German Multicenter Study Analyzing Antimicrobial Activity of Ceftazidime-Avibactam of Clinical Meropenem-Resistant Pseudomonas aeruginosa Isolates Using a Commercially Available Broth Microdilution Assay

Jana Manzke; Raphael Stauf; Bernd Neumann; Ernst Molitor; Gunnar Hischebeth; Michaela Simon; Jonathan Jantsch; Jürgen Rödel; Sören L Becker; Alexander Halfmann; Thomas A Wichelhaus; Michael Hogardt; Annerose Serr; Christina Hess; Andreas F Wendel; Ekkehard Siegel; Holger Rohde; Stefan Zimmermann; Jörg Steinmann

doi:10.3390/antibiotics11050545

German Multicenter Study Analyzing Antimicrobial Activity of Ceftazidime-Avibactam of Clinical Meropenem-Resistant Pseudomonas aeruginosa Isolates Using a Commercially Available Broth Microdilution Assay

Antibiotics (Basel). 2022 Apr 19;11(5):545. doi: 10.3390/antibiotics11050545.

Authors

Jana Manzke¹, Raphael Stauf¹, Bernd Neumann¹, Ernst Molitor², Gunnar Hischebeth², Michaela Simon³, Jonathan Jantsch^{3

4}, Jürgen Rödel⁵, Sören L Becker⁶, Alexander Halfmann⁶, Thomas A Wichelhaus⁷, Michael Hogardt⁷, Annerose Serr⁸, Christina Hess⁸, Andreas F Wendel⁹, Ekkehard Siegel¹⁰, Holger Rohde¹¹, Stefan Zimmermann¹², Jörg Steinmann^{1

13}

Affiliations

¹ Institute of Clinical Hygiene, Medical Microbiology and Infectiology, Paracelsus Medical University, Klinikum Nürnberg, 90419 Nuremberg, Germany.
² Institute of Medical Microbiology, Immunology and Parasitology, University Hospital Bonn, 53127 Bonn, Germany.
³ Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, 93053 Regensburg, Germany.
⁴ Institute for Medical Microbiology, Immunology, and Hygiene, University Hospital Cologne and Faculty of Medicine, University of Cologne, 50937 Cologne, Germany.
⁵ Institute of Medical Microbiology, Jena University Hospital, 07743 Jena, Germany.
⁶ Institute of Medical Microbiology and Hygiene, Saarland University, 66421 Homburg, Germany.
⁷ German National Consiliary Laboratory on Cystic Fibrosis Bacteriology, Institute of Medical Microbiology and Infection Control, University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany.
⁸ Department for Medical Microbiology and Hygiene, University Hospital Freiburg, 79106 Freiburg, Germany.
⁹ Institute of Hygiene, Cologne Merheim Medical Centre, University Hospital of Witten/Herdecke, 51058 Cologne, Germany.
¹⁰ Institute for Medical Microbiology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
¹¹ Institute for Medical Microbiology, Virology and Hygiene, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
¹² Department of Infectious Diseases, University Hospital Heidelberg, 69120 Heidelberg, Germany.
¹³ Institute of Medical Microbiology, University Hospital Essen, 45122 Essen, Germany.

Abstract

Multidrug resistance is an emerging healthcare issue, especially concerning Pseudomonas aeruginosa. In this multicenter study, P. aeruginosa isolates with resistance against meropenem detected by routine methods were collected and tested for carbapenemase production and susceptibility against ceftazidime-avibactam. Meropenem-resistant isolates of P. aeruginosa from various clinical materials were collected at 11 tertiary care hospitals in Germany from 2017−2019. Minimum inhibitory concentrations (MICs) were determined via microdilution plates (MICRONAUT-S) of ceftazidime-avibactam and meropenem at each center. Detection of the presence of carbapenemases was performed by PCR or immunochromatography. For meropenem-resistant isolates (n = 448), the MIC range of ceftazidime-avibactam was 0.25−128 mg/L, MIC90 was 128 mg/L and MIC50 was 16 mg/L. According to EUCAST clinical breakpoints, 213 of all meropenem-resistant P. aeruginosa isolates were categorized as susceptible (47.5%) to ceftazidime-avibactam. Metallo-β-lactamases (MBL) could be detected in 122 isolates (27.3%). The MIC range of ceftazidime-avibactam in MBL-positive isolates was 4−128 mg/L, MIC90 was >128 mg/L and MIC50 was 32 mg/L. There was strong variation in the prevalence of MBL-positive isolates among centers. Our in vitro results support ceftazidime-avibactam as a treatment option against infections caused by meropenem-resistant, MBL-negative P. aeruginosa.

Keywords: carbapenemases; ceftazidime-avibactam; susceptibility testing.

Abstract

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