Open Access“One-Two Punch”: Synergistic ß-Lactam Combinations forMycobacterium abscessusand Target Redundancy in the Inhibition of Peptidoglycan Synthesis Enzymes
Author(s) -
David C. Nguyen,
Khalid M Dousa,
Sebastian Kurz,
Sheldon T. Brown,
George L. Drusano,
Steven M. Holland,
Barry N Kreiswirth,
W. Henry Boom,
Charles L. Daley,
Robert A. Bonomo
Publication year - 2021
Publication title -
clinical infectious diseases/clinical infectious diseases (online. university of chicago. press)
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.44
H-Index - 336
eISSN - 1537-6591
pISSN - 1058-4838
DOI - 10.1093/cid/ciab535
Subject(s) - mycobacterium abscessus , peptidoglycan , medicine , microbiology and biotechnology , cephalosporin , lactam , enzyme , antibiotics , mycobacterium , biology , biochemistry , chemistry , pathology , stereochemistry , tuberculosis
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.