Slow Initial β-lactam Infusion With High-dose Paracetamol to Improve the Outcomes of Childhood Bacterial Meningitis
Condition: Bacterial Meningitis
MeSH terms: Meningitis, Bacterial; Meningitis
Intervention: Infusion with paracetamol; Bolus without paracetamol
Intervention description: The administration of 250 mg/kg/24 hours cefotaxime during the first 4 days as continuous intravenous infusion, each single infusion lasting for 12 hours (to prevent degradation of the agent), combined with high-dose paracetamol orally; the first dose is 30 mg/kg, then 20 mg/kg every 6 hours for 4 full days.; The control intervention consists of 250 mg/kg/24 hours cefotaxime administered traditionally with intermittent i.v. boluses and the place bo of paracetamol orally, both repeated every 6 hours (qid) for 4 days.
Intervention MeSH terms: Acetaminophen
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 375.0
Sex: All
Minimum age: 2 Months
Maximum age: 15 Years
Healthy volunteers: No
Keywords: Bacterial meningitis; infusion; bolus; paracetamol

Summary:

      The main purpose of this trial is to test if mortality of childhood bacterial meningitis can
      be reduced by slow, continuous infusion of cefotaxime initially, instead of the traditional
      bolus administration four times daily (qid), combined with high-dose paracetamol orally, when
      both treatments are executed for the first 4 days. The series will be collected at Hospital
      Pediátrico David Bernardino, Luanda, Angola.

      The recruitment of patients begins, the conditions permitting, in early 2012. The criteria
      for patient participation is a child at the age of 2 months to 15 years who presents with the
      symptoms and signs suggestive of bacterial meningitis, for whom a lumbar puncture is
      performed, and the cerebrospinal fluid analysis suggests bacterial meningitis.
    

Eligibility criteria:

        Eligibility criteria:

        The study entry is assessed for all children at age 2 months - 15 years who present at
        these centers with the symptoms and signs suggestive of bacterial meningitis (BM), and to
        whom lumbar puncture is performed.

        Inclusion criteria:

        All patients whose cerebrospinal fluid (CSF) turns out to be cloudy, positive by Gram
        staining or latex agglutination, or shows at least 50 leukocytes per mm3, will be enrolled
        in the study.

        Participants: Exclusion criteria

        Exclusion criteria:

          1. Trauma, or relevant underlying illness such as intracranial shunt, previous
             neurological abnormality (cerebral palsy, Down's syndrome, meningitis)

          2. Previous hearing impairment (if known)

          3. Immunosuppression, except HIV infection

          4. More than one parenteral dose of a pretreatment antimicrobial. Children with oral
             antimicrobials are included, this information being marked in the FOLLOW-UP sheet.

          5. Active tuberculosis (if tuberculotic meningitis is diagnosed during trial, it will be
             included in intention-to-treat (ITT) analysis)

          6. Known hepatic disease.