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

Saverio De Lorenzo, Jan Wilem Alffenaar, Giovanni Sotgiu, Rosella Centis, Lia D'Ambrosio, Simon Tiberi, Mathieu S. Bolhuis, Richard Van Altena, Piero Viggiani, Andrea Piana, Antonio Spanevello, Giovanni Battista Migliori

Research output: Contribution to journalArticlepeer-review

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 (p5 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. Copyright

Original languageEnglish
Pages (from-to)1386-1392
Number of pages7
JournalEuropean Respiratory Journal
Volume41
Issue number6
DOIs
Publication statusPublished - Jun 1 2013

Keywords

  • Efficacy
  • Linezolid-containing regimens
  • Meropenem-clavulanate
  • Multidrugresistant tuberculosis
  • Safety
  • Tolerability

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Medicine(all)

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