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Background Currently, there are no clinical data regarding the use of baloxavir marboxil in patients with complicated influenza infection. A study in a mouse model of influenza A infection suggested that there may be a potential benefit of combination therapy with neuraminidase inhibitors. We present the first reported use of baloxavir marboxil in combination with oseltamivir in two critically ill patients requiring veno-venous extracorporeal membrane oxygenation (VV-ECMO) support due to severe acute respiratory distress syndrome (ARDS) caused by influenza AH1N1 2009. Methods Cases: (1) 56-year-old man with a history of coronary artery disease who was vaccinated for flu this season, presented with 5 days of cough and dyspnea and required cannulation for VV-ECMO due to severe ARDS. He was placed on continuous renal replacement therapy (CRRT) for renal failure as well as vasopressor and inotropic support. Bronchoalveolar lavage (BAL) polymerase chain reaction (PCR) was positive for Influenza A H1N1 2009 strain. He received a dose of baloxavir 80 mg on Day 1 and a 7-day course of oseltamivir which was started on Day 0. Influenza PCR testing obtained 5 days after receipt of baloxavir was negative. The patient was decannulated on hospital day 7 and extubated at 14 days. (2) 50-year-old man with a history of hypertension and dyslipidemia who was not flu vaccinated, presented with symptoms of cough and dyspnea for 3 days. He was cannulated due to severe ARDS. He required CRRT for renal failure. BAL PCR tested positive for Influenza A H1N1 2009 strain. He was given two 80 mg doses of baloxavir on hospital days 1 and 5 and treated with oseltamivir for 10 days. Despite a negative PCR test for influenza on day 15, the patient remained critically ill on ECMO with multisystem organ failure. Results - Conclusion We describe the first reported clinical use of baloxavir in combination with oseltamivir for influenza A H1N1 infection in two critically ill patients with respiratory failure requiring VV ECMO. Further pharmacokinetic/pharmacodynamic analysis is needed to determine optimal dosing in critically ill patients, and those requiring CRRT. Baloxavir synergy with the neuraminidase inhibitors may be of benefit in critically ill patients, and additional prospective clinical study is needed. Disclosures All authors: No reported disclosures.

open forum infectious diseases

2256. Baloxavir Marboxil in Combination with Oseltamivir in Two Critically Ill Patients with Influenza A (H1N1; 2009 strain) on Veno-Venous Extra-Corporal Membranous Oxygenation