Carbapenems against Mycobacterium tuberculosis: a review of the evidence

Int J Tuberc Lung Dis. 2016 Nov;20(11):1436-1447. doi: 10.5588/ijtld.16.0498.

Abstract

Carbapenems, a more recent β-lactam class, represent a unique anti-tuberculosis option, as emerging evidence demonstrates that they target the Mycobacterium tuberculosis cell wall and β-lactamase. This provides a potentially new agent against M. tuberculosis, in particular for multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), where options are limited. In this review, we examine the current evidence on the activity of carbapenems against M. tuberculosis. The predominance of work is in vitro, and suggests that carbapenems kill M. tuberculosis at least in the active phase, with possible greater potency with the addition of a β-lactamase inhibitor. The few in vivo and clinical studies suggest that there are benefits and that they are generally tolerated, although the variability in duration, dosing, and background regimen and lack of pharmacokinetic analyses limit interpretation of efficacy. We outline further areas of research to better understand the role of carbapenems to add a needed new agent to the treatment of MDR- and XDR-TB.

Publication types

  • Review
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antitubercular Agents / pharmacokinetics
  • Antitubercular Agents / therapeutic use
  • Carbapenems / pharmacokinetics
  • Carbapenems / therapeutic use*
  • Cell Wall / drug effects
  • Disease Models, Animal
  • Drug Resistance, Multiple, Bacterial
  • Extensively Drug-Resistant Tuberculosis / drug therapy*
  • Humans
  • Incidence
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Mycobacterium tuberculosis / isolation & purification
  • Prevalence
  • Randomized Controlled Trials as Topic
  • beta-Lactamases / metabolism

Substances

  • Antitubercular Agents
  • Carbapenems
  • beta-Lactamases