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Treatment of Infections by OXA-48-Producing Enterobacteriaceae

Journal

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
Volume 62, Issue 11, Pages -

Publisher

AMER SOC MICROBIOLOGY
DOI: 10.1128/AAC.01195-18

Keywords

Enterobacteriaceae; Gram-negative bacteria; antibiotic resistance; carbapenems

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Carbapenemase-producing Enterobacteriaceae (CPE) contribute significantly to the global public health threat of antimicrobial resistance. OXA-48 and its variants are unique carbapenemases with low-level hydrolytic activity toward carbapenems but no intrinsic activity against expanded-spectrum cephalosporins. blaOXA-48 is typically located on a plasmid but may also be integrated chromosomally, and this gene has progressively disseminated throughout Europe and the Middle East. Despite the inability of OXA-48-like carbapenemases to hydrolyze expanded-spectrum cephalosporins, pooled isolates demonstrate high variable resistance to ceftazidime and cefepime, likely representing high rates of extended-spectrum beta-lactamase (ESBL) coproduction. In vitro data from pooled studies suggest that avibactam is the most potent beta-lactamase inhibitor when combined with ceftazidime, cefepime, aztreonam, meropenem, or imipenem. Resistance to novel avibactam combinations such as imipenem-avibactam or aztreonam-avibactam has not yet been reported in OXA-48 producers, although only a few clinical isolates have been tested. Although combination therapy is thought to improve the chances of clinical cure and survival in CPE infection, successful outcomes were seen in similar to 70% of patients with infections caused by OXA-48-producing Enterobacteriaceae treated with ceftazidime-avibactam monotherapy. A carbapenem in combination with either amikacin or colistin has achieved treatment success in a few case reports. Uncertainty remains regarding the best treatment options and strategies for managing these infections. Newly available antibiotics such as ceftazidime-avibactam show promise; however, recent reports of resistance are concerning. Newer choices of antimicrobial agents will likely be required to combat this problem.

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