Pharmacokinetics (PK) of Antistaphylococcal Antibiotics in Infants (NICHD-2012-02-Staph Trio)

Study Overview
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Brief Summary
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Multiple center, open-label, PK study

Detailed Description
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Pharmacokinetics of rifampin, ticarcillin-clavulanate, and clindamycin antibiotics in hospitalized infants with suspected systemic infection or receiving one of the study drugs per local standard of care. Number of participants are 16-32 evaluable per each study drug of rifampin, ticarcillin-clavulanate, and clindamycin antibiotics.

Official Title
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Pharmacokinetics of Antistaphylococcal Antibiotics in Infants

Conditions
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Systemic Infection

Intervention / Treatment
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* Drug: Antibiotic


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Sufficient intravascular access Suspected systemic infection or receiving 1 of the study drugs per standard of care informed consent from legal guardian Exclusion Criteria: history of allergic reaction to study drugs urine output <0.5 mL/hr/kg over the prior 24 hours serum creatinine >1.7 mg/dl Any condition in investigator judgment precludes participation because it could affect participant safety

Ages Eligible for Study
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Minimum Age: 14 Days
Maximum Age: 32 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ticarcillin-clavulanate antibiotic<br>Cohort Gestational Age (GA) Postnatal Age (PNA) Dose <30 weeks <14 days: 75 mg/kg Q12 hrs x 6 doses <30 weeks ≥14 days-45 days 75 mg/kg Q 8 hours x 6 doses <30 weeks >45 days-90 days 75 mg/kg Q 6 hours x 6 doses Brand name is Timentin. This drug is an antibiotic used to treat a wide variety of bacterial infections. It is a combination of two drugs & both treat bacterial infections. Ticarcillin is a penicillin-type antibiotic that stops bacterial growth & clavulanate potassium is an enzyme inhibitor that helps the ticarcillin work better. | Drug: Antibiotic<br>* Ticarcillin-clavulanate/Timentin is an antibiotic used to treat a wide variety of bacterial infections. Rifampin/Rifadin/Rimatane is an antibiotic and first line antituberculotic. Clindamycin/Cleocin is an antibiotic used to treat a wide variety of bacterial infections and serious bacterial infections.<br>* Other names: Clindamycin generic; Brand Cleocin;|
| Experimental: Rifampin generic antibiotic<br>Cohort GA PNA Dose <32 weeks <14 days 10 mg/kg Q 24 hours x 4 doses <32 weeks ≥14 days-120 days 15 mg/kg Q 24 hours x 4 doses ≥32 weeks <14 days 15 mg/kg Q 24 hours x 4 doses ≥32 weeks ≥14 days-120 days 20 mg/kg Q 24 hours x 4 doses The brand name is Rifadin, Rimatane. This drug is an antibiotic and a first line antituberculotic and unlabeled use for infections caused by staphylococcus aureus & staphylococcus epidermis. | Drug: Antibiotic<br>* Ticarcillin-clavulanate/Timentin is an antibiotic used to treat a wide variety of bacterial infections. Rifampin/Rifadin/Rimatane is an antibiotic and first line antituberculotic. Clindamycin/Cleocin is an antibiotic used to treat a wide variety of bacterial infections and serious bacterial infections.<br>* Other names: Clindamycin generic; Brand Cleocin;|
| Experimental: Clindamycin Generic Antibiotic<br>Cohort GA PNA Dose <30 weeks <14 days 10 mg/kg Q 12 hours x 6 doses <30 weeks ≥14 days-45 days 10 mg/kg Q 8 hours x 6 doses <30 weeks >45 days-120 days 10 mg/kg Q 6 hours x 6 doses The brand name is Cleocin. This drug is an antibiotic used to treat a wide variety of bacterial infections and serious infections. | Drug: Antibiotic<br>* Ticarcillin-clavulanate/Timentin is an antibiotic used to treat a wide variety of bacterial infections. Rifampin/Rifadin/Rimatane is an antibiotic and first line antituberculotic. Clindamycin/Cleocin is an antibiotic used to treat a wide variety of bacterial infections and serious bacterial infections.<br>* Other names: Clindamycin generic; Brand Cleocin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1: Area under the curve infinity (AUCinfinity) for rifampin | Pharmacometric analysis of area under the curve at steady state for cohort 1 participants who were dosed with rifampin 10mg/kg Q 24 hours x 4 doses (GA < 32 weeks, PNA < 14 days) | 72 hours | 
| Cohort 1: Maximum concentration (Cmax) of rifampin | Pharmacometric analysis of maximum concentration after first dose for cohort 1 participants who were dosed with rifampin 10 mg/kg Q 24 hours x 4 doses (GA < 32 weeks, PNA < 14 days) | 72 hours | 
| Cohort 1: Clearance (CL) of rifampin | Pharmacometric analysis of the clearance for cohort 1 participants who were dosed with rifampin 10 mg/kg Q 24 hours x 4 doses (GA < 32 weeks, PNA < 14 days) | 72 hours | 
| Cohort 1: Volume of distribution at steady state (Vss) of rifampin | Pharmacometric analysis of volume of distribution at steady state for cohort 1 participants who were dosed with rifampin 10 mg/kg Q 24 hours x 4 doses (GA < 32 weeks, PNA < 14 days) | 72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cohort 1: Adverse events for participants receiving rifampin | Adverse events experienced by cohort 1 participants receiving rifampin 10 mg/kg Q 24 hours x 4 doses (GA < 32 weeks, PNA > 14 days). An adverse event is any untoward medical occurrence in humans, whether or not considered drug-related, that occurs during the conduct of a clinical trial. Any change in clinical status (routine labs, physical examinations, etc.) that is considered clinically significant | 7 days after last study dose | 
| Cohort 1 participants: serious adverse events for participants receiving rifampin | Serious adverse events experienced by cohort 1 participants receiving rifampin 10 mg/kg Q 24 hours x 4 doses(GA < 32 weeks, PNA > 14 days)Any event that results in any of the following outcomes: death, life-threatening adverse vent, persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, inpatient hospitalization or prolongation of existing hospitalization, or important medical event that may jeopardize the health of the study participant or require medical or surgical intervention to prevent another outcome listed above | 7 days after last study dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Staphylococcal