Development of a penem antibiotic against Mycobacteroides abscessus.
Hunter R BatchelderElizabeth Story-RollerEvan P LloydAmit KaushikKristina M BigelowEmily C MaggioncaldaEric L NuermbergerGyanu LamichhaneCraig A TownsendPublished in: Communications biology (2020)
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.
Keyphrases
- drug resistant
- multidrug resistant
- gram negative
- cystic fibrosis
- escherichia coli
- acinetobacter baumannii
- end stage renal disease
- klebsiella pneumoniae
- newly diagnosed
- ejection fraction
- pseudomonas aeruginosa
- oxidative stress
- pulmonary hypertension
- peritoneal dialysis
- candida albicans
- skeletal muscle
- patient reported outcomes
- anti inflammatory
- combination therapy
- human health
- high fat diet induced
- real time pcr
- oxide nanoparticles