Seventeen Cases of Daptomycin-Induced Eosinophilic Pneumonia in a Cohort of Patients Treated for Bone and Joint Infections: Proposal for a New Algorithm

Abstract

Background Daptomycin is increasingly used in the treatment of bone and joint infections (BJI) and may be responsible for daptomycin-induced eosinophilic pneumonia (DIEP), a potentially severe adverse drug reaction. The aim of this study was to describe DIEP in patients treated at a referral centre for the management of BJI, and to revisit current definitions of this disease. Method Patients treated from 01.01.2012 to 31.03.2021 were included in a prospective cohort (NCT02817711), in which all potential serious adverse events are prospectively recorded. Patients diagnosed with DIEP were retrospectively analysed using different definitions. Results In a total of 4,664 patients included in the cohort during the study period, 1,021 patients (21.9%) received daptomycin, of whom 17 (1.7%) were diagnosed with DIEP. Most patients were male (n = 11, 64.7%) and peri-prosthetic joint infection was the commonest BJI (n = 12, 70.6%). Only one patient had bronchoalveolar lavage (BAL) eosinophil count ≥25%, while most patients had peripheral blood eosinophilia (n = 15, 88.2%). Chest CT was compatible with eosinophilic pneumonia in 13/14 cases (92.9%). All patients recovered upon discontinuation of daptomycin. Using the different definitions available, only a minority of cases fulfilled existing criteria for DIEP. We propose a new algorithm that includes specific CT scan signs, and systemic instead of BAL eosinophilia. Conclusion DIEP is a rare event that requires prompt discontinuation of the causative antibiotic. Current criteria to diagnose definite DIEP are too restrictive and not easily applicable in clinical practice. A new algorithm is proposed here (Lyon algorithm) to facilitate the early identification of DIEP.

Daptomycin-Induced Pulmonary Toxicity: A Case Series

“…Area under the concentration time curve (AUC) >939 mg.h/L is a similar measure used by Pham et al as a measure of the risk for DEP. They recommend targeting a therapeutic AUC range of 666 to 939 mg.h/L to minimize the risk of adverse effects [ 3 ]. Our patients had TCDD of 9.7 gm and 12.7 gm respectively.…”

“…A review of the diagnostic criteria proposes a cut-off of 25% eosinophilia in BAL to be restrictive and invasive, in place of which a substitution with peripheral eosinophilia was suggested. A comparison of lung biopsy and BAL revealed eosinophilia in cases where BAL eosinophils were <25% implying that 25% might be too harsh a limit [ 3 ]. Kim et al stratified 77 cases of DEP reported on the Adverse Event Reporting System database into definite, probable, possible, and unlikely.…”

“…It was first approved by the United States Food and Drug Administration (FDA) in 2003 and only a limited number of pulmonary daptomycin toxicity cases resulting in acute eosinophilic pneumonia (AEP) have been reported since [ 2 ]. Diagnostic criteria for eosinophilic pneumonia (EP) secondary to daptomycin include exposure to daptomycin, fever, dyspnea, hypoxia, infiltrates on chest imaging, pulmonary eosinophilia (bronchoalveolar lavage (BAL) eosinophil count 25%), and clinical improvement after discontinuation of daptomycin [ 3 ].…”

Daptomycin-Induced Eosinophilic Pneumonia: A Case Report and Systematic Review

“…Zimmer et al [105] reported a similar case, in which the patient presented a daptomycin-induced AEP with sudden respiratory distress 9 days after a 3-day re-challenge of daptomycin, 2 weeks after priming. A third case by Pham et al reported an AEP upon re-exposure to daptomycin firstly occurred 6 months prior [75].…”

Daptomycin-Induced Eosinophilic Pneumonia: Can an Antibiotic Cause Pneumonia?

“…However, when the differential blood count was obtained, it showed significant eosinophilia of greater than 1000. Considering that the patient is on daptomycin and the findings of eosinophilia and chest imaging, our final diagnosis was daptomycin-induced eosinophilic pneumonia [ 5 , 6 ]. Daptomycin was stopped and steroids were added.…”