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My Febrile Patient is on an Immunomodulator ! What now?

My Febrile Patient is on an Immunomodulator ! What now?. Dr. Eric D. Katz Program Director Vice-Chair for Education Maricopa Medical Center. Disclosures No Relevant Financial Relationships. Your first case…. 60yo AAM presents with T 38.8 VS otherwise stable

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My Febrile Patient is on an Immunomodulator ! What now?

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  1. My Febrile Patient is on an Immunomodulator! What now? Dr. Eric D. Katz Program Director Vice-Chair for Education Maricopa Medical Center

  2. Disclosures No Relevant Financial Relationships

  3. Your first case… • 60yo AAM presents with T 38.8 • VS otherwise stable • Physical exam is unremarkable • So what’s the problem?

  4. Your Second Case • 60yo AAM presents with T 38.8 • VS otherwise stable • Physical exam is unremarkable • So what’s the problem?

  5. By the end of this lecture • Define neutropenic fever • Understand guidelines for IV antibiotics and admission for patients with neutropenic fever • Recognize causes of febrile states in transplant patients • Recognize tools that may be introduced in the near future to assist with early detection of infectious processes

  6. The Neutropenic Patient

  7. Your first case… • 60yoAAM presents with T 38.8 • VS otherwise stable • Physical exam is unremarkable • So what’s the problem?

  8. What is your definition of neutropenia? Neutropenia: ANC <500 OR ANC<1000 and dropping Fever: T>38.3 once or 1-hour >38.0

  9. Neutropenic Fever • 2/3 are caused by infection • 85+% of these are bacterial • The remaining 1/3 are drug, transfusion, virus • Longer duration of neutropenia predicts fever (if>7days, maybe 100%)

  10. Not a controversy • Neutropenics show few signs • Culture everything other than CSF • No growth in 49% of children and 38% of adults • Check a CBC • ANC predicts risk

  11. First Controversy • The rectal exam • Classic teaching: causes abscesses and bacteremia • Current teaching: hemorrhoids predict worse outcomes

  12. Second controversy • Admission Criteria • High fever (undefined) • Co-morbidities • Uncontrolled cancer

  13. Escalante et al. 2004 • Augmentin/Cipro vs. Ceftaz/clinda • 80% could be treated as outpatient • Still hard to discharge

  14. Third Controversy • IV vs. Oral antibiotics • 2004 cochrane review show no difference in outcomes

  15. How fast to treat • No standard • Some oncology centers want door to drug of <30 minutes

  16. Spectrum • Shift from GNB to GPC over the past 20 years • GNB – Pseudom, E. Coli, Klebsiella • GPC – S. aureus/epidermis, Strep sp.

  17. Monotherapy options • Monotherapy with broad-spectrum antipseudomonal cephalosporin (Cefipime or ceftazidime) • Monotherapy with carbapenem (imipenem or carbopenem) • Monotherapy with Pip/Tazo

  18. Double down… • Add an aminoglycoside when… • Critically ill • Septic • High suspicion of GNB • Add vanco when… • Catheter related infection • SSTI • Colonization with MRSA

  19. Viral and fungal • Antiviral drugs for cutaneous or mucous membrane HSV or VZV • Candid = fluconazole • Mucor = ampho

  20. Take home points – neutropenic fever • Neutropenic fever is: • T>38.3 once or 1-hour >38.0 PLUS • ANC <500 OR ANC<1000 and dropping • Guidelines show 80% can be treated as outpatients • Guidelines say oral antibiotics work

  21. The Transplant patient Our next several patients

  22. Solid Organ Transplant Patient • Fever is the most common ED presentation • Bacterial Infection • Viral Infection • Rejection (when severe) • Neoplasm • Medications

  23. What part of the history helps? • Time since transplant • Cadaveric or living donor (renal) • Medication compliance/changes • History of rejection • Ill contacts • Esp. CMV, EBV, Varicella, TB • History of chronic infections • Esp CMV, EBV, hepatitis

  24. The physical exam • Renal: • Inspect the transplant site • Erythema? Tender? • Obstruction/occlusion? • Liver • Inspect site • Jaundice appears early

  25. Infections in Renal Transplants • VERY common in first year • Most common sites: • Mucocutaneous (41%) • GU (17%) • Respiratory (14%) • Bacterial (46%) vs. viral (41%) • Viruses: CMV, HSV, HVZ

  26. Time from transplant • 1st month – surgical infections • 1st 6 months = highest immunosuppression • 2-5X higher rate of cancer than non immunosuppressed

  27. Time from transplant • 1st month: staph/strep, e. coli • 1st 6 months: viral – CMV (67%) Lymphadenopathy, myalgias, fever • After the second year, malignancy

  28. Solid organ transplant patient: Fever workup • UA • CBC with differential • CMP • Cultures • CMV titers • CXR • US (renal) vs. CT (liver) • Evaluation of catheters

  29. Antimicrobials • Antibiotics for any suspected infection (remember clearance!) • Anitvirals: discuss with ID or transplant • Antifungals in prolonged fevers

  30. Unfortunatemetabolic fact • Most anti-rejection meds are metabolized by the transplanted organ

  31. So our 60 yo AAM… • Recent decrease in medications • Rejection • Do the workup and give steroids

  32. Our 60 yo AAM 2. Recent increase in medications with elevating (liver/renal) enzymes • Do the workup and hold meds

  33. Our 60 yo AAM 3. Hemodynamic instability • EGDT • antibiotics

  34. Our 60 yo AAM 4. Solid organ txplt <1 month ago? • Antibiotics and imaging

  35. What about BMT patients? • BEFORE transplant, their immune system is wiped out • UTI (60%) – e. coli, klebsiella • Skin/soft tissue • Oral cavity • PNA uncommon (<10%) • Drug fever is rare • Usually low morbidity

  36. Day 0-30 • Neutropenic fever • Look for a source but may not find one • Drug fever/regrowth common but don’t assume • HSV – treat after d/w ID

  37. Day 30-100 • GVHD • CMV • Weird pathogens Aspergillus, candida, adenovirus, RSV • General recommendations: • Unlikely to be neutropenic • Can treat with abx but better to call oncology

  38. Changing our diagnostic abilities The future of managing infectious diseases

  39. Shortincubation culture systems • Now on the market • Faster detection of infection and rapid susceptibility testing • Sensitivity variable • Poor detection of resistance

  40. Direct Antigen Testing • Available for legionella, hemophilus, strep and mycoplasma • Sensitivity and specificity are very variable • Use in clincial practice not defined • At best level 2C indication

  41. Proteonomics • Assessment of upregulation and downregulation of several thousand proteins in different disease states. • Role in clinical care not established.

  42. Take home points • Neutropenic fever is: • T>38.3 once or 1-hour >38.0 PLUS • ANC <500 OR ANC<1000 and dropping • Patients with neutropenic fever can often get outpatient, oral antibiotics

  43. MoreTake Home Points 3. Transplant patients become febrile from drugs, rejection, infection, GVHD and need careful assessment. 4. Our diagnostic modalities will likely change in the next few years – and for the better.

  44. Questions?

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