Acute respiratory failure due to daptomycin induced eosinophilic pneumonia
Article Outline
Summary
Daptomycin is an antibiotic that is being used with increasing frequency for the treatment of methicillin resistant Staphylococcus aureus (MRSA) infections. We report a 65-year-old male patient with vertebral osteomyelitis due to MRSA who developed acute respiratory failure secondary to eosinophilic pneumonia after starting daptomycin therapy. Bronchoscopy showed a bronchoalveolar lavage (BAL) with 33% eosinophilia and the transbronchial biopsies revealed organizing pneumonia with many eosinophils. The patient responded rapidly to drug cessation and steroid therapy. Eosinophilic pneumonia is a rare but potentially serious complication of daptomycin therapy that, if recognized early, responds quickly to drug cessation and steroid therapy.
Keywords: Acute respiratory failure, Antibiotic, Eosinophilic lung disease, Eosinophilic pneumonia, Drug induced
The eosinophilic lung diseases are a heterogenous group of disorders characterized by an increased number of eosinophils within in the lung. Allen and Davis described the most recent classification of these diseases which includes drug induced eosinophilic lung disease.1 In this report we present a case of daptomycin induced eosinophilic pneumonia resulting in acute respiratory failure.
Case presentation
A 65-year-old man was admitted with vertebral osteomyelitis due to methicillin resistant Staphylococcus aureus (MRSA) and complicated by an epidural abscess. His past medical history was significant for obstructive sleep apnea, coronary bypass surgery, and hypothyroidism; he denied any history of asthma and was a non-smoker. Treatment was initiated with vancomycin and rifampin. Four weeks into his hospitalization, he was felt to be failing medical therapy based on progressive changes on his MRI, so vancomycin was replaced by daptomycin 1000
mg (6mg/kg) daily and rifampin was continued. Other medications at that time included gabapentin, sotalol, atorvastatin, levothyroxine, pantoprazole, aspirin, and subcutaneous heparin.
One week after starting daptomycin the patient had a white blood cell (WBC) count of 8.0k/μl and had developed a peripheral eosinophilia of 7%; he remained afebrile and had no respiratory symptoms. About one week later he began developing shortness of breath and within 24h he had progressed to respiratory failure requiring mechanical ventilation. He was afebrile and his white blood cell (WBC) count was 8.6k/μl with 7% eosinophilia. A chest radiograph showed diffuse patchy bilateral airspace disease (Fig. 1A), and a right heart catheterization revealed a normal pulmonary capillary wedge pressure. Bronchoscopy was performed and the bronchoalveolar lavage (BAL) culture grew Pseudomonas aeruginosa. Antibiotics at this time included, levofloxicin, meropenem, and tobramycin.
Figure 1
A) Chest radiograph showing bilateral airspace disease. (B) CT chest obtained 10 days later shows persistent bilateral airspace disease with some peripheral predominance.
During the next 10 days he had intermittent low grade fever with persistent eosinophilia ranging from 6 to 10%, his chest radiograph remained unchanged, and he continued to require mechanical ventilation. A CT scan showed diffuse bilateral airspace sparing the bases disease with some peripheral predominance, and small bilateral pleural effusions (Fig. 1B). A repeat bronchoscopy with transbronchial biopsies was performed. The BAL showed a WBC count of 725/μl with 33% eosinophilia, and the biopsies showed organizing pneumonia with many eosinophils. Occasional multinucleated giant cells were also noted; however, no well formed granulomas or vasculitis was seen. All cultures for bacteria, fungi, and mycobacteria were negative. The daptomycin was immediately discontinued and methylprednisolne 100mg IV every 8h was started; all other medications were continued. Within 72h, his oxygenation and the chest radiograph had significantly improved (Fig. 2). Over the next three days the patient was weaned from mechanical ventilation.
Figure 2
Chest radiograph 72
h after stopping daptomycin and starting steroids showing significant resolution of bilateral infiltrates.
The patient was discharged from hospital three weeks later and tapered off steroids over the next six weeks. A follow-up CT scan 3 months later was completely normal.
Discussion
Many drugs have been associated with eosinophilic pneumonia; however, antibiotics and non-steroidal anti-inflammatory drugs are amongst the most common.2, 3 A complete and updated list of drugs suspected of causing lung disease can be found at a web site maintained by the Groupe Etude de la Pathologie Pulmonaire Iatrogene at www.pneumotox.com.
The clinical presentation of drug induced eosinophilic pneumonia may be similar to other forms of eosinophilic lung diseases.2, 3 A subacute presentation with cough and dyspnea lasting weeks or months may be confused with chronic eosinophilic pneumonia (CEP) while a more acute presentation with fever, dyspnea, hypoxemia and diffuse airspace disease on chest radiograph occurring shortly after being exposed to the drug is more similar to acute eosinophilic pneumonia (AEP). Peripheral eosinophilia may be present with drug induced eosinophilic pneumonia and is more common than with CEP or AEP; however, its absence does not exclude the possibility. On imaging, drug induced eosinophilic pneumonia most often manifests as areas of consolidation and ground glass opacity usually involving the outer third of the lungs,4 a pattern very similar to CEP. In a study on the diagnostic accuracy of CT imaging in eosinophilic lung disease, a correct CT diagnosis of drug induced eosinophilic pneumonia was made in only 27% of those who had drug induced eosinophilic pneumonia.5
To attribute eosinophilic pneumonia to a drug, the following conditions should be met: the diagnosis of simple, acute, or chronic eosinophilic pneumonia must be made by the usual criteria (BAL eosinophilia usually>25%), the presence of a likely drug and a temporal relationship with the onset of findings, no other cause of pulmonary eosinophilia may be present (i.e., parasites or fungal infection), clinical improvement after cessation of the drug, and recurrence of eosinophilic pneumonia after rechallenge with the drug. In most cases, rechallenge is unnecessary and potentially dangerous.2, 3
In addition to our case, two other cases of eosinophilic pneumonia implicating daptomycin have been previously reported.6, 7 The first case described an acute onset of respiratory symptoms one week after starting daptomycin. The patient subsequently developed respiratory failure and bronchoscopy revealed a BAL eosinophilia of 26%; no peripheral eosinophilia was reported. Daptomycin was stopped, steroids were started, and the patient improved rapidly.6 The second case described a patient with a gradual onset of constitutional symptoms 4–6 weeks after starting daptomycin. CT scan revealed ill-defined nodules and CT guided biopsy revealed organizing pneumonia with some eosinophilic infiltrate. No BAL was performed. The daptomycin was stopped and the symptoms improved over several weeks.7
Daptomycin is a cyclic lipopeptide antibiotic with in vitro activity against a broad spectrum of gram-positive bacteria, including isolates resistant to methicillin and vancomycin.8 These types of serious infections are particularly common in patients in the intensive care unit setting, so it is important for intensivists and pulmonologists to be aware of this potential drug induced lung toxicity due to daptomycin.
Conflict of interest statement
The authors have no conflicts of interest to disclose.
References
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PII: S1755-0017(08)00053-5
doi:10.1016/j.rmedc.2008.07.010
© 2008 Elsevier Ltd. All rights reserved.
