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PubMed1995

Distribution of cphA or related carbapenemase-encoding genes and production of carbapenemase activity in members of the genus Aeromonas.

The prevalence of the cphA gene or related carbapenemase-encoding genes was investigated in 114 Aeromonas strains belonging to the six species of major clinical interest. A species-related distribution of cphA-related sequences was observed. Similar sequences were found in A. hydrophila, A. veronii bv. sobria, A. veronii bv. veronii, and A. jandaei, but not in A. caviae, A. trota, or A. schubertii. However, a single A. caviae strain (of 62 tested) was found carrying cphA-related sequences, suggesting the possibility of the horizontal transfer of this gene to species which normally do not carry it. Production of carbapenemase activity was detectable in 83% of the hybridization-positive strains but in none of the hybridization-negative ones. When it was present, carbapenemase activity was always inhibitable by EDTA. Either carbapenemase-producing or not, Aeromonas strains appeared to be susceptible to imipenem when in vitro susceptibility testing was performed with inocula of conventional size (10(5) CFU), for which MICs were always < or = 1 microgram/ml. With a larger inoculum (10(8) CFU), the MICs for carbapenemase-negative strains always remained < or = 1 microgram/ml, while those for carbapenemase-producing strains were always > or = 4 micrograms/ml, being usually higher than the breakpoint for susceptibility. The present results indicate that the production of metallocarbapenemase activity, apparently encoded by cphA homologs, is widespread among some of the Aeromonas species of clinical interest (A. hydrophila, A. veronii bv. sobria, A. veronii bv. veronii, and A. jandaei) and that imipenem MICs for carbapenemase-producing strains are subjected to a relevant inoculum size effect.

Aeromonas↗

PubMed2026

Performance of seven carbapenemase detection assays in Pseudomonas aeruginosa across different epidemiological settings: a multicenter cross-sectional study.

The detection of carbapenemases in Pseudomonas aeruginosa remains challenging due to a great variety of other resistance mechanisms, and most laboratories, therefore, do not test for them. This study aimed to comparatively evaluate seven phenotypic carbapenemase detection assays across three epidemiological settings. A total of 320 P. aeruginosa isolates from three German centers with varying carbapenemase prevalences (5.8%-51.4%), including 113 carbapenemase-producing isolates carrying VIM-2 (n = 58), NDM-1 (n = 19), and GIM-1 (n = 16), underwent whole-genome sequencing as reference to assess seven phenotypic carbapenemase-detection tests: modified- and modified-zinc-supplemented carbapenem inactivation method (mCIM and mzCIM), simplified carbapenem inactivation method (sCIM), Carba NP, imipenem-cloxacillin test (IC-4000), and two imipenem-EDTA disk assays. Of all confirmation assays, mzCIM and sCIM showed the best overall performance for carbapenemase detection (sensitivity/specificity: 100%/94.2% and 99.1%/92.8%), followed by mCIM (93.8%/96.1%). Carba NP achieved the highest specificity (99.0%), but the lowest sensitivity (85.8%). EDTA-based assays and IC-4000 were highly sensitive (96.5%-100%) but less specific (79.7%-87.0%). Negative predictive values were consistently high (≥98%-100%) across all assays and prevalence settings, whereas positive predictive values varied (72.5%-98.0%). Both mzCIM and sCIM exhibited robust performance for carbapenemase detection in P. aeruginosa, representing the most suitable approach across diverse epidemiological settings. Their high negative predictive values indicate that these assays are particularly effective for ruling out carbapenemase production. Furthermore, both assays are cost-effective, simple to perform, and can be readily implemented in any routine microbiology laboratory.IMPORTANCEThis study provides comparative diagnostic accuracy data for seven phenotypic carbapenemase detection assays in Pseudomonas aeruginosa (PA) across different prevalence settings. Modified-zinc-supplemented carbapenem inactivation method (mzCIM) and simplified carbapenem inactivation method (sCIM) are the most robust screening tools and show that local carbapenemase-producing P. aeruginosa (CP-PA) prevalence substantially influences the utility of all evaluated assays.

CIM↗

PubMed2006

OXA-type carbapenemases.

In recent years, the number of class D beta-lactamases with carbapenem-hydrolysing properties has increased substantially. Based on amino acid sequence identities, these class D or OXA-type carbapenemases are divided into eight distantly related groups, and they are only remotely related to other class D beta-lactamases. A putative ancestor to one of the plasmid-encoded OXA-type carbapenemases has been found. OXA-type carbapenemases are not integrated into integrons as gene cassettes like many class D oxacillinases, but most of the OXA-type carbapenemases are instead encoded by chromosomal genes. Some of these OXA-type carbapenemases are widely dispersed in Pseudomonas aeruginosa and especially in Acinetobacter baumannii. Although most of the OXA-type carbapenemases show only weak carbapenemase activity, carbapenem resistance may result from a combined action an OXA-type carbapenemase and a secondary resistance mechanism such as porin deficiencies or overexpressed efflux pumps. This article reviews the phylogeny and the genetic environments of the encoding genes and kinetic properties of the OXA-type carbapenemases.

