Discussion
Daptomycin is a commonly used cyclic lipopeptide IV antibiotic with broad activity against gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Daptomycin has emerged as a convenient alternative for infections typically treated with IV vancomycin: shorter infusion time (2-30 minutes vs 60-180 minutes), daily administration, and less need for dose adjustments. A recent survey reported higher satisfaction and less disruption in patients receiving daptomycin compared with vancomycin.2 The main daptomycin-specific adverse effect (AE) that warrants close monitoring is elevated creatine kinase (CK) levels and skeletal muscle breakdown (reversible after holding medication).3 Other rarely reported AEs include drug reaction with eosinophilia and systemic symptoms (DRESS), acute eosinophilic pneumonitis, hepatitis, and peripheral neuropathy.4-6 Consequently, weekly monitoring for this drug should include symptom inquiry for cough and muscle pain, and laboratory testing with CBC with differential, comprehensive metabolic panel (CMP), and CK.
Daptomycin-induced eosinophilic pneumonia has been described in several case reports and in a recent study, the frequency of this event was almost 5% in those receiving long-term daptomycin therapy.7 The most common symptoms include dyspnea, fever, infiltrates/opacities on chest imaging, and peripheral eosinophilia. It is theorized that the chemical structure of daptomycin causes immune-mediated pulmonary epithelial cell injury with eosinophils, resulting in increased peripheral eosinophilia.3 Risk factors that have been identified for daptomycin-induced eosinophilia include age > 70 years; the presence of comorbidities of heart and pulmonary disease; duration of daptomycin beyond 2 weeks; and cumulative doses over 10 g. Average onset of illness from initiation of daptomycin has been reported to be about 3 weeks.7,8 The diagnosis of daptomycin-induced eosinophilic pneumonitis is made on several criteria per the FDA. These include exposure to daptomycin, fever, dyspnea with oxygen requirement, new infiltrates on imaging, bronchoalveolar lavage with > 25% eosinophils, and last, clinical improvement on removal of the drug.9 However, as bronchoscopy is an invasive diagnostic modality, it is not always performed or necessary as seen in this case. Furthermore, not all patients will have peripheral eosinophilia, with only 77% of patients having that finding in a systematic review.10 Taken together, the overall true incidence of daptomycin-induced eosinophilia may be underestimated. Treatment involves discontinuation of the daptomycin and initiation of steroids. In a review of 35 cases, the majority did receive systemic steroids, usually 60 to 125 mg of IV methylprednisolone every 6 hours, which was converted to oral steroids and tapered over 2 to 6 weeks.10 However, all patients including those who did not receive steroids had symptom improvement or complete resolution, highlighting that prompt discontinuation of daptomycin is the most crucial intervention.
Conclusions
As home IV antibiotic therapy becomes increasingly used to facilitate shorter lengths of stay in hospitals and enable more patients to receive their infectious disease care at home, the general practitioner must be aware of the potential AEs of commonly used IV antibiotics. While acute cutaneous reactions and disturbances in renal and liver function are commonly recognized entities of adverse drug reactions, symptoms of fever and cough are more likely to be interpreted as acute viral or bacterial respiratory infections. A high index of clinical suspicion is needed for eosinophilic pneumonitis secondary to daptomycin. A simple and readily available test, such as a CBC with differential may facilitate the identification of this potentially serious AE, allowing prompt discontinuation of the drug.