Synergistic Effect of Liquid Phase Nitric Oxide Donor with Beta-Lactam antibiotics: an In-vitro Study.
Year: 2026
Type: conference-paper
Abstract: Background: Antimicrobial resistance (AMR) is a major healthcare challenge, with 4.95 million deaths associated with bacterial AMR in 2019. Key pathogens contributing to these deaths include E. coli, S. aureus, K. pneumoniae, S. pneumoniae, A. baumannii, and P. aeruginosa. Nitric oxide (NO) has antibacterial properties through multiple mechanisms. Multiple preclinical studies from our group showed that 300 ppm inhaled NO reduced bacterial load in the lungs during pneumonia. In the first human study, 160ppm inhaled NO improved the antibiotic susceptibility of B. multivorans in a cystic fibrosis patient. We hypothesize that NO enhances antibiotic efficacy, supporting its potential role in combating antimicrobial resistance. Method: K. pneumoniae was tested using an eTEST assay with ertapenem and 2 NO donors (DETA-NONOate and spermine-NONOate). A time-kill assay was performed with P. aeruginosa using sub-MIC cefepime (1/16 and 1/8 MIC [3 µg/mL]), and spermineNONOate (9 and 27µM). Results: In K. pneumoniae, NO reduced ertapenem MIC in a dose-dependent manner (24 to 12µg/mL [DETA-NONOate 15mM], 16µg/mL [spermineNONOate 1.1mM], and 8µg/mL [spermineNONOate 11mM]). In P. aeruginosa, NO reduced the bacterial concentration by 0.42 log, 95%CI [0.29-0.56] with spermineNONOate at 9µM; and by 0.98 log [0.85 to 1.11] with spermineNONOate at 27µM when compared to bacteria exposed to antibiotic alone. Nitric Oxide demonstrated an additive effect with cefepime, although no synergy was observed. Discussion: Liquid-phase NO demonstrates an additive antibacterial effect with beta-lactams and may allow for reduced antibiotic dosing. Further studies should evaluate the interactions of different NO donors and NO gas with different antibiotic classes.
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W7163127925