Acinetobacter baumannii↗

PubMed2026

Emergence of Acinetobacter soli harboring three carbapenemase-encoding genes (blaNDM-1, blaIMP-14, and blaOXA-58) on a single plasmid in an ICU patient.

Acinetobacter soli is an environmentally adaptable species increasingly recognized as an emerging pathogen in hospital settings, particularly in intensive care units (ICUs). In this study, we report the first A. soli isolate from an ICU patient that co-harbors three carbapenemase-encoding genes (blaNDM-1, blaIMP-14, and blaOXA-58) on a single plasmid. Whole-genome sequencing revealed that multidrug resistance in this strain is mediated by a 294,790 bp plasmid, pSLAB-A, carrying 16 antimicrobial resistance genes, including all three carbapenemases. Comparative plasmid analysis showed a highly conserved backbone but identified a unique ~40 kb multidrug-resistance region containing blaNDM-1, blaIMP-14, and eight additional resistance genes. Genetic context analysis indicated that insertion sequences (ISAba125 and ISAba3) and class 1 integrons contribute to the mobilization and accumulation of carbapenemase-encoding genes. Plasmid stability assays demonstrated that pSLAB-A remained stably maintained for more than 90 generations without antibiotic selection. A global survey of the NCBI database identified 15 A. soli strains carrying carbapenemase-encoding genes, most of which were isolated from China, with clinical specimens representing the predominant source. Seven carbapenemase-encoding genes were detected, with blaNDM-1 being the most prevalent. Among eight isolates with complete genomes, all carried carbapenemase-encoding genes on plasmids. Phylogenetic analysis revealed regional dissemination of a clonal lineage across hospitals in Zhejiang Province and sustained nosocomial transmission within a hospital in Taiwan. These findings suggest that the spread of carbapenem resistance in A. soli is largely driven by multidrug-resistance plasmids, facilitating clonal expansion in hospital environments and posing a growing challenge for antimicrobial therapy and infection control in ICUs.IMPORTANCECarbapenem-resistant A. soli is an emerging clinical concern, capable of causing severe invasive infections, including bacteremia, in intensive care unit settings, and its emergence poses substantial challenges to antimicrobial therapy. In this study, we demonstrate that carbapenem resistance in A. soli is predominantly mediated by the acquisition of multidrug-resistance plasmids carrying carbapenemase-encoding genes. Owing to its strong environmental persistence, A. soli can readily undergo nosocomial clonal dissemination once carbapenem resistance is acquired. Moreover, the spread of multidrug plasmids co-harboring multiple carbapenemase-encoding genes may accelerate the evolutionary trajectory of resistance in A. soli, further exacerbating the threat to clinical management. Given its demonstrated capacity to cause hospital-associated infections and to rapidly acquire multidrug resistance, A. soli warrants heightened vigilance from both clinical and public health perspectives.

beta-Lactamases↗

PubMed2026

Evaluation of carbapenem inactivation method-based phenotypic assays for the detection of GES-type carbapenemases in Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii.

