Combinations of ibuprofen with aztreonam and ceftazidime display synergistic antimicrobial activity against drug-resistant Pseudomonas aeruginosa isolates in vitro, and efficacy of ceftazidime combined with ibuprofen was shown in vivo in a murine P aeruginosa pneumonia model, according to research presented at American Society of Microbiology (ASM) Microbe 2019 held from June 20-24, 2019 in San Francisco, California.
Approximately 50% of the lungs of patients with cystic fibrosis have detectable P aeruginosa, and 20% of adults with cystic fibrosis hold multi-drug resistant isolates that have limited treatment options. The presenters have previously confirmed that high-dose ibuprofen demonstrates antimicrobial activity against P aeruginosa both in vitro and in vivo. The current study assessed possible synergistic activity of combining ibuprofen with FDA-approved antibiotics aztreonam and ceftazidime.
A disc diffusion assay against P aeruginosa isolates from patients with cystic fibrosis was used to screen drug combinations, and drugs demonstrating a significant increase in the zone of inhibition when in the presence of ibuprofen were further characterized with a checkerboard assay and end point colony-forming units determined at 24 hours to verify synergistic effects between ibuprofen and antimicrobials. Synergy was defined according to Clinical & Laboratory Standards Institute guidelines.
In the presence of 100 μg/mL ibuprofen, aztreonam and ceftazidime displayed significant increases in the zones of inhibition against P aeruginosa isolate HP3. Fractional inhibitory concentrations demonstrated additive effects between ibuprofen and aztreonam and between ibuprofen and ceftazidime. Further, in a 24-hour endpoint colony-forming unit assay, P aeruginosa HP3 treated with ceftazidime or aztreonam showed a greater than 2-log reduction compared with antibiotics alone, which also indicated significant synergy.
The efficacy of a synergistic oral ibuprofen and intraperitoneal ceftazidime combination was further evaluated in a mouse model in regards to P aeruginosa pneumonia. Infected mice were treated with ibuprofen and ceftazidime every 8 hours. Mice treated with ibuprofen combined with ceftazidime showed a significant survival advantage compared with groups treated with either ibuprofen or ceftazidime alone.
Study investigators concluded that “[c]ombinations of with [aztreonam] or [ceftazidime] demonstrate synergistic antimicrobial activity against drug resistant, clinical [P aeruginosa] isolates in vitro…Thus, therapy with high-dose [ibuprofen] in combination with a standard-of-care antibiotic including [aztreonam] or [ceftazidime] may improve outcomes in patients infected with multidrug resistant [P aeruginosa].”
Chen Q, Illanga M, Chirra B, et al. Ibuprofen displays synergistic antibacterial activity with FDA approved antibiotics against Pseudomonas aeruginosa. Presented at: ASM Microbe 2019; June 20-24, 2019; San Francisco, California. Poster P589.