Efficacy of Betalactam Antibiotics in Prolonged Infusion Compared to Intermittent in Pediatric Patients With Sepsis

Coordinación de Investigación en Salud, Mexico

Status: Completed

Conditions: Sepsis

Treatments: Drug: Intermittent Piperacillin/tazobactam; Drug: Continuous Piperacillin/tazobactam; Drug: Intermittent Imipenem; Drug: Extended Imipenem; Drug: Extended Meropenem; Drug: Intermittent Meropenem

Study type: Interventional

Funder types: Other

Identifiers

NCT03019965

2016-785-099

Details and patient eligibility

About

This study evaluates the efficacy and safety of the administration of betalactam antibiotics in prolonged infusion compared to intermittent infusion in children with sepsis. Half of participants will receive piperacillin/tazobactam, imipenem or meropenem in continuous or extended infusion, while the other half will receive piperacillin/tazobactam, imipenem or meropenem in intermittent infusion.

Full description

Sepsis is the leading cause of morbidity and mortality in hospitalised patients globally. Betalactams are time-dependent antibiotics, and so, the duration of time for which the free drug plasma concentration remains above the minimum inhibitory concentration (fT > MIC) is the pharmacokinetic/pharmacodynamic index associated with bacterial killing and clinical improvement. Numerous studies have demonstrated that continuous infusion (infusion in 24 hours) and extended infusion (through prolonging the infusion time to greater than 3 hours) allows the maintenance of concentrations above the MIC for a longer period of time within the dosing interval (30 minute or 1 hour), and so, capitalises on the pharmacodynamic properties of betalactams and maximises bacterial killing, therefore potentially improving clinical outcomes. In adult patients, the several studies suggest that prolonged infusion may offer clinical benefits and significant reduction in mortality without increasing the risk of toxicity, however, there is limited information about these dosing strategies in pediatric patients.

Enrollment: 426 patients

Sex: All

Ages: 1 month to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients diagnosed with sepsis, who have been evaluated by an infectious physician and are candidates to receive piperacillin/tazobactam, imipenem or meropenem as empiric treatment.

Exclusion criteria

• Patients with a history of allergy to one or more of the proposed antibiotics.
• Patients with chronic kidney disease or acute renal failure.
• Patients with acute liver failure of any cause.
• Patients in palliative or supportive care only.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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426 participants in 6 patient groups

Intermittent Piperacillin/tazobactam

Active Comparator group

Description:

Piperacillin/tazobactam 300mg/kg/day, divided into 4 doses/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 30 minutes infusion every 6 hours.

Treatment:

Drug: Intermittent Piperacillin/tazobactam

Continuous Piperacillin/tazobactam

Experimental group

Description:

Piperacillin/tazobactam initial doses 75mg/kg in 30 minutes infusion, immediately thereafter continue 300mg/kg/day, diluted in 5% glucose solution, at a concentration of 50mg/ml, to be administered in 24 hours infusion every 24 hours, as determined by antibiotic stability at room temperature.

Treatment:

Drug: Continuous Piperacillin/tazobactam

Intermittent Imipenem

Active Comparator group

Description:

Imipenem 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes infusion every 6 hours.

Treatment:

Drug: Intermittent Imipenem

Extended Imipenem

Experimental group

Description:

Imipenem initial doses 20mg/kg in 60 minutes infusion, immediately thereafter continue 80mg/kg/day, divided into 4 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 6 hours infusion every 6 hours, as determined by antibiotic stability at room temperature.

Treatment:

Drug: Extended Imipenem

Intermittent Meropenem

Active Comparator group

Description:

Meropenem 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution, at a concentration of 7mg/ml, to be administered in 60 minutes every 8 hours.

Treatment:

Drug: Intermittent Meropenem

Extended Meropenem

Experimental group

Description:

Meropenem initial doses 35mg/kg in 60 minutes infusion, immediately thereafter continue 100mg/kg/day, divided into 3 doses/day, diluted in 0.9% saline solution at a concentration of 7mg/ml, to be administered in 8 hours infusion every 8 hours, as determined by antibiotic stability at room temperature.

Treatment:

Drug: Extended Meropenem