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

Abstract

Objetives: 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 Colombia. The study aimed was to determine the resistome of a CZA-resistant Enterobacter cloacae isolate and 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 an initial treatment with CZA for a bla_KPC-positive E. cloacae (CZA-susceptible) bacteremia. Later, the patient suffered a urinary tract infection where an E. cloacae (ST456) carbapenem and CZA-resistant (≥ 256/4 ug/mL) was isolated. The genome of 37Ecl06 was sequenced by NovaSeq (Illumina) and MinION (Oxford NanoporeTechnologies), antibiotic resistance genes were determined with ResFinder and CARD, and mobile genetic elements with PlasmidFinder and ISFinder.

Results: Whole genome sequencing (WGS) revealed 10 resistance determinants in addition to blaKPC-33, this gene was mobilized within the conventional Tn4401b transposon, which was in turn apparently transposed within a small pHAD28-like plasmid. The 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 harboring bla_KPC-33. These findings are relevant to continue to understand the antimicrobial resistance dissemination mechanisms and to strengthen the one health approach.