OXA-48-like carbapenemases: the phantom menace

Abstract

OXA-48-type carbapenem-hydrolysing class D β-lactamases are increasingly reported in enterobacterial species. To date, six OXA-48-like variants have been identified, with OXA-48 being the most widespread. They differ by a few amino acid substitutions or deletions (one to five amino acids). The enzymes hydrolyse penicillins at a high level and carbapenems at a low level, sparing broad-spectrum cephalosporins, and are not susceptible to β-lactamase inhibitors. When combining permeability defects, OXA-48-like producers may exhibit a high level of resistance to carbapenems. OXA-163 is an exception, hydrolysing broad-spectrum cephalosporins but carbapenems at a very low level, and being susceptible to β-lactamase inhibitors. The bla(OXA-48)-type genes are always plasmid-borne and have been identified in association with insertion sequences involved in their acquisition and expression. The current spread of the bla(OXA-48) gene is mostly linked to the dissemination of a single IncL/M-type self-transferable plasmid of 62 kb that does not carry any additional resistance gene. OXA-48-type carbapenemases have been identified mainly from North African countries, the Middle East, Turkey and India, those areas constituting the most important reservoirs; however, occurrence of OXA-48 producers in European countries is now well documented, with some reported hospital outbreaks. Since many OXA-48-like producers do not exhibit resistance to broad-spectrum cephalosporins, or only decreased susceptibility to carbapenems, their recognition and detection can be challenging. Adequate screening and detection methods are therefore required to prevent and control their dissemination.

VIM‐1 carbapenemase‐producing Escherichia coli in gulls from southern France

“…Acquired carbapenemases currently pose one of the most worrying public health threats related to antibiotic resistance (Gupta, Limbago, Patel, & Kallen, 2011; Poirel, Potron, & Nordmann, 2012). They confer resistance to carbapenems, but also to almost all β‐lactams, the most widely used class of antibiotic, and are encoded by genetic elements that are transferable between bacteria (Krahn et al., 2016; Luca et al., 2017; Potron, Poirel, & Nordmann, 2014).…”

Carbapenem-resistant Enterobacteriaceae in special populations: Solid organ transplant recipients, stem cell transplant recipients, and patients with hematologic malignancies

“…16 Metallob-lactamases (MBLs), including the Verona integronencoded and IMP MBLs, are also present among the Enterobacteriaceae. In contrast to KPC, MBLs require zinc at their active site and do not hydrolyze monobactams.…”

Сarbapenemase-Producing Gram-Negative Bacteria in a Specialized Hospital of St. Petersburg

“…[11]. Начиная с 2010 г. она была об-наружена у госпитальных штаммов бактерий семейства Enterobacteriaceae в cтранах Сред-него Востока, Северной Африки и Европе, а с 2011 г. в России [5,23]. В 2012 г. OXA-48-карбапенемаза была выявлена у мультирези-стентного штамма K. pneumoniae, вызвавшего вспышку госпитальной инфекции в одном из стационаров Москвы [16].…”

“…Различие в уровне чувствительности к карбапенемам может быть связано с функ-ционированием различных механизмов рези-стентности как у наших штаммов, так и у вы-деленных в России другими исследователями. OXA-48 фермент имеет слабую активность в отношении карбапенемов, однако у мульти-резистентных энтеробактерий она часто соче-тается с повышенной экспрессией бета-лакта-маз расширенного спектра (extended-spectrum β-lactamase -ESBL), имеющих некоторую карбапенемазную активность (например, CTX-M бета-лактамаза), и уменьшенной про-ницаемостью наружной мембраны, чем может достигаться высокий уровень резистентности к карбапенемам у OXA-48 продуцентов [23].…”