8/11/2015. Febrile neutropenia Bone marrow transplant Immunosuppressant medications

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1 Dean Van Loo Pharm.D. Febrile neutropenia Bone marrow transplant Immunosuppressant medications Steroids Biologics Antineoplastic Most data from cancer chemotherapy Bone marrow suppression Fever is the only main indicator of infection Absolute neutrophil count (ANC) <500 cells/mm 3 <100 cells/mm 3 Duration of neutropenia of >7days ANC <100 cells/mm 3 Co morbid conditions Suggestive of infections Suggestive of SIRS 1

2 High Risk Anti pseudomonal monotherapy Cefepime Piperacillin/Tazobactam Meropenem Add on therapy for complications Fluoroquinolone Aminoglycoside Vancomycin MRSA positive Catheter site inflammation Low Risk Amoxicillin/Clavulanate + Ciprofloxacin Levofloxacin or Ciprofloxacin monotherapy Ciprofloxacin + Clindamycin Duration High risk + Prolonged neutropenia >7 days and Profound neutropenia ANC<100 Agents Ciprofloxacin Levofloxacin Acute myelogenous leukemia chemotherapy Posaconazole Antivirals Treatment only After 2 4 days if clinically stable no change If clinically unstable broaden therapy Vancomycin Consideration of resistance Antifungal therapy Duration Given if the anticipated chemotherapeutic regimen is has a >20% likelihood of having febrile neutropenia Agents Filgrastim (G CSF), peg, tbo, Sargramostim (GM CSF) 2

3 Only in Graft Versus Host Disease (GVHD) Streptococcus pneumoniae Penicillin V orally Macrolides, FQs, 2 nd Gen ceph s Hypogammaglobulinemic IVIG Vaccines Biol Blood Marrow Tansplant 15: Biol Blood Marrow Tansplant 15: All CMV positive patients Induction 7 14 days Maintenance (minimum of 2 weeks) Agents Ganciclovir Valganciclovir Foscarnet Cidofovir Biol Blood Marrow Tansplant 15: If neutropenia is anticipated for >7days Levofloxacin Ciprofloxacin Alternative Azithromycin Hypogammaglobulinemia IVIG Valganciclovir pro drug of ganciclovir Adverse effects Bone marrow suppression Neutropenia most likely Neurotoxicity Peripheral neuropathy Seizures Hepatotoxicity Biol Blood Marrow Tansplant 15:

4 Most common alternative due to efficacy Adverse effects Thrombophlebitis (give through central line) Nephrotoxicity Anemia Electrolyte abnormalities Lymphocyte suppression Respiratory burst suppression Organisms Bacterial Viral Fungal Other Pneumocystis jiroveci Tertiary alternative systemically Adverse effects Renal toxicity Decreased with probenecid and good hydration Neutropenia (less than with ganciclovir) Most closely identified as a fungal pathogen Typically causes a pneumonia Most common in HIV(+) patients Most common risk factor in non HIV(+) patients is glucocorticoid use Jeffery Hodges is a 53 year old man with chronic obstructive pulmonary disease requiring prednisone 20mg orally daily. 116 patients without AIDS admitted to Mayo for PCP 90.5% of the patients received systemic steroid therapy within one month of PCP diagnosis Median prednisone equivalent dose was 30mg/day 25% of patients had doses as low as 16mg/day 4

5 Key factor in inflammation/immunity Important in T cell function Also necessary for granuloma maintenance Infectious pathogens Increases risk for nearly all Especially intracellular pathogens Tb, Histoplasma, Coccidioides, Blastomycosis Legionella, Listeria Mayo Clin Proc 1996;71:5 13 Prednisone equivalents of 16mg or more for 8 weeks or more confer a significant risk of PCP If other treatment modalities cannot be employed to reduce Mr. Hodges systemic steroid exposure he should consider prophylaxis TMP/SMZ DS 1 tablet daily Dapsone 100mg daily if severe sulfa allergy Starts with the macrophage Results in a collection of macrophages as well as other inflammatory cells Most commonly thought of with mycobacterium J Clin Pathol 2012;65:51 7. Ginger Lee is a 36 year old woman with Crohn s disease. She is not receiving any current therapy nor does she have any other significant medical conditions. The doctor would like to begin therapy with infliximab monotherapy but is interested in what you think the risk of infection is. J Clin Pathol 2012;65:

6 Infliximab Chimeric monoclonal antibody against TNF alpha Etanercept Fusion protein against TNF alpha for rheumatoid arthritis 2/ Clin Infect Dis2005;41:S Clin Infect Dis 2005;41:S Increase risk for most infections Of special concern are the granulomatous infections Tb Histoplasmosis In patients with no evidence of disease take precaution to avoid exposure In patients with possible latent disease search for alternatives. 6

7 Ginger receives a PPD which is negative, but she has a few granulomas on chest x ray. Would you choose an alternative therapy? Discover and treat the cause of the granulomas? Semin Hematol 47: Barry Garcia is a 48 year old man with Wegener s Granulomatosis who is having a poor response to steroids and cyclophosphamide. The physician is considering a course of rituximab but knows little about it and asks you for a refresher. Barry receives the hepatitis B panel and all the markers are negative. Barry receives a series of the hepatitis B vaccine and begins rituximab therapy. Targets the CD20 protein on B cells Leads to B cell depletion Increases risk for multiple infections Hepatitis B JC virus (PML) Harriet Fengirouch is a 57 year old lady with newly diagnosed rheumatoid arthritis. The physician you work with decides to try and treat this himself rather than refer to a rheumatologist. She saw that Methotrexate was a commonly used first line DMARD. She is scared that it will cause infections since it is a chemo drug. 7

8 Folate antagonist Main immunosuppressant effect is through T cell suppression. Bacterial infection remains low Viral infection potential Herpes Zoster Rheumatology 2009;48: Start Methotrexate 7.5mg orally once per week. Should she also get the Zostavax? 8