To Be or Not to Be an OXA-48 Carbapenemase

Abstract

Since the first description of OXA-48, more than forty variants have been recovered from Enterobacterales isolates. Whereas some OXA-48-related enzymes have been reported as conferring similar resistance patterns, namely, the hydrolysis of carbapenems and penicillins with very weak or almost no activity against expanded-spectrum cephalosporins, some have reduced carbapenem and temocillin hydrolysis, and others hydrolyze expanded-spectrum cephalosporins and carbapenems only marginally. With such drastic differences in the hydrolytic profile, especially of carbapenems, it becomes urgent to establish hydrolytic cutoffs in order to determine when an OXA-48-like enzyme may be considered as a carbapenemase or not. With this aim, the coefficient of activity for imipenem (kcat/Km) was determined for a total of 30 enzymes, including OXA-48, OXA-48-like natural variants, and OXA-48 synthetic mutants. In addition, six different methods for the detection of carbapenemase-producers were performed. The coefficients of activity for imipenem for all the different enzymes went from 550 mM−1·s−1 to 0.02 mM−1·s−1. In order to match the coefficient of activity results with the biochemical confirmatory tests, we suggest the value of 0.27 mM−1·s−1 as the cutoff above which an OXA-48 variant may be considered a carbapenem-hydrolyzing enzyme.

Detection of Acquired Antibiotic Resistance Genes in Domestic Pig (Sus scrofa) and Common Carp (Cyprinus carpio) Intestinal Samples by Metagenomics Analyses in Hungary

“…OXA-type carbapenemases have not yet been reported from livestock samples in Hungary. The carbapenem-hydrolyzing class D β-lactamases of the OXA-48-type are of great concern because of their rapid worldwide spread and their propensity to evolve by mutations, leading to various phenotypic characteristics, wherein OXA-48-type enzymes have so far been identified only in the Enterobacterales [ 66 ]. Over the past two decades, OXA-48-like enzymes have become the most prevalent carbapenemases among the Enterobacteriaceae across much of Europe, North Africa, and the Middle East.…”

Structural and Biochemical Features of OXA-517: a Carbapenem and Expanded-Spectrum Cephalosporin Hydrolyzing OXA-48 Variant

“…OXA-48 hydrolyzes penicillins at a high level, carbapenems at a low level and lacks significant hydrolytic activity towards expanded-spectrum cephalosporin (ESC) (5). While some OXA-48-variants with single amino acid substitutions have similar hydrolytic profiles as OXA-48, others, such as OXA-163 or OXA-405, carry a four-amino-acid deletion that results in the loss of carbapenemase activity and a gain of the ability to hydrolyze expanded-spectrum cephalosporins (5,(7)(8)(9). A novel OXA-48-variant, OXA-438, with two AA deletions and four AA changes in the β5-β6 loop, has been described with increased ability to hydrolyze carbapenems and decreased inactivation of oxyimino-cephalosporins compared to OXA-163 (9,10).…”

Recombinase Polymerase Amplification Combined with Lateral Flow Strip for Rapid Detection of OXA-48-like Carbapenemase Genes in Enterobacterales

“…To date, OXA-48-like-producing Enterobacterales clinical isolates have emerged globally, including Europe, North Africa, the Middle East, the Indian subcontinent, Asia and sub-Saharan African countries [ 9 , 10 ]. The OXA-48 carbapenemase group includes OXA-48, OXA-162, OXA-181, OXA-204, OXA-232, OXA-244, OXA-245, OXA-438, OXA-484, OXA-517 and OXA-519.…”

“…The common variants from most to least are OXA-48, OXA-181, OXA-232, OXA-204, OXA-162 and OXA-244. However, some OXA-48-like enzymes, such as OXA-163, OXA-247 and OXA-405, have no carbapenemase activity [ 10 ]. Phenotypic tests for identifying OXA-48-like carbapenemases have drawbacks due to their weak carbapenemase activity and the unavailability of suitable inhibitors [ 11 ].…”