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Cefepime-tazobactam (FEP-TAZ) consists of cefepime combined with tazobactam, a penicillanic acid-sulfone recognized as an established beta-lactamase inhibitor. This study aims to investigate the in-vitro effectiveness of FEP-TAZ against cefepime-resistant clinical isolates of Escherichia coli (E. coli). A total of 105 E. coli clinical isolates characterized by cefepime-resistant/susceptible dose-dependent and carbapenem-sensitive profiles were tested for susceptibility by broth microdilution (BMD) method against cefepime and FEP-TAZ (tazobactam at a fixed concentration of 4 mg/L). Minimum inhibitory concentration (MIC) values for cefepime were determined using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method (M100–2022). Simultaneously, we also performed Disk-diffusion (DD) to observe the concordance between BMD and DD. FEP-TAZ exhibited inhibitory efficacy against 83.8% of E. coli isolates, markedly reducing the geometric mean from 20.4 to 1.9. Comparative analysis with DD revealed concordance with MIC for all isolates except four isolates. FEP-TAZ demonstrated potent activity against E.coli. This may be used as a carbapenem-sparing agent for the treatment of serious infections caused by cefepime-resistant Gram-negative bacilli. Furthermore, in settings where BMD implementation poses challenges, the pragmatic application of DD proves to be a viable alternative. [ABSTRACT FROM AUTHOR]

Background: The emergence of antimicrobial resistance in Gram-negative bacteria (GNB) is a major global concern. Ceftazidime–avibactam (CAZ–AVI) has been identified as a potential treatment option for complicated infections. Objectives: This meta-analysis aimed to evaluate the global resistance proportions of GNB to CAZ–AVI comprehensively. Methods: Studies were searched in Scopus, PubMed, and EMBASE (until September 2024), and statistical analyses were conducted using STATA software (version 20.0). Results: CAZ–AVI resistance proportions were determined in 136 studies, with 25.8% (95% CI 22.2–29.7) for non-fermentative gram-negative bacilli and 6.1% (95% CI 4.9–7.4) for Enterobacterales. The CAZ–AVI resistance proportion significantly increased from 5.6% (95% CI 4.1–7.6) of 221,278 GNB isolates in 2015–2020 to 13.2% (95% CI 11.4–15.2) of 285,978 GNB isolates in 2021–2024. Regionally, CAZ–AVI resistance was highest in Asia 19.3% (95% CI 15.7–24.23.4), followed by Africa 13.6% (95% CI 5.6–29.2), Europe 11% (95% CI 7.8–15.2), South America 6.1% (95% CI 3.2–11.5) and North America 5.3% (95% CI 4.2–6.7). Among GNB resistance profiles, colistin-resistant isolates and XDR isolates exhibited the highest resistance proportions (37.1%, 95% CI 14–68 and 32.1%, 95% CI 18.5–49.6), respectively), followed by carbapenem-resistant isolates and MDR isolates [(25.8%, 95% CI 22.6–29.3) and (13%, 95% CI 9.6, 17.3)]. Conclusion: A high proportion of GNB isolates from urinary tract infections remained susceptible to CAZ–AVI, indicating its potential as a suitable treatment option. However, the increasing resistance trends among GNB are concerning and warrant continuous monitoring to maintain CAZ–AVI's effectiveness against GNB infections. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the genetic and clinical characteristics of carbapenem-resistant Enterobacterales (CRE) isolates carrying metallo-β-lactamases (MBLs) genes. Methods: A total of 146 non-duplicated isolates of CRE were collected in 2022. Their ceftazidime/avibactam (CZA) susceptibilities were determined using the E test. The phenotypic identification of carbapenemases was conducted using the modified carbapenem inactivation method, followed by sequencing of the five common carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48). Multilocus sequence typing of selected Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae complex isolates were performed. Results: Among the 146 CRE isolates, 52 (35.6%) were resistant to CZA. MBL-encoding genes were detected in 46 (31.5%) of all tested CRE isolates, with 82.6% (n = 38) of them exhibiting resistance to CZA. Fourteen isolates were resistant to CZA without any detected MBL genes. The most commonly identified MBL genes were blaIMP (n = 20), followed by blaNDM (n = 19), and blaVIM (n = 5). In CZA-R, the most common definite antibiotic before the CZA E test was CZA (n = 18), followed by tigecycline (n = 13), and fluroquinolone (n = 10). The 14-day and 30-day mortality rates were 9.0% (n = 13) and 22.8% (n = 34), and were associated with intensive care unit admission at onset (P = 0.029 and P = 0.001, respectively). The sequence types of CRE isolates carrying MBLs were diverse without major clones. Conclusion: The continuous emergence of MBL gene-encoding CRE with multiple clones has led to reduced CZA susceptibilities and worse outcomes. [ABSTRACT FROM AUTHOR]

Antibiotic resistance poses a significant global threat, particularly in the context of bloodstream infections. Early antimicrobial susceptibility testing plays a crucial role in guiding clinicians to optimize treatment and enhance patient outcomes. Direct disk diffusion testing (dDDT), utilizing positive blood culture broth as an inoculum, provides results one day earlier than the standard method using bacterial colonies. This retrospective study evaluated the ability of dDDT to predict nonsusceptibility to commonly used antibiotics. From January 2021 to December 2023, a total of 1473 blood cultures positive for a single pathogen (Enterobacterales, Pseudomonas aeruginosa, Staphylococcus aureus, β-hemolytic streptococci, or Enterococcus spp.) were examined. The results of dDDT were compared against the standard disk diffusion method as the reference standard. A total of 9754 organism–antibiotic pairs were analyzed. The positive predictive values were more than 98% for clinically significant resistant phenotypes, including ceftriaxone, ceftazidime, cefepime, and meropenem nonsusceptibility in Enterobacterales, ceftazidime and meropenem nonsusceptibility in P. aeruginosa, and cefoxitin resistance in S. aureus. Overall, sensitivities exceeded 98% for the majority of organism–antibiotic pairs, with specificities ranging from 88.4% to 100%. Categorical agreement was high at 97.9%, ranging from 88.8% to 100% across organism groups. The overall rates of major error and very major error were very low, at 0.2% and 0.04%, respectively, and ranged from 0% to 1.5% and 0% to 0.04%, respectively, across organism groups. In conclusion, dDDT is a reliable and expedient method for detecting antibiotic nonsusceptibility, making it a valuable tool for the timely management of bloodstream infections caused by resistant organisms. [ABSTRACT FROM AUTHOR]

