Co-resistance to ceftazidime-avibactam and cefiderocol in clinical isolates producing KPC variants

Laurent Poirel; Mustafa Sadek; Ayda Kusaksizoglu; Patrice Nordmann

doi:10.1007/s10096-021-04397-x

Co-resistance to ceftazidime-avibactam and cefiderocol in clinical isolates producing KPC variants

Eur J Clin Microbiol Infect Dis. 2022 Apr;41(4):677-680. doi: 10.1007/s10096-021-04397-x. Epub 2022 Jan 28.

Authors

Laurent Poirel^{1

2

3}, Mustafa Sadek^{1

4}, Ayda Kusaksizoglu¹, Patrice Nordmann^{5

6

7

8}

Affiliations

¹ Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Chemin du Musée 18, CH-1700, Fribourg, Switzerland.
² INSERM European Unit (IAME), University of Fribourg, Fribourg, Switzerland.
³ Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland.
⁴ Department of Food Hygiene and Control, Faculty of Veterinary Medicine, South Valley University, Qena, 83523, Egypt.
⁵ Medical and Molecular Microbiology Unit, Department of Medicine, Faculty of Science, University of Fribourg, Chemin du Musée 18, CH-1700, Fribourg, Switzerland. patrice.nordmann@unifr.ch.
⁶ INSERM European Unit (IAME), University of Fribourg, Fribourg, Switzerland. patrice.nordmann@unifr.ch.
⁷ Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland. patrice.nordmann@unifr.ch.
⁸ Institute for Microbiology, University of Lausanne and University Hospital Centre, Lausanne, Switzerland. patrice.nordmann@unifr.ch.

PMID: 35088164
DOI: 10.1007/s10096-021-04397-x

Abstract

Cefiderocol (FDC) and ceftazidime-avibactam (CZA) are among the latest generation of commercialized antibiotics against carbapenem-resistant Gram negatives. However, emergence of CZA resistance is being increasingly reported, involving different KPC variants in Enterobacterales. By analyzing two CZA-resistant KPC-3 clinical variants, KPC-41 and KPC-50, we showed that KPC-41, and to a lesser extent KPC-50, may also have an impact on susceptibility to FDC leading to a cross-resistance. This feature highlights that a susceptibility testing to FDC is mandatory prior any clinical use of FDC for treating infections due to KPC producers.

Keywords: Cefiderocol; Ceftazidime-avibactam; Cross-resistance; KPC-41; KPC-50.

MeSH terms

Anti-Bacterial Agents / pharmacology
Anti-Bacterial Agents / therapeutic use
Azabicyclo Compounds
Bacterial Proteins / genetics
Cefiderocol
Ceftazidime* / pharmacology
Ceftazidime* / therapeutic use
Cephalosporins
Drug Combinations
Humans
Klebsiella pneumoniae
Microbial Sensitivity Tests
beta-Lactamases*

Substances

Anti-Bacterial Agents
Azabicyclo Compounds
Bacterial Proteins
Cephalosporins
Drug Combinations
avibactam, ceftazidime drug combination
Ceftazidime
beta-Lactamases