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Title: | Comparative Efficacy of Continuous Ceftazidime Infusion vs. Intermittent Bolus against In Vitro Ceftazidime-Susceptible and -Resistant Pseudomonas aeruginosa Biofilm |
Author: | El Haj, Cristina Agustí, Eugènia Benavent, Eva Soldevila-boixader, Laura Rigo-bonnin, Raül Tubau, Fe Torrejón, Benjamín Esteban, Jaime Murillo, Oscar |
Issue Date: | 9-Apr-2024 |
Publisher: | MDPI AG |
Abstract: | Background: As the anti-biofilm pharmacokinetic/pharmacodynamic (PK/PD) properties of antibiotics are not well-defined, we have evaluated the PK/PD indices for different regimens of ceftazidime (CAZ; with/without colistin) against Pseudomonas aeruginosa biofilm. Methods: We have used the Center for Disease Control and Prevention Biofilm Reactor with two susceptible (PAO1 and HUB-PAS) and one resistant (HUB-XDR) strains of P. aeruginosa. The regimens were CAZ monotherapies (mimicking a human dose of 2 g/8 h, CAZ-IB; 6 g/daily as continuous infusion at 50 mg/L, CAZ-CI50; and 9 g/daily at 70 mg/L, CAZ-CI70) and CAZ-colistin combinations. Efficacy was correlated with the CAZ PK/PD parameters. Results: CAZ-CI70 was the most effective monotherapy against CAZ-susceptible strains (Delta log CFU/mL 54-0 h = -4.15 +/- 0.59 and -3.05 +/- 0.5 for HUB-PAS and PAO1, respectively; p <= 0.007 vs. other monotherapies), and adding colistin improved the efficacy over CAZ monotherapy. CAZ monotherapies were ineffective against the HUB-XDR strain, and CAZ-CI50 plus colistin achieved higher efficacy than CAZ-IB with colistin. The PK/PD index that correlated best with anti-biofilm efficacy was fAUC(0-24h)/MIC (r(2) = 0.78). Conclusions: CAZ exhibited dose-dependent anti-biofilm killing against P. aeruginosa, which was better explained by the fAUC(0-24h)/MIC index. CAZ-CI provided benefits compared to CAZ-IB, particularly when using higher doses and together with colistin. CAZ monotherapies were ineffective against the CAZ-resistant strain, independently of the optimized strategy and only CAZ-CI plus colistin appeared useful for clinical practice. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/antibiotics13040344 |
It is part of: | Antibiotics, 2024, vol. 13, issue. 4, p. 344 |
URI: | http://hdl.handle.net/2445/214370 |
Related resource: | https://doi.org/10.3390/antibiotics13040344 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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antibiotics-13-00344.pdf | 679.99 kB | Adobe PDF | View/Open |
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