1. Management of Neutropenic Fevers in cancer patients Jerry Yu

2. Definition Fever: IDSA guidelines: single oral temperature > 38.3 C (101 F) or 38.0 C sustained for > 1 hour Neutropenia: ANC <1500, severe neutropenia ANC <500

3. Background Most commonly observed in: – the pre-engraftment phase of hematopoietic cell transplantation – Patients undergoing induction therapy for acute leukemia – Less common in standard-dose chemotherapy

4. Risk Assessment High Risk patients: – Anticipated prolonged neutropenia (>7 days) – ANC <100 cells/mm3 – Significant medical comorbidities: HTN, PNA, abdominal pain, neurologic changes High risk patients should be admitted to the hospital for empiric therapy Low risk patients are eligible for oral empirical therapy Can use Multinational Association for Supportive Care in Cancer (MASCC) score: http://www.qxmd.com/calculate- online/hematology/febrile-neutropenia-mascchttp://www.qxmd.com/calculate- online/hematology/febrile-neutropenia-mascc – MASCC >21 = low risk; may be eligible for oral/outpatient empiral abx treatment – MASCC<21= high risk; need inpatient hospitalization

5. Antibiotic therapy: general principles Early administration of antibiotics- within 60 mins of presentation Empiric coverage for most life threatening infections Even when pathogen is known, consider broad spectrum coverage for possibility of other infections

6. Antibiotic selection Initial regimen: – Antipseudomonal monotherapy: cefepime, meropenem, imipenem, zosyn Additional rx: two drug regimen – Aminoglycoside, fluroquinolones, vancomycin if hypotensive or altered mental status Avoid ceftazidime monotherapy due to rising resistance

7. Empiric Gram (+) coverage Not proven to improve survival Vancomycin is NOT recommended as part of initial therapy unless you suspect: Catheter related infection Soft tissue/skin infection Pneumonia Hemodynamic instability Positive blood cultures MRSA colonization Other alternatives: linezolid, daptomycin (if not pulmonary source)

8. Antibiotics coverage cont. Specific anaerobic coverage – NOT included in initial empiric therapy unless you suspect necrotizing mucositis, sinusitis, periodontal cellulitis, perirectal cellulitis, intraabdominal infection, pelvic infection Anti-fungal coverage – Persistent fevers after 4-7 days in high risk patients without clearly defined source – Candida is most common organism – Amphotericin, caspofungin, voriconazole,itraconazole

10. Modifying your abx regimen No need to modify initial coverage if only persistent fever in a patient who is stable If vancomycin or empiric gram (+) was started, may be stopped after 2-3 days if no evidence of gram positive infection If hemodynamically unstable after initial empiric abx, increase to cover gram (+), anaerobes, and fungi

11. Colony stimulating factors No survival benefit in routine administration. IDSA does NOT recommend ASCO: Consider in High Risk Patients: – prolonged (>10 day) – profound (<100 cells/microL) neutropenia – age >65 – uncontrolled primary disease – Pneumonia – hypotension – multiorgan dysfunction (sepsis syndrome) – invasive fungal infection – being hospitalized at the time of the development of fever.