The antibiotic arms race: current and emerging therapy for Klebsiella pneumoniae carbapenemase (KPC) - producing bacteria

ABSTRACT

Introduction

The rapid spread of Klebsiella pneumoniae Carbapenemase (KPC)-producing bacteria comprises one of the greatest challenges to global health. Historically, clinicians were limited to therapies with suboptimal efficacy and intolerable toxicity until the FDA approved ceftazidime-avibactam and meropenem-vaborbactam, adding two essential pharmacotherapies to our antibiotic armamentarium. These agents display superior efficacy and safety compared to historical treatment options; however, resistance has already been reported. Several antimicrobials currently in the drug pipeline exhibit early promise and may fill needed gaps in therapy.

Areas covered

This article encompasses both the past and present treatment options for the management of KPC-producing bacterial infections via an extensive review and critical appraisal of the current literature.

Expert opinion

Traditional treatment options can no longer be recommended as first-line options for the management of KPC-producing bloodstream infections. Ceftazidime-avibactam or meropenem-vaborbactam plus or minus an aminoglycoside or polymyxin should be utilized as backbone therapies given their superior efficacy and safety profiles when compared to traditional treatment options. For susceptible KPC-producing urinary tract infections, it is reasonable to consider treatment with an aminoglycoside or with fosfomycin as a monotherapy. All of these decisions should be based on patient-specific characteristics, severity of infection and source control, susceptibility patterns, and input from infectious diseases experts.

KEYWORDS:

• Infectious disease
• multidrug resistance
• carbapenem-resistant
• carbapenemase-producing
• Klebsiella pneumoniae carbapenemase

Article highlights

• Polymyxins, aminoglycosides, tigecycline, fosfomycin, and carbapenems in combination or as monotherapy have traditionally been used for the treatment of KPC-producing bacterial infections; however, these agents lack reliable efficacy and carry an increased risk of toxicity.

• Mortality remains in excess of 20% for BSIs caused by KPC-producing bacteria despite combination therapy with the traditional agents.

• The novel βLβLIs, ceftazidime-avibactam, and meropenem-vaborbactam, display superior efficacy and safety when compared to the traditional treatment options.

• KPC-producing UTIs may still be managed with fosfomycin or aminoglycoside monotherapy.

• Resistance to ceftazidime-avibactam is increasingly reported in the literature, indicating a potential need for combination therapy with an aminoglycoside or polymyxin in severe infections.

• Imipenem-cilastatin/relebactam, aztreonam-avibactam, plazomicin, eravacycline, and cefidericol are in various stages of drug development and FDA approval and may soon play a major role in the management of KPC-producing bacterial infections.

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Declaration of interest

PD Tamma has an investigator-initiated research study funded by Merck and Co, which is unrelated to this work. 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

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Additional information

Funding

This manuscript was not funded.