Management of Neutropenic Fevers in cancer patients Jerry Yu 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 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 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/calculateonline/hematology/febrile-neutropenia-mascc – MASCC >21 = low risk; may be eligible for oral/outpatient empiral abx treatment – MASCC<21= high risk; need inpatient hospitalization 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 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 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) 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 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 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.