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:
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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:
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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.