Purpose: Infective endocarditis caused by non-HACEK gram-negative bacilli (GNB-IE) is rare but associated with significant morbidity and case fatality. Evidence on optimal treatment and management is limited. We aimed to describe the characteristics and management of GNB-IE patients, investigating factors associated with disease acquisition and unfavorable outcomes. Methods: We conducted a retrospective descriptive single-center study (tertiary care and referral hospital) between 2015 and 2021, including adult patients with definite GNB-IE. We reviewed demographic, clinical and microbiological data, focusing on predisposing factors, clinical outcomes and 1-year mortality. Results: Of 1093 patients with probable or definite IE, 19 patients (median age 69 years) had definite GNB-IE, with an increasing incidence throughout the study period. Median age-adjusted Charlson Comorbidity Index score was 4 points. Prosthetic valve IE (PVIE) was present in 7/19 (37%) patients. Nosocomial acquisition occurred in 8/19 (42%) patients. Escherichia coli and Klebsiella pneumoniae were the most common pathogens. Beta-lactam (BL) based combination therapy was applied in 12/19 (63%) patients (58% BL + fluoroquinolone, 42% BL + aminoglycoside). Cardiac surgery was required in 8/19 (42%) patients (PVIE 71%, native valve IE 25%), primarily for embolism prevention and heart failure. Complications occurred in 14/19 (74%) patients. The in-hospital mortality rate was 21% (4/19); the one-year mortality rate was 44% (7/16). One-year mortality did not significantly differ between patients who underwent cardiac surgery and patients managed with anti-infective treatment alone (p = 0.633). Conclusions: GNB-IE affects elderly patients with high comorbidity levels and recent health-care exposure. GNB-IE was associated with high complication rates and high mortality. [ABSTRACT FROM AUTHOR]

Background: Initial antimicrobial therapy for pneumonia is frequently empirical and resistance to antimicrobial agents represents a great challenge to the treatment of patients hospitalized with pneumonia. We evaluated the frequency and antimicrobial susceptibility of Gram-negative bacteria causing pneumonia in US hospitals. Methods: Bacterial isolates were consecutively collected (1/patient) from patients hospitalized with pneumonia and the susceptibility of Gram-negative bacilli (3,911 Enterobacterales and 2,753 non-fermenters) was evaluated by broth microdilution in a monitoring laboratory. Isolates were collected in 69 medical centers in 2020–2022. Aztreonam-avibactam was tested with avibactam at fixed 4 mg/L and a pharmacokinetic/pharmacodynamic susceptible (S) breakpoint of ≤ 8 mg/L was applied for comparison. Carbapenem-resistant Enterobacterales (CRE; isolates with MIC values of > 2 mg/L for imipenem and/or meropenem) isolates were screened for carbapenemases by whole genome sequencing. Results: Gram-negative bacilli represented 71.1% of organisms. The most common Gram-negative species were Pseudomonas aeruginosa (22.4% of organisms), Klebsiella pneumoniae (8.8%), Escherichia coli (6.6%), Serratia marcescens (6.2%), Stenotrophomonas maltophilia (4.9%), and Enterobacter cloacae complex (4.8%). Aztreonam-avibactam inhibited 100.0% of Enterobacterales at ≤ 8 mg/L and 99.9% at ≤ 4 mg/L and showed potent activity against CRE (MIC50/90, 0.25/1 mg/L). Ceftazidime-avibactam and meropenem-vaborbactam were active against 89.4% and 88.5% of CREs, respectively. Aztreonam-avibactam retained activity against Enterobacterales non-susceptible to ceftazidime-avibactam and/or meropenem-vaborbactam (n = 19; MIC50/90, 0.25/4 mg/L). The most common carbapenemases were KPC (69.2% of CREs), NDM (9.6%), and SME (4.8%). A carbapenemase gene was not identified in 16.3% of CREs. Ceftazidime-avibactam and meropenem-vaborbactam were highly active against KPC and SME producers but showed limited activity against MBL producers. The most active comparators against CRE were tigecycline (95.2%S), amikacin (73.1%S), and gentamicin (60.6%S). Among Pseudomonas aeruginosa, 79.1% were inhibited at ≤ 8 mg/L of aztreonam-avibactam, 77.2% were meropenem susceptible, and 77.2% were piperacillin-tazobactam susceptible. Aztreonam-avibactam was highly active against S. maltophilia, inhibiting 99.5% of isolates at ≤ 8 mg/L. Conclusions: Aztreonam-avibactam displayed potent in vitro activity against a large collection of contemporary Gram-negative organisms isolated from patients hospitalized with pneumonia, including CRE isolates resistant to ceftazidime-avibactam and/or meropenem-vaborbactam. Results of surveillance programs are valuable for planning empiric antimicrobial therapy guidelines and infection control measures. [ABSTRACT FROM AUTHOR]

From a One Health perspective, dogs and cats have begun to be recognized as important reservoirs for clinically significant multidrug-resistant bacterial pathogens. In this study, we investigated the occurrence and genomic features of ESβL producing Enterobacterales isolated from dogs, in the province of Imbabura, Ecuador. We identified four isolates expressing ESβLs from healthy and diseased animals. In this regard, two Escherichia coli strains producing CTX-M-55-like or CTX-M-65 ESβLs belonged to the international ST10 and ST162, whereas two Klebsiella pneumoniae producing CTX-M-14 or CTX-M-27 belonged to ST35 and ST661. Phylogenomic analysis clustered (95-105 SNP differences) CTX-M-55/ST10 E. coli from companion animal with food and human E. coli strains of ST10 isolated in 2016, in Australia and Cambodia, respectively; whereas CTX-M-27-positive K. pneumoniae ST661 was clustered (201-216 SNP differences) with human strains identified in Italy, in 2013 and 2017, respectively. In summary, we report the presence and genomic data of global human-associated clones of CTX-M-producing E. coli and K. pneumoniae in dogs, in Ecuador. The implementation of a national epidemiological surveillance program is necessary to establish future strategies to control the dissemination of antibiotic-resistant priority pathogens using a One Health approach. [ABSTRACT FROM AUTHOR]

