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Multidrug-resistant and extensively drug-resistant Gram-negative pathogens: current and emerging therapeutic

Ilias Karaiskos1, Helen Giamarellou

  • 1Hygeia General Hospital, 6th Department of Internal Medicine , Erythrou Stavrou Str & Kifisias Avenue, Marousi, Athens, 15123 , Greece.

Expert Opinion on Pharmacotherapy
|April 29, 2014
PubMed
Abstract

Insights

The rise of drug-resistant Gram-negative bacteria necessitates exploring new antibiotics. Current options like colistin show promise against extensively drug-resistant (XDR) infections, but newer agents require further clinical trials.

Area of Science:

  • Microbiology
  • Infectious Diseases
  • Pharmacology

Background:

  • The increasing prevalence of multidrug-resistant (MDR), extensively drug-resistant (XDR), and pandrug-resistant Gram-negative bacteria poses a significant threat.
  • Carbapenemase-producing bacteria, including Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii, are responsible for untreatable infections.

Purpose of the Study:

  • To review currently available and emerging antibiotics effective against Gram-negative microorganisms.
  • To discuss antimicrobial agents that can overcome existing resistance mechanisms.

Main Methods:

  • Review of current knowledge on mechanisms of action, in vitro activity, and pharmacokinetics/pharmacodynamics.
  • Evaluation of clinical efficacy and toxicity of revived and novel antimicrobial agents.
  • Discussion of antibiotics such as colistin, tigecycline, fosfomycin, temocillin, carbapenems, plazomicin, eravacycline, and carbapenemase inhibitors.

Main Results:

  • Colistin demonstrates in vitro activity and in vivo efficacy against XDR carbapenemase-producing microorganisms in critically ill patients.
  • Tigecycline exhibits a similar spectrum of activity, excluding P. aeruginosa.
  • Combination therapy appears essential for bacteremias and ventilator-associated pneumonia caused by K. pneumoniae carbapenemase producers, but its efficacy is uncertain for P. aeruginosa and A. baumannii.

Conclusions:

  • Fosfomycin shows activity against P. aeruginosa and K. pneumoniae but has limited documented use in XDR infections.
  • The clinical validity of novel potent antimicrobial compounds requires further evaluation through Phase III clinical trials, especially for XDR infections.
Keywords:
avibactamcarbapenem resistancecarbapenem-producing β-lactamasesceftolozanecolistineravacyclineextended spectrum β lactamaseextensively drug-resistantfosfomycinmultidrug-resistantpandrug-resistantplazomicintigecycline

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