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Distribution of carbapenem resistance mechanisms in clinical isolates of XDR Pseudomonas aeruginosa

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Abstract

Our study aims to define the epidemiology of carbapenem resistance mechanisms in clinical isolates of Pseudomonas aeruginosa (PA). We evaluated 11,457 clinical PA strains isolated between 2009 and 2015 at the tertiary care University Hospital in Heidelberg, Germany. Thirty-four percent of the isolates (3867/11,457) were MDR (multidrug-resistant), 16% (1816/11,457) were XDR (extensively drug resistant), and less than 1% (82/11,457) had a PDR (pandrug-resistant) profile. Of those, 23% carried a carbapenemase gene (CPM positive) with 12% VIM-2, 10% VIM-1, and less than 1% IMP-1. Comparing MIC (minimal inhibitory concentration) distributions, the mean rank for meropenem, imipenem, gentamicin, and fosfomycin was significantly higher in the CPM-positive group than in the CPM-negative XDR group (p ≤ 0.004). oprD (outer membrane protein) mutations were found in 19/19 tested strains; 12/19 carried a CPM and had a higher mutation rate. Meropenem resistance was mostly associated with the presence of CPM. Only 1/19 strains was meropenem resistant in the absence of CPM genes; nevertheless, it carried an oprD mutation in a strategic site (loop 2). Of 19 CPM-negative strains tested, 7 (36%) showed EP (efflux pumps) hyperexpression versus 12 in the CPM-positive strains. In our study, nearly 50% of the PA isolates exhibited resistance to the tested first-line antibiotics. Our study also demonstrates that carbapenemase genes can be isolated in approximately 23% of XDR PA strains in our population. This finding supports the clinical relevance of PA driven by the possible presence of multiple resistance mechanisms acquired under exposure to antibiotics or by horizontal transfer of resistance genes.

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Abbreviations

PA:

Pseudomonas aeruginosa

MDR:

Multidrug-resistant

XDR:

Extensively drug-resistant

PDR:

Pandrug-resistant

PTZ:

Piperacillin tazobactam

CAZ:

Ceftazidime

GEN:

Gentamicin

IMP:

Imipenem

MEM:

Meropenem

FOS:

Fosfomycin

ICU:

Intensive care unit

ESBL:

Extended spectrum beta-lactamase

CPM:

Carbapenemases

oprD:

Outer membrane protein gene

OprD:

Outer membrane protein amino acid sequence

EP:

Efflux pumps

PaβN:

Phe-Arg-β-naphthylamide

MBL:

Metallo-beta-lactamases

MIC:

Minimal inhibitory concentration

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Funding

The study was supported by a grant from the Ministry of Science, Research and the Arts of Baden-Württemberg (MWK) within the project “Surveillance von Mehrfach-Antibiotika-Resistenzen“; grant recipient NTM.

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Author notes

  1. Annalisa De Rosa and Nico T. Mutters contributed equally to this work.

Authors and Affiliations

  1. Centre for Infectious Diseases, Heidelberg University Hospital, Heidelberg, Germany

    Annalisa De Rosa, Nico T. Mutters, Stefan J. Kaiser & Frank Günther

  2. Department of Internal Medicine III, Ulm University Hospital, Ulm, Germany

    Annalisa De Rosa

  3. Institute for Infection Prevention and Hospital Epidemiology, Medical Center – University of Freiburg, Freiburg, Germany

    Nico T. Mutters

  4. Department of Infectious Diseases, Sapienza University of Rome, Rome, Italy

    Claudio M. Mastroianni

  5. Institute for Medical Microbiology and Hygiene, Marburg University Hospital, Marburg, Germany

    Frank Günther

Authors
  1. Annalisa De Rosa
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  2. Nico T. Mutters
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  3. Claudio M. Mastroianni
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  4. Stefan J. Kaiser
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  5. Frank Günther
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Corresponding author

Correspondence to Frank Günther.

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Competing interests

The authors declare that they have no competing interests.

Ethical approval

All used isolates were routinely collected in the microbiology laboratory of the Heidelberg University Hospital and stored at − 70 °C. The current study thus is descriptive of those isolates. Data collected from patients was anonymized and restricted to possible clinical symptoms of infection. Ethical approval and informed consent statements were therefore not required.

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De Rosa, A., Mutters, N.T., Mastroianni, C.M. et al. Distribution of carbapenem resistance mechanisms in clinical isolates of XDR Pseudomonas aeruginosa. Eur J Clin Microbiol Infect Dis 38, 1547–1552 (2019). https://doi.org/10.1007/s10096-019-03585-0

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  • DOI: https://doi.org/10.1007/s10096-019-03585-0

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