UNLABELLED: Detection of GES-type carbapenemases remains challenging because of their low prevalence and frequently weak hydrolytic activity against carbapenems. Carbapenem inactivation method (CIM)-based assays are widely used as phenotypic screening tools for carbapenemase detection; however, their performance in large collections of GES producers has not been systematically evaluated. We assessed the performance of CIM, modified CIM (mCIM), and CIM-Tris in a diverse collection of GES-producing clinical isolates, including 110 Enterobacterales and 108 Pseudomonas aeruginosa, recovered from Spanish hospitals (2010-2024), and 10 Acinetobacter baumannii isolates, mostly obtained from a hospital in Egypt. Whole-genome sequencing was carried out for species confirmation and resistome analysis. Meropenem MICs were determined by broth microdilution. Overall, 92.1% of isolates were GES-carbapenemase producers (CP), whereas 7.9% expressed GES-type extended-spectrum β-lactamases (ESBLs). In Enterobacterales (predominantly carrying blaGES-6), mCIM improved sensitivity compared with CIM (63.6% vs 40.0%), although many isolates remained undetected due to low meropenem MICs (MIC50, 0.5 µg/mL). In CP-P. aeruginosa (mainly blaGES-5), CIM, mCIM, and CIM-Tris showed sensitivities of 89.1%, 94.6%, and 100%, respectively; however, CIM-Tris yielded false-positive results in 50% of non-CP isolates (mostly blaGES-1 producers). Meropenem MICs in P. aeruginosa were higher (MIC50, >32 µg/mL). In A. baumannii, CIM-Tris improved sensitivity compared with CIM (100% vs 25.0%). These findings indicate that CIM-based methods can detect GES-type carbapenemases, but performance varies according to bacterial species and GES variant, and reduced specificity may occur in isolates producing GES-type ESBLs. Complementary molecular testing may therefore be necessary to ensure accurate detection of GES-type carbapenemases in routine clinical laboratories. IMPORTANCE: GES-type carbapenemases represent an important but underrecognized diagnostic challenge due to their low global prevalence, heterogeneous hydrolytic activity, and the limited performance data available for routine phenotypic detection methods. Although CIM-based assays are widely implemented in clinical microbiology laboratories for carbapenemase screening, their performance against GES-producing organisms has not been comprehensively evaluated across different bacterial genera and GES variants. In this study, we evaluated the performance of CIM, modified CIM (mCIM), and CIM-Tris in a large multicenter collection of well-characterized GES-producing clinical isolates, including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. Our findings demonstrate substantial variability in assay performance according to bacterial species and GES variant. Notably, mCIM improved sensitivity among Enterobacterales with low meropenem MICs, whereas CIM-Tris achieved excellent sensitivity in P. aeruginosa and A. baumannii but at the expense of reduced specificity in isolates producing GES-type ESBLs. To the best of our knowledge, this is the first study directly comparing multiple CIM-based approaches in such a large and taxonomically diverse collection of GES-producing isolates.

beta-Lactamases↗

PubMed2025

Global emergence and transmission dynamics of carbapenemase-producing Citrobacter freundii sequence type 22 high-risk international clone: a retrospective, genomic, epidemiological study.

BACKGROUND: Carbapenemase-producing Citrobacter (CPC) species have recently been recognised as emerging pathogens associated with nosocomial infections in humans. The increased rate of Citrobacter freundii infections is a public health concern and there is a paucity of genomic data regarding its global transmission dynamics. We aimed to characterise the genetic features of CPC species, and their associated carbapenemase-encoding plasmids, obtained from hospitalised patients in China and from publicly available global data, with a particular focus on high-risk clones. METHODS: This was a retrospective, genomic epidemiological study of CPC species obtained from a tertiary hospital in Zhejiang Province, China, from March 5, 2013, to March 5, 2023. We used antimicrobial susceptibility testing, short-read and long-read whole-genome sequencing, phylogenomic analysis, and plasmid structure analysis. A global dataset of complete plasmid sequences encoding blaKPC, blaNDM, and blaIMP was constructed from the National Center for Biotechnology Information (NCBI) RefSeq database to provide insights into their diversity and distribution. All carbapenemase-producing Citrobacter freundii genomes from the NCBI GenBank database were incorporated in the comparative genomic analyses. Bayesian phylogeographical analysis and growth rate assays were carried out to characterise the high-risk C freundii sequence type (ST) 22 clone. FINDINGS: 1724 Citrobacter species isolates were collected from diverse clinical specimens, with 48 identified as CPC species. Citrobacter koseri (22 [46%] of 48) and C freundii (20 [42%]) were the predominant CPC species. Comparative analysis found C freundii carried significantly higher median numbers of plasmid replicons (5·0 [IQR 3·3-6·0] vs 2·0 [2·0-3·0]; p<0·0001) and acquired antimicrobial resistance genes (12·0 [7·3-15·8] vs 3·0 [3·0-5·3]; p<0·0001) than did C koseri. Molecular characterisation identified Inc-type plasmids, In823::Kl.pn.I3/In1589-like/In837-like integrons, Tn6296/Tn125/Tn5060 transposons, and insertion sequences (eg, IS26, IS3000, IS5, ISAba125, ISCR1), collectively facilitating the dissemination of carbapenemase genes. Global analysis of 3126 carbapenemase-encoding plasmids found epidemic plasmids with broad host ranges and global diversity. Phylogenetic investigation of predominant carbapenemase-encoding plasmids showed their persistence across geographical regions, temporal spans, and Enterobacterales species, exhibiting high genetic similarity to our clinical plasmids. A phylogenetic tree of 726 global carbapenemase-producing C freundii genomes showed that ST22 (227 [31·3%]) represents the predominant multidrug-resistant clone across community, health-care, and environmental niches. Transmission across continents contributes to the global predominance of the ST22 clone, which carries a high load of resistance genes (median 15·0 [IQR 11·0-17·0] vs 12·0 [3·0-16·0]; p<0·0001) and enhanced plasmid maintenance capacity (median replicons 5·0 [IQR 4·0-7·0] vs 4·0 [3·0-6·0]; p<0·0001) relative to non-ST22 clones. INTERPRETATION: Our study provides evidence to suggest that Citrobacter species are emerging carriers of carbapenem-resistance genes. These findings provide insight into the population structure of CPC species and highlight C freundii ST22 as a prominent high-risk international clone. FUNDING: National Natural Science Foundation of China, National Health Commission Scientific Research Fund-Zhejiang Provincial Major Health Science and Technology Plan Project, Zhejiang Province Natural Science Foundation Project, Outstanding Youth Foundation of Jiangsu Province of China, the Priority Academic Program Development of Jiangsu Higher Education Institutions, and Postgraduate Research and Practice Innovation Program of Jiangsu Province.

