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Efficacy of meropenem extended infusion vs intermittent bolus monotherapy and in combination with colistin against Pseudomonas aeruginosa biofilm. | LitMetric

Efficacy of meropenem extended infusion vs intermittent bolus monotherapy and in combination with colistin against Pseudomonas aeruginosa biofilm.

Int J Antimicrob Agents

Infectious Diseases Department, Laboratory of Experimental Infection, Hospital Universitari de Bellvitge, IDIBELL, Universitat de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red en Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain. Electronic address:

Published: August 2023

AI Article Synopsis

  • Device-related infections are tough to treat because of biofilms, which protect bacteria, making traditional antibiotic studies less effective, particularly against multi-drug-resistant strains like Pseudomonas aeruginosa.
  • This study evaluated the effectiveness of meropenem, a commonly used antibiotic, in fighting these biofilms by comparing two dosing methods: intermittent bolus and extended infusion, particularly with and without the addition of colistin.
  • Results indicated that the extended infusion method was more effective for both susceptible and resistant strains of P. aeruginosa, as it significantly enhanced bactericidal activity, especially when combined with colistin, suggesting an optimal treatment strategy.

Article Abstract

Introduction: Device-related infections are difficult to treat due to biofilms. In this setting, optimizing antibiotic efficacy is difficult as most pharmacokinetic/pharmacdynamic (PK/PD) studies have been performed on planktonic cells, and therapies are limited when multi-drug-resistant bacteria are involved. This study aimed to analyse the PK/PD indices of meropenem predicting anti-biofilm efficacy against meropenem-susceptible and meropenem-resistant strains of Pseudomonas aeruginosa.

Materials And Methods: Pharmacodynamics of meropenem dosages mimicking those of clinical practice (intermittent bolus of 2 g every 8 h; extended infusion of 2 g over 4 h every 8 h), with and without colistin, were evaluated with the CDC Biofilm Reactor in-vitro model for susceptible (PAO1) and extensively-drug-resistant (XDR-HUB3) P. aeruginosa. Efficacy was correlated with the PK/PD indices for meropenem.

Results: For PAO1, both meropenem regimens were bactericidal, with higher killing for extended infusion [∆log colony-forming units (CFU)/mL 54-0h=-4.66±0.93 for extended infusion vs ∆log CFU/mL 54-0h=-3.4±0.41 for intermittent bolus; P<0.001]. For XDR-HUB3, the intermittent bolus regimen was non-active, but extended infusion showed bactericidal effect (∆log CFU/mL 54-0h=-3.65±0.29; P<0.001). Time above minimum inhibitory concentration (f%T) had the best correlation with efficacy for both strains. The addition of colistin always improved meropenem activity, and resistant strains did not emerge.

Conclusion: f%T was the PK/PD index that best correlated with the anti-biofilm efficacy of meropenem; it was better optimized when using the extended infusion regimen, allowing recovery of bactericidal activity in monotherapy, including activity against meropenem-resistant P. aeruginosa. Combining meropenem by extended infusion with colistin offered the most effective therapy for both strains. Optimizing meropenem dosing by extended infusion should be encouraged when treating biofilm-related infections.

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Source
http://dx.doi.org/10.1016/j.ijantimicag.2023.106856DOI Listing

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