Dissemination and clinical implications of multidrug-resistant Klebsiella pneumoniae isolates producing OXA-48 in a Spanish hospital

Madueño, Ana; García, J González; Fernández-Romero, Sara; Oteo, Jesús; Lecuona, Marı́a

doi:10.1016/j.jhin.2017.02.024

Cited by 16 publications

(11 citation statements)

References 25 publications

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“…It is important to know the local prevalences of OXA-48 and OXA-48-like ␤-lactamases among clinical isolates so that infections caused by isolates with a higher MIC value for a carbapenem, even if the MIC does not cross the threshold of "resistant," should be considered for treatment options other than carbapenems. Therapeutic options available for treating infections caused by carbapenem-resistant Enterobacteriaceae are often limited to older agents, often with impaired safety profiles, such as aminoglycosides, tigecycline, fosfomycin, and polymyxins (8); in this light, recent reports of colistin-resistant OXA-48-producing isolates are very concerning (67)(68)(69)(70). This study also showed an increased incidence of colistin resistance in OXA-48-producing isolates, with 21.3% of the isolates being nonsusceptible to colistin, compared to only 17% for all Enterobacteriaceae.…”

Section: Discussionmentioning

confidence: 99%

In Vitro Activity of Ceftazidime-Avibactam and Aztreonam-Avibactam against OXA-48-Carrying Enterobacteriaceae Isolated as Part of the International Network for Optimal Resistance Monitoring (INFORM) Global Surveillance Program from 2012 to 2015

Kazmierczak¹,

Bradford

Stone

et al. 2018

Antimicrob Agents Chemother

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Enterobacteriaceae producing the Ambler class D OXA-48 carbapenemase, combined with additional resistance mechanisms, such as permeability defects or cocarriage of class A, B, or C β-lactamases, can become highly resistant to most β-lactams currently in use, including carbapenems. A total of 45,872 Enterobacteriaceae clinical isolates collected in 39 countries as part of the International Network for Optimal Resistance Monitoring (INFORM) global surveillance study in 2012 to 2015 were tested for susceptibility to β-lactams and comparator agents using the Clinical and Laboratory Standards Institute broth microdilution methodology and screened for the presence of β-lactamases. The blaOXA-48 and blaOXA-48-like genes were detected in 333 isolates across 14 species of Enterobacteriaceae collected in 20 countries across the globe. Few agents tested were effective in vitro against the overall collection of OXA-48-producers (n = 265), with tigecycline (MIC90, 2 µg/ml; 92.5% susceptible), ceftazidime-avibactam (MIC90, 4 µg/ml; 92.5% susceptible), and aztreonam-avibactam (MIC90, 0.5 µg/ml; 99.6% of isolates with MIC ≤8 µg/ml) demonstrating the greatest activity. Similarly, colistin (MIC90, 1 µg/ml; 94.2% susceptible), tigecycline (MIC90, 2 µg/ml; 92.6% susceptible), ceftazidime-avibactam (MIC90, >128 µg/ml; 89.7% susceptible), and aztreonam-avibactam (MIC90, 4 µg/ml; 100% of isolates with MIC ≤8 µg/ml) were most active against OXA-48-like-positive isolates (n = 68). The in vitro activity of ceftazidime-avibactam was improved against the subset of metallo-β-lactamase (MBL)-negative, OXA-48- and OXA-48-like-positive isolates (99.2% and 100% susceptible, respectively). The data reported here support the continued investigation of ceftazidime-avibactam and aztreonam-avibactam for the treatment of infections caused by carbapenem-resistant Enterobacteriaceae carrying OXA-48 and OXA-48-like β-lactamases in combination with serine- or metallo-β-lactamases.

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Section: Discussionmentioning

confidence: 99%

In Vitro Activity of Ceftazidime-Avibactam and Aztreonam-Avibactam against OXA-48-Carrying Enterobacteriaceae Isolated as Part of the International Network for Optimal Resistance Monitoring (INFORM) Global Surveillance Program from 2012 to 2015

Kazmierczak¹,

Bradford

Stone

et al. 2018

Antimicrob Agents Chemother

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“…8 It is associated with high-level resistance to β-lactam antibiotics due to the production of extendedspectrum β-lactamases (ESBLs), mainly CTX-M-15, 9 and a diversity of carbapenemases such as KPC-2, KPC-3, NDM-1, OXA-48 and OXA-232. [10][11][12][13][14][15][16] K. pneumoniae ST15 strains in different regions are variable in terms of antimicrobial resistance patterns and resistance genes, which is likely related to the differences in plasmid types carrying antimicrobial resistance genes. 17 Here, we report a clustering of K. pneumoniae ST15 isolates in the cardiac surgery intensive care unit (CSICU), and investigate its molecular characteristics and drug resistance mechanisms, which can provide a basis for the control and prevention of nosocomial infections.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Carbapenem-Resistant Klebsiella pneumoniae ST15 Clone Coproducing KPC-2, CTX-M-15 and SHV-28 Spread in an Intensive Care Unit of a Tertiary Hospital

