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Treatment of Infections by OXA-48-Producing Enterobacteriaceae

Adam Stewart1, Patrick Harris2, Andrew Henderson2

  • 1Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Royal Brisbane and Women's Hospital Campus, Brisbane, Australia adm_stewart@hotmail.com.

Antimicrobial Agents and Chemotherapy
|August 15, 2018
PubMed

Insights

Carbapenemase-producing Enterobacteriaceae (CPE) are a growing threat. New antibiotics like ceftazidime-avibactam show promise for OXA-48 infections, but emerging resistance necessitates further research into effective treatments.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Antimicrobial Resistance

Background:

  • Carbapenemase-producing Enterobacteriaceae (CPE) represent a significant global health challenge due to antimicrobial resistance.
  • OXA-48 carbapenemases, while having low carbapenem activity, are often associated with extended-spectrum beta-lactamase (ESBL) coproduction, leading to resistance against cephalosporins.
  • The blaOXA-48 gene is increasingly prevalent, particularly in Europe and the Middle East, often plasmid-mediated but sometimes chromosomally integrated.

Purpose of the Study:

  • To review the characteristics of OXA-48-like carbapenemases and their impact on antimicrobial resistance.
  • To evaluate the efficacy of various antimicrobial agents, including novel combinations, against OXA-48 producing Enterobacteriaceae.
  • To discuss current treatment strategies and the emerging challenge of resistance in managing these infections.

Main Methods:

  • Literature review of studies on OXA-48 carbapenemases and their resistance patterns.
  • Analysis of in vitro data regarding the activity of beta-lactamase inhibitors, particularly avibactam, in combination with various antibiotics.
  • Review of clinical outcomes and case reports for patients with OXA-48 producing Enterobacteriaceae infections.

Main Results:

  • Avibactam demonstrated potent inhibition of beta-lactamases in vitro, especially when combined with ceftazidime, cefepime, aztreonam, meropenem, or imipenem.
  • Ceftazidime-avibactam monotherapy achieved successful outcomes in approximately 70% of patients with OXA-48 producing Enterobacteriaceae infections.
  • While resistance to novel avibactam combinations is not widely reported, a few clinical isolates have been tested, and emerging resistance is a concern.

Conclusions:

  • Managing infections caused by OXA-48 producing Enterobacteriaceae remains challenging, with ongoing uncertainty regarding optimal treatment strategies.
  • Newer antibiotics like ceftazidime-avibactam offer a promising therapeutic option, but the recent emergence of resistance is a significant concern.
  • Continued development of novel antimicrobial agents is crucial to effectively combat the evolving threat of carbapenemase-producing Enterobacteriaceae.
Keywords:
EnterobacteriaceaeGram-negative bacteriaantibiotic resistancecarbapenems

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