Bolus Versus Prolonged Infusion of Meropenem in Newborn With Late Onset Sepsis

Study Overview
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Brief Summary
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Newborns in the neonatal intensive care unit (NICU), especially premature ones with immature organ systems, frequently suffer nosocomial infections caused by microorganisms resistant to narrow-spectrum antibiotics like ampicillin and gentamicin and require introduction of new agents with a wider spectrum of activity. Meropenem has activity against wide variety of Gram-negative and Gram-positive bacteria. It is well tolerated by children and neonates, including preterm babies, and allowing monotherapy instead of combined therapy. Severe neonatal infections with increasing antibiotic resistance are major problems affecting morbidity and mortality in the NICU. Few number of new antibacterial agents entering the clinic and new agents for multi-drug resistant Gram-negative bacteria will unlikely be available in the near future.

Detailed Description
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More research into existing antibiotics with novel mechanisms of action are required to combat the increased resistance and decreased development of antibiotics. Efforts were exerted to maximize antibiotic efficacy by optimal dosing based on pharmacodynamic and pharmacokinetic properties of antibiotics. Meropenem is administered mostly via a 30-min infusion, as some data indicate rapid degradation after reconstitution. Dose recommendations from two pediatric studies using Monte Carlo simulation have emphasized that a 4-h infusion may be needed if microorganisms showed increased minimal inhibitory concentrations (MICs), more specifically, for Pseudomonas aeruginosa. A prolonged-infusion strategy has not been tested in neonates, although some data suggest that extremely small infusion volumes may significantly affect the drug amount actually delivered. Aim of work: The objective of our study is to compare the clinical and bacteriological efficacy of conventional intermittent dosing of meropenem to the prolonged infusions in critically-ill neonates, with a proactive focus on reducing ventilator days in ventilated patients, length of stay in NICU, and neonatal mortality.

Official Title
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Bolus Versus Prolonged Infusion of Meropenem in Newborn With Late Onset Sepsis: A Randomized Control Trial

Conditions
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Late Onset Neonatal Sepsis

Intervention / Treatment
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* Drug: Meropenem.


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Neonates admitted to the neonatal care unit (NCU) who suffer from late onset sepsis (LOS) at admission or during their NICU stay and receive meropenem for at least four days Exclusion Criteria: Acute or chronic renal failure Hypersensitivity or allergy to meropenem

Ages Eligible for Study
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Minimum Age: 3 Days
Maximum Age: 4 Weeks

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Infusion arm<br>Infants will receive a loading dose of 20 mg/kg/dose every 8 hours for sepsis and 40 mg/kg/dose every 8 hours in meningitis and pseudomonas infection. Each dose will be infused over four hours. | Drug: Meropenem.<br>* Infants in both groups will receive a loading dose of 20 mg/kg/dose every 8 hours for sepsis and 40 mg/kg/dose every 8 hours in meningitis and pseudomonas infection<br>|
| Active Comparator: Bolus group<br>Infants will receive a loading dose of 20 mg/kg/dose every 8 hours for sepsis and 40 mg/kg/dose every 8 hours in meningitis and pseudomonas infection. Each dose will be infused over thirty minutes. | Drug: Meropenem.<br>* Infants in both groups will receive a loading dose of 20 mg/kg/dose every 8 hours for sepsis and 40 mg/kg/dose every 8 hours in meningitis and pseudomonas infection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical outcome | Success is defined as complete or partial resolution of leukocytosis, temperature, and clinical signs and symptoms of infection. Failure consists of persistence or progression of signs and symptoms of infection, development of new clinical findings consistent with active infection, or death from infection. | 15-28 days from Meropenem treatment | 
| Microbiological outcome | Success is defined as eradication of infection or colonization which means detection of a new pathogen from the site of infection during meropenem therapy and no new antibiotic is indicated Failure is defined as persistence of infection and superinfection which means detection of a new pathogen from the site of infection during meropenem therapy and new antibiotic is indicated. | 7-21 days from Meropenem treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Meropenem-related length of mechanical ventilation | The number of mechanical ventilation days from the start of meropenem administration | 0-31 days from Meropenem treatment | 
| Meropenem-related length of NICU stay | The number of days from the beginning of meropenem therapy to discharge from NICU | 10 weeks from Meropenem treatment | 
| NICU mortality | Death before discharge | 12 weeks from time of admission | 
| Duration of meropenem treatment | Total days of meropenem treatment | 3-28 days | 
| Clinical side effects of meropenem treatment | Safety of meropenem therapy will be evaluated by clinical symptoms (diarrhea, rash, vomiting and seizures). | 3-28 days from meropenem treatment | 
| Laboratory derangement related to meropenem treatment | Assessment of laboratory parameters and their changes during meropenem therapy (transaminases, alkaline phosphatase, bilirubin). | 3-28 days from meropenem treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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newborn, meropenem, infusion, late-onset sepsis, management