Citrobacter freundii↗

PubMed2000

Carbapenemases: a problem in waiting?

Carbapenems are stable to most prevalent beta-lactamases, and chromosomal carbapenemases are restricted to Stenotrophomonas maltophilia, to a few Bacteroides fragilis, and to rare pathogens. Nevertheless, an acquired metallo-beta-lactamase called IMP-1 is beginning to emerge in Pseudomonas aeruginosa and Enterobacteriaceae isolates in Japan, and has also been found in isolates from Singapore. Furthermore, IMP-producing Acinetobacter spp. have been identified in Italy and Hong Kong. Recently a second group of acquired metallo-carbapenemases, the VIM types, has been recorded from P. aeruginosa isolates in five Eurasian countries. Weak carbapenemases belonging to molecular class D are emerging in A. baumannii world-wide, with two sub-groups apparent. A few acquired carbapenemases belonging to molecular class A also have been reported. Finally it has also been shown that enzymes with feeble carbapenemase activity (e.g. AmpC types and some SHV enzymes) may confer resistance in exceptionally impermeable strains; counterwise, even potent carbapenemases, such as IMP-1, may only give a small reduction in susceptibility in Enterobacteriaceae that lack permeability lesions. Is the emergence of carbapenemase a problem waiting to happen?

Carbapenems↗

PubMed2002

Emerging carbapenemases in Gram-negative aerobes.

Carbapenemases may be defined as beta-lactamases that significantly hydrolyze at least imipenem or/and meropenem. Carbapenemases involved in acquired resistance are of Ambler molecular classes A, B, and D. Class A, clavulanic acid-inhibited carbapenemases are rare. They are either chromosomally encoded (NMC-A, Sme-1 to Sme-3, IMI-1) in Enterobacter cloacae and Serratia marcescens, or plasmid encoded, such as KPC-1 in Klebsiella pneumoniae and GES-2 in Pseudomonas aeruginosa, the latter being a point-mutant of the clavulanic acid-inhibited extended-spectrum beta-lactamase GES-1. The class B enzymes are the most clinically significant carbapenemases. They are metalloenzymes of the IMP or VIM series. They have been reported worldwide but mostly from South East Asia and Europe. Metalloenzymes, whose genes are plasmid and integron located, hydrolyze virtually all beta-lactams except aztreonam. Finally, the class D carbapenemases are increasingly reported in Acinetobacter baumannii but compromise imipenem and meropenem susceptibility only marginally. The sources of the acquired carbapenemase genes remain unknown, as does the relative importance of the spread of epidemic strains as opposed to the spread of plasmid- or integron-borne genes. Because most of these carbapenemases confer only reduced susceptibility to carbapenems in Enterobacteriaceae, they may remain underestimated as a consequence of the lack of their detection.

Amino Acid Sequence↗

PubMed2006

Occurrence and characterization of carbapenemase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program (2000-2004).

Emergence and dissemination of Enterobacteriaceae isolates harboring carbapenemases in various geographic regions represents a significant threat to the management of nosocomial infections. Enterobacteriaceae isolates from the SENTRY Antimicrobial Surveillance Program (2000-2004) demonstrating decreased susceptibility to imipenem and meropenem (minimum inhibitory concentration [MIC], > or =2 mg/L) were evaluated for the production of metallo-beta-lactamases and serine carbapenemases using disk approximation and polymerase chain reaction (PCR) tests. Carbapenemase-producing strains were epidemiologically typed by automated riboprinting and pulsed-field gel electrophoresis (PFGE) to establish clonality. Among 37,557 Enterobacteriaceae (5 genus groups) evaluated, 119 (0.32%) had increased carbapenem MIC values, and a carbapenemase was identified in 51 (42.9%) of these strains. KPC-2 and KPC-3 were the most frequently occurring carbapenemases (24 isolates, 20.2%) in the United States and were detected in Klebsiella spp, Citrobacter spp., Enterobacter spp., and Serratia marcescens strains isolated in New York, Arkansas, and Virginia. SME-2-producing S. marcescens were isolated in the New York City area, Texas, and Ohio, while NMC-A was found in one E. cloacae strain from New York. In contrast, metallo-beta-lactamases were prevalent in Europe. IMP-1-producing E. cloacae (11 isolates) were detected in Turkey, while VIM-1-producing strains were found in Italy (Enterobacter spp.) and Greece (Klebsiella pneumoniae). Clonal dissemination of carbapenemase-producing strains was observed in several medical centers on both continents. The occurrence of carbapenemases in various Enterobacteriaceae remains rare but appears to be spreading geographically (not in Latin America), mainly with metallo-beta-lactamases being found in Mediterranean Europe and KPC enzymes in the New York City area.

