Ceftazidime/avibactam resistance in Enterobacter cloacae due to the acquisition of a small pHAD28-like plasmid harbouring blaKPC-33

Abstract

Objective

Ceftazidime/avibactam (CZA) is a β-lactam/β-lactamase inhibitor combination with potent activity against class A β-lactamases of Gram-negative bacilli. In recent years, its use and the emergence of CZA-resistant isolates have increased worldwide, including in Colombia. This study aimed to determine the resistome of a CZA-resistant Enterobacter cloacae isolate and a mobile genetic element related to the bla_KPC-33 gene.

Methods

The isolate was recovered from a patient with a long hospital stay who had received initial CZA treatment for bla_KPC-positive E. cloacae (CZA-susceptible) bacteraemia. Later, the patient suffered a urinary tract infection where a carbapenem- and CZA-resistant E. cloacae (ST456; ≥256/4 µg/mL) was isolated. The genome of 37Ecl06 was sequenced via NovaSeq (Illumina, San Diego, CA, USA.) and MinION (Oxford Nanopore Technologies, Oxford, UK), antibiotic resistance genes were determined with ResFinder and CARD, and mobile genetic elements identified with PlasmidFinder and ISFinder.

Results

Whole-genome sequencing revealed 10 resistance determinants in addition to bla_KPC-33, which was mobilised within the conventional Tn4401b transposon, which in turn appeared to be transposed within a small pHAD28-like plasmid. pHAD28-backbone plasmids have mainly been identified in Salmonella spp. isolates recovered from humans, animals, and food.

Conclusion

This is the first report of an E. cloacae isolate harbouring bla_KPC-33. These findings are relevant to continue to understand antimicrobial resistance dissemination mechanisms and to strengthen the One Health approach.