Continuous vs intermittent meropenem administration in critically ill patients and renal function. A secondary post-hoc analysis of the MERCY trial

Objective In septic patients renal function changes are common, potentially affecting antibiotic therapies. Time-dependent antibiotics, administered as continuous infusion, can improve the time above the minimal inhibitory concentration, but the relationship between meropenem administration strategy and renal function remains unclear. This study aimed to investigate such relationship for a composite primary outcome of 28-day mortality and emergence of pandrug (PDR) or extensively drug-resistant (XDR) pathogens. Secondary aims were to investigate the impact of renal function on clinical and microbiological outcomes, regardless of meropenem administration strategy.Design Secondary analysis of the MERCY randomized controlled trial (Continuous Infusion versus Intermittent Administration of MERopenem in CriticallY Ill Patients).Setting Thirty-one ICUs in 4 countries.Patients MERCY patients with available estimated glomerular filtration rate (eGFR).Interventions Meropenem administration as continuous infusion or intermittent boluses.Main variables of interest eGFR, mortality, PDR/XDR pathogens.Results Among MERCY patients, eGFR was available at randomization for 586 patients: 311 had an eGFR 2, 181 between 60-129 ml/min/1.73m2, and 94 patients ≥130 ml/min/1.73m2. Meropenem administration strategy did not affect the primary outcome across eGFR categories (p for interaction = 0.60). Considering renal subgroups regardless of randomization arm, patients with eGFR 2 had a lower incidence of new XDR/PDR pathogens compared with the normal renal function group (adjusted RR 0.65, 95% CI 0.45 to 0.95, p = 0.026).Conclusions Among the MERCY population, there was no benefit from meropenem continuous infusion or intermittent boluses in any renal function subgroup. Having a lower eGFR was associated with a reduced emergence of PDR/XDR pathogens.