A Phase 4 interventional study of Meropenem in Antibiotic Resistant Infection and Critical Illness, sponsored by Università Vita-Salute San Raffaele. Completed at 26 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2025-08-06.
Sponsored by Università Vita-Salute San Raffaele · Phase 4, Interventional, and Treatment
This study arises from the need to optimize antibacterial drug usage to face increasing drug resistance among gram-negative pathogens in intensive care units. Gram-negative organisms are responsible for 70% of drug-resistant infections acquired in the intensive care unit. Meropenem is a β-lactam, carbapenem, antibacterial agent usually administered by intermittent infusion. As β-lactam efficacy is determined by the time in which the drug concentration exceeds the minimum inhibiting concentration of the target pathogen, intermittent infusion of this short half-lived drug can lead to precipitous drops in serum drug levels, an occurrence linked to emergence of resistant pathogens. The investigators hypothesize a beneficial effect of a continuous meropenem infusion on mortality and emergence of drug resistant pathogens. All patients enrolled will receive 1 g of meropenem bolus. After that, subjects will be randomized to receive a continuous infusion of study drug 3g/day or a bolus administration of the same amount of drugs. The investigators expect a reduction of mortality and emergence of extensive or pan drug resistant pathogens from 52 to 40% in the continuous infusion group.
Will be enrolled patients who:
Exclusion Criteria:
Will be excluded patients who:
Patient randomized to continuous infusion group, will receive a continuous infusion of meropenem according to their renal function (creatinine clearance -ClCr- estimated by Cockcroft-Gault formula and study day 1. for ClCr \> 50 ml/min: 3 g / day, prepared as follows: 10 mg/ml of meropenem in NaCl 0.9% at 12,5 ml/h. 2. for ClCr \< 50 ml/min: 2 g / day, prepared as follows: 10 mg/ml of meropenem in NaCl 0.9% at 8,3 ml/h. This solution will be replaced every time its duration exceeds the stability in use stated by the producer
Drug: Meropenem
Patient randomized to bolus group, will receive a bolus infusion of meropenem according to their renal function (creatinine clearance -ClCr- estimated by Cockcroft-Gault formula): 1. for Cl-Cr \> 50 ml/min 1 g every 6 hours on first 24 hours, every 8 hours after 2. for Cl-Cr \< 50 ml/min 1 g every 8 hours on first 24 hours, every 12 hours after
Drug: Meropenem
Meropenem or injection vials to be re-constituted in a solution of NaCl 0.9%.
Death or Emergence of new resistant bacteria
composite outcome: 1. death from any cause at day 28 2. emergence of new XDR (extended drug resistant) or PDR (pan drug resistant) bacteria at day 28
Time frame: day 28
Death from any cause
Death from any cause
Time frame: day 90
Antibiotic-free days
Proportion of days from randomization to day 28 or death in which subject didn't receive any antibiotics (excluding anti-fungal anti-viral drugs)
Time frame: up to day 28 or death
ICU - free days
Number of days from randomization to day 28 (or death) in which the subject is outside the ICU. For any discharge lasting less than 48h, no ICU-free day will be computed. Re-admission lasting less than 24 hours will not reduce ICU-free days. Patients that will not survive outside ICU for at least 48 hours, will have a ICU-free day of zero
Time frame: day 28 or death
Cumulative SOFA-free point
SOFA score will be evaluated every day up to day 28. SOFA-free daily score is 24 (maximum SOFA) minus actual SOFA. Cumulative SOFA-free is the sum of SOFA-free daily from randomization to date 28. Patients dead before day 28 can't ameliorate their SOFA-free score. This way, the higher the cumulative SOFA-free, the higher is the amelioration of the patient and his probability of survival.
Time frame: up to day 28
This study is completed, as verified in Aug 2025. You cannot join it, but the record below documents what was studied.
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Università Vita-Salute San Raffaele