Efficacy and safety of meropenem-clavulanate added to linezolid-containing regimens in the treatment of MDR-/XDR-TB

Eur Respir J. 2013 Jun;41(6):1386-92. doi: 10.1183/09031936.00124312. Epub 2012 Sep 20.

Abstract

Clinical experience on meropenem-clavulanate to treat tuberculosis (TB) is anecdotal (according to case reports on 10 patients). The aim of our case-control study was to evaluate the contribution of meropenem-clavulanate when added to linezolid-containing regimens in terms of efficacy and safety/tolerability in treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) TB cases after 3 months of second-line treatment. 37 cases with MDR-/XDR-TB were prescribed meropenem-clavulanate (3 g daily dose) in addition to a linezolid-containing regimen (dosage range 300-1200 mg·day(-1)), designed according to international guidelines, which was prescribed to 61 controls. The clinical severity of cases was worse than that of controls (drug susceptibility profile, proportion of sputum-smear positive and of re-treatment cases). The group of cases yielded a higher proportion of sputum-smear converters (28 (87.5%) out of 32 versus nine (56.3%) out of 16; p=0.02) and culture converters (31 (83.8%) out of 37 versus 15 (62.5%) out of 24; p=0.06). Excluding XDR-TB patients (11 (11.2%) out of 98), cases scored a significantly higher proportion of culture converters than controls (p=0.03). One case had to withdraw from meropenem-clavulanate due to increased transaminase levels. The results of our study provide: 1) preliminary evidence on effectiveness and safety/tolerability of meropenem-clavulanate; 2) reference to design further trials; and 3) a guide to clinicians for its rationale use within salvage/compassionate regimens.

Keywords: Efficacy; linezolid-containing regimens; meropenem–clavulanate; multidrug-resistant tuberculosis; safety; tolerability.

Publication types

  • Observational Study

MeSH terms

  • Acetamides / administration & dosage*
  • Adult
  • Antitubercular Agents / administration & dosage*
  • Case-Control Studies
  • Clavulanic Acid / administration & dosage*
  • Drug Therapy, Combination
  • Extensively Drug-Resistant Tuberculosis / drug therapy*
  • Female
  • Humans
  • Linezolid
  • Male
  • Meropenem
  • Middle Aged
  • Oxazolidinones / administration & dosage*
  • Thienamycins / administration & dosage*
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / drug therapy*

Substances

  • Acetamides
  • Antitubercular Agents
  • Oxazolidinones
  • Thienamycins
  • Clavulanic Acid
  • Meropenem
  • Linezolid