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@article{Boyd:2022:10.1128/aac.00216-22,
author = {Boyd, SE and Holmes, A and Peck, R and Livermore, DM and Hope, W},
doi = {10.1128/aac.00216-22},
journal = {Antimicrobial Agents and Chemotherapy},
title = {OXA-48-like β-lactamases: global epidemiology, treatment options, and development pipeline},
url = {http://dx.doi.org/10.1128/aac.00216-22},
volume = {66},
year = {2022}
}

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TY  - JOUR
AB  - Modern medicine is threatened by the rising tide of antimicrobial resistance, especially among Gram-negative bacteria, where resistance to β-lactams is most often mediated by β-lactamases. The penicillin and cephalosporin ascendancies were, in their turn, ended by the proliferation of TEM penicillinases and CTX-M extended-spectrum β-lactamases. These class A β-lactamases have long been considered the most important. For carbapenems, however, the threat is increasingly from the insidious rise of a class D carbapenemase, OXA-48, and its close relatives. Over the past 20 years, OXA-48 and "OXA-48-like" enzymes have proliferated to become the most prevalent enterobacterial carbapenemases across much of Europe, Northern Africa, and the Middle East. OXA-48-like enzymes are notoriously difficult to detect because they often cause only low-level in vitro resistance to carbapenems, meaning that the true burden is likely underestimated. Despite this, they are associated with carbapenem treatment failures. A highly conserved incompatibility complex IncL plasmid scaffold often carries blaOXA-48 and may carry other antimicrobial resistance genes, leaving limited treatment options. High conjugation efficiency means that this plasmid is sometimes carried by multiple Enterobacterales in a single patient. Producers evade most β-lactam-β-lactamase inhibitor combinations, though promising agents have recently been licensed, notably ceftazidime-avibactam and cefiderocol. The molecular machinery enabling global spread, current treatment options, and the development pipeline of potential new therapies for Enterobacterales that produce OXA-48-like β-lactamases form the focus of this review.
AU  - Boyd,SE
AU  - Holmes,A
AU  - Peck,R
AU  - Livermore,DM
AU  - Hope,W
DO  - 10.1128/aac.00216-22
PY  - 2022///
SN  - 0066-4804
TI  - OXA-48-like β-lactamases: global epidemiology, treatment options, and development pipeline
T2  - Antimicrobial Agents and Chemotherapy
UR  - http://dx.doi.org/10.1128/aac.00216-22
UR  - https://www.ncbi.nlm.nih.gov/pubmed/35856662
UR  - https://journals.asm.org/doi/10.1128/aac.00216-22
UR  - http://hdl.handle.net/10044/1/98647
VL  - 66
ER  -

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