Neutropenic Fever

Etiology

Common gram-positive pathogens
Coagulase-negative staphylococci
Staphylococcus aureus, including methicillin-resistant strains
Enterococcus species, including vancomycin-resistant strains
Viridans group streptococci
Streptococcus pneumoniae
Streptococcus pyogenes
Common gram-negative pathogens
Escherichia coli
Klebsiella
Enterobacter
Pseudomonas aeruginosa
Citrobacter
Acinetobacter
Stenotrophomonas maltophilia

Laboratory tests should include a complete blood cell (CBC) count with differential leukocyte count and platelet count; measurement of serum levels of creatinine and blood urea nitrogen; and measurement of electrolytes, hepatic transaminase enzymes, and total bilirubin (A-III Recommendation)
At least 2 sets of blood cultures are recommended, with a set collected simultaneously from each lumen of an existing central venous catheter (CVC), if present, and from a peripheral vein site; 2 blood culture sets from separate venipunctures should be sent if no central catheter is present (A-III Recommendation)
- Blood culture volumes should be limited to <1% of total blood volume (Usually Approximately 70 mL/kg) in patients weighing <40 kg (C-III Recommendation)
Culture specimens from other sites of suspected infection should be obtained as clinically indicated (A-III Recommendation)
A chest radiograph is indicated for patients with respiratory signs or symptoms (A-III Recommendation)

At Presentation with Neutropenic Fever, Risk of Complications of Severe Infection Should Be Assessed (A-II Recommendation)
- Risk Assessment Determines the Type of Empiric Antibiotic Therapy (Oral vs Intravenous), Venue of Treatment (Inpatient vs Outpatient), and Duration of Antibiotic Therapy (A-II Recommendation)
  - Formal Risk Assessment Can Be Performed Using the Multinational Association for Supportive Care in Cancer (MASCC) Scoring System (B-I Recommendation)
High-Risk
- Anticipated Prolonged Neutropenia (>7 Days Duration) and Profound Neutropenia (Absolute Neutrophil Count <100 Cells/mm3 Following Cytotoxic Chemotherapy) and/or Significant Medical Comorbidities (Including Hypotension, Pneumonia, New-Onset Abdominal Pain, or Neurologic Changes)
  - High-Risk Patients Should Be Admitted to the Hospital for Inpatient Empiric Antibiotic Therapy (A-II Recommendation)
- MASCC Score <21 = High Risk (B-I Recommendation)
  - Patients with High-Risk by MASCC Score Should Be Admitted to the Hospital for Empiric Therapy (B-I Recommendation)
Low Risk
- Anticipated Brief Neutropenia (<7 Days Duration) or No/Few Comorbidities
  - Low-Risk Patients Can Receive Oral Empiric Antibiotic Therapy (A-II Recommendation)
- MASCC Score >21 = Low Risk (B-I Recommendation)
  - Carefully Selected Patients with Low-Risk by MASCC Score May Be Treated with Oral and/or Outpatient Empiric Antibiotic Therapy (B-I Recommendation)

Brazilian Cohort Study of Impact of Time to Antibiotic Administration in Neutropenic Fever (Antimicrob Agents Chemother, 2014) [MEDLINE]
- Early Antibiotic Administration (within 30 min) was Associated with Decreased 28-Day Mortality Rate, as Compared to Administration Between 31-60 min
- Each Increase of 1 hr in Time to Antibiotic Administration in Neutropenic Fever was Associated with an 18% Increase in the 28-Day Mortality Rate

Treatment of patients with hematologic neoplasm, fever, and neutropenia. Clin Infect Dis. 2005 Apr 1;40 Suppl 4:S253-6 [MEDLINE]
Liposomal amphotericin B: a review of its use as empirical therapy in febrile neutropenia and in the treatment of invasive fungal infections. Drugs. 2009;69(3):361-92. doi: 10.2165/00003495-200969030-00010 [MEDLINE]
Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011 Feb 15;52(4):e56-93. doi: 10.1093/cid/cir073 [MEDLINE]
Cohort study of the impact of time to antibiotic administration on mortality in patients with febrile neutropenia. Antimicrob Agents Chemother. 2014 Jul;58(7):3799-803. doi: 10.1128/AAC.02561-14. Epub 2014 Apr 21 [MEDLINE]
Executive Summary: Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Feb 15;62(4):409-17. doi: 10.1093/cid/civ1194 [MEDLINE]