Aminoglycosides against carbapenem-resistant Enterobacteriaceae in the critically ill: the pitfalls of aminoglycoside susceptibility

ABSTRACT

Introduction: The emergence of carbapenem-resistant Enterobacteriaceae (CRE) has brought aminoglycosides to the frontline since an aminoglycoside may be the only antimicrobial to which CRE isolates show in vitro susceptibility. The appropriateness of aminoglycoside-based therapies for severe infections by CRE is discussed considering the current breakpoints and recent pharmacokinetic (PK) studies in critically ill patients.

Areas covered: Many aminoglycoside-susceptible CRE isolates present minimal inhibitory concentrations (MICs) at or slightly below the breakpoint of amikacin or gentamicin. However, recent PK studies with these aminoglycosides in critically ill have invariably shown that the PK/pharmacodynamic (PD) target is very unlikely attained even when high doses are administered, if the MICs are near the breakpoint.

Expert commentary: While new antimicrobials are not widely available, the authors forecast an increasing use of aminoglycosides as backbone antibiotics against CRE isolates. However, the altered PK of aminoglycosides in critically ill patients severely impairs their predicted efficacy in these patients. Aminoglycoside breakpoints may hide ‘aminoglycoside-susceptible’ CRE isolates for that aminoglycosides will unlikely be effective if used in monotherapy. Therefore, these breakpoints may need to be revised due to the increasing use of aminoglycosides as backbone antibiotics to treat severe infections by CRE isolates in critically ill patients.

KEYWORDS:

• Amikacin
• gentamicin
• tobramycin
• pharmacokinetics /pharmacodynamics
• Klebsiella pneumoniae carbapenemase
• resistance
• combination therapy

Declaration of interest

A.P. Zavascki. has received honoraria for speaking engagements and consultancy from Merck, AstraZeneca, Pfizer and United Pharmaceuticals. J.B. Bulitta has received research support (not related to the content of this review) from Pfizer, Cubist, Trius, Cempra, Novartis, and Johnson & Johnson. 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.

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Funding

This paper was not funded.