Neutropenic Fever

Approach to and Overview of Neutropenic Fever - adapted from the 2002 IDSA guidelines.

• Definition: T > 38.3 x 1 occurence, or T > 38 for 1 hour, in pt with ANC < 500 (or ANC < 1000 with expected nadir of < 500)
• Source is identified in only ~30% of cases, and bacteremia documented in only 25%
• Infectious workup should proceed as usual with careful H+P, blood cultures, UA/Ucx, CXR at the minimum.  On exam, pay special attention to lines, skin, mucositis, perirectal area.  Keep in mind that in neutropenic pts, signs and symptoms of inflammation are often subtle (i.e. no raging cellulitis, minimal infiltrate on CXR, no pyuria on UA or sputum cxs). 
• If source identified, treatment will be aimed there (i.e. Vanc/Zosyn/Cipro for health-care associated PNA).
• If not, next step = determine if pt high risk or low risk.  Factors that favor low risk pt are: young age (<60), less severe neutropenia (ANC > 100), short duration of neutropenia (<7 days), cancer in remission, lack of significant comorbidities, asymptomatic, stable vitals, no clear source identified.  If low risk, can consider oral abxs with cipro + augmentin.
• If high risk (like this patient, and most of the patients we see) with no clear source, empiric therapy should involve a beta-lactam with antipseudomonal activity.  Choices include Cefepime, Imipenem or Meropenem, or double coverage with Gentamicin or cipro added to Zosyn or to Cefepime or Carbapenem (but no clear benefit to dual therapy).
• Vancomycin for select groups - see below
• If fever persists after 3-5 days, should intensify search for a source - repeat imaging or cultures.  Also, r/o inadequate Abx levels.  Consider broadening coverage.
• Empiric antifungals are added on day 5 for persistent neutropenic fever: 2009 IDSA guidelines recommend Voriconazole, Echinocandin, or Liposomal Amphoterecin B as first-line therapy.  Should consider CT scan of the chest prior to antifungals, to evaluate for pulmonary nodules which can signify fungal disease.

Indications for Vancomycin in empiric treatment of neutropenic fever
Should NOT routinely add Vancomycin without thinking.  The below are the generally accepted indications:

1. Hypotension - for "crumping" patients, want to cover broadly.
2. Known MRSA colonization - they are high risk for MRSA infection
3. Suspected catheter-related infection
4. Gram stain or initial cultures showing gram positive cocci
5. Severe mucositis - predisposed to PCN-resistant strep
6. History of fluoroquinolone ppx - be concerned about breakthrough resistant gram positive infections

Outpatient therapy ?

• Factors that favor a low risk for severe infection: ANC >100, nl CXR, duration of expected neutropenia <7 days, malignancy in remission, no clinical symptoms, peak temp <39.0
• Oral abx: quinolones are generally not as effective as cephalosporins or carbapenems in treating gram + infxns. Ciprofloxacin plus amoxicillin/clavulanate is the only currently recommended regimen (not recommended for children).

(Victoria Kelly MD, 8/30/10)

(Chanu Rhee MD, 8/13/10)