Introduction: The global rise of extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) challenges resource-limited countries with insufficient laboratory infrastructure. This study investigates fecal carriage and risk factors for ESBL-PE and carbapenemase-producing organisms among patients with urinary tract infection (UTI) in rural Tanzania. Methods: This cross-sectional study was conducted at St. Francis Regional Referral Hospital, Ifakara, Tanzania, from October 2021 to August 2023, involving 326 UTI patients. Demographic data and resistance risk factors were collected via structured questionnaires. Stool samples collected pre-antibiotic treatment were screened for ESBL-PE and carbapenemase locally. Positive samples underwent further analysis in Switzerland using MALDI-ToF, Vitek MS, and whole-genome sequencing. Multivariable analysis assessed predictors associated with ESBL-PE carriage for risk factors with p < 0.05. Results: We enrolled 326 UTI patients (median age: 35.5 years, range: 25–52) and 189 (58.0%) were females. Fecal ESBL-PE colonization was detected in 70.9% of patients, predominantly E. coli (62.8%) and K. pneumoniae (33.0%). Whole-genome sequencing identified diverse phylogroups and sequence types, with CTX-M-15 being the most common ESBL gene. IncF plasmids were the primary carriers. Younger age (aOR: 0.98, 95% CI: 0.97–0.99; p = 0.0239) and inpatient status (aOR: 1.77, 95% CI: 1.08–2.91; p = 0.0036) were significant risk factors for ESBL-PE carriage. Conclusion: The high prevalence of ESBL-PE fecal carriage in rural Tanzania highlights the need for improved infection control and further research into community transmission dynamics. [ABSTRACT FROM AUTHOR]

Objectives To evaluate the in vitro susceptibility of recent Gram-negative pathogens collected from pediatric patients to imipenem/relebactam (IMI/REL) and comparator agents. Methods From 2018 to 2022 254 hospitals in 62 countries collected Enterobacterales or Pseudomonas aeruginosa isolates from patients <18 years old as part of the SMART global surveillance program. Minimum inhibitory concentrations (MIC)s were determined using CLSI broth microdilution and interpreted with 2024 CLSI breakpoints. Most isolates non-susceptible to IMI/REL were queried for their acquired β-lactamase content. Results Overall, 96.8% of all non- Morganellaceae Enterobacterales (NME) isolates from pediatric patients (n  = 12 060) were IMI/REL-susceptible. Most NME were also susceptible to imipenem alone (93.9%), meropenem (96.0%), and ertapenem (94.4%); isolates were less susceptible to piperacillin/tazobactam (82.8%), cefepime (76.3%), and ceftazidime (74.4%). Non- Morganellaceae Enterobacterales collected in Asia were the least susceptible to IMI/REL (91.6%), while those from Australia/New Zealand were the most (99.3%). Imipenem/relebactam was equally potent against NME isolates regardless of infection source, hospital ward, age, and length of hospitalization. In total, 90.8% of all Pseudomonas aeruginosa isolates (n  = 3046) were IMI/REL-susceptible; ceftolozane/tazobactam also inhibited >90% of the P. aeruginosa. Regionally, P. aeruginosa isolates from Eastern Europe were least susceptible to IMI/REL. Molecular characterization revealed that, globally, most resistance to IMI/REL among the NME could be attributed to the presence of NDM-type metallo-β-lactamases, while no acquired β-lactamases were detected in approximately half the IMI/REL non-susceptible P. aeruginosa examined. Conclusion Based on in vitro data, IMI/REL represents a good therapeutic option for most hospitalized pediatric patients infected with common Gram-negative pathogens. [ABSTRACT FROM AUTHOR]

ABSTRACT: Background: Multidrug resistant (MDR) Gram negative organisms are becoming increasingly common. Carbapenem resistant Enterobacterales (CRE) pose a major threat and necessitate the development of new antibiotics. MDR and carbapenem resistant infections, which are common in intensive care units and hospitals, lead to increased morbidity, mortality, prolonged hospital stays, and higher healthcare costs. New antimicrobials such as ceftazidime avibactam offer potential alternatives to conventional treatments such as tigecycline and colistin, which have significant side effects and limitations. Aim: This study focuses on the antibiotic susceptibility of ceftazidime/ avibactam to Gram negative bacilli found in a large number of clinical samples collected from a tertiary care facility in Netaji Subhas Medical University and Hospital, Bihta, India. Methodology: The study included 81 Gram negative bacteria isolated from patient samples. Based on the Clinical Laboratory Standards Institute guidelines mentioned in the Kirby Bauer disc diffusion method. Result and Conclusion: the results showed that ceftazidime avibactam inhibited 89.9% of the Enterobacteriaceae isolates, which was higher than the 80.3% of amikacin and the 85.1% of meropenem. Ceftazidime avibactam was effective against CRE isolates in 69.9% of cases and against MDR isolates in urine in 94% of cases, which was higher than the 40% of ceftriaxone and 94% of nitrofurantoin. The results show that ceftazidime avibactam can cure MDR and CRE infections, especially urinary tract infections, better than conventional antibiotics, which is a great help in the fight against increasing antibiotic resistance. [ABSTRACT FROM AUTHOR]

Background: Monomicrobial Enterobacterales necrotizing fasciitis is associated with exceedingly high mortality rates. Although effective antimicrobial therapy is an important part of treatment, the traditional microbiological diagnostic methods are not fast enough to meaningfully influence early therapeutic decisions. Methods: Here, we report the application of the BioMérieux Biofire Filmarray Joint Infection Panel (BFJIP) for the rapid detection of the causative agent and susceptibility prediction in such a case. Aside from the BFJIP-based rapid diagnostic approach and culturing, the whole genome sequencing (WGS) of the causative agent was performed using Illumina MiSeq and Oxford Nanopore MinION platforms. Results: The BFJIP indicated the presence of K. pneumoniae, without KPC, VIM, IMP, NDM, OXA-48 carbapenemase genes, and CTX-M-type extended-spectrum beta-lactamases. Based on the WGS data, the isolate belonged to the K1-capsule-type ST23, harboured a pNTUH-2044-like plasmid, and was positive for all the virulence factors associated with this lineage. The conventional susceptibility results were also in accordance with the BFJIP results; the isolate lacked any of these acquired resistance mechanisms. Conclusions: Despite this being the first case of the successful identification of pathogenic bacteria in necrotising fasciitis using this assay, the BFJIP may become a useful tool for rapid identification of pathogens in necrotising fasciitis cases and guiding antimicrobial therapy for better clinical outcomes. [ABSTRACT FROM AUTHOR]

