Clinical and microbiological efficacy of continuous versus intermittent application of meropenem in critically ill patients: a randomized open-label controlled trial

Abstract

IntroductionMeropenem bactericidal activity depends on the time when the free drug concentrations remain above the minimum inhibitory concentration of pathogens. The goal of this study was to compare clinical and bacteriological efficacy of continuous meropenem infusion versus bolus administration in critically ill patients with severe infection, and to evaluate the safety of both dosing regimens.MethodsPatients admitted to the interdisciplinary Intensive Care Unit (ICU) who suffered from severe infections and received meropenem were randomized either in the Infusion group (n = 120) or in the Bolus group (n = 120). Patients in the Infusion group received a loading dose of 2 g of meropenem followed by a continuous infusion of 4 g of meropenem over 24 hours. Patients in the Bolus group were given 2 g of meropenem over 30 minutes every 8 hours. Clinical and microbiological outcome, safety, meropenem-related length of ICU and hospital stay, meropenem-related length of mechanical ventilation, duration of meropenem treatment, total dose of meropenem, and ICU and in-hospital mortality were assessed.ResultsClinical cure at the end of meropenem therapy was comparable between both groups (83.0% patients in the Infusion vs. 75.0% patients in the Bolus group; P = 0.180). Microbiological success rate was higher in the Infusion group as opposed to the Bolus group (90.6% vs. 78.4%; P = 0.020). Multivariate logistic regression identified continuous administration of meropenem as an independent predictor of microbiological success (OR = 2.977; 95% CI = 1.050 to 8.443; P = 0.040). Meropenem-related ICU stay was shorter in the Infusion group compared to the Bolus group (10 (7 to 14) days vs. 12 (7 to 19) days; P = 0.044) as well as shorter duration of meropenem therapy (7 (6 to 8) days vs. 8 (7 to 10) days; P = 0.035) and lower total dose of meropenem (24 (21 to 32) grams vs. 48 (42 to 60) grams; P < 0.0001). No severe adverse events related to meropenem administration in either group were observed.ConclusionsContinuous infusion of meropenem is safe and, in comparison with higher intermittent dosage, provides equal clinical outcome, generates superior bacteriological efficacy and offers encouraging alternative of antimicrobial therapy in critically ill patients.

Dosing Nomograms for Attaining Optimum Concentrations of Meropenem by Continuous Infusion in Critically Ill Patients with Severe Gram-Negative Infections: a Pharmacokinetics/Pharmacodynamics-Based Approach

“…This approach has been recently assessed by several authors for meropenem in the clinical setting (9,22,25,35,40).…”

The Japanese Clinical Practice Guidelines for Management of Sepsis and Septic Shock 2016 (J‐SSCG2016)

“…We referred to 4 RCT reports 72, 90, 91, 92. Among these studies, no significant differences were observed between the respective study groups with respect to 90‐day mortality rate (odds ratio: 0.94; 95% confidence interval [CI]: 0.69–1.28, P  =   0.68), ICU mortality rate (odds ratio: 0.79; 95% CI: 0.59–1.06, P  =   0.11), in‐hospital mortality rate (odds ratio: 0.78; 95% CI: 0.59–1.03, P  =   0.08), or target serum drug concentration achievement rate (odds ratio: 1.88; 95% CI: 0.89–3.98, P  =   0.10).…”

Infusão Contínua Versus Intermitente De Meropenem Na Prática Clínica

“…A avaliação da eficácia dos métodos de infusão contínua versus infusão intermitente foi variada nos diversos artigos selecionados, variou desde a análise do pico de concentração plasmática do Meropenem, alcance de determinados percentuais da CIM, tempo de concentrações plasmáticas acima do CIM (T >CIM), cura e até mesmo a comparação direta dos dois métodos, também fatores como segurança, perfil farmacocinético, perfil farmacodinâmico e mortalidade (JARURATANASIRIKUL; SRIWIRIYAJAN, 2003;CHYTRA et al, 2012).…”

“…Já no trabalho conduzido por Chytra et al (2012), foi realizada avaliação da eficácia clínica e microbiológica da aplicação de Meropenem por infusão contínua (4 g em 24 horas) em comparação com o método de bolus (2 g durante 30 minutos a cada 8 horas). A cura clínica no fim da terapia com o antibiótico foi comparável para ambos os grupos (83% para o grupo da infusão e 75% para o grupo do bolus; P = 0,180).…”