Evaluation of Carbapenems for Treatment of Multi- and Extensively Drug-Resistant Mycobacterium tuberculosis

Abstract

Multi- and extensively drug-resistant tuberculosis (M/XDR-TB) has become an increasing threat not only in countries where the TB burden is high but also in affluent regions, due to increased international travel and globalization. Carbapenems are earmarked as potentially active drugs for the treatment of Mycobacterium 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 to detect 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 laboratory 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, it is impossible in practice to prescribe carbapenems in combination with clavulanate at this time. Few in vivo studies have been performed, including one prospective, two observational, and seven retrospective clinical studies to assess the effectiveness, safety, and tolerability of three different carbapenems (imipenem, meropenem, and ertapenem). We found no clear evidence at the present time 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.

N-Thio-β-lactams targeting L,D-transpeptidase-2, with activity against drug-resistant strains of Mycobacterium tuberculosis

“…The MIC for meropenem in the presence of clavulanate resulted in 32 mg/mL for H37Rv, 8 mg/mL for the drug-susceptible isolate, and 8 mg/mL for the two MDR isolates MDR-1 and MDR-2 (Table 2). These data are in agreement with literature data (Forsman et al, 2015;van Rijn et al, 2019).…”

Drug-Resistant Tuberculosis 2020: Where We Stand

“…In Mtb, the PG is remodeled by nonclassical l,d-transpeptidases (LDT). The structural basis and the inactivation mechanism of LDT and the active role of carbapenems were investigated, providing a basis for their potential use in inhibiting Mtb [54]. Indeed, the carbapenems IPM-CLN and MPM (both to be used with CLV, available only in formulations combined with amoxicillin) have been listed as add-on drugs in the recent WHO treatment guidelines of MDR/XDR TB [8].…”

Herausforderungen in der Diagnostik der Darmtuberkulose – Pitfalls einer vergessenen infektiösen Erkrankung: Eine Fallserie und Literaturübersicht

“…Jedoch besitzen einige Antibiotika (▶ Tab. 3) eine tuberkulostatische Wirksamkeit und können so den Nachweis einer Tuberkulose nach initiierter Antibiose erschweren [4,39,40].…”