Anti-Bacterial Agents↗

PubMed2002

The impact of carbapenemases on antimicrobial development and therapy.

Carbapenems have been the most successful beta-lactam antibiotics in evading bacterial resistance. Nevertheless, acquired carbapenemases are increasingly reported, mostly in Pseudomonas and Acinetobacter isolates but occasionally also in Enterobacteriaceae. They include beta-lactamases of classes B (IMP and VIM), D (OXA-23 to -27) and A (IMI, KPC, NMC and SME). Major outbreaks of producers have occurred in a few centers and, in the US, there has been progressive erosion of carbapenem activity against Acinetobacter species, maybe due to carbapenemases. Acquired carbapenemases are still sufficiently rare not to have placed widespread constraints on chemotherapy, but there is reasonable concern that they will become a greater problem in the future. This is a good argument for continued caution with carbapenem use, and for extending this prudence to the oral and long half-life carbapenems shortly to become available. Most carbapenemase producers are broadly resistant to beta-lactams, and many are also resistant to fluoroquinolones and aminoglycosides. Clinicians facing infections caused by carbapenemase producers consequently are forced to use 'unusual' antibiotics such as polymyxins, isepamicin, minocycline and sulbactam (Pfizer Inc), which has inherent activity against A baumannii. Carbapenemase inhibitors might be developed in the future, despite difficulties in choosing the range of enzymes to target and obtaining broad-spectrum inhibition. For now, the best pharmaceutical strategy seems to lie in the development of novel antimicrobial classes with anti-Gram-negative activity, rather than in overcoming carbapenemases directly.

Acinetobacter↗

PubMed2026

Persistent spread of carbapenemase-producing Klebsiella pneumoniae in acute care hospitals in 36 European countries (the CCRE survey): a prospective, multicentre, cross-sectional, epidemiological, microbiological, and genomic surveillance study.

BACKGROUND: Carbapenem-resistant Enterobacterales pose a substantial threat to patients and health-care systems. We conducted a survey of carbapenem-resistant and/or colistin-resistant Enterobacterales (CCRE survey) in 37 European countries to describe their occurrence, geographical distribution, and population dynamics and inform control policies. We report the results of Klebsiella pneumoniae species complex isolates in this study. METHODS: In this cross-sectional, epidemiological, microbiological, and genomic study conducted in all EU, European Economic Area and EU candidate countries as of 2019, hospital microbiology laboratories were selected on the basis of population coverage. Participating laboratories collected, from patient samples, the first ten successive isolates of carbapenem-resistant or carbapenem-susceptible increased exposure (carbapenem-R/I) K pneumoniae species complex or Escherichia coli, and carbapenem-susceptible (carbapenem-S) comparator isolates of the same species, accompanied by patient epidemiological and clinical information. Isolate collection started in 2019, with three possible starting dates-ie, March 1, April 1, or May 1, 2019, and ended after collection of ten carbapenem-R/I and carbapenem-S isolates or a maximum period of 6 months. Isolates were tested for phenotypic susceptibility to 16 antimicrobial agents of relevance to K pneumoniae species complex. Whole-genome sequencing was performed centrally using Illumina technology. Isolates from the CCRE survey were compared with those from the European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) study. FINDINGS: 1566 carbapenem-R/I and 1407 carbapenem-S K pneumoniae species complex isolates collected from patients in 302 hospitals in 36 countries (one country did not send isolates) were analysed in this study. The high-risk lineages identified during a previous similar survey in 2013-14 (EuSCAPE) were found to continue to circulate across European hospitals in 2019 (ST11, ST15, ST101, and ST258/512). Moreover, concerning shifts in the pathogen population were observed. First, a higher proportion of carbapenem-R/I isolates was found to carry a carbapenemase gene in the CCRE survey (1398 [89·3%] of 1566) than in EuSCAPE (657 [69·6%] of 944), mainly related to increased acquisition of carbapenemase genes by high-risk lineages. Of note, among ST307 isolates from all hospitals, the proportion of carbapenem-R/I isolates carrying a carbapenemase gene increased from 14 (60·9%) of 23 in EuSCAPE to 164 (91·1%) of 180 in the CCRE survey. Second, an expansion of emerging multidrug-resistant lineages (ST147, ST307, and ST39) was also noted: Among 113 hospitals that contributed K pneumoniae species complex isolates to both EuSCAPE and the CCRE survey, the proportion of ST147 increased from 16 (3·4%) of 476 in EuSCAPE to 49 (7·4%) of 662 carbapenem-R/I isolates in the CCRE survey, that of ST307 increased from 15 (3·2%) of 476 to 88 (13·3%) of 662, and that of ST39 increased from 3 (0·6%) of 476 to 10 (1·5%) of 662. Third, there was an increased spread of isolates harbouring acquired virulence loci: isolates with the highest Kleborate virulence score of five increased from 7 (0·4%) of 1717 in EuSCAPE to 40 (1·3%) of 2973 in the CCRE survey. Notably, the increase was mainly observed in the carbapenem-S-group. INTERPRETATION: The survey findings portray an escalating epidemiological situation and suggest that control measures have not been able to interrupt transmission of high-risk lineages of carbapenemase-producing K pneumoniae in European hospitals. The heterogeneous and evolving situation with regards to circulating lineages and dominant carbapenemase genes requires strengthening and continuous adaptation of diagnostic, treatment, and control measures guided by genomic surveillance. FUNDING: European Centre for Disease Prevention and Control and Centre for Genomic Pathogen Surveillance.

