Treatment of Infections by OXA-48-Producing Enterobacteriaceae

Abstract

Carbapenemase-producing (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. 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. 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 ∼70% of patients with infections caused by OXA-48-producing 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.

Genomic Epidemiology of Carbapenem- and Colistin-Resistant Klebsiella pneumoniae Isolates From Serbia: Predominance of ST101 Strains Carrying a Novel OXA-48 Plasmid

“…In fact, even if most isolates (91%) were susceptible to imipenem, carbapenems have been proven to be not effective in an in vivo murine model (Wiskirchen et al, 2014). Moreover, there have been a number of case reports and series describing treatment failures with carbapenemcontaining regimens in the treatment of OXA-48-producing bacterial infections (Stewart et al, 2018). Ceftazidime-avibactam may represent an effective alternative against such isolates, as previously reported (Kazmierczak et al, 2018).…”

Phenotypic and Molecular Characterization of Carbapenem-Resistant Enterobacteriaceae from Clinical Bacterial Isolates: A Multicenter Retrospective Chart Review Study in western of Saudi Arabia

“…(20,31) Furthermore, though OXA-48 pathogens have a high ability to rapidly mutate and thereby expanding their spectrum of activity (7), less resistance was observed in them. (32,33). These results show that there is signi cant variability in the susceptibility of different CRE isolates to different antimicrobial agents.…”

Managing All the Genotypic Knowledge: Approach to a Septic Patient Colonized by Different Enterobacteriales with Unique Carbapenemases

“…The advent of combination antibiotics containing novel beta-lactamase inhibitors (BLI) has expanded treatment options for CPE infections; however, these agents are not created equal, and physicians should be familiar with the treatment implications of common carbapenemases. Avibactam is a novel diazabicyclooctane non-beta-lactam BLI that has demonstrated inhibition of class A and C beta-lactamases as well as class D OXA-48 carbapenemase (5). Thus, ceftazidime-avibactam may be a treatment option for both KPC-and OXA-48-producing CPE.…”

“…b Species identification was conducted using matrix-assisted laser desorption ionization-time of flight mass spectrometry (Biomerieux, Durham, North Carolina providers may prefer meropenem-vaborbactam for infections due to KPC producers (9). However, vaborbactam does not inhibit the activity of OXA-48 (5). While this patient did not survive the hospitalization, ceftazidime-avibactam monotherapy appeared to successfully treat his infection due to OXA-48-producing R. planticola based on his initial clinical improvement and negative follow-up blood cultures.…”

“…Furthermore, OXA-48 is not inhibited by traditional betalactamase inhibitors, including clavulanic acid, tazobactam, and sulbactam (6). Clinical evidence regarding treatment is limited-OXA-48 producers have not been included in recent trials assessing performance of the novel beta-lactamase inhibitors, which may be helpful but remain clinically untested (5). We report a case in which the simultaneous potential for KPC-producing and OXA-48-producing organisms complicated the choice of empirical treatment, a situation which may become more common for clinicians, as nosocomial risk factors for CPE often overlap and the molecular epidemiology of CPE continues to evolve.…”