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