Structure-Activity Relationship of Penem Antibiotic Side Chains Used against Mycobacteria Reveals Highly Active Compounds.

The rise of antibiotic-resistant and non-tuberculous mycobacterial infections has placed ever-increasing importance on discovering new antibiotics to treat these diseases. Recently, a new penem, , was discovered to have strong antimicrobial activity against and . Here, a penem library of C2 side-chain variants was synthesized, and their antimicrobial activities were evaluated against HRv and ATCC 19977.

T405, a New Penem, Exhibits Efficacy against M. abscessus and Synergy with β-Lactams Imipenem and Cefditoren.

Mycobacteroides abscessus () is an emerging environmental microbe that causes chronic lung disease in patients with compromised lung function such as cystic fibrosis and bronchiectasis. It is intrinsically resistant to most antibiotics, therefore there are only few antibiotics that can be repurposed to treat disease. Although current recommendations require daily intake of multiple antibiotics for more than a year, cure rate is low and often associated with significant adverse events.

Penicillin Binding Proteins and β-Lactamases of Mycobacterium tuberculosis: Reexamination of the Historical Paradigm.

Penicillin binding proteins (PBPs) have been extensively studied due to their importance to the physiology of bacterial cell wall peptidoglycan and as targets of the most widely used class of antibiotics, the β-lactams. The existing paradigm asserts that PBPs catalyze the final step of peptidoglycan biosynthesis, and β-lactams inhibit their activities. According to this paradigm, a distinct enzyme class, β-lactamases, exists to inactivate β-lactams.

Development of a penem antibiotic against Mycobacteroides abscessus.

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.