Piperacillin/Tazobactam in Continuous Infusion versus Intermittent Infusion in Children with Febrile Neutropenia

Abstract

Background: Febrile neutropenia (FN) is a common complication in children who receive chemotherapy for cancer. Objective: The objective of this study was to evaluate the clinical efficacy of the continuous versus intermittent infusion of piperacillin/ tazobactam (TZP) in febrile neutropenic pediatric patients. Methods: This is a non-blinded randomized controlled clinical trial. Eligible group consisted of hemato-oncological patients with FN who were candidates to receive TZP. Patients were randomized to one of two groups: Group 1 received antibiotic treatment through intravenous intermittent infusion of TZP 300 mg/kg/day based on piperacillin, divided into four doses, not exceeding 16 g/day; Group 2 received an initial TZP loading dose of 75 mg/kg infusion over 30 min, and then a continuous infusion of TZP 300 mg/kg/day through central line with pump over 24 h. Results: There were 176 episodes that could be assessed, 100 in Group 1 and 76 in Group 2. There was no statistically significant difference in treatment failure in the experimental group (continuous infusion) compared with the intermittent group, 21% versus 13% (p = 0.15). The increase in the absolute risk reduction was 0.08% (95% confidence interval 0.12-0.30), and the number needed to treat was 12.4. One patient in each group died. Conclusions: There were no differences in fever resolution, clinical cure rate, or mortality when comparing the continuous with the intermittent TZP infusion.

Diagnosis and Management of Febrile Neutropenia in Pediatric Oncology Patients—A Systematic Review

“…Accepted values for single measurements are between >38.3 °C and >38.5 °C, but certain studies [ 4 ] consider values as low as ≥37.8 °C in their definitions of fever. Multiple readings >/≥38 °C at least one hour after the first reading are also considered to be fever; one study [ 15 ] considered three temperature measurements between 37.5 and 38 °C over 24 h to be fever [ 2 , 4 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ].…”

“…When each study was analyzed individually, however, only two of them [ 12 , 24 ] listed Gram-positive bacteria as being the primary pathogen of their MDI, while all the rest described Gram-negative bacteria to be the leading cause of the infections, with Gram-positive pathogens taking up the second place. The third place was occupied by fungi in all but one study [ 14 ], where there were more fungi identified as Gram-positive bacteria.…”

“…One-fourth of the studies [ 21 , 23 , 24 , 25 ] included here considered Piperacillin/Tazobactam as either their first choice of antibiotic or mentioned this antibiotic combination first in their list of used antibiotic schemes. Six further studies [ 4 , 15 , 18 , 19 , 20 , 25 ] mentioned using Piperacillin/Tazobactam or Piperacillin alone, but these antibiotics are not necessarily the first line of treatment.…”

“… Individual look upon the pathogens involved in the MDIs: Alali M. et al (2020) [ 13 ]; Suttitossatam I. et al (2020) [ 15 ]; Janssens K.P. et al (2020) [ 4 ]; Lee N.H. et al (2020) [ 16 ]; Kamonrattana R. et al (2019) [ 19 ]; Reinecke J. et al (2018) [ 22 ]; Kobayashi R. et al (2020) [ 23 ]; Fortino S.S. et al (2019) [ 24 ]; Raad C. et al (2021) [ 25 ]. …”

Optimizing Antibiotic Treatment Strategies for Neonates and Children: Does Implementing Extended or Prolonged Infusion Provide any Advantage?

“…Continuous infusion included a loading dose of 75 mg/kg over 30 min, followed by a 24 h continuous infusion of 300 mg/kg/day. Among 176 episodes assessed, no statistically significant difference was found in fever resolution, clinical cure rate or mortality between the continuous Infusion group and the intermittent administration group, with respectively 16 and 13 cases of treatment failure; one patient in each group died [58].…”