O12 Circulating concentrations of broad-spectrum beta-lactams in children with cancer: beware of glomerular hyperfiltration!

Background Broad-spectrum beta-lactams such as meropenem (MER) and piperacillin-tazobactam (PIP) are commonly prescribed in children with cancer having febrile neutropenia. They are introduced at intensive dosage, unless decreased renal function calls for dose reduction. Recently, glomerular hyperfiltration (HF) was recognized to be frequent among children with cancer during initial cycles of chemotherapy.1 We evaluated the impact of HF on therapeutic exposure to MER and PIP. Methods We retrieved retrospectively all MER and PIP plasma levels measured in children with cancer in our hospital between 2012 and 2018. We compared trough levels with usual therapeutic ranges (derived from reference values of minimum inhibitory concentrations). We classified the children according to plasma creatinine and estimated glomerular filtration rate (Schwartz formula) as either altered-normal ( Results We collected 120 concentration values (53 MER, 67 PIP) measured in 50 children with cancer. Among them, 74 (62%) had concomitant creatinine values suggestive of HF, and 80 (67%) were neutropenic. Overall, 67% of trough levels were below usual therapeutic ranges (MER: 2–8 mg/L, PIP 8–30 mg/L). This was more often the case in presence of concomitant HF (MER: 92%, PIP: 83%), often associated with neutropenia. Low exposure was observed not only at initial intensive dosage (MER: 120 mg/kg/day, PIP: 400 mg/kg/day)2 but tended to persist despite dosage readjustment based on concentration monitoring. Moreover, bacteremia was diagnosed in 38 cases. Conclusion Current recommended doses of MER and PIP do not provide optimal concentration coverage throughout the dosing interval in a large fraction of children with cancer and febrile neutropenia as a result of HF. Monitoring of beta-lactams should be offered to all children with cancer to ensure best therapeutic success and avoid the development of resistance. References Kwatra NS, Meany HJ, Ghelani SJ, Zahavi D, Pandya N, Majd M. Glomerular hyperfiltration in children with cancer: prevalence and a hypothesis. Pediatr Radiol 2017;47(2):221–226. The Lexicomp Pediatric & Neonatal Dosage Handbook, 21st edition, Lexicomp, USA. Disclosure(s) Nothing to disclose