Pharmacokinetics of piperacillin/tazobactam in cancer patients with hematological malignancies and febrile neutropenia after chemotherapy

Abstract

IntroductionPatients with febrile neutropenia (FN) exhibit changes in extracellular fluid that may alter the plasma concentrations of beta-lactams and result in therapeutic failure or toxicity. We evaluated the pharmacokinetics of piperacillin/tazobactam in patients with hematological malignancies and FN after receiving chemotherapy at a primary public cancer center.MethodsThis was an open, nonrandomized, observational, descriptive, and prospective study. Samples from 15 patients with hematological malignancies and FN were evaluated after the administration of chemotherapy. Five blood samples were taken from each patient when the antibiotic level was at steady-state 10, 60, 120, 180, and 350 min after each dose. Antibiotic concentrations were measured using gel diffusion with Bacillus subtilis. All study participants provided written informed consent.ResultsWe investigated the pharmacokinetics of piperacillin in 14 patients between the ages of 18 years and 59 years and with a mean absolute neutrophil count of 208 cells per mm3 (standard deviation (SD) ± 603.2). The following pharmacokinetic measurements were obtained: maximum concentration, 94.1–1133 mg/L; minimum concentration, 0.47–37.65 mg/L; volume of distribution, 0.08–0.65 L/kg (mean, 0.34 L/kg); drug clearance (CL), 4.42–27.25 L/h (mean, 9.93 L/h); half-life (t1/2), 0.55–2.65 h (mean, 1.38 h); and area under the curve, 115.12–827.16 mg · h/L.ConclusionPatients with FN after receiving chemotherapy exhibited significant variations in the pharmacokinetic parameters of piperacillin compared with healthy individuals; specifically, FN patients demonstrated an increase in t1/2 and decreased CL.

Managing febrile neutropenia in adult cancer patients: an integrative review of the literature

“…This integrative review located a sample of 12 articles (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) which met the inclusion criteria and are presented in Chart 1.…”

“…Regarding the interventions for management of CT-induced FN, there was a prevalence of studies focused on pharmacological treatment (use of empiric ABT in hospital and outpatient settings, adherence to an antimicrobial management protocol and use of prophylactic or non-prophylactic growth factor) (14)(15)(18)(19)(20)(21)(22)(23)(24) and improvement in the diagnostics (association of biomarkers with the MASCC risk index) (17) . Only one study (16) investigated pharmaceutical management in relation to the efficacy of antibiotic dosage and a study which implied that nurses could contribute to the identification of elderly patients who would benefit from prophylactic use of growth factor in order to reduce the occurrence of FN (13) .…”

“…Regarding the efficacy of antimicrobial use, a study demonstrated the benefits of using piperacillin/tazobactam in the treatment of FN and prevention of complications (15) . In another study, adherence to an antimicrobial management protocol enabled a reduction in the mortality rate (21) .…”

“…Data collection of primary articles (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) included in the integrative review was made possible through an instrument detailing: identification of the original article (title, periodical, authors, specialism of authors, year of publication); objective(s); methodological characteristics of the study (type, sample, specialism of the professionals involved in FN management); intervention for FN management; and main findings, conclusions and identification of limitations and/or biases. For the analysis and synthesis of these articles, we used synoptic tables (11) containing: title, author/year and professional category; interventions realized; results; and recommendations/conclusions.…”

“…Evaluate the pharmacokinetics of administering piperacillin/tazobactam in patients with hematologic neoplasms and FN after CT (15) .…”