An advanced biochemical assay named modified Carba PBP test was innovated to identify and differentiate distinct categories of clinically significant carbapenemases (Ambler classes A, B, and D) within the Enterobacterales. The mechanism of mCarba PBP hinges on two core attributes: (i) the hydrolysis of the meropenem substrate by various carbapenemases, (ii) the immobilized penicillin and free meropenem in their affinity to interact with a limited quantity of penicillin-binding protein (PBP). Specific inhibitors for class A (phenylboronic acid, PBA) and class B (ethylenediaminetetraacetic acid, EDTA) were employed to inhibit the hydrolysis activity of carbapenemase and facilitate the classification of carbapenemase classes within 25 min. A comprehensive evaluation was undertaken using 94 clinical Enterobacterales isolates, comprising 75 carbapenemase-producing strains and 19 non-carbapenemase-producing strains. Its overall specificity and sensitivity were 100% and 97.3%, respectively, including detection of all types of OXA-48-like carbapenemases. For precise carbapenemase type identification, the assay exhibited remarkable sensitivities for class A, class B, and class D detection at 94.7%, 100%, and 100%, respectively. This user-friendly test presents a promising tool for carbapenemase identification, refining the selection of β-lactam/β-endoenzyme inhibitor combinations for effectively treating infections due to carbapenemase-producing organisms. [ABSTRACT FROM AUTHOR]

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ABSTRACT: Objectives: Critical priority carbapenem-resistant pathogens constitute a worldwide public health problem. Escherichia coli (E. coli) ST1193 is an emerging high-risk clone that demonstrates prolonged gut persistence, and association with community-onset urinary and bloodstream infections. The purpose of this study is to report microbiological and genomic data on the emergence of KPC-2-producing E. coli ST1193 in ready-to-eat (RTE) vegetables. Methods: RTE vegetables were purchased from markets in southeastern Brazil. Epiphytic and endophytic Gram-negative bacteria displaying resistance to broad-spectrum beta-lactams were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Whole-genome sequence was conducted using the Illumina NextSeq platform. Antimicrobial susceptibility, conjugation, and acid tolerance assays were performed. Virulence behaviour was evaluated using the Galleria mellonella (G. mellonella) infection model. Results: Epiphytic KPC-2-producing E. coli belonging to pandemic ST1193 was identified in RTE arugula. Genomic analysis predicted clinically relevant genes conferring resistance to β-lactams, fluoroquinolones, hazardous heavy metals, pesticides, disinfectants, and chlorine sanitizer. The blaKPC-2 gene was carried by a conjugative IncF plasmid. Acid tolerance of E. coli KPC-2/ST1193 during exposure to pH 2.0 was confirmed, being associated with gadWX and ibaG pH tolerance genes, supporting survival to stomach acid prior to reaching the small intestine, and potential for a dietary mode of host colonization. Virulent behaviour was supported by wide virulome of the highly virulent phylogroup B2, whereas single nucleotide polymorphisms of core genes (cgSNP)-based phylogenomics revealed clonal relationship with healthcare-associated lineages circulating in the United States, China, Mexico, France, and Brazil. Conclusions: We report the occurrence of KPC-2-producing E. coli of the highly virulent B2-ST1193 clone in RTE vegetables, highlighting a possible route of dissemination of the World Health Organization (WHO) priority pathogens to humans. © 2024 The Author(s). Published by Elsevier Ltd on behalf of International Society for Antimicrobial Chemotherapy.

Abstract Background Initial antimicrobial therapy for pneumonia is frequently empirical and resistance to antimicrobial agents represents a great challenge to the treatment of patients hospitalized with pneumonia. We evaluated the frequency and antimicrobial susceptibility of Gram-negative bacteria causing pneumonia in US hospitals. Methods Bacterial isolates were consecutively collected (1/patient) from patients hospitalized with pneumonia and the susceptibility of Gram-negative bacilli (3,911 Enterobacterales and 2,753 non-fermenters) was evaluated by broth microdilution in a monitoring laboratory. Isolates were collected in 69 medical centers in 2020–2022. Aztreonam-avibactam was tested with avibactam at fixed 4 mg/L and a pharmacokinetic/pharmacodynamic susceptible (S) breakpoint of ≤ 8 mg/L was applied for comparison. Carbapenem-resistant Enterobacterales (CRE; isolates with MIC values of > 2 mg/L for imipenem and/or meropenem) isolates were screened for carbapenemases by whole genome sequencing. Results Gram-negative bacilli represented 71.1% of organisms. The most common Gram-negative species were Pseudomonas aeruginosa (22.4% of organisms), Klebsiella pneumoniae (8.8%), Escherichia coli (6.6%), Serratia marcescens (6.2%), Stenotrophomonas maltophilia (4.9%), and Enterobacter cloacae complex (4.8%). Aztreonam-avibactam inhibited 100.0% of Enterobacterales at ≤ 8 mg/L and 99.9% at ≤ 4 mg/L and showed potent activity against CRE (MIC50/90, 0.25/1 mg/L). Ceftazidime-avibactam and meropenem-vaborbactam were active against 89.4% and 88.5% of CREs, respectively. Aztreonam-avibactam retained activity against Enterobacterales non-susceptible to ceftazidime-avibactam and/or meropenem-vaborbactam (n = 19; MIC50/90, 0.25/4 mg/L). The most common carbapenemases were KPC (69.2% of CREs), NDM (9.6%), and SME (4.8%). A carbapenemase gene was not identified in 16.3% of CREs. Ceftazidime-avibactam and meropenem-vaborbactam were highly active against KPC and SME producers but showed limited activity against MBL producers. The most active comparators against CRE were tigecycline (95.2%S), amikacin (73.1%S), and gentamicin (60.6%S). Among Pseudomonas aeruginosa, 79.1% were inhibited at ≤ 8 mg/L of aztreonam-avibactam, 77.2% were meropenem susceptible, and 77.2% were piperacillin-tazobactam susceptible. Aztreonam-avibactam was highly active against S. maltophilia, inhibiting 99.5% of isolates at ≤ 8 mg/L. Conclusions Aztreonam-avibactam displayed potent in vitro activity against a large collection of contemporary Gram-negative organisms isolated from patients hospitalized with pneumonia, including CRE isolates resistant to ceftazidime-avibactam and/or meropenem-vaborbactam. Results of surveillance programs are valuable for planning empiric antimicrobial therapy guidelines and infection control measures.