Humans↗

PubMed1996

The 'hidden' carbapenemase of Aeromonas hydrophila.

It has been presumed that there are just two beta-lactamases in the motile Aeromonas species, a carbapenemase and a cephalosporinase, based on the premise that all beta-lactamases can be detected by hydrolysis of the chromogenic cephalosporin, nitrocefin. However, when it was recently found that a non-motile species of Aeromonas that causes furunculosis in salmon, contained three beta-lactamases, one of which was a carbapenemase which could not be detected with nitrocefin, it was hypothesised that genetic exchange could occur between fish pathogens and human pathogens resulting in the transfer of the carbapenemase-encoding gene. This could have a potentially serious impact on intensive therapy units where carbapenems are employed. The purpose of this study was to determine whether the human pathogen Aeromonas hydrophila demonstrated the same beta-lactamase profile. After anion and cation exchange chromatography had been employed to separate the beta-lactamases of a clinical strain of A. hydrophila, three different beta-lactamases were found, one of which is a carbapenemase which does not hydrolyse nitrocefin. It is, therefore, probable that many strains of Aeromonas spp. contain a similar array of beta-lactamases which include a carbapenemase that cannot be detected with nitrocefin. Similar carbapenemases may well remain hidden in other species of bacteria unless appropriate techniques to detect the enzymes are employed.

Aeromonas hydrophila↗

PubMed2026

Coexistence of carbapenemase and hypervirulence-associated genes among Klebsiella pneumoniae high-risk clones in Hungary.

INTRODUCTION: Strains of Klebsiella pneumoniae carrying hypervirulence and carbapenemase genes represent a rapidly emerging global public health threat. Our study aimed to comprehensively characterise the genomics of hypervirulence-associated and carbapenemase genes carrying K. pneumoniae (hv(a)CpKp) isolates in Hungary. MATERIALS AND METHODS: Between January 2022 and April 2024, 89 aerobactin (iucA-D/iutA)-positive non-duplicate carbapenemase-producing K. pneumoniae isolates from 15 Hungarian healthcare institutes underwent short-read (Illumina, MiSeq, NextSeq) whole-genome sequencing, followed by detailed plasmid analysis using long-read sequencing (Nanopore, MinION) in a representative subset of 32 strains. RESULTS: Most isolates (79/89) belonged to the high-risk clone ST147. Hypervirulence-associated (hva) genes-including rmpA/rmpA2, peg344, shiF, iucA-D, and iutA-were universally present, and 59 isolates possessed chromosomally integrated yersiniabactin loci. Most isolates (87/89) carried the bla NDM-1 carbapenemase gene. Hypervirulence-associated genes were most frequently (29/32) associated with IncHI1B/IncFIB(Mar) plasmids. Notably, we identified plasmids carrying both hva and carbapenemase genes-designated as hybrid plasmids-in 13 of 32 strains. The bla NDM-1 was linked to the IS26 transposase and was present in conserved, identical cassettes on all bla NDM-1-carrying plasmids. DISCUSSION/CONCLUSION: Our study identified hv(a)CpKp strains, particularly the ST147 clone, circulating in Hungary. Our findings highlight the need for routine virulence gene monitoring and continuous genomic and plasmid-based surveillance to mitigate the clinical and epidemiological impact of emerging hv(a)CpKp lineages.

