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

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; p50.02) and culture converters (31 (83.8%) out of 37 versus 15 (62.5%) out of 24; p50.06). Excluding XDR-TB patients (11 (11.2%) out of 98), cases scored a significantly higher proportion of culture converters than controls (p50.03). One case had to withdraw from meropenemclavulanate 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.

Costs of tuberculosis disease in the European Union: a systematic analysis and cost calculation

“…As it must be recognised, following current trends, Europe is unlikely to achieve elimination of the disease by the target date of 2050 [23,24], we urgently need new vaccines, as well as improved diagnostics [25,26] and new drugs [27][28][29]. With respect to economic considerations, the aim of the present study was to evaluate the costs associated with TB disease in order to determine whether they outweigh the investment needed to generate a new vaccine.…”

Pulmonary Tuberculosis Management: 2015 Update

“…In a case-control study 62 it demonstrated, when added to linezolid-containing OBR, to improve sputum smear and culture conversion in MDRand XDR-TB cases. Further studies are necessary to define the role of this drug within the anti-MDR-TB armamentarium.…”

Classification of drugs to treat multidrug-resistant tuberculosis (MDR-TB): evidence and perspectives

“…Imipenem/cilastatin and meropenem, combined with clavulanic acid, seem to have a promising activity, while being well tolerated (34)(35)(36)(37). In the direct comparison meropenem performs better than imipenem (37).…”