In vitro and intracellular activity of imipenem combined to rifabutin and avibactam against Mycobacterium abscessus.

In vitro and intracellular activity of imipenem combined to rifabutin and avibactam against Mycobacterium abscessus. Antimicrob Agents Chemother. 2018 Jun 04;: Authors: Le Run E, Arthur M, Mainardi JL Abstract Repurposing drugs may be useful as an add-on in the treatment of Mycobacterium abscessus pulmonary infections, which are particularly difficult to cure. M. abscessus naturally produces a β-lactamase, BlaMab, which is inhibited by avibactam. The recommended regimens include imipenem, which is hydrolyzed by BlaMab and used without any β-lactamase inhibitor. Here, we determine whether the addition of rifabutin improves the activity of imipenem alone or in combination with avibactam against M. abscessus CIP104536. Rifabutin at 16 μg/ml was only bacteriostatic (MIC = 4 μg/ml) and was moderately synergistic in combination with imipenem (FIC index of 0.38). Addition of rifabutin (16 μg/ml) moderately increased killing by a low (8 μg/ml) but not by a high (32 μg/ml) concentration of imipenem. Addition of avibactam (4 μg/ml) did not further increase killing by the former combination. In infected macrophages, rifabutin (16 μg/ml) increased the activity of imipenem at 8 and 32 μg/ml achieving 3- and 100-fold reductions in the number of intracellular bacteria, respectively. Avibactam (16 μg/ml) improved killing by imipenem at 8 μg/ml. A 5-fold killing was obtained for a triple combination comprising avibactam (16 μg/ml) and th...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research