Pharmacokinetics of meropenem in burn patients with infections caused by Gram-negative bacteria: Are we getting close to the right treatment?. (March 2020)

• Record Type: Journal Article
• Authors: Corcione, Silvia; D'Avolio, Antonio; Loia, Riccardo Corgiat; Pensa, Anna; Segala, Francesco Vladimiro; De Nicolò, Amedeo; Fatiguso, Giovanna; Romeo, Mariarosa; Di Perri, Giovanni; Stella, Maurizio; De Rosa, Francesco Giuseppe
• Is Part Of: Journal of global antimicrobial resistance. Volume 20(2020)
• Page Start: 22
• Page End: 27
• Publication Date: 2020-03
• Subjects: Burn -- Meropenem -- Pharmacokinetics -- Pharmacodynamics -- Multidrug-resistant -- Infection; Drug resistance -- Periodicals; Drug resistance -- Periodicals; Drug resistance; Periodicals; 616.9041
• DOI: 10.1016/j.jgar.2019.06.011
• Languages: English
• ISSNs: 2213-7165

Abstract

Highlights: Severe infections due to multidrug-resistant Gram-negative bacteria are a rising cause of death among burn patients. Altered PK parameters in burn patients may result in serum drug concentrations below those required for efficacy. Despite prolonged (2 h) intravenous infusion of meropenem, burn patients had lower PK/PD parameters. Prolonged infusion with higher meropenem dosage, especially for MIC > 0.5 μg/mL, may be needed to achieve PK/PD targets. Routinely use of TDM in burn patients may be a useful tool to reduce toxicity and to improve efficacy. Abstract: Objectives: Infections caused by multidrug-resistant Gram-negative bacteria are associated with high mortality. A relevant concern is the efficacy of antibiotic therapy in burn patients in whom pathophysiological changes strongly influence pharmacokinetic (PK) parameters. This study aimed to describe the PK parameters of meropenem in a population of burn patients. Methods: Blood samples were collected immediately before and 2 h and 5 h after the start of intravenous drug administration. Plasma meropenem concentrations were determined using an ultra-performance liquid chromatography–photodiode array method. Results: Seventeen burn patients were enrolled in the study. Thirteen patients (76%) were treated with meropenem for infections by Pseudomonas aeruginosa or Acinetobacter baumannii isolated from blood or wounds. Mean C max, C min, AUC0–24, half-life, drug clearance and volume of distribution were 28.9 mg/L, 3.7 mg/L, 280.2 mg h/L, 2.0 h, 19.0 L/h and 44.4 L, respectively. Six patients (35%) achieved a C min ≥3.3 mg/L and seven patients (41%) achieved a C max ≥ 28.4 mg/L, whilst nine patients (53%) achieved an AUC0–24 of >226 mg h/L. Given a minimum inhibitory concentration (MIC) of 0.5 mg/L, all patients satisfied the target AUC/MIC of >125, but when the MIC rises to 2 mg/L (the ECOFF), only five patients reached the desired AUC/MIC. Regarding f T>MIC at an MIC of 2 mg/L with a 2-h infusion time, 13 patients (76%) achieved the PK target (>75%). Conclusion: These data suggest that a combined 2-h infusion with a higher dosage of meropenem, including a loading dose, may be successful to achieve effective PK parameters.