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.
Highlights
Publisher’s Note: MDPI stays neutralCarbapenem-hydrolyzing class D β-lactamases (CHDLs) have been most frequently found in Acinetobacter spp. [1–3], whereas OXA-48-type enzyme have been identified only in Enterobacterales [4–8]
The range in the kcat /Km covered all the possible scenarios regarding the hydrolysis of imipenem, and how the different possibilities of action for OXA-48 variants with carbapenemase activity were implied, or not
A sensitivity and specificity of 100% for carbapenemase-producing carbapenem-resistant Enterobacterales was initially reported for the Carba NP [30], but other studies have subsequently reported sensitivities
Summary
Publisher’s Note: MDPI stays neutralCarbapenem-hydrolyzing class D β-lactamases (CHDLs) have been most frequently found in Acinetobacter spp. [1–3], whereas OXA-48-type enzyme have been identified only in Enterobacterales [4–8]. [1–3], whereas OXA-48-type enzyme have been identified only in Enterobacterales [4–8]. Since its initial identification in a clinical Klebsiella pneumoniae isolate recovered in Istanbul, Turkey, in 2001 [4,5], an endemic spread of these bacteria has been reported in countries such as Turkey, Morocco, Libya, Egypt, Tunisia, and India [4–8]. In other countries (such as France, Spain, Italy, Belgium, the Netherlands, the UK, Germany, Switzerland, Lebanon, Israel, Kuwait, Saudi Arabia, China, and Japan), increasing descriptions are reported [4–8]. In many western European countries, high prevalence rates of OXA-48 carbapenemases among carbapenemase-producing Enterobacterales (CPEs) have been reported, best exemplified by Spain and France, with 74% and 70%, respectively [8,9]. More than 30 OXA-48-like variants have been reported from clinical. For a complete list of variants, see the “BetaLactamase DataBase” [3], http://bldb.eu/BLDB.php?class=D#OXA, accessed on 13 January
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