M/XDR-TB has become an increasing threat in high burden countries but also in affluent regions due to increased international travel and globalization. Carbapenems are earmarked as potentially active drugs for the treatment of M. tuberculosis. To better understand the potential of carbapenems for the treatment of M/XDR-TB, the aim of this review was to evaluate the literature on currently available in vitro, in vivo and clinical data on carbapenems in the treatment of M. tuberculosis and detection of knowledge gaps, in order to target future research.
In February 2018, a systematic literature search of PubMed and Web of Science was performed. Overall the results of the studies identified in this review, which used a variety of carbapenem susceptibility tests on clinical and lab strains of M. tuberculosis, are consistent. In vitro the activity of carbapenems against M. tuberculosis is increased when used in combination with clavulanate, a BLaC inhibitor. However, clavulanate is not commercially available alone, and therefore is it practically impossible to prescribe carbapenems in combination with clavulanate at this time. Few in vivo studies have been performed, one prospective, two observational and seven retrospective clinical studies to assess effectiveness, safety and tolerability of three different carbapenems (imipenem, meropenem and ertapenem). Presently we found no clear evidence to select one particular carbapenem among the different candidate compounds, to design an effective M/XDR-TB regimen. Therefore more clinical evidence and dose optimization substantiated by hollow fiber infection studies are needed to support repurposing carbapenems for the treatment of M/XDR-TB.
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