Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of multidrug-resistant tuberculosis

Abstract

Background: Meropenem/clavulanate (MC) has been prescribed to treat MDR/XDR-TB cases, although limited scientific evidence exists. Aim: To retrospectively evaluate the effectiveness, safety, and tolerability of MC added to build an optimal regimen when treating MDR/XDR-TB patients. Methods: An observational, retrospective, cohort study was performed in 5 countries across Europe and South America, where consecutive patients with bacteriologically proven MDR-TB were recruited and divided by MC exposure. Information on demographic, epidemiological, microbiological, and clinical variables were collected from the clinical files using standardized e-forms. Results: A cohort of 264 MDR-TB patients was established: 96 patients were treated with MC-containing regimens and 168 without. Only thirteen (5.2%) were HIV-infected. The proportion of XDR-TB was higher in those exposed to MC-containing regimens (49.0% vs. 6.0%), as was the median (IQR) number of antibiotic resistances (8[6-9] vs 5[4-6]). Sputum smear and culture conversion rates were not statistically different in MDR-TB cases exposed and not exposed to MC-containing regimens, including the XDR-TB subgroup (88.0% vs. 100.0%, P=1.00, and 88.0% vs. 100.0%, P=1.00, respectively). Only 6 MC-related adverse events were reported. In 4 cases, MC was re-started after interruption Conclusion: MC-containing regimens can help achieve sputum culture conversion in MDR/XDR-TB cases with no significant toxicity. This study suggests a potential added value of MC in severe forms of drug-resistant TB when an optimal regimen can not be built with available drugs.