Daptomycin is a cyclic lipopeptide antibiotic approved by the FDA in 2003. Daptomycin provides great coverage for gram positive cocci. Shortly after its approval, concerns were raised regarding the pulmonary side effects of daptomycin and potential development of acute eosinophilic pneumonia (AEP) secondary to daptomycin therapy. About 35 cases were reported in the literature. We present a case of AEP caused by daptomycin, with complete recovery after discontinuation of daptomycin and administration of steroids. The patient had AEP after almost 6 weeks of daptomycin therapy which has not been reported in the literature. The patient achieved complete recovery in less than 48 hours of appropriate management.
A 64-year-old male, with past medical history of peripheral arterial disease, had a left groin graft placement that was complicated with Methicillin Resistant
After almost six weeks of daptomycin therapy, the patient presented with progressive shortness of breath of two-day duration with associated fever and productive cough. Initial vital signs upon presentation were temperature 38.6°C (101.5°F), heart rate 100 beats per minute, respiratory rate 22 breaths per minute, oxygen saturation 93% on room air, and blood pressure 92/66 mmHg. Chest exam revealed coarse rhonchi bilaterally.
The initial white blood cells count was 18.0 K/UL, elevated eosinophil count 1 K/UL, and elevated erythrocyte sedimentation rate (ESR) 60 mm/hr. Initial chest-X-ray showed acute bilateral interstitial infiltrates.
The patient was admitted for presumed hospital acquired pneumonia (HCAP) and started on intravenous piperacillin-tazobactam and levofloxacin. However, his clinical condition did not improve. He had progressive cough and increasing oxygen requirements. Chest Computed Tomography (CT) angiogram obtained to rule out pulmonary embolism (PE) showed diffuse bilateral pulmonary infiltrates, mediastinal lymphadenopathy, and small bilateral pleural effusions (Figures
Chest Computed Tomography (CT) angiogram obtained to rule out pulmonary embolism (PE) showed diffuse bilateral pulmonary infiltrates, mediastinal lymphadenopathy, and small bilateral pleural effusions.
Chest Computed Tomography (CT) angiogram obtained to rule out pulmonary embolism (PE) showed diffuse bilateral pulmonary infiltrates, mediastinal lymphadenopathy, and small bilateral pleural effusions.
Bronchoscopy to obtain bronchoalveolar lavage could not be done due to high oxygen requirements the patient needed and the patient was not intubated at that point to do it safely. Thus, the patient was sent for open lung biopsy via video assisted thoracoscopic surgery (VATS). The lung biopsy revealed chronic inflammatory changes, dense fibrinous airspace exudates, areas of organization, and prominent eosinophils, consistent with eosinophilic pneumonia (Figure
Picture of the lung tissue obtained showing chronic inflammatory changes, dense fibrinous airspace exudates, areas of organization, and prominent eosinophils, consistent with eosinophilic pneumonia.
The patient improved within 48 hours after discontinuation of daptomycin and initiation of intravenous methylprednisolone. The patient was oxygenating well on room air on day 2 of steroids therapy. IV methylprednisolone was tapered gradually to oral prednisone 40 mg daily then prednisone was stopped in five days. Repeat Chest CT, after one week of the initial CT, showed almost complete resolution of previous infiltrates, disappearance of mediastinal lymphadenopathy, and resolution of bilateral pleural effusions (Figure
Repeat Chest CT, after one week of the initial CT, showing almost complete resolution of previous infiltrates, disappearance of mediastinal lymphadenopathy, and resolution of bilateral pleural effusions.
AEP is a subtype of acute pneumonia which is idiopathic or induced by drugs or toxins. It is distinct from atopic diseases and autoimmune, parasitic, or fungal infections that can also cause pulmonary eosinophilia. Multiple medications are associated with acute eosinophilic pneumonia including nonsteroidal anti-inflammatory drugs, minocycline [
Daptomycin is a cyclic lipopeptide antibiotic which was approved by the FDA in 2003. Daptomycin inhibits DNA, RNA, and protein synthesis by causing depolarization of the membrane potential when it binds the bacterial membrane [
Early after the approval of daptomycin by the FDA, multiple cases of daptomycin-induced eosinophilic pneumonia have been reported. Hayes Jr. et al. reported the first case of daptomycin-induced eosinophilic pneumonia in 2007 [
Diagnosis of daptomycin-induced AEP is based on clinical history, laboratory results, and radiographic findings. Usually these patients present with dyspnea and cough with or without fever. The clinical presentation may vary from mild respiratory complaints to minimal requirement of oxygen, up to acute respiratory distress syndrome (ARDS). Laboratory workup may reveal peripheral eosinophilia, leukocytosis, or elevated markers of inflammation such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Chest X-ray reveals bilateral pulmonary infiltrates. Chest CT may reveal bilateral consolidation, infiltrates, pulmonary nodules [
The criteria to diagnose AEP consist of 4 components: presence of febrile illness of less than 5-day duration, diffuse bilateral pulmonary infiltrates, hypoxemia defined as partial pressure of oxygen of less than 60 mmHg or oxygen saturation less than 90% on room air, and bronchoalveolar lavage with greater than 25% eosinophils or eosinophilic pneumonia on lung biopsy [
In Idiopathic AEP, most of the time, the peripheral eosinophil count is not elevated in the early phases but may become elevated later on during the course of the disease [
The pathophysiology of daptomycin-induced AEP is unclear. Daptomycin binds the lung surfactant irreversibly and may act like an antigen taken up by alveolar macrophages which then leads to inflammatory cascade and tissue damage. Alveolar macrophages present the antigen to T-helper 2 lymphocytes, which release multiple inflammatory factors like IL-5 and Eotaxin. IL-5 is known to induce production of eosinophils in bone marrow and recruit them to inflammatory sites. Eotaxin is a chemokine and acts as a chemoattractant which causes migration and recruitment of eosinophils [
The histologic findings of drug-induced eosinophilic pneumonia have been described in multiple case reports. Most of the reported cases diagnosed daptomycin-induced AEP based on BAL findings. In cases where lung biopsies were obtained, the majority revealed organizing pneumonia with eosinophilic infiltrates and chronic inflammatory changes [
The mainstay treatment of daptomycin-induced AEP, and any other drug-induced AEP, is to give corticosteroids and to stop the offending drug. This practice is based on previous case reports of daptomycin-induced AEP and other medication induced lung injuries. Steroids are recommended to patients with acute lung injuries caused by amiodarone, cocaine, and bleomycin [
Daptomycin is not widely used, yet physicians should be aware of daptomycin-induced AEP in any patient actively on daptomycin and presenting with respiratory complaints. Daptomycin-induced AEP is not related to therapy timing. It may occur as early as day three of treatment and as late as week six of the treatment course. AEP is a serious side effect of daptomycin but easily treatable if diagnosed early during the course of the disease. High clinical suspicion and thorough workup are needed for diagnosis of AEP. The current mainstay therapy is stopping daptomycin with or without steroid therapy. Further research is needed to assess the role of steroids in the treatment of AEP, including the optimal dose and duration of therapy.
This case is unique because the patient had daptomycin-induced AEP after almost six weeks of daptomycin therapy, which has not been previously reported in the literature. As long as the patient is undergoing daptomycin therapy, the risk of AEP still exists, even after a considerable amount of time has passed.
The authors declare that there are no conflicts of interest regarding the publication of this paper.