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MANAGEMENT OF NEUTROPENIC FEVERS IN CANCER PATIENTS Jerry Yu Objective • 1. Identify neutropenic fevers • 2. Risk stratify patients with neutropenic fevers • 3. Selecting the appropriate antibiotics for neutropenic fevers • 64 y/o M with hx of oral squamous cell carcinoma with local invasion into the neck s/p chemotherapy infusion 8 days prior via a R subclavian portacath, DM, HTN who presented with chief complaint of fatigue. In the ED, found to have WBC 0.1 (ANC 15). Observed to have temperature 38.4 with blood pressure 103/77 and pulse 88. CXR and U/A was normal. Medicine was called to admit patient. Definition • Fever: IDSA guidelines: single oral temperature > 38.3 C (101 F) or 38.0 C sustained for > 1 hour AND • Neutropenia: ANC <1500, severe neutropenia ANC <500 • Most commonly observed in leukemia undergoing induction therapy and less commonly seen in solid tumor receiving 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 • 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 empirical antibiotic treatment • MASCC<21= high risk; need inpatient hospitalization T> 38.3 + ANC <1500 Start anti-gram (-) abx w/ pseudomonas coverage Hemodynamically stable? Risk factors for gram (+)? Yes No Yes Start vancomycin No Suspect anaerobic infections? Yes Start anaerobic coverage No Source Search Start anti-fungal treatment if persistent Fevers after 4-7 days Start gram (+) and anaerobic coverage Antibiotic selection • Initial regimen: First line treatment is gram (-) antibiotic that covers pseudomonas • Antipseudomonal monotherapy: cefepime, meropenem, imipenem, zosyn • *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 no evidence of pulmonary source) Anaerobic treatment • 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 treatment • NOT included in initial empiric coverage • Persistent fevers after 4-7 days in high risk patients without clearly defined source • Candida is most common organism • Amphotericin, caspofungi, voriconazole, itraconazole Modifying your antibiotic regimen • No need to modify initial coverage if only persistent fever in a patient who is hemodynamically stable • If vancomycin or empiric gram (+) was started, may be stopped after 2-3 days if no evidence of gram positive infection • If patient is hemodynamically unstable after initial empiric abx, increase to cover gram (+), anaerobes, and fungi How long to give antibiotics for? • With clinically or microbiologically diagnosed infection, treat for full course of the infection • In unexplained fever, continue antibiotics for the duration of neutropenia until ANC >500 Colony stimulating factors • No survival benefit in routine administration. • Administer only if high risk: • prolonged (>10 day) neutropenia • profound (<100 cells/microL) neutropenia • age >65 • uncontrolled primary disease • Pneumonia • hypotension • multiorgan dysfunction • invasive fungal infection • being hospitalized at the time of the development of fever. Neutropenic Precautions • Hand Hygiene- most effective means of preventing transmissions • Standard barrier precautions for all neutropenic patients • HSCT recipients should be placed in private rooms • Plants and dried or fresh flowers should not be allowed into patient rooms Our patient • Patient was started on vancomycin + cefepime. Blood cultures drawn from portacath were positive for MRSA. Line was removed by IR. Patient’s antibiotics were narrowed to vancomycin only. Patient received vancomycin for a total of 2 weeks with repeat blood cultures negative for further infections. Summary • Neutropenic fever: T38.3 + ANC <1500 • Empirically start broad spectrum antibiotics for with anti- gram (-)pseudomonas regimen • In an otherwise hemodynamically stable patient, no immediate indication to start gram (+) or anti-fungal coverage • Proper antibiotic use requires aggressive source searching References • Treatment of neutropenic fever syndromes in adults with hematologic malignancies and hematopoietic cell transplant. UpToDate Jan 2015 • Greifeld AG, Wingard, JR. Clinical Practice Guideline for the Use of antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update by the infectious Disease Society of America. IDSA guidelines. 2011; 52(4): e56e93