When Daptomycin Turns on the Lungs: A Wolf in Antibiotic Clothing

Document Type

Conference Proceeding

Publication Date

5-2026

Publication Title

American Journal of Respiratory and Critical Care Medicine

Abstract

Introduction: Daptomycin-induced eosinophilic pneumonia (DIEP) is a recognized but uncommon adverse effect of daptomycin therapy, with an estimated incidence of 0.1-2% among treated patients. Differentiating DIEP from bacterial pneumonia can be challenging due to overlapping clinical and radiographic features, including fever, dyspnea, hypoxia, and bilateral pulmonary infiltrates. The diagnostic hallmark of eosinophilic pneumonia is the presence of ≥ 25% eosinophils on bronchoalveolar lavage (BAL). Case: A 65-year-old man with recent MRSA bacteremia and epidural abscess (status post AICD explantation and laminectomy) was discharged on intravenous daptomycin and re-presented with dyspnea, cough, and fever (39.4 °C). On admission, he was hypoxic (SpO 2 80%) requiring heated high-flow nasal cannula. Examination revealed diffuse bilateral wheezing. Arterial blood gas showed pH 7.49, pCO2 29.7 mmHg, pO 2 72 mmHg (pO 2/FiO 2 = 163.6), and HCO 3 22.4 mmol/L. Laboratory findings included leukocytosis (16,600 cells/ μL) and elevated absolute eosinophil count (0.47 × 109 /L). Chest CT revealed bilateral, centrally distributed consolidations and air bronchograms in the upper lobes and superior segments of the lower lobes. Empiric vancomycin and cefepime were initiated for presumed multifocal pneumonia. By day two, he improved rapidly with resolution of fever and hypoxia; eosinophil count peaked at 0.82 × 10 9 /L. Given the temporal relationship to daptomycin and absence of an infectious source, daptomycin-induced eosinophilic pneumonia (DIEP) was suspected. Bronchoscopy was deferred due to clinical improvement, and the patient was discharged after completing a short antibiotic course. Discussion: Daptomycin is a cyclic lipopeptide antibiotic with potent activity against Gram-positive organisms, including MRSA and vancomycin-resistant enterococci (VRE). Daptomycin-induced eosinophilic pneumonia (DIEP) is postulated to result from immune-mediated inflammation triggered by the drug’s irreversible binding to pulmonary surfactant. This interaction activates alveolar macrophages, leading to T-helper 2 lymphocyte recruitment and subsequent release of interleukin-5 (IL-5), which promotes eosinophil proliferation and pulmonary migration. Three clinical phenotypes of daptomycin-associated eosinophilic syndromes have been described: (1) mild peripheral eosinophilia, typically emerging 10-14 days after initiation; (2) primary DIEP, developing approximately 28 days after exposure; and (3) recurrent DIEP, manifesting within about one week of re-exposure. Recent literature estimates the incidence of daptomycin-induced eosinophilic pneumonia at 4.8-15%. Identified risk factors include male sex, prolonged therapy duration, higher cumulative daptomycin doses, and hemodialysis. Diagnostic evaluation is often confounded by concurrent empiric antibiotic therapy and the timing of bronchoscopy, particularly following corticosteroid initiation. Bronchoscopy may be deferred in hemodynamically unstable patients or considered unnecessary in cases demonstrating clinical improvement with treatment.

Volume

212

Issue

S1

First Page

S2263

Comments

American Thoracic Society International Conference, May 15-20, 2026, Orlando, FL

Last Page

S2263

DOI

10.1093/ajrccm/aamag162.2988

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