A 56-Year-Old Woman With Systemic Lupus Erythematosus on Trimethoprim-Sulfamethoxazole Prophylaxis Presenting With Breakthrough Nocardiosis

Objective: Unusual clinical course Background:Patients with primary or secondary immunosuppression can be treated with trimethoprim-sulfamethoxazole (TMP-SMX) as long-term prophylaxis to prevent opportunistic infections.Nocardia africana/nova is an aerobic, gram-positive opportunistic organism.This case report describes a patient with systemic lupus erythematosus (SLE) on low-dose TMP-SMX prophylaxis who developed nocardiosis due to N. africana/nova. Case Report:A 56-year-old Chinese woman with SLE on long-term low-dose TMP-SMX prophylaxis underwent partial right lung lobectomy in July 2023 after incidental pulmonary lesions were detected.Pathology revealed a cryptococcal granuloma, which was treated with fluconazole.In November 2024, chest computed tomography (CT) showed progressive pulmonary nodules and right upper lobe consolidation despite antibacterial and antifungal therapy, including voriconazole guided by next-generation sequencing.CT-guided lung biopsy confirmed pulmonary nocardiosis caused by N. africana/nova, susceptible in vitro to TMP-SMX.High-dose TMP-SMX plus linezolid led to radiologic improvement, after which TMP-SMX monotherapy was continued.In March 2025, she was readmitted with acute altered mental status, recurrent cavitary pulmonary disease, pleural effusion, and multiple ring-enhancing cerebral abscesses, consistent with disseminated nocardiosis.Further aggressive treatment was declined, and she was discharged for palliative care. Conclusions:Nocardiosis is challenging to diagnose and treat in immunocompromised patients, as breakthrough infections can occur despite in vitro susceptibility, reflecting the roles of host immunity and drug factors.Clinicians should maintain a high index of suspicion for nocardiosis in patients receiving corticosteroids or other immunosuppressive therapies and recognize that in vitro susceptibility does not always predict in vivo therapeutic success.This report highlights that breakthrough nocardia can occur with appropriate low-dose TMP-SMX prophylaxis.