Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB

Eur Respir J. 2016 Apr;47(4):1235-43. doi: 10.1183/13993003.02146-2015. Epub 2016 Mar 10.

Abstract

No large study has ever evaluated the efficacy, safety and tolerability of meropenem/clavulanate to treat multidrug- and extensively drug-resistant tuberculosis (MDR- and XDR-TB). The aim of this observational study was to evaluate the therapeutic contribution, effectiveness, safety and tolerability profile of meropenem/clavulanate added to a background regimen when treating MDR- and XDR-TB cases.Patients treated with a meropenem/clavulanate-containing regimen (n=96) showed a greater drug resistance profile than those exposed to a meropenem/clavulanate-sparing regimen (n=168): in the former group XDR-TB was more frequent (49% versus 6.0%, p<0.0001) and the median (interquartile range (IQR)) number of antibiotic resistances was higher (8 (6-9)versus 5 (4-6)). Patients were treated with a meropenem/clavulanate-containing regimen for a median (IQR) of 85 (49-156) days.No statistically significant differences were observed in the overall MDR-TB cohort and in the subgroups with and without the XDR-TB patients; in particular, sputum smear and culture conversion rates were similar in XDR-TB patients exposed to meropenem/clavulanate-containing regimens (88.0% versus 100.0%, p=1.00 and 88.0% versus 100.0%, p=1.00, respectively). Only six cases reported adverse events attributable to meropenem/clavulanate (four of them then restarting treatment).The nondifferent outcomes and bacteriological conversion rate observed in cases who were more severe than controls might imply that meropenem/clavulanate could be active in treating MDR- and XDR-TB cases.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Antitubercular Agents / administration & dosage*
  • Clavulanic Acid / administration & dosage*
  • Extensively Drug-Resistant Tuberculosis / drug therapy*
  • Female
  • Humans
  • Male
  • Meropenem
  • Retrospective Studies
  • Thienamycins / administration & dosage*
  • Treatment Outcome
  • Tuberculosis, Multidrug-Resistant / drug therapy*

Substances

  • Antitubercular Agents
  • Thienamycins
  • Clavulanic Acid
  • Meropenem