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cc by (c) El Haj, Cristina et al., 2024
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/214370

Comparative Efficacy of Continuous Ceftazidime Infusion vs. Intermittent Bolus against In Vitro Ceftazidime-Susceptible and -Resistant Pseudomonas aeruginosa Biofilm

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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.

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EL HAJ, Cristina, AGUSTÍ, Eugènia, BENAVENT PALOMARES, Eva, SOLDEVILA-BOIXADER, Laura, RIGO BONNIN, Raúl, TUBAU, Fe, TORREJÓN, Benjamín, ESTEBAN, Jaime, MURILLO RUBIO, Óscar. Comparative Efficacy of Continuous Ceftazidime Infusion vs. Intermittent Bolus against In Vitro Ceftazidime-Susceptible and -Resistant Pseudomonas aeruginosa Biofilm. _Antibiotics_. 2024. Vol. 13, núm. 4, pàgs. 344. [consulta: 25 de febrer de 2026]. ISSN: 2079-6382. [Disponible a: https://hdl.handle.net/2445/214370]

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