Antibiotic Resistant Infection, Critical Illness
Conditions
Keywords
meropenem, antibiotic resistance, critical illness, β-lactams, continuous antibacterial drug infusion, mortality
Brief summary
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.
Interventions
DRUGMeropenem
Meropenem or injection vials to be re-constituted in a solution of NaCl 0.9%.
Sponsors
Università Vita-Salute San Raffaele
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Will be enrolled patients who: * Are able to express informed consent or the latter can be given by his/her next of kin or as requested by Ethical Committee. * Need a new antibiotic treatment, by clinical judgment, with meropenem * Are admitted to ICU * Have Sepsis or septic shock. Sepsis defined as having all the following 1. SIRS (Systemic Inflammatory Response Syndrome); 2. suspected or documented infection; 3. a SOFA score ≥ 2. Septic shock defined as having all the following 1.Sepsis; 2. Persisting hypotension requiring vasopressors to maintain MAP ≥65mmHg and having a serum lactate level \>2 mmol/L (18mg/dL) despite adequate volume resuscitation.
Exclusion criteria
Will be excluded patients who: * Are able to express informed consent and deny it * Are already receiving study drug or other carbapenem both as a bolus or continuous infusion * Have a known allergy or intolerance to study drug, to other carbapenem antibacterial agents or severe allergic reaction to β-lactam antibacterial agents or to anhydrous sodium carbonate (study drug excipient) * Have a little chance of survival, as defined by a SAPS II score greater than 65 * Have concomitant acquired immunodeficiency syndrome (stage 3 according to CDC) * Received immunosuppressant or long-term corticosteroid therapy (more than 0.5 mg/kg/day for over 30 days)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Death or Emergence of new resistant bacteria | day 28 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Death from any cause | day 90 | Death from any cause |
| Antibiotic-free days | up to day 28 or death | Proportion of days from randomization to day 28 or death in which subject didn't receive any antibiotics (excluding anti-fungal anti-viral drugs) |
| ICU - free days | day 28 or death | 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 |
| Cumulative SOFA-free point | up to day 28 | 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. |
Countries
Croatia, Italy, Kazakhstan, Russia
Outcome results
None listed