[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]
Avibactam Sensitizes Carbapenem-Resistant NDM-1-Producing Klebsiella pneumoniae to Innate Immune Clearance
Erlinda R Ulloa, Nicholas Dillon, Hannah Tsunemoto, Joe Pogliano, George Sakoulas, Victor Nizet
The Journal of Infectious Diseases, jiz128, https://doi.org/10.1093/infdis/jiz128
Published: 29 March 2019
Infections caused by New Delhi metallo-β-lactamases (NDM)-producing strains of multidrug-resistant (MDR) Klebsiella pneumoniae (KP) are a global public health threat lacking reliable therapies. NDM is impervious to all existing β-lactamase inhibitor (BLI) drugs, including the non-β-lactam structure BLI, avibactam (AVI). Though lacking direct activity against NDM enzymes, AVI can interact with penicillin-binding protein 2 in a manner that may influence cell wall dynamics. We found that exposure of NDM KP to AVI led to striking bactericidal interactions with human cathelicidin antimicrobial peptide LL-37, a frontline component of host innate immunity. Moreover, AVI markedly sensitized NDM KP to killing by freshly isolated human neutrophils, platelets, and serum when complement was active. Finally, AVI monotherapy reduced lung NDM KP counts in a murine pulmonary challenge model. AVI has immune sensitizing activities against NDM KP not appreciated by standard antibiotic testing and meriting further study.
New Delhi metallo-β-lactamase (NDM), Klebsiella pneumoniae, non-β-lactam-β-lactamase-inhibitors, avibactam, innate immunity, platelet, neutrophil, human serum
Topic: antibiotics – blood platelets – lung – drug clearance – cell wall – complement system proteins – immunity, natural – klebsiella pneumoniae – lactams – neutrophils – peptides – infection – enzymes – mice – public health medicine – antimicrobials – penicillin-binding proteins – ll-37 peptide – cathelicidin – killing – host (organism) – avibactam – carbapenem resistance
Issue Section: Major Article
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Keywords: Antibiotics; Drugs Resistance; Klebsiella pneumoniae; Carbapenem; NDM1; Avibactam.