own horizons.

The distribution of carbapenemases in Carbapenem-Resistant Enterobacterales (CRE) has recently undergone a change in our region. According to the Colombian National Institute of Health, there is an increasing prevalence of NDM and NDM-KPC co-producing strains. We carried-out an ambispective cohort study of adult inpatients from Hospital Universitario San Ignacio (2021-2023), infected or colonized with CRE, in which carbapenemases immunochromatographic assay was performed. Out of the 150 patients included in the study, 71.3 % presented with an infection, and carbapenemases were detected in 92.7 % of these cases. Among them, KPC predominated (54 %), while 16.7 % demonstrated enzyme coproductions, mainly KPC-NDM. CRE infected patients had an 18.7 % 30-days mortality, but we could not demonstrate an association between type of carbapenemase and mortality rate (p = 0.82). Logistic regression analysis suggested that ICU admission was independently correlated to fatality (OR 5.08; CI 1.68-16.01). NDM and KPC-NDM presence in CRE poses a public health threat and a therapeutic challenge, with unknown mortality differences according to the carbapenemases pattern. Nevertheless, there was not an association between enzyme type and mortality.