Abstract Introduction Daptomycin-induced pneumonitis (DIP) is a rare but serious complication that typically resolves with drug cessation and corticosteroids. Reactivation of pneumonitis months after exposure in the absence of re-challenge is exceedingly rare. We report a striking case of delayed DIP flare mimicking post-surgical sepsis and pneumonia, in a patient with complex comorbidities and limited antibiotic options. Case Presentation A 62-year-old woman with psoriatic arthritis and a history of recurrent prosthetic joint infections (PJIs) previously developed hypoxic respiratory failure eight months prior while on daptomycin for MRSA PJI. She was diagnosed with DIP based on CT imaging showing diffuse ground-glass opacities and improved with corticosteroid taper after stopping the medication.In March 2025, she was readmitted for elective I&D and revision of her infected left total hip arthroplasty, with recent cultures showing Serratia marcescens. On postoperative day 4, she developed high-grade fever, leukocytosis, escalating oxygen requirements, and new bilateral infiltrates on chest X-ray. CT imaging mirrored her previous DIP presentation, showing diffuse ground-glass opacities with interstitial thickening and traction bronchiectasis.Despite concern for hospital-acquired pneumonia or sepsis, infectious workup was unrevealing. Deterioration continued—she required high-flow oxygen and was transferred to the ICU with suspected acute respiratory distress syndrome (ARDS). Given her prior history and lack of new infectious trigger, the working diagnosis shifted to a flare of prior daptomycin-induced lung injury, likely reactivated by surgical stress or immunologic factors. She was started on high-dose IV methylprednisolone 60 mg q8h. Hospital Course and Outcome Within 48 hours, the patient improved and her oxygen requirement began to decline. She avoided intubation, and over the next week, she weaned down to 2 L nasal cannula. She was discharged on a tapering dose of prednisone and home oxygen. Discussion This case highlights several important lessons:•Delayed flares of DIP can occur even months after initial exposure, particularly in immunologically primed or stressed hosts.•DIP recurrence can clinically mimic sepsis, pneumonia, or ARDS, especially in postoperative patients.•Steroids may be both diagnostic and therapeutic in cases of suspected immune-mediated pneumonitis.•Early recognition can avoid unnecessary broad-spectrum antibiotics, especially critical inpatients with extensive drug allergies and resistant infections. Conclusion This case reinforces the need for high clinical suspicion of non-infectious pneumonitis inpatients with a history of drug-induced lung injury. When traditional diagnostics fail to explain acute hypoxemia and imaging reveals classic patterns, early corticosteroid therapy may be lifesaving—even months after the offending drug is gone. This abstract is funded by: None
Prathiraja et al. (Fri,) studied this question.