“One-Two Punch”: Synergistic ß-Lactam Combinations for<i>Mycobacterium abscessus</i>and Target Redundancy in the Inhibition of Peptidoglycan Synthesis Enzymes
David C. Nguyen, Khalid M Dousa, Sebastian G. Kurz, Sheldon T. Brown, George L. Drusano, Steven M. Holland, Barry N. Kreiswirth, W. Henry Boom, et al. (10 authors)
Clinical Infectious Diseases · 2021-06
Abstract
Mycobacterium abscessus subsp. abscessus is one of the most difficult pathogens to treat and its incidence in disease is increasing. Dual β-lactam combinations act synergistically in vitro but are not widely employed in practice. A recent study shows that a combination of imipenem and ceftaroline significantly lowers the minimum inhibitory concentration of clinical isolates, despite both drugs targeting the same peptidoglycan synthesis enzymes. The underlying mechanism of this effect provides a basis for further investigations of dual β-lactam combinations in the treatment of M. abscessus subsp. abscessus, eventually leading to a clinical trial. Furthermore, dual β-lactam strategies may be explored for other difficult mycobacterial infections.
MeSH terms
- Mycobacterium abscessus
- Peptidoglycan
- Microbiology
- Medicine
- Cephalosporin
- Lactam
- Enzyme
- Mycobacterium
- Antibiotics