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- Title
"One-Two Punch": Synergistic ß-Lactam Combinations for Mycobacterium abscessus and Target Redundancy in the Inhibition of Peptidoglycan Synthesis Enzymes.
- Authors
Nguyen, David C; Dousa, Khalid M; Kurz, Sebastian G; Brown, Sheldon T; Drusano, George; Holland, Steven M; Kreiswirth, Barry N; Boom, W Henry; Daley, Charles L; Bonomo, Robert A
- 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.
- Subjects
ENZYME inhibitors; ANTIBIOTICS; MYCOBACTERIUM; BETA lactam antibiotics; BACTERIAL antigens; DRUG synergism; BACTERIAL diseases; MOLECULAR structure; IMIPENEM
- Publication
Clinical Infectious Diseases, 2021, Vol 73, Issue 8, p1532
- ISSN
1058-4838
- Publication type
Article
- DOI
10.1093/cid/ciab535