Abstract Background Carbapenemase-producing Enterobacterales isolates are associated with significant mortality and have emerged as a major problem in healthcare settings worldwide. Objective Our aim was to investigate the epidemiological and genotypic characteristics of carbapenemase-positive Enterobacterales isolates from patients hospitalised in three hospitals in the city of Batna, Algeria. Methods Between 2016 and 2019, a total of 5,316 clinical isolates were obtained. The collected isolates were identified using the VITEK-2 system. Demographic and microbiological data were collected as well as the antimicrobial susceptibility testing, phenotypic and molecular characterisation of carbapenemase and mcr-1 genes were performed. Results Out of the 5,316 isolates, 201 were carbapenem-resistant Enterobacterales isolates and 179 of them (89.05%) were positive for the production of carbapenemase, of which Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae were the most common. The bla OXA−48−like gene alone was detected in 147 isolates (82.12%) moreover, the bla NDM gene was detected in ten isolates (5.59%). Dual and triple combinations of carbapenemase genes were also observed here for the first time in Algeria: bla VIM and bla OXA−48−like; bla KPC, bla VIM and bla OXA−48−like; bla VIM and bla NDM; bla KPC, bla NDM and bla VIM; bla NDM and bla OXA−48−like genes. In addition, resistance to both colistin and carbapenem antibiotics was detected in eight isolates, however none of them was positive for the mcr-1 gene. Conclusion This is the first study reporting the detection of carbapenemase genes in Klebsiella aerogenes, Enterobacter sakazakii, Raoultella ornithinolytica, Serratia ficaria, and Serratia marcescens and specific carbapenemase gene combinations in Algeria. The present study revealed that bla OXA−48−like were found to be the predominant carbapenemase genes in Batna hospitals.

Chen-Huan Yu,1 Mao-Song Tsai,2 Chun-Hsing Liao,2 Chia-Jui Yang2 1Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan; 2Division of Infectious Disease, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, TaiwanCorrespondence: Chia-Jui Yang, Division of Infectious Disease, Department of Internal Medicine,Far Eastern Memorial Hospital, No. 21, Sec. 2, Nanya S. Road, Banciao Dist, New Taipei City, Taiwan, Fax +886 2 77281321, Email yangcj1206@gmail.comPurpose: Ceftazidime-avibactam (CZA), a novel beta-lactam/beta-lactamase inhibitor, plays an important role in the threat of emerging carbapenem-resistant Enterobacterales (CRE) infection. The study aims to analyze the clinical effectiveness and factors influencing treatment response to CZA for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections.Patients and Methods: From February 2020 to December 2021, patients with CRKP infection treated with CZA were enrolled in this retrospective, single-center cohort study in northern Taiwan. The primary outcome was 28-day survival rate. The secondary outcomes were clinical success, and microbiological cure. Multivariate regression analysis was used to evaluate factors associated with 28-day survival.Results: A total of 142 patients treated with CZA alone (n=82) or in combination therapy (n=60) were included. We found 28-day survival rate, microbiological cure, and clinical success rate were 78% (111/142), 86% (87/101), and 48% (63/132), respectively. In multivariate analysis, there were no significant differences in 28-day survival between monotherapy group and combination therapy group (P=0.424). A relative lower microbiological cure rate can be observed in lower respiratory tract infection from univariate analysis (P=0.07). In addition, significantly better survival was observed in patients with creatinine clearance rate (CCr) ≥ 50 mL/min than CCr < 50 mL/min (P=0.005).Conclusion: CZA is an effective and important treatment option for CRKP infection even when it is treated as monotherapy. In patients with impaired renal function, a potential impact of CZA dose adjustments on poor survival outcomes has been observed, indicating the need for further research to determine optimal renal dose adjustment strategies.Keywords: enterobacterales, Klebsiella pneumoniae, ceftazidime-avibactam

Abstract Background ESBL-producing Enterobacteriaceae (ESBL-PE) represent a significant global health threat. In response to this growing concern and the lack of a surveillance system for ESBL-PE infections in Egypt, we conducted this meta-analysis. In this study, we aimed to quantify the prevalence of ESBL-PE based on the source of infection and characterize their molecular dissemination. Additionally, we sought to uncover temporal trends to assess the spread of ESBL-PE over time. Methods A comprehensive literature search was conducted in PubMed, Scopus, Google Scholar, Web of Science, and the Egyptian Knowledge Bank to identify studies that: (1) report the prevalence of ESBL-PE in Egypt; (2) use valid detection methods; (3) involve clinical specimens; and (4) were published between 2010 and 2024. The quality of the included studies was evaluated using the “Joanna Briggs Institute Critical Appraisal Checklist”. Meta-analysis was performed using the R meta package, reporting pooled prevalence with 95% confidence intervals (CI) via a random effects model. Results This meta-analysis included 34 studies with 4,528 isolates, spanning 2007 to 2023. The overall prevalence of ESBL-PE in Egypt was 60% (95% CI: 54–65). The leave-one-out meta-analysis demonstrated the absence of influential outliers and Egger’s test indicated no evidence of publication bias (P = 0.25). The prevalence of ESBL-PE was 62% (95% CI: 55–68) in nosocomial infections and 65% (95% CI: 52–75) in community-acquired infections, with no statistically significant difference (P = 0.68). The prevalence of ESBL producers in E. coli (64%) and K. pneumoniae (63%) is higher than in Proteus mirabilis (46%) (P = 0.06). Temporal analysis showed a stable ESBL prevalence over time. Moreover, in phenotypically confirmed ESBL-producing, E. coli harboring bla CTX−M was most prevalent (73%), followed by bla TEM (60%) and bla SHV (22%), with significant differences (P

