Is daptomycin (cyclic lipopeptide antibiotic) associated with eosinophilia?

From the Guidelines

Daptomycin can cause eosinophilia as a side effect, and its management should prioritize patient safety and effective infection control. The incidence of eosinophilia associated with daptomycin is not explicitly stated in the provided evidence, but it is acknowledged as a potential side effect 1. If a patient develops eosinophilia while on daptomycin, clinical assessment is necessary to determine if the medication should be continued or discontinued, considering the severity of eosinophilia and the presence of symptoms such as rash, fever, or organ dysfunction. For mild, asymptomatic eosinophilia, continued therapy with close monitoring may be reasonable, but severe eosinophilia or eosinophilia accompanied by symptoms may necessitate discontinuation of daptomycin and consideration of alternative antibiotics such as linezolid, telavancin, or vancomycin, depending on the infection being treated and antimicrobial susceptibility patterns 1. Regular complete blood count monitoring is recommended during daptomycin therapy, particularly in the first few weeks of treatment when most hypersensitivity reactions occur. The mechanism behind daptomycin-induced eosinophilia is thought to involve immune system activation, with the drug potentially acting as a hapten that triggers an allergic-type response. In the context of managing infections due to multidrug-resistant organisms, daptomycin is a valuable option, but its use must be balanced against the potential for adverse effects like eosinophilia, and high-dose daptomycin (8-12 mg/kg daily) may be used to treat certain infections, with monitoring for toxicity including eosinophilic pneumonia 1. Given the potential for daptomycin to cause eosinophilia and other adverse effects, alternative antibiotics should be considered based on the specific infection, antimicrobial susceptibility patterns, and patient factors, ensuring that the chosen therapy optimizes outcomes in terms of morbidity, mortality, and quality of life.

From the FDA Drug Label

5.3 Eosinophilic Pneumonia Eosinophilic pneumonia has been reported in patients receiving daptomycin for injection [see Adverse Reactions (6. 2)] . 5. 4 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) DRESS has been reported in post-marketing experience with daptomycin for injection [see Adverse Reactions (6. 2)] . In the S. aureus bacteremia/endocarditis trial involving adult patients, the following adverse reactions were reported: Body as a Whole: fatigue, weakness, rigors, flushing, hypersensitivity Blood/Lymphatic System: leukocytosis, thrombocytopenia, thrombocytosis, eosinophilia, increased International Normalized Ratio (INR)

Eosinophilia has been reported in patients receiving daptomycin for injection, as part of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) and as an isolated adverse reaction.

• Eosinophilic pneumonia has also been reported in patients receiving daptomycin for injection.
• Patients who develop signs and symptoms of eosinophilia, such as fever, dyspnea, and peripheral eosinophilia, while receiving daptomycin for injection should undergo prompt medical evaluation, and daptomycin for injection should be discontinued immediately.
• Treatment with systemic steroids is recommended for patients with eosinophilic pneumonia. 2 2 2

From the Research

Daptomycin Eosinophilia

• Daptomycin has been associated with eosinophilic syndromes, including peripheral eosinophilia, primary daptomycin pulmonary eosinophilia (DPE), and re-exposure DPE 3.
• The presence of an elevated peripheral eosinophilia of ≥5% during daptomycin usage was significantly associated with primary and re-exposure DPE 3.
• Acute eosinophilic pneumonia (AEP) is a rare but serious adverse effect of daptomycin, caused by accumulation of eosinophils in the lung tissues, and can lead to respiratory failure 4.
• Early diagnosis and management of AEP is crucial to avoid severe complications, including death, and typically involves discontinuation of daptomycin and starting a steroid course 4.

Clinical Characteristics

• Typical initial symptoms of daptomycin-induced eosinophilic pneumonia include fever, cough, and dyspnea 5, 6, 7.
• The median onset time of symptoms is around 3 weeks 7.
• EP can recur in patients after re-administration of daptomycin, with 57.1% of recurrences happening within 24 hours 7.
• Most cases are accompanied by marked accumulation of eosinophils in peripheral and/or bronchoalveolar lavage fluid 7.

Management and Outcome

• Discontinuation of daptomycin is the primary treatment for daptomycin-induced eosinophilic pneumonia 3, 4, 6, 7.
• Corticosteroids have been shown to help with symptom relief in some cases 4, 7.
• The median time to symptom relief after discontinuation of daptomycin is around 3 days 7.
• All patients had symptom resolution after discontinuation of daptomycin, except for one patient who died due to the progression of the primary disease 7.