Comparative Efficacy of Continuous Ceftazidime Infusion vs. Intermittent Bolus against In Vitro Ceftazidime-Susceptible and -Resistant Pseudomonas aeruginosa Biofilm
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...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universidad Autónoma de Madrid |
| Repositorio: | Biblos-e Archivo. Repositorio Institucional de la UAM |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.uam.es:10486/720896 |
| Acceso en línea: | http://hdl.handle.net/10486/720896 https://dx.doi.org/10.3390/antibiotics13040344 |
| Access Level: | acceso abierto |
| Palabra clave: | beta-lactams biofilm foreign-body infection P. aeruginosa PK/PD Medicina |
| Sumario: | 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-CI<inf>50</inf>; and 9 g/daily at 70 mg/L, CAZ-CI<inf>70</inf>) and CAZ-colistin combinations. Efficacy was correlated with the CAZ PK/PD parameters. Results: CAZ-CI<inf>70</inf> was the most effective monotherapy against CAZ-susceptible strains (Δlog 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-CI<inf>50</inf> plus colistin achieved higher efficacy than CAZ-IB with colistin. The PK/PD index that correlated best with anti-biofilm efficacy was fAUC<inf>0–24h</inf>/MIC (r<sup>2</sup> = 0.78). Conclusions: CAZ exhibited dose-dependent anti-biofilm killing against P. aeruginosa, which was better explained by the fAUC<inf>0–24h</inf>/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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