Background: Carbapenem-resistant Enterobacterales (CRE) have been identified as a public health problem. Treatment options for CRE are limited as they are mostly resistant to βeta-lactams, aminoglycosides, and fluoroquinolones as well as carbapenems. The present study aims to evaluate the performance of three phenotypic methods compared to a molecular-based technique for carbapenemase detection in Enterobacterales and determining their applicability in clinical and epidemiological settings. Methods: A total of 1,158 Enterobacterales were isolated from the urine samples in the microbiology laboratory of Alexandria main university hospital during the period from April 2020 to April 2021. Fifty randomly selected (39 Klebsiella and 11 E. coli) Enterobacterales were screened for carbapenem resistance by disc diffusion method. They were subjected to 3 phenotypic tests which are: Carba NP method, Modified carbapenem inactivation method (m CIM) and EDTA- modified carbapenem inactivation method (e CIM). Detection of 5 carbapenemase genes (blaKPC, blaIMP, blaVIM, blaOXA-48 and blaNDM-1) was performed using real time PCR. Results: CRE represented 33% of Enterobacterales isolates. Twenty-six cases (52%) were males and 94% of the cases were above 40 years old. Carba NP test was positive in 43/50 (86%) of the selected isolates, m CIM was positive in 35/50 (70%) and e CIM was positive in 30/50 (60%). The most common carbapenemase gene detected was blaNDM-1 (94%), followed by blaOXA-48 gene (72%) and blaVIM gene (24%). The blaKPC gene and blaIMP gene were not detected. Coexistence of the blaOXA-48 and the blaNDM-1 genes was detected in 48% isolates, while the blaNDM-1, the blaOXA-48 and the blaVIM genes were found in 22% isolates. The sensitivity of Carba NP, m CIM and e CIM was 87.5%, 72.9%, and 85.7% respectively. Conclusion: The study highlights the necessity of early detection of CRE. Carba NP test assists in the rapid identification of carbapenemase production. However, the genotypic test remains the gold standard for detection of CRE.

Caiyun Li,1,&ast; Fa Zhang,1,&ast; Gang Li,2,3 Wen Wang2,3 1Department of Clinical Laboratory, Nanjing Pukou People’s Hospital, Nanjing, 211800, People’s Republic of China; 2Center of Medical Laboratory, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of China; 3Ningxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical University, Yinchuan, 750004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen Wang, Email 42170662@qq.comObjective: To analyze the prevalence and molecular characteristics of 16S rRNA methylase genes in clinical isolates of carbapenem-resistant Enterobacterales, for clinical doctors provide a reference basis for the rational use of drugs.Methods: The Enterobacterales isolated from our hospital from 2020 to 2022 were selected and identified by VITEK 2 Compact automatic bacterial identification instrument. Resistance genes were detected by polymerase chain reaction.Results: A total of 180 carbapenem-resistant Enterobacterales were isolated, of which 158 (87.8%) were resistant to at least one aminoglycoside. The resistance rates to gentamicin, tobramycin and amikacin were 85.0%,82.8% and 54.4%, respectively. Compared with 16S rRNA methyltransferase negative isolates, the positive isolates were more sensitive to trimethoprim-sulfamethoxazole, tetracycline and minocycline, but had higher resistance rates to aztreonam, tobramycin, gentamicin, amikacin and ciprofloxacin. The resistance rates of 16S rRNA methyltransferase gene positive strains to most commonly used antibiotics were more than 80%. But the rates for colistin and tigecycline were less than 10%. There were 114 strains (63.3%) positive for 16S rRNA methyltransferase genes, mainly rmtB, accounting for 70.2%. The positive rates of other armA, rmtA and armA+rmtB genes were 22.8%, 4.4% and 2.6%, respectively. No rmtC, rmtD, rmtE and npmA genes were detected. In addition, 175 of the 180 carbapenem-resistant Enterobacterales carried at least one carbapenemase genes. The blaKPC was the main one (115, 65.7%). There were 111 (61.7%) strains carried both carbapenemase and 16S rRNA methyltransferase genes, simultaneously. Compared with 16S rRNA methyltransferase negative strains, the positive strains carried more blaKPC genes and less blaNDM genes, with P values of 0.034 and 0.003, respectively.Conclusion: blaKPC and rmtB genes are the main resistance mechanisms of Enterobacterales to carbapenems and aminoglycosides in our hospital. It is necessary to strengthen the detection of multi-drug resistant strains to provide scientific basis for clinical rational drug use.Keywords: enterobacterales, carbapenemase, 16S rRNA methylase

Abstract Background Bloodstream infection (BSI) is associated with poor outcomes especially when effective antimicrobial therapy and control of infection source are delayed. As the frequency of Enterobacterales producing metallo-β-lactamases (MBL) and/or OXA-48–like carbapenemases is increasing in some United States (US) medical centres, effective antimicrobials to treat the infections caused by these organisms are urgently needed. Aztreonam-avibactam is under clinical development for treatment of infections caused by Gram-negative bacteria, including MBL producers. Objectives To evaluate the antimicrobial susceptibility of Enterobacterales causing BSI in US medical centres and compare the activity of aztreonam-avibactam with ceftazidime-avibactam, meropenem-vaborbactam, imipenem-relebactam, cefiderocol, and other antimicrobials used to treat BSI. Methods 4,802 Enterobacterales were consecutively collected (1/patient) from 72 US medical centres in 2020–2022 and susceptibility tested by broth microdilution. Aztreonam-avibactam was tested with avibactam at a fixed concentration of 4 mg/L. A pharmacokinetic/pharmacodynamic susceptible breakpoint of ≤ 8 mg/L was applied for aztreonam-avibactam for comparison. Carbapenem-resistant Enterobacterales (CRE) isolates were tested for β-lactamase–encoding genes using Next-generation sequencing. Results Aztreonam-avibactam was highly active against Enterobacterales; only 2 isolates showed aztreonam-avibactam MICs > 8 mg/L: 1 meropenem-susceptible E. coli and 1 K. aerogenes (CRE). All carbapenemase producers and 98.0% of CRE were inhibited at an aztreonam-avibactam MIC of ≤ 8 mg/L. CRE susceptibility rates were 81.6% for ceftazidime-avibactam, 65.3% for meropenem-vaborbactam, 61.2% for imipenem-relebactam, and 87.8% for cefiderocol. Aztreonam-avibactam retained activity (MIC, ≤ 8 mg/L) against all (100.0%) meropenem-vaborbactam nonsusceptible (n = 17), 99.5% of imipenem-relebactam nonsusceptible (n = 206), and 90.0% of ceftazidime-avibactam nonsusceptible (n = 10) isolates. The most common carbapenemases were KPC-2/3 (57.1% of CREs), OXA-48–like (16.3%), and NDM (14.3%). A carbapenemase gene was not observed in 12.3% of CREs. Ceftazidime-avibactam and meropenem-vaborbactam were active against 100.0% of KPC producers, but ceftazidime-avibactam showed limited activity against MBL producers and meropenem-vaborbactam showed limited activity against OXA-48–like and MBL producers. The most active non–β-lactam comparators against CRE were gentamicin (49.0% susceptible) and amikacin (44.9% susceptible). Conclusions Aztreonam-avibactam demonstrated potent activity against a large collection of Enterobacterales isolated from patients with BSI in US hospitals, including CRE, MBL producers, and isolates resistant to recently approved β-lactamase inhibitor combinations.

