Evolution toward extremely high imipenem resistance in outbreak strains.

Treatment of pulmonary disease requires multiple antibiotics including intravenous β-lactams (e.g., imipenem).

Evolution towards extremely high β-lactam resistance in outbreak strains.

Treatment of pulmonary disease requires multiple antibiotics including intravenous β-lactams (e.g., imipenem, meropenem).

Impact of relebactam-mediated inhibition of Mycobacterium abscessus BlaMab β-lactamase on the in vitro and intracellular efficacy of imipenem.

Objectives: Imipenem is one of the recommended β-lactams for the treatment of Mycobacterium abscessus pulmonary infections in spite of the production of BlaMab β-lactamase. Avibactam, a second-generation β-lactamase inhibitor, was previously shown to inactivate BlaMab, but its partner drug, ceftazidime, is devoid of any antibacterial activity against M. abscessus.

and Intracellular Activity of Imipenem Combined with Tedizolid, Rifabutin, and Avibactam against .

infections are difficult to treat because of their resistance to many antibiotics. , tedizolid combined with imipenem displayed a moderate synergistic effect (fractional inhibitory concentration index, 0.41) but no bactericidal activity.

and Intracellular Activity of Imipenem Combined with Rifabutin and Avibactam against Mycobacterium abscessus.

Repurposing drugs may be useful as an add-on in the treatment of pulmonary infections, which are particularly difficult to cure. naturally produces a β-lactamase, Bla, which is inhibited by avibactam. The recommended regimens include imipenem, which is hydrolyzed by Bla and used without any β-lactamase inhibitor.

Synthesis of Avibactam Derivatives and Activity on β-Lactamases and Peptidoglycan Biosynthesis Enzymes of Mycobacteria.

There is a renewed interest for β-lactams for treating infections due to Mycobacterium tuberculosis and M. abscessus because their β-lactamases are inhibited by classical (clavulanate) or new generation (avibactam) inhibitors, respectively. Here, access to an azido derivative of the diazabicyclooctane (DBO) scaffold of avibactam for functionalization by the Huisgen-Sharpless cycloaddition reaction is reported.