头孢他啶持续输注与间歇推注对体外头孢他啶敏感和耐药生物膜的疗效比较
Comparative Efficacy of Continuous Ceftazidime Infusion vs. Intermittent Bolus against In Vitro Ceftazidime-Susceptible and -Resistant Biofilm.
作者信息
El Haj Cristina, Agustí Eugènia, Benavent Eva, Soldevila-Boixader Laura, Rigo-Bonnin Raül, Tubau Fe, Torrejón Benjamín, Esteban Jaime, Murillo Oscar
机构信息
Infectious Diseases Service, Laboratory of Experimental Infection, Hospital Universitari de Bellvitge and Bellvitge Biomedical Research Institute, Universitat de Barcelona, 08907 Barcelona, Spain.
Department of Clinical Laboratory, Hospital Universitari de Bellvitge and Bellvitge Biomedical Research Institute, Universitat de Barcelona, 08907 Barcelona, Spain.
出版信息
Antibiotics (Basel). 2024 Apr 9;13(4):344. doi: 10.3390/antibiotics13040344.
: 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 biofilm. : 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 . 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; and 9 g/daily at 70 mg/L, CAZ-CI) and CAZ-colistin combinations. Efficacy was correlated with the CAZ PK/PD parameters. : CAZ-CI 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; ≤ 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 plus colistin achieved higher efficacy than CAZ-IB with colistin. The PK/PD index that correlated best with anti-biofilm efficacy was AUC/MIC (r = 0.78). : CAZ exhibited dose-dependent anti-biofilm killing against , which was better explained by the AUC/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.
由于抗生素的抗生物膜药代动力学/药效学(PK/PD)特性尚未明确界定,我们评估了不同头孢他啶(CAZ;联合或不联合黏菌素)方案针对生物膜的PK/PD指标。我们使用了美国疾病控制与预防中心生物膜反应器,其中包含两种敏感菌株(PAO1和HUB - PAS)和一种耐药菌株(HUB - XDR)。方案包括CAZ单药治疗(模拟人类剂量2 g/8小时,CAZ - IB;以50 mg/L持续输注每日6 g,CAZ - CI;以及以70 mg/L每日9 g,CAZ - CI)和CAZ - 黏菌素联合治疗。疗效与CAZ的PK/PD参数相关。CAZ - CI是针对CAZ敏感菌株最有效的单药治疗(HUB - PAS和PAO1在0至4小时的Δlog CFU/mL分别为 - 4.15±0.59和 - 3.05±0.5;与其他单药治疗相比,P≤0.007),并且添加黏菌素比CAZ单药治疗提高了疗效。CAZ单药治疗对HUB - XDR菌株无效,且CAZ - CI加黏菌素比CAZ - IB加黏菌素疗效更高。与抗生物膜疗效相关性最佳的PK/PD指标是AUC/MIC(r = 0.78)。CAZ对[具体细菌名称未给出]表现出剂量依赖性的抗生物膜杀伤作用,这通过AUC/MIC指标能得到更好解释。与CAZ - IB相比,CAZ - CI具有优势,特别是在使用更高剂量以及与黏菌素联合使用时。CAZ单药治疗对CAZ耐药菌株无效,无论优化策略如何,只有CAZ - CI加黏菌素似乎对临床实践有用。