Yan

Huang

Liu

et al. 2021

IDR

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Objective Nosocomial infection caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) is a great threat to severely ill patients. Here we report an outbreak of K. pneumoniae ST15 isolates co-producing KPC-2, CTX-M-15, and SHV-28 in the cardiac surgery intensive care unit (CSICU) of a tertiary hospital. Materials and Methods From November 2019 to August 2020, all non-duplicated CRKP isolates were collected from the CSICU. The VITEK-2 compact system was used for bacterial identification and antimicrobial susceptibility testing. Clinical data were retrieved from electronic case records. All strains were also subjected to antibiotic resistance genes detection. Clonal relationships were analyzed by multilocus sequence typing (MLST) and pulsed-field gel electrophoresis (PFGE). Results A total of 28 non-duplicated CRKP isolates were collected, including 23 strains belonging to ST15 and 5 strains belonging to ST11. All ST15 isolates were susceptible to amikacin, tigecycline, polymyxin B and ceftazidime/avibactam, but resistant to carbapenems, cephalosporins, quinolones, tobramycin and gentamicin. The detection of resistant determinants showed that 21 strains of ST15 CRKP co-harboured bla KPC-2 , bla CTX-M-15 , bla SHV-28 , bla TEM-1 , bla OXA-1 and aac(6ʹ)-Ib-cr . All the 28 CRKP isolates were classified into five PFGE patterns (A, B, C, D and E), of which type A and B belonged to ST15 and type C, D and E belonged to ST11. PFGE type A was the predominant clonotype of this nosocomial infection and belonged to ST15. Conclusion K. pneumoniae ST15 co-producing KPC-2, CTX-M-15, SHV-28, TEM-1, OXA-1 and aac(6ʹ)-Ib-cr is the predominant clone spread in the CSICU. Surveillance and comprehensive infection control measures should be strengthened in clinical practice.

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“… K. pneumoniae CC15 is a global clone associated with both human and animal infections, identified as an important carrier of extended-spectrum β-lactamases (ESBLs) and carbapenemases, particularly metallo-β-lactamases and OXA-48-like enzymes, worldwide ( 12 – 14 ). There are several reports of ST15 harboring NDM-1 in both Nepal and Pakistan ( 15 , 16 ); OXA-48-like (OXA-48 and OXA-232) in China, Vietnam, Pakistan, and Spain ( 17 – 20 ); KPC-3 in Portugal; and KPC-2 in Bulgaria and China ( 21 – 23 ). The diversity of resistance determinants and plasmid backbones acquired by ST15 clones in the different study locations suggests a high capacity for horizontal acquisition of resistance.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Molecular Description of a High-Copy IncQ1 KPC-2 Plasmid Harbored by the International ST15 Klebsiella pneumoniae Clone

Martins

Nicolás

et al. 2020

mSphere

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This study provides the genomic characterization and clinical description of bloodstream infections (BSI) cases due to ST15 KPC-2 producer Klebsiella pneumoniae. Six KPC-K. pneumoniae isolates were recovered in 2015 in a tertiary Brazilian hospital and were analyzed by whole-genome sequencing (WGS) (Illumina MiSeq short reads). Of these, two isolates were further analyzed by Nanopore MinION sequencing, allowing complete chromosome and plasmid circularization (hybrid assembly), using Unicycler software. The clinical analysis showed that the 30-day overall mortality for these BSI cases was high (83%). The isolates exhibited meropenem resistance (MICs, 32 to 128 mg/liter), with 3/6 isolates resistant to polymyxin B. The conjugative properties of the blaKPC-2 plasmid and its copy number were assessed by standard conjugation experiments and sequence copy number analysis. We identified in all six isolates a small (8.3-kb), high-copy-number (20 copies/cell) non-self-conjugative IncQ plasmid harboring blaKPC-2 in a non-Tn4401 transposon. This plasmid backbone was previously reported to harbor blaKPC-2 only in Brazil, and it could be comobilized at a high frequency (10−4) into Escherichia coli J53 and into several high-risk K. pneumoniae clones (ST258, ST15, and ST101) by a common IncL/M helper plasmid, suggesting the potential of international spread. This study thus identified the international K. pneumoniae ST15 clone as a carrier of blaKPC-2 in a high-copy-number IncQ1 plasmid that is easily transmissible among other common Klebsiella strains. This finding is of concern since IncQ1 plasmids are efficient antimicrobial resistance determinant carriers across Gram-negative species. The spread of such carbapenemase-encoding IncQ1 plasmids should therefore be closely monitored. IMPORTANCE In many parts of the world, carbapenem resistance is a serious public health concern. In Brazil, carbapenem resistance in Enterobacterales is mostly driven by the dissemination of KPC-2-producing K. pneumoniae clones. Despite being endemic in this country, only a few reports providing both clinical and genomic data are available in Brazil, which limit the understanding of the real clinical impact caused by the dissemination of different clones carrying blaKPC-2 in Brazilian hospitals. Although several of these KPC-2-producer K. pneumoniae isolates belong to the clonal complex 258 and carry Tn4401 transposons located on large plasmids, a concomitant emergence and silent dissemination of small high-copy-number blaKPC-2 plasmids are of importance, as described in this study. Our data identify a small high-copy-number IncQ1 KPC plasmid, its clinical relevance, and the potential for conjugative transfer into several K. pneumoniae isolates, belonging to different international lineages, such as ST258, ST101, and ST15.

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Dissemination and clinical implications of multidrug-resistant Klebsiella pneumoniae isolates producing OXA-48 in a Spanish hospital

Cited by 16 publications

References 25 publications

In Vitro Activity of Ceftazidime-Avibactam and Aztreonam-Avibactam against OXA-48-Carrying Enterobacteriaceae Isolated as Part of the International Network for Optimal Resistance Monitoring (INFORM) Global Surveillance Program from 2012 to 2015

In Vitro Activity of Ceftazidime-Avibactam and Aztreonam-Avibactam against OXA-48-Carrying Enterobacteriaceae Isolated as Part of the International Network for Optimal Resistance Monitoring (INFORM) Global Surveillance Program from 2012 to 2015

Characterization of Carbapenem-Resistant Klebsiella pneumoniae ST15 Clone Coproducing KPC-2, CTX-M-15 and SHV-28 Spread in an Intensive Care Unit of a Tertiary Hospital

Clinical and Molecular Description of a High-Copy IncQ1 KPC-2 Plasmid Harbored by the International ST15 Klebsiella pneumoniae Clone

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