LAUSR

β-lactams are the most widely used antibiotic class to treat bacterial infections in humans. Mycobacteroides abscessus is an emerging pulmonary pathogen resistant to most antibiotics, including penicillins and cephalosporins. With no current FDA-approved treatment and cure rates <50%, there is a pressing need for effective therapies. Here we report T405, a new β-lactam of the penem subclass that exhibits potent activity against M. abscessus and a panel of drug-resistant strains isolated from cystic fibrosis patients. Additionally, in combination with the β-lactamase inhibitor avibactam, the rate of spontaneous resistance of M. abscessus to T405 approached the limit of detection. Lastly, we show the favorable pharmacokinetic profile of T405 in mice and the absence of toxicity at elevated dosage, which support the clinical potential of this compound. Batchelder et al. report a new penem class antibiotic, T405, which exhibits potent activity against M. abscessus and clinical isolates from cystic fibrosis patients. The development of resistance to T405 is inhibited with the addition of a β-lactamase inhibitor, avibactam. Its clinical potential is further demonstrated by T405 displaying a favourable pharmacokinetic profile in mice with an absence of toxicity.