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

• Main Authors: Cristina El Haj (Author), Eugènia Agustí (Author), Eva Benavent (Author), Laura Soldevila-Boixader (Author), Raül Rigo-Bonnin (Author), Fe Tubau (Author), Benjamín Torrejón (Author), Jaime Esteban (Author), Oscar Murillo (Author)
• Format: Book
• Published: MDPI AG, 2024-04-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

<b>Background</b>: 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 <i>Pseudomonas aeruginosa</i> biofilm. <b>Methods</b>: 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 <i>P. aeruginosa</i>. 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. <b>Results</b>: CAZ-CI₇₀ 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; <i>p</i> ≤ 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 <i>f</i>AUC_0-24h/MIC (r² = 0.78). <b>Conclusions</b>: CAZ exhibited dose-dependent anti-biofilm killing against <i>P. aeruginosa</i>, which was better explained by the <i>f</i>AUC_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.

Item Description

10.3390/antibiotics13040344
2079-6382