Pharmacokinetic and Safety Study of Ceftolozane/Tazobactam in Pediatric Participants Receiving Antibiotic Therapy for Proven or Suspected Gram-negative Infection or for Peri-operative Prophylaxis (MK-7625A-010)
Condition: Proven or Suspected Gram-negative Bacterial Infection; Peri-operative Prophylaxis
MeSH terms: Infections; Communicable Diseases; Bacterial Infections; Gram-Negative Bacterial Infections
Intervention: Ceftolozane/Tazobactam 1000/500 mg; Ceftolozane/Tazobactam 30/15 mg/kg; Ceftolozane/Tazobactam 20/10 mg/kg; Ceftolozane/Tazobactam 18/9 mg/kg; Ceftolozane/Tazobactam 12/6 mg/kg
Intervention description: A fixed dose combination (FDC) of 1000 mg ceftolozane and 500 mg tazobactam as a 60 minute infusion.; A FDC of 30 mg/kg of ceftolozane and 15 mg/kg of tazobactam as a 60 minute infusion.; A FDC of 20 mg/kg of ceftolozane and 10 mg/kg of tazobactam as a 60 minute infusion.; A FDC of 18 mg/kg of ceftolozane and 9 mg/kg of tazobactam as a 60 minute infusion.; A FDC of 12 mg/kg of ceftolozane and 6 mg/kg of tazobactam as a 60 minute infusion.
Intervention MeSH terms: Tazobactam; Ceftolozane; Cephalosporins; Ceftolozane, tazobactam drug combination; Penicillanic Acid
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 43.0
Sex: All
Minimum age: 7 Days
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      The purpose of this study was to assess the pharmacokinetics, safety, and tolerability of a
      single intravenous dose of ceftolozane/tazobactam (MK-7625A) in pediatric participants. In
      each of the 6 age cohorts, an interim analysis of pharmacokinetics (PK) and safety data was
      conducted after approximately 3 participants had received the initially proposed dose. The
      interim analysis was to determine whether the initial dose was appropriate based on
      pre-defined criteria. If data from the interim analysis demonstrated that the initially
      proposed dose met the above criteria, enrollment was to continue with the same dose
      administered to approximately 3 additional participants of the same age range. However, if
      the interim analysis demonstrated that a new optimized dose was required, the new dose was to
      be administered to approximately 3 additional participants of the same age range.
    

Eligibility criteria:

        Key Inclusion Criteria:

          1. Males or non-pregnant females from birth to <18 years of age

          2. Receiving standard of care antibiotic therapy for suspected or diagnosed Gram-negative
             infection or for peri-operative prophylaxis

          3. Groups 1-4: Calculated creatinine clearance rate (CLCR) ≥ 80 ml/min/1.73m2 at baseline

          4. Group 5: CLCR ≥ 50 ml/min/1.73m2 at baseline

          5. Group 6: CLCR ≥ 20 ml/min/1.73m2 at baseline

        Key Exclusion Criteria:

          1. Known allergy/hypersensitivity to any β-lactam antibacterial

          2. History of clinically significant renal, hepatic, or hemodynamic instability

          3. Planned use of cardiopulmonary bypass or dialysis

          4. Planned blood transfusion within 24 hours of study drug administration

          5. Clinically significant abnormal laboratory test results not related to the underlying
             infection

          6. Receipt of piperacillin/tazobactam within 24 hours of study drug administration

          7. Likely to be at risk of hemodynamic disturbance following collection of the required
             PK blood samples