Treatment strategies for OXA-48-like and NDM producing Klebsiella pneumoniae infections

ABSTRACT

Introduction

OXA-48 and NDM are amongst the most prevalent carbapenemase types associated with Klebsiella pneumoniae worldwide, with an increase in their prevalence in recent years. Knowledge on the treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) comes from KPC-producing CRKP with limited data available for OXA-48-like and NDM producers. Our aim is to review the literature on the treatment of OXA-48-like and NDM-producing CRKP with the goal of providing an update on the available antibiotic treatment strategies, particularly in light of changing carbapenemase epidemiology and increasing antimicrobial resistance.

Areas covered

We reviewed studies looking at the antibiotic treatment and outcome of OXA-48-like and/or NDM-producing CRKP.

Expert opinion

The best available treatment option for OXA-48 producers is ceftazidime-avibactam, where available and when the price permits its use. Colistin remains as the second-line option if in vitro susceptibility is demonstrated with an appropriate method. There is not enough evidence to support the use of meropenem-containing combination therapies for meropenem-resistant OXA-48 producers. Treatment of NDM producers is an unmet need. Ceftazidime-avibactam and aztreonam combination or cefiderocol can be used for NDM producers, where available. Higher cefiderocol MICs against NDM producers is concerning. Aztreonam–avibactam provides hope for the treatment of NDM producers.

KEYWORDS:

• OXA-48
• NDM
• Klebsiella pneumoniae
• carbapenem resistant
• ceftazidime-avibactam

Article highlights

• Ceftazidime-avibactam is the first-line option for the treatment of severe OXA-48-like producing CRKP infections.

• Ceftazidime-avibactam plus aztreonam or cefiderocol are the first-line treatment options for NDM-producing CRKP infections.

• Colistin- or tigecycline-based regimens may be considered for the treatment of severe CRKP infections only when new generation antimicrobials are not available, are inactive or are not tolerated due to side effects.

• If colistin needs to be used for a severe CRKP infection, it should be combined with another active antibiotic.

• Tigecycline is not recommended for the treatment of BSI, cUTI and if it needs to be used for HAP/VAP, higher doses should be preferred.

• Due to scarcity of data and low quality of evidence, iv fosfomycin and double carbapenem regimens should not be used for the treatment of CRKP infections.

• Meropenem monotherapy or meropenem-containing combination therapies should be avoided for OXA-48- and/or NDM-producing CRKP infections.

Declaration of Interests

M Akova received honoraria for educational activities from Pfizer, MSD, Gilead and Genentech, and research support from Pfizer and Gilead. M Paterson reports research grants from Merck, Pfizer, and Shionogi. David Paterson has received honoraria for advisory board membership from Merck, Pfizer, Shionogi, GSK, QPex, Entasis, VenatoRx, BioMerieux, and Accelerate. All other authors declare that they have no conflicts of interest. Dr Harris has received research grants from Sandoz, Merck/MSD and Shionogi, speaker’s fees from Pfizer and honoraria for advisory board membership from Merck and Sandoz, paid to the University of Queensland. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

All authors have substantially contributed to the conception and design of the review article and interpreting the relevant literature, and been involved in writing the review article or revised it for intellectual content.

Additional information

Funding

This paper was not funded