Klebsiella pneumoniae↗

PubMed2005

Comparison of two methods to detect carbapenemase & metallo-beta- lactamase production in clinical isolates.

BACKGROUND & OBJECTIVE: Bacterial resistance has greatly hampered effective treatment of patients in clinical settings. Non-fermenting Gram-negative bacilli (NFGNB) are common nosocomial pathogens. In this study we attempted to develop a convenient test for early detection of carbapenemase and metallo-beta-lactamase (MbetaL) production in NFGNB. Lack of sufficient reports from India in this area indicated the need for this study. METHODS: A total of 50 imipenem resistant NFGNB were speciated, and their resistance reconfirmed by disk diffusion and minimum inhibitory concentration (MIC) determination by agar dilution. Two different methods namely modified Hodge and EDTA disk synergy tests were evaluated for carbapenemase and metallo-beta-lactamase (MbetaL) production. RESULTS: Of the 50 imipenem resistant NFGNB, 48 and two respectively fell in the resistant and intermediate range in MIC using agar dilution. Majority of these were Pseudomonas aeruginosa (n=28), followed by Burkholderia cepacia (n=9). The modified Hodge test could detect 28 strains as carbapenemase and MbetaL producers, while the EDTA disk synergy test was able to detect an additional 8 strains producing MbetaL and carbapenemase. INTERPRETATION & CONCLUSION: Pseudomonas aeruginosa was found to be the predominant NFGNB in our hospital setting and EDTA disk synergy could detect more carbapenemase and metallo-beta- lactamase producers compared to modified Hodge test.

Anti-Bacterial Agents↗

PubMed2000

Carbapenemases of Chryseobacterium (Flavobacterium) meningosepticum: distribution of blaB and characterization of a novel metallo-beta-lactamase gene, blaB3, in the type strain, NCTC 10016.

Genes encoding carbapenemases in 15 reference strains of Chryseobacterium (Flavobacterium) meningosepticum from the United Kingdom National Collection of Type Cultures and in one recent clinical isolate were investigated. All the strains hydrolyzed imipenem, but their levels of resistance to carbapenems varied, with imipenem and meropenem MICs ranging from 2 to >32 microg/ml. The blaB gene, which encodes a molecular-class B carbapenemase, was detected in only six reference strains and in clinical isolate 97/P/5448. The gene from 97/P/5448 had 98% nucleotide identity with the published sequence of blaB (from strain NCTC 10585) and was designated blaB2. A distinct carbapenemase gene, designated blaB3, was cloned from the type strain of C. meningosepticum, NCTC 10016. blaB3 had an open reading frame of 750 bp with 82% nucleotide identity to blaB and blaB2 and encoded a beta-lactamase of 249 amino acids, including the putative signal peptide. This beta-lactamase showed 87.6 and 86.7% amino acid homology with BlaB and BlaB2, respectively. blaB3 was detected in one other reference strain besides NCTC 10016, but the genetic basis of the carbapenemase activity detected in the other seven reference strains was not defined. Thus, neither blaB nor blaB3 was ubiquitous in the strains of C. meningosepticum studied, indicating that the reference strains may represent more than one bacterial species, each with its own intrinsic metallo-beta-lactamase. Further taxonomic studies of C. meningosepticum are necessary to resolve this topic. Chryseobacterium spp. are environmental organisms and occasional opportunist pathogens. They apparently represent a reservoir of diverse metallo-beta-lactamases, which potentially spread to gram-negative bacteria of greater clinical significance.

Amino Acid Sequence↗

PubMed2026

Emergence and persistence of ESBL- and carbapenemase-producing Klebsiella pneumoniae-related species in Barcelona wastewater treatment plants.

