Tatchanapong Chongcharoenyanon1, Noppadol Wacharachaisurapol2, Suvaporn Anugulruengkitt3, Passara Maimongkol4, Orawan Anunsittichai5, Jiratchaya Sophonphan6, Tanittha Chatsuwan7, Thanyawee Puthanakit3. 1. Department of Paediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 2. Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. Electronic address: Noppadol.W@chula.ac.th. 3. Department of Paediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand; Center of Excellence for Paediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 4. Clinical Pharmacokinetics and Pharmacogenomics Research Unit, Department of Pharmacology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 5. Center of Excellence for Paediatric Infectious Diseases and Vaccines, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 6. The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT), Bangkok, Thailand. 7. Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
Abstract
OBJECTIVES: To be effective, piperacillin/tazobactam (PTZ) unbound plasma levels need to be above the minimum inhibitory concentration (MIC) at least 50% of the time between dosing intervals (50% fT>MIC). This study aimed to compare the plasma piperacillin concentrations at the mid-dosing intervals (Cmid, 50% fT) and the proportion of patients achieving 50% fT>MIC between extended infusion (EI) and intermittent bolus (IB) methods in children. METHODS: A prospective, randomised trial of EI versus IB of PTZ was conducted in children aged 1 month to 18 years. The PTZ dose was 100 mg/kg intravenously every 8 h. Patients were randomly assigned to receive EI (4-h infusion) or IB (30-min infusion). The primary outcome that was measured was plasma piperacillin Cmid. RESULTS:Ninety patients with a median age (IQR) of 48 months (16-127) were enrolled. The most common indication for PTZ use was pneumonia (32.2%). Geometric mean (95% CI) plasma piperacillin Cmid of EI versus IB was 51.9 mg/L (40.6-66.6) versus 6.0 mg/L (4.2-8.6) (P < 0.01). The EI group had a trend of higher proportion of patients who achieved 50% fT>4xMIC (72.7% versus 30.0%; P = 0.06). CONCLUSIONS:PTZ administration with EI resulted in a higher Cmid compared with IB. In settings with increased piperacillin MICs, this approach should be implemented, particularly during the empirical treatment period.
RCT Entities:
OBJECTIVES: To be effective, piperacillin/tazobactam (PTZ) unbound plasma levels need to be above the minimum inhibitory concentration (MIC) at least 50% of the time between dosing intervals (50% fT>MIC). This study aimed to compare the plasma piperacillin concentrations at the mid-dosing intervals (Cmid, 50% fT) and the proportion of patients achieving 50% fT>MIC between extended infusion (EI) and intermittent bolus (IB) methods in children. METHODS: A prospective, randomised trial of EI versus IB of PTZ was conducted in children aged 1 month to 18 years. The PTZ dose was 100 mg/kg intravenously every 8 h. Patients were randomly assigned to receive EI (4-h infusion) or IB (30-min infusion). The primary outcome that was measured was plasma piperacillin Cmid. RESULTS: Ninety patients with a median age (IQR) of 48 months (16-127) were enrolled. The most common indication for PTZ use was pneumonia (32.2%). Geometric mean (95% CI) plasma piperacillin Cmid of EI versus IB was 51.9 mg/L (40.6-66.6) versus 6.0 mg/L (4.2-8.6) (P < 0.01). The EI group had a trend of higher proportion of patients who achieved 50% fT>4xMIC (72.7% versus 30.0%; P = 0.06). CONCLUSIONS:PTZ administration with EI resulted in a higher Cmid compared with IB. In settings with increased piperacillin MICs, this approach should be implemented, particularly during the empirical treatment period.
Authors: Ronaldo Morales Junior; Gabriela Otofuji Pereira; Gustavo Magno Baldin Tiguman; Vanessa D'Amaro Juodinis; João Paulo Telles; Daniela Carla de Souza; Silvia Regina Cavani Jorge Santos Journal: Front Pediatr Date: 2022-03-10 Impact factor: 3.418