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(1/10) Pt on D7 daptomycin (DAP) for MRSA 
BSI develops dyspnea, fever 
, diffuse bilateral infiltrates on CXR. Intubated 
Bronch w/BAL NGTD. WBC 12 (Neuts 0.6 / Eos 0.3 /Lymphs 0.18). Likely diagnosis?
BSI develops dyspnea, fever , diffuse bilateral infiltrates on CXR. Intubated Bronch w/BAL NGTD. WBC 12 (Neuts 0.6 / Eos 0.3 /Lymphs 0.18). Likely diagnosis?
Let's start by exploring the DAP MOA
DAP binds and depolarizes the cell membrane, allowing efflux of K+ 
. https://www.cubicin.com/mechanism-of-action/moa/
DAP binds and depolarizes the cell membrane, allowing efflux of K+ . https://www.cubicin.com/mechanism-of-action/moa/
(3/10) DAP is a workhorse 
for MRSA, but this MOA results in 2 respiratory 
tract problems.
for MRSA, but this MOA results in 2 respiratory tract problems.
(4/10) #1 DAP is deactivated by lung surfactant making it ineffective for PNA. This 
model demonstrates little/no DAP lung activity. 
https://pubmed.ncbi.nlm.nih.gov/15898002/
model demonstrates little/no DAP lung activity. https://pubmed.ncbi.nlm.nih.gov/15898002/
(5/10) #2: DAP interaction with surfactant inflammation T-cell activation IL-5 release eosinophil production eotaxin attraction of eosinophils to the . (Picture: https://onlinelibrary.wiley.com/doi/full/10.1002/iid3.238)
inflammation T-cell activation IL-5 release eosinophil production eotaxin attraction of eosinophils to the . (Picture: https://onlinelibrary.wiley.com/doi/full/10.1002/iid3.238)
(6/10) DAP-induced eosinophilic PNA (AEP) should be suspected with DAP exposure + >25% eosinophils in bronch +
fever + 
dyspnea + new diffuse bilateral infiltrates on CT/CXR. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207288/figure/FIG2/
fever + dyspnea + new diffuse bilateral infiltrates on CT/CXR. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207288/figure/FIG2/
(7/10) There are <700 FAERS reports of DAP AEP over 15 years, with a majority of patients requiring hospitalization 
and intervention. ( https://fis.fda.gov/sense/app/d10be6bb-494e-4cd2-82e4-0135608ddc13)
and intervention. ( https://fis.fda.gov/sense/app/d10be6bb-494e-4cd2-82e4-0135608ddc13)
(8/10) Common
? Incidence independent of dose (4-10 mg/kg), median duration of therapy 2.8 weeks, 77% pts had 
peripheral EOS. Resolution occurred within 
48-72 hours DAP D/C. https://aricjournal.biomedcentral.com/track/pdf/10.1186/s13756-016-0158-8.pdf
? Incidence independent of dose (4-10 mg/kg), median duration of therapy 2.8 weeks, 77% pts had peripheral EOS. Resolution occurred within 48-72 hours DAP D/C. https://aricjournal.biomedcentral.com/track/pdf/10.1186/s13756-016-0158-8.pdf
(9/10) Management: 
stop daptomycin. Consider corticosteroids: IV methylprednisolone 
60-125 mg Q6H 
prednisone 40-60 mg taper over 2-6 weeks. DAP rechallenge not 
recommended. https://aricjournal.biomedcentral.com/track/pdf/10.1186/s13756-016-0158-8.pdf
stop daptomycin. Consider corticosteroids: IV methylprednisolone 60-125 mg Q6H prednisone 40-60 mg taper over 2-6 weeks. DAP rechallenge not recommended. https://aricjournal.biomedcentral.com/track/pdf/10.1186/s13756-016-0158-8.pdf
(10/10) Recap:
AEP is a serious ADE of DAP and is under-reported
DAP attracted to alveolar surfactant inflammation recruits eosinophils
Mgmt = Discontinue DAP and consider corticosteroids
DAP rechallenge NOT recommended
AEP is a serious ADE of DAP and is under-reportedDAP attracted to alveolar surfactant inflammation recruits eosinophilsMgmt = Discontinue DAP and consider corticosteroidsDAP rechallenge NOT recommended