The World Health Organization classifies extended-spectrum beta-lactamase (ESBL) and carbapenemase-producing Klebsiella pneumoniae as critical-priority pathogens due to their high incidence, mortality, transmissibility, rapid resistance acquisition, and limited treatment options. Beyond clinical settings, their detection in wastewater treatment plants (WWTPs) provides an opportunity to assess their prevalence, persistence, and circulation within wastewater systems. This study characterized 37 antibiotic-resistant K. pneumoniae-related species strains isolated from two WWTPs in the metropolitan area of Barcelona, analyzing their antimicrobial resistance (AMR) profiles, antimicrobial resistance genes (ARGs), biocide and heavy metal tolerance genes (HMTGs), virulence factor genes (VFGs), biofilm-forming capacity, and conjugation ability. Among them, 70.3% were multidrug-resistant (MDR), and 16.2% were extensively drug-resistant. Whole-genome sequencing revealed diverse ARGs; all strains carried β-lactam resistance genes (14 ESBL and 12 carbapenemase producers), nearly all (96.9%) carried biocide or HMTGs, 64.9% harbored integrases, and all carried VFGs. Core-genome SNP analysis identified closely related strains across sampling periods and treatment stages, suggesting long-term persistence within the wastewater treatment system, despite biological and chemical processes in secondary treatment. Most strains (67.6%) displayed biofilm-forming capacity, and conjugation assays confirmed horizontal gene transfer in five of the seven ESBL-producing strains tested. High-risk clones were predominantly detected in the IFAS secondary treatment stage of the Gavà-Viladecans WWTP. The three strains recovered from the reclaimed water of the Baix Llobregat WWTP were ESBL or carbapenemase producers. Altogether, these results provide genomic and phenotypic evidence of the persistence and circulation of antibiotic-resistant K. pneumoniae-related species within wastewater treatment systems.IMPORTANCEWWTPs are essential for urban sanitation and environmental protection. Understanding how clinically relevant pathogens, such as ESBL and carbapenemase-producing K. pneumoniae-related species strains, behave in these settings may inform public health considerations. Investigating the presence and persistence of high-risk MDR pathogens in WWTPs helps identify circulation of AMR, assess the risk of gene transfer, and evaluate the potential for co-selection with other contaminants. This knowledge supports efforts to improve wastewater treatments, strengthen environmental surveillance, and develop integrated One Health strategies to limit the spread of AMR across human, animal, and environmental sectors.

Wastewater↗

PubMed2006

Outbreaks of imipenem-resistant Acinetobacter baumannii producing carbapenemases in Korea.

Among 53 Acinetobacter baumannii isolates collected in 2004, nine imipenem-resistant isolates were obtained from clinical specimens taken from patients hospitalized in Busan, Korea. Nine carbapenemase-producing isolates were further investigated in order to determine the mechanisms underlying resistance. These isolates were then analyzed via antibiotic susceptibility testing, microbiological tests of carbapenemase activity, pI determination, transconjugation test, enterobacterial repetitive consensus (ERIC)-PCR, and DNA sequencing. One outbreak involved seven cases of infection by A. baumannii producing OXA-23 beta-lactamase, and was found to have been caused by a single ERIC-PCR clone. During the study period, the other outbreak involved two cases of infection by A. baumannii producing IMP-1 beta-lactamase. The two clones, one from each of the outbreaks, were characterized via a modified cloverleaf synergy test and an EDTA-disk synergy test. The isoelectric focusing of the crude bacterial extracts detected nitrocefin-positive bands with pI values of 6.65 (OXA-23) and 9.0 (IMP-1). The PCR amplification and characterization of the amplicons via direct sequencing showed that the clonal isolates harbored blaIMP-1 or blaOXA-23 determinants. The two clones were characterized by a multidrug resistance phenotype that remained unaltered throughout the outbreak. This resistance encompassed penicillins, extended-spectrum cephalosporins, carbapenems, monobactams, and aminoglycosides. These results appear to show that the imipenem resistance observed among nine Korean A. baumannii isolates could be attributed to the spread of an IMP-1- or OXA-23-producing clone. Our microbiological test of carbapenemase activity is a simple method for the screening of clinical isolates producing class D carbapenemase and/or class B metallo-beta-lactamase, in order both to determine their clinical impact and to prevent further spread.

Acinetobacter Infections↗

PubMed2026

Global epidemiology, genomic evolution, and clinical implications of dual- and multiple-carbapenemase-producing Klebsiella pneumoniae: A systematic qualitative review.

BACKGROUND: The global emergence of dual- and multiple-carbapenemase-producing Klebsiella pneumoniae, particularly isolates co-harbouring blaNDM and blaOXA-48/OXA-48-like determinants, represents a critical threat to global health because of limited therapeutic options and expanding genomic complexity. METHODS: This systematic qualitative review synthesized evidence from 44 English-language peer-reviewed studies published between 2017 and 2026 and indexed in Scopus, with a focus on genomic evolution and spatiotemporal distribution. RESULTS: High-risk clones ST147, ST101, and ST11 were identified as major drivers of dissemination. Genomic analysis revealed key adaptive mechanisms, including stable IncL 96-kb fusion plasmids and IS10-mediated truncation of blaNDM-1, potentially reducing fitness costs while preserving resistance. Convergence events were also documented in which dual-carbapenemase-producing isolates acquired additional colistin resistance determinants (mcr-1 or mgrB alterations) and virulence-associated markers such as iuc1. Importantly, related resistance determinants were identified beyond hospital settings, including community, environmental, and food-associated reservoirs. CONCLUSION: The shift from single to dual and multiple carbapenemase production in K. pneumoniae underscores the need for integrated genomic surveillance, improved antimicrobial stewardship, and broader reservoir monitoring to address this evolving public health threat.

Klebsiella pneumoniae↗