Abstract Background Enterobacterales infections in immunocompromised individuals are associated with considerable morbidity, mortality, and health care costs. This study aimed to assess the faecal carriage of extended-spectrum β-lactamase (ESBL) and carbapenemase-producing Enterobacterales (CPE) among HIV-infected patients at Jimma Medical Center. A total of 344 stool samples were collected and inoculated on Mac-Conkey and Eosin-Methylene Blue agar and incubated at 35–37 °C aerobically. ESBL and carbapenemase production were detected using D68C ESBL/AmpC and D73C CARBA plus (Mast Group, UK). Results A total of 376 Enterobacterales were isolated. The prevalence of ESBL-PE and CPE carriage rate was 13.3% (50/376) and 4.3% (16/376) respectively. The highest proportion of ESBL producing isolates were found in K. pneumoniae 29.0% (9/31) followed by E. coli 13.4% (39/292). Similarly, K. pneumoniae 12.9% (4/31) was the most common carbapenem-resistant isolate followed by E. coli 3.8% (11/292). Multi-drug resistance was observed in 66.5% (250/376) of the isolates. Prior cephalosporin use (AOR = 7.9; 2.31–27.29), CD4 count (≤ 350 cells/µL) (AOR = 3.8; 1.12–12.9), and comorbidities (AOR = 2.3; 1.24–4.32) were significantly associated with ESBL production. Additionally, cephalosporin use (AOR = 6.34; 1.27–31.66) was significantly associated with the presence of CRE. Conclusions This study revealed a high prevalence of ESBL-PE and CPE among HIV patients, with K. pneumoniae and E. coli being the dominant isolates. MDR was common, with key risk factors being prior cephalosporin use, low CD4 counts, and comorbidities. These findings emphasize the need for enhanced infection prevention and control, regular screening, and improved antibiotic stewardship to curb the spread of resistant bacteria in immunocompromised individuals.

Abstract Carbapenem resistant (CRE) and carbapenemase producing Enterobacterales (CPE) in particular, represent a major threat for healthcare systems worldwide. Rapid, reliable, and easy to perform assays are required to enable targeted and effective therapy. MALDI-TOF MS based carbapenemase diagnostics has potential advantages over molecular and phenotypic sensitivity tests, especially in terms of time to result. So far, only one mass spectrometry (MS)-based carbapenemase test system is commercially available for routine use. The aim of this study was to compare the performance of the established system to a novel MS-based test to identify CPE isolates. Forty consecutive CRE isolates (70% CPEs) were pre-screened for carbapenemase activity by routine laboratory methods. Isolates then were tested using the to date only IVD CE certified MALDI-TOF MS carbapenemase detection assay (MBT STAR-Carba IVD Kit; Bruker Daltonics) and a novel test designed for the recently launched EXS2600 MALDI-TOF MS system (Carbapenemase Activity Kit; Zybio). Valid results were obtained for 93% and 85% isolates by the Bruker and the Zybio assay, respectively. Sensitivities, specificities, positive and negative predictive values were 92%, 91%, 96%, and 83% for the Bruker assay and 96%, 64%, 85%, and 88% for the Zybio assay. There are notable differences concerning the handling of the assays. In summary, both systems featured high sensitivities for the detection of carbapenemases, but the Bruker assay yielded less false-positive results. There are advantages and disadvantages concerning the handling for each system, but both proved to be suitable for the use in a routine laboratory.

We examined the emergence and characteristics of oxacillinase-484–producing Enterobacterales in France during 2012–2023. Genomic analysis identified 2 predominant sequence types in Escherichia coli: ST410 and ST1722. Plasmid analysis revealed that blaOXA-484 genes were carried mostly on an IncX3-type plasmid associated with genetic elements including insertion sequences IS3000 and ISKpn19.

The in vitro susceptibility testing interpretive criteria (STIC) for piperacillin/tazobactam (TZP) against Enterobacterales were recently updated by the US Food and Drug Administration, Clinical and Laboratory Standards Institute, and European Committee on Antimicrobial Susceptibility Testing. The United States Committee on Antimicrobial Susceptibility Testing (USCAST) also recently reviewed TZP STIC for Enterobacterales and arrived at different STIC for Enterobacterales. Here, we explain our recommendations and rationale behind them. Based on our review of the available data, USCAST does not recommend TZP STIC for certain Enterobacterales species that have a moderate to high likelihood of clinically significant AmpC production (Enterobacter cloacae , Citrobacter freundii , and Klebsiella aerogenes only) or for third-generation cephalosporin-nonsusceptible Enterobacterales. USCAST recommends a TZP susceptibility breakpoint of ≤ 16/4 mg/L for third-generation cephalosporin-susceptible Enterobacterales and only endorses the use of extended infusion TZP regimens for patients with infections due to these pathogens. [ABSTRACT FROM AUTHOR]

