A Rare but Potentially Fatal Reaction in Plain Sight: Trimethoprim- Sulfamethoxazole Induced Acute Lung Injury

Document Type

Conference Proceeding

Publication Date

5-21-2024

Publication Title

Am J Respir Crit Care Med

Abstract

Introduction: Trimethoprim/Sulfamethoxazole (TMP/SMX) is a commonly prescribed antibiotic for skin and genito-urinary tract infections. Adverse pulmonary reactions are infrequent, mild, and self-limiting with withdrawal of TMP/SMX1. Recently, however, its use has been associated with severe acute respiratory distress syndrome (ARDS) in adolescents and young adults1. It is associated with a distinct pathology termed diffuse alveolar injury with delayed epithelialization2. Case description: Case #1: A 34-year-old man presented to hospital with cough, shortness of breath, fever, and a rash, three weeks after starting TMP/SMX for prostatitis. He was febrile, tachycardic, and hypoxic, with a diffuse maculo-papular rash and bilateral wheezing. Laboratory findings included leukopenia, mild thrombocytopenia. Chest imaging revealed peripheral lower lobe opacities with subpleural sparing, which progressed to include pneumothoraces, pneumomediastinum and subcutaneous emphysema (Fig 1). Infectious and autoimmune workup was unrevealing. Despite discontinuation of TMP/SMX, empiric antibiotics and steroids, he progressed to fulminant ARDS requiring mechanical ventilation and extracorporeal membranous oxygenation (ECMO). After a prolonged and complicated course, he expired from refractory respiratory failure and septic shock. Case #2: A 26-year-old woman presented to hospital with fever, rash, shortness of breath, and chest pain, one week after starting TMP/SMX for recurrent vaginal cysts. On presentation, she was febrile, tachycardic, and hypoxic with diffuse wheezing on exam and leukopenia on labs. Chest imaging showed bibasilar ground-glass opacities which progressed to include pneumothoraces, pneumomediastinum, and subcutaneous emphysema. Despite discontinuation of TMP/SMX, empiric antibiotics, and steroids she developed fulminant ARDS requiring mechanical ventilation and subsequently ECMO. Ultimately, she underwent bilateral lung transplantation after nearly 80 days on ECMO. Explanted lung pathology showed severe fibrosing cellular and interstitial pneumonia. Discussion: TMP/SMX-associated ARDS is rare, but lifethreatening. Our cases are consistent with the largest case series published where 74% of patients developed pneumomediastinum and or pneumothorax, 84% required ECMO, 32% required lung transplant, and 37% died1. Conclusions: TMP/SMX-associated ARDS is a rare occurrence in previously healthy young adults with distinct pathology and proposed clinical diagnostic criteria2. Given its high mortality and the common use of TMP/SMX, clinicians should be aware of this entity. Early recognition and transfer to an ECMO and/or transplant center may improve outcomes. (Figure Presented).

Volume

209

Issue

9

First Page

A2027

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