Mathematical pharmacodynamic modeling for antimicrobial assessment of ceftazidime/colistin versus gentamicin/meropenem combinations against carbapenem-resistant Pseudomonas aeruginosa biofilm

Annals of Clinical Microbiology and Antimicrobials

Research

Mona Shaban E. M. Badawy¹  Rania I. Shebl²  Walid F. Elkhatib³ 

[1] Department of Microbiology and Immunology, Faculty of Pharmacy (Girls), El-Azhar University, Cairo, Egypt;Department of Microbiology and Immunology, Faculty of Pharmacy, Ahram Canadian University, 6th October city, 4th industrial zone, 12451, Giza, Egypt;Microbiology and Immunology Department, Faculty of Pharmacy, Ain Shams University, African Union Organization St., 11566, Abbassia, Cairo, Egypt;Department of Microbiology & Immunology, Faculty of Pharmacy, Galala University, New Galala City, Suez, Egypt;

关键词: Pharmacodynamic;    Pseudomonas aeruginosa;    Ceftazidime;    Colistin;    Meropenem;    Gentamicin;    Biofilm;   

DOI  :  10.1186/s12941-023-00597-9

 received in 2023-02-03, accepted in 2023-05-29,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundCarbapenem-resistant Pseudomonas aeruginosa (CRPA) represents an escalating healthcare hazard with high mortality worldwide, especially in presence of biofilm. The current study aimed to evaluate the anti-biofilm potentials of ceftazidime, colistin, gentamicin, and meropenem alone and in combinations against biofilm-forming CRPA. MethodsBiofilm killing and checkerboard assay were performed to detect the effectiveness of combined antibiotics against biofilms and planktonic cells, respectively. The bacterial bioburden retrieved from the established biofilms following treatment with combined antibiotics was utilized to construct a three-dimensional response surface plot. A sigmoidal maximum effect model was applied to determine the pharmacodynamic parameters (maximal effect, median effective concentration, and Hill factor) of each antibiotic to create a mathematical three-dimensional response surface plot.ResultsData revealed statistically significant (p < 0.05) superior anti-biofilm potential in the case of colistin followed by a lower effect in the case of gentamicin and meropenem, while ceftazidime exhibited the least anti-biofilm activity. The fractional inhibitory concentration index (FICI ≤ 0.5) indicated synergism following treatment with the combined antibiotics. An elevated anti-biofilm activity was recorded in the case of gentamicin/meropenem compared to ceftazidime/colistin. Synergistic anti-biofilm potentials were also detected via the simulated pharmacodynamic modeling, with higher anti-biofilm activity in the case of the in vitro observation compared to the simulated anti-biofilm profile.ConclusionsThe present study highlighted the synergistic potentials of the tested antibiotic combinations against P. aeruginosa biofilms and the importance of the mathematical pharmacodynamic modeling in investigating the efficacy of antibiotics in combination as an effective strategy for successful antibiotic therapy to tackle the extensively growing resistance to the currently available antibiotics.

【 授权许可】

CC BY   
© The Author(s) 2023

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