Piperacillin‐tazobactam concentration target attainment in children with cancer

Abstract

tration target attainment in 482 PIP samples from 43 children treated for febrile neutropenia. 1 Patients received 5 min infusion of PIP/TAZ at 100 mg/kg q8h.This dosage provided subtherapeutic drug concentration and insufficient probability of target attainment (PTA). The authors also simulated different dosages including 400 mg/kg/day (PIP) divided into four daily doses, but this schedule also did not affect the PTA. A possible, partial explanation could be augmented renal clearance of antibiotics observable in critically ill children, including those with febrile neutropenia, 2,3 a factor not considered in the study, combined with a very short infusion time. A randomized controlled trial in adults demonstrated the inadequacy of the dose of 4.5 g (PIP/TAZ) q8h to attain 100% fT >MIC and also 50% fT >MIC, 4 while a study in pediatric oncology patients with febrile neutropenia showed that a 0.5-3 h infusion of 100 mg/kg of PIP obtained a plasma concentration of at least 16 mg/L in 86.5% and 100% of cases. 5 Partially in line with these results were those obtained in a Monte Carlo simulation for Pseudomonas aeruginosa infection using 400 mg/kg/day of PIP with a loading dose followed by continuous infusion. 6 At the Istituto Giannina Gaslini, Genoa, Italy, febrile neutropenic children with cancer receive PIP/TAZ at 100 mg/kg (PIP) q6h infused over 30-60 min. We collected 49 specimens for determination of PIP plasma concentrations by volumetric absorptive microsampling (VAMS TM )-LC-MS/MS. 7 The median (first to third quartile, interquartile range [IQR]) concentration was 42.5 mg/L (IQR 4.6-72.6) with a range of 0.9-190.0. The proportion of plasma concentrations >16 mg/L (minimally inhibitory concentration breakpoint of PIP for Enterobacteriales and Pseudomonas according to EUCAST rules) 8 was 71.4%.It is likely that with prolonged infusion (3 h), an effective therapeutic concentration could be obtained in all patients, with a very low likelihood of achieving concentrations that put patients at risk of neurotoxicity. 9 In any case, our "real-life" data and previous pediatric studies demonstrate that the correct dosage of PIP/TAZ in children with cancer is 1-3 h infusion of 100 mg/kg (PIP) q6h, or a schedule with a bolus followed by continuous infusion of the same total daily dose. CONFLICT OF INTERESTThe authors report no conflict of interest. ORCID Carolina Saffiotihttps://orcid.org/0000-0001-5336-0235Alessio Mesini https://orcid.org/0000-0003-0593-4112Elio Castagnola

Estimating glomerular filtration rate from serum creatinine concentration in children with augmented renal clearance: all formulas are equivocal, but some are more equivocal than others

“…The limitations of our study are its retrospective nature and a rather limited number of samples. Yet we did not identify any previous study having assessed MER and PIP exposures in cancer children clearly taking the impact of ARC into account (26,40). This could be explained by the restricted hematology-oncology patient population and the still restricted availability or adopted practice of TDM for beta-lactams.…”

“…This requires to draw and measure plasma concentrations of the drug, and eventually adapt the dosage according to the result, in order to prevent treatment failure due to underexposure, or toxicity. Insufficient exposure to MER and PIP has been observed in adults (24,25), and to PIP in children (26). Underexposure to antibiotics may lead to therapeutic failure and the emergence of resistant germ strains (21,27).…”

Ensuring Sufficient Trough Plasma Concentrations for Broad-Spectrum Beta-Lactam Antibiotics in Children With Malignancies: Beware of Augmented Renal Clearance!

“…This requires to draw and measure plasma concentrations of the drug, and eventually adapt the dosage according to the result, in order to prevent treatment failure due to underexposure, or toxicity. Insufficient exposure to MER and PIP has been observed in adults ( 24 , 25 ), and to PIP in children ( 26 ). Underexposure to antibiotics may lead to therapeutic failure and the emergence of resistant germ strains ( 21 , 27 ).…”