Nemours Alfred I DuPont Hospital for Children, Delaware
Disclosure(s): No relevant financial relationship(s) to disclose.
Introduction: ECMO is known to impact the pharmacokinetic properties of medications. There is limited literature describing its effect on the serum levels of sulfamethoxazole/trimethoprim. Failure to attain target concentrations may lead to therapeutic failure.
Description: A 7-year-old female with a past medical history of juvenile dermatomyositis was admitted to the PICU for acute hypoxic respiratory failure secondary to multifocal pneumonia with ground glass opacities on chest radiograph. Initially treated with ceftriaxone and azithromycin she was subsequently found to be positive for Pneumocystis jirovecii on bronchoalveolar lavage PCR and was transitioned to sulfamethoxazole-trimethoprim (SMX/TMP) 5 mg TMP/kg/dose IV every 8 hours on hospital day 1 (HD1). As her respiratory status declined, she progressed to severe pARDS requiring intubation and mechanical ventilation. On HD12, due to the development of air leak syndrome and a significant fiO2 requirement with persistent hypoxemia she was cannulated on VV ECMO with a 27 Fr Avalon bicaval VV catheter. ECMO components included a 3/8-inch circuit with a Thoratec CentraMag pump head and an AMG pediatric Euroset oxygenator with integrated blood warmer. Due to the potential impact of ECMO on the pharmacokinetics of SMX/TMP, peak levels were obtained twice on HD14, one 48 minutes and one 63 minutes after completion of a 1-hour infusion, with a goal TMP level of 3-5 mcg/mL and SMX level of 100-150 mcg/mL. TMP resulted at 2.2 & 2.7 mcg/mL and SMX at 96 & 83 mcg/mL. In response dosing was increased to 5 mg TMP/kg/dose IV every 6 hours on HD17. Repeat levels were obtained on HD20 116 minutes after dose completion. TMP was reported at 2.2 mcg/mL and SMX at 70 mcg/mL. Repeat bronchoalveolar lavage after 21 days of treatment demonstrated clearance of Pneumocystis jirovecii.
Discussion: Serum assays demonstrated subtherapeutic peak levels for TMP and SMX when using 5 mg TMP/kg/dose IV q8h. Due to delayed repeat sample timing we were unable to assess the true peak with increased dosing. Given the variable effects of ECMO on SMX/TMP pharmacokinetics reported in the literature, this case highlights the need for therapeutic drug monitoring to ensure therapeutic success of SMX/TMP for the treatment of Pneumocystis jirovecii pneumonia in patients on VV ECMO.
