Daptomycin-induced Eosinophilic Pneumonia and a Review of the Published Literature

Abstract

A 53-year-old man was admitted to the hospital with a diagnosis of cellulitis and osteomyelitis. Twenty-four days after the initiation of daptomycin and sulbactam/ampicillin, he developed a fever and pulmonary infiltration. Bronchoalveolar lavage revealed a high number of eosinophils, while an intracutaneous test revealed positivity for daptomycin. The patient improved after discontinuing antimicrobial therapy. The plasma daptomycin minimum concentration (Cmin) was elevated (27.4 μg/mL), but plasma protein binding of daptomycin was low (87.8%). Although the pathophysiology of eosinophilic pneumonia remains unclear, antigenic stimulation due to daptomycin accumulation in the alveoli may have caused continuous immune activation.

Acute Eosinophilic Pneumonia: A Rare Complication of Daptomycin Therapy

“…In reported cases, dosing is significantly varied, suggesting that the development of AEP may occur at any dose, however, among patients who develop AEP, those receiving higher doses had a shorter time to develop [6,9]. Additionally, elevated serum concentration due to chronic kidney disease may play a role in some cases, although a correlation between serum levels of daptomycin, and accumulation within pulmonary surfactant has not been definitively established [6]. In the present case, the patient had a normal renal function, with a creatinine of 0.96 mg/dL and blood urea nitrogen of 14 mg/dL.…”

“…Acute eosinophilic pneumonia is a pulmonary condition characterized by eosinophilia of pulmonary secretions, which may be idiopathic or induced by various exposures, including drugs, infections, and smoking [10]. In the case of daptomycin-induced AEP, it is thought that the accumulation of the drug within a pulmonary surfactant plays a key role in the induction of an inflammatory reaction [6]. In reported cases, dosing is significantly varied, suggesting that the development of AEP may occur at any dose, however, among patients who develop AEP, those receiving higher doses had a shorter time to develop [6,9].…”

“…In the case of daptomycin-induced AEP, it is thought that the accumulation of the drug within a pulmonary surfactant plays a key role in the induction of an inflammatory reaction [6]. In reported cases, dosing is significantly varied, suggesting that the development of AEP may occur at any dose, however, among patients who develop AEP, those receiving higher doses had a shorter time to develop [6,9]. Additionally, elevated serum concentration due to chronic kidney disease may play a role in some cases, although a correlation between serum levels of daptomycin, and accumulation within pulmonary surfactant has not been definitively established [6].…”

“…Kim et al identified 7 definite, 13 probable, and 38 possible cases between 2004 and 2010 via review of the FDA Adverse Event Reporting System [5]. Its etiology is poorly understood but is thought to involve the accumulation of the drug within pulmonary surfactant, inducing an inflammatory response [6]. 1 2…”

“…Multiple diagnostic criteria have been established, including one by the FDA and another by Solomon and Schwarz [7][8]. Treatment involves cessation of the drug, and in a majority of cases, intravenous steroids [6,9]. We present a case of this rare complication of daptomycin therapy.…”