Background: Carbapenemase-producing Enterobacterales isolates are associated with significant mortality and have emerged as a major problem in healthcare settings worldwide. Objective: Our aim was to investigate the epidemiological and genotypic characteristics of carbapenemase-positive Enterobacterales isolates from patients hospitalised in three hospitals in the city of Batna, Algeria. Methods: Between 2016 and 2019, a total of 5,316 clinical isolates were obtained. The collected isolates were identified using the VITEK-2 system. Demographic and microbiological data were collected as well as the antimicrobial susceptibility testing, phenotypic and molecular characterisation of carbapenemase and mcr-1 genes were performed. Results: Out of the 5,316 isolates, 201 were carbapenem-resistant Enterobacterales isolates and 179 of them (89.05%) were positive for the production of carbapenemase, of which Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae were the most common. The blaOXA−48−like gene alone was detected in 147 isolates (82.12%) moreover, the blaNDM gene was detected in ten isolates (5.59%). Dual and triple combinations of carbapenemase genes were also observed here for the first time in Algeria: blaVIM and blaOXA−48−like; blaKPC, blaVIM and blaOXA−48−like; blaVIM and blaNDM; blaKPC, blaNDM and blaVIM; blaNDM and blaOXA−48−like genes. In addition, resistance to both colistin and carbapenem antibiotics was detected in eight isolates, however none of them was positive for the mcr-1 gene. Conclusion: This is the first study reporting the detection of carbapenemase genes in Klebsiella aerogenes, Enterobacter sakazakii, Raoultella ornithinolytica, Serratia ficaria, and Serratia marcescens and specific carbapenemase gene combinations in Algeria. The present study revealed that blaOXA−48−like were found to be the predominant carbapenemase genes in Batna hospitals. [ABSTRACT FROM AUTHOR]

Adequate empiric therapy is difficult to choose without monitoring the local distribution of antibiotic-resistant bacteria in each hospital. The frequency of β-lactamase-producing Enterobacterales was compared in patients of therapeutic and surgical units. Antibiotic susceptibility was evaluated by the disk diffusion test. Production of extended-spectrum β-lactamases (ESBLs) was detected by the double-disk test, and carbapenemases were determined by a modified carbapenem inactivation method. Carbapenemase genes and their expression were quantified by real-time PCR and immunochromatography. More than one-third of Enterobacterales isolates produced ESBLs in both the therapeutic (35.51%) and surgical (39.85%) units. The proportions of carbapenemase producers was comparable in the two groups, amounting to 8.41 and 9.77%, respectively. Metallo-β-lactamases predominated in the surgical units; and serine β-lactamases, in the therapeutic units. β-Lactamase producers were less frequent among community-acquired isolates than among nosocomial ones in both therapeutic (31.48 and 56.6%) and surgical (45.45 and 51%) units, but the differences were nonsignificant. Although the proportion of β-lactamase producers in the surgical and therapeutic units was not found to increase over three years of the study, local monitoring should certainly be continued in order to develop a local strategy for adequate use of antibacterial drugs. [ABSTRACT FROM AUTHOR]

The bulb onion (Allium cepa) is second only to tomatoes in value of vegetable crops cultivated worldwide. Water-soaked lesions, bleaching and blight on leaves and slippery skin, sour skin, soft rot near the neck and centre rot on onion bulbs were observed in surveys of the onion fields, storage as well as fruit and vegetable markets of northwestern provinces of Iran in 2020. Thirty-four samples were collected from onion fields of East Azerbaijan, West Azerbaijan and Zanjan provinces and the central storage of Bonab city. Fifty bacterial strains were isolated from symptomatic samples. Pathogenicity of the strains was confirmed by inoculating on onion bulb cultivars Azarshahr and Ghermez Anari. Twenty-eight strains were able to induce soft rot on the inoculated sites of cut onion bulbs. Onion bulbs turned dark brown at lesion sites and became odorous over time. All pathogenic strains were Gram-negative, facultative aerobic and catalase positive. Strains mainly varied in starch and aesculin hydrolysis, potato rot and hypersensitive reaction. Pathogenic strains separated into four groups based on phenotypic assays. In the phylogenetic tree based on concatenated sequences of gyrB and infB genes, the strains were divided into four clusters containing the type strains of Enterobacter ludwigii, Klebsiella variicola, Proteus mirabilis and Pantoea agglomerans, confirming their identity as belonging to these four species. This is the first report of P. mirabilis as a plant pathogen and of K. variicola as a causal agent of onion bulb rot. Moreover, this is the first report of E. ludwigii and P. agglomerans associated with onion bulb rot in Iran. [ABSTRACT FROM AUTHOR]

Plasmid-mediated resistance is a major mechanism that contributes to the gradual decline in the effectiveness of antibiotics from different classes, including carbapenems. Antibiotics can significantly contribute to the efficiency of plasmid transfer between bacterial strains. To investigate the potential effect of an antibiotic on the efficacy of conjugative plasmid transfer, we conducted mating experiments with Klebsiella pneumoniae strains. Donor strains of K. pneumoniae that carry plasmids with blaKPC or blaOXA-48 carbapenemase genes and recipient plasmid-free K. pneumoniae strains were used in matings. Matings were conducted on the agar with or without meropenem at 1/8×, 1/4×, or 1/2×MIC against the respective recipients. In the second part of our study, we investigated the pharmacodynamic properties of meropenem against transconjugant strains of K. pneumoniae, which were obtained in the first part of this study. As a result, at a concentration equivalent to 1/8×MIC, meropenem primarily inhibited conjugation among K. pneumoniae strains, while at a concentration equal to 1/2×MIC, it facilitated conjugation. Transconjugants derived from K. pneumoniae with intermediate MICs failed to respond to simulated treatment with meropenem using prolonged infusion and a high-dose regimen. This finding suggests that such transconjugants may potentially pose a risk if involved in an infectious process. [ABSTRACT FROM AUTHOR]

Aztreonam/avibactam (ATM/AVI) has been recently approved drug for clinical use in the European Union. The aim of this study was to develop and evaluate a novel selective medium for the isolation of ATM/AVI-resistant strains (Super ATM/AVI selective medium) to help to control their spread. Minimum inhibitory concentrations of ATM/AVI were determined using the broth microdilution method for 77 Gram-negative isolates, including 62 Enterobacterales and 15 Pseudomonas aeruginosa. The Super ATM/AVI selective medium was elaborated using optimal final concentrations of ATM at 5 mg/L and AVI at 4 mg/L, being supplemented with amphotericin B and vancomycin to prevent growth of yeasts and Gram-positive bacteria and with ZnSO4 to optimize the expression of metallo-β-lactamase producers. Super ATM/AVI showed high sensitivity (94.6%) and specificity (100%) at a detection limit of 103 CFU/mL. [ABSTRACT FROM AUTHOR]