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Neutropenia & Neutropenic Fever

Jennifer Marvin-Peek


  • Neutropenia: absolute neutrophil count (ANC) < 1500
    • Severe neutropenia: absolute neutrophil count (ANC) <500 (Use manual count if available)
Mechanism Causes Example(s)
Neutrophil production Drug associated - Cytotoxic or immunosuppressive agents
- Methimazole, PTU, colchicine
- Macrolides, bactrim, dapsone, vancomycin
- Amphotericin, acyclovir, ganciclovir
- TCAs, clozapine, carbamazepine, valproate
- ACEI, digoxin, propranolol, procainamide
Radiation exposure
Infection - Hepatitis, HIV, EBV, CMV
- Rickettsia, tularemia, typhoid, TB
Nutritional deficiency Vitamin B12, folate, copper
Other Aplastic anemia, benign ethnic neutropenia
Redistribution Splenomegaly Margination and sequestration
Congenital Genetics Benign ethnic neutropenia, familial neutropenia
Immune destruction Autoimmune RA, SLE
Other Autoimmune neutropenia


  • If ANC <500
    • Check all lines/IVs for erythema and induration daily
    • Check mouth for mucositis, mouth care after meals and before bed
    • Assess for Neutropenic Fever and Complications – see below
    • Evaluate for indications for prophylaxis – see below
    • No evidence to support use of neutropenic diet
    • No digital rectal exams or enemas/suppositories (risk of bacterial translocation)

Neutropenic Fever


  • ANC <500 and T> 100.4 °F or 38.0 °C
  • Neutropenic pts are unable to mount an adequate immune response and can become critically ill very quickly
  • Do not wait for a temp re-check, you need to start antibiotics immediately


  • Chest X-ray
  • Two sets of blood cultures (one from PICC/port if present)
  • Urinalysis AND urine culture (not the reflex order set)
  • If diarrhea, get C. diff PCR
  • If abdominal pain, get CT A/P with IV contrast


  • Empirically treat with cefepime
  • Indications for vancomycin
    • Hemodynamically unstable
    • Severe mucositis
    • Focal consolidation on CXR
    • Erythema/induration around line
    • Concern for skin/soft tissue infection
    • GPCs in blood
    • Fever continues >24h on cefepime
  • Additional Coverage:
    • If abdominal pain/diarrhea: Flagyl 500mg q8h
    • Concern for C-diff: PO vancomycin 125mg q6h
    • Still fevering on cefepime at 72 hrs (differs by attending): meropenem
  • Fungal coverage: consider if risk factors (TPN) or persistent fevers (>72hrs)
  • Micafungin 100 mg IV daily or voriconazole 200mg PO BID

Neutropenic Complications


  • Can range from mouth soreness to severe erosions preventing eating/drinking
  • Can become secondarily infected with Candida, HSV
    • Management:
      • Routine oral care with a soft toothbrush to remove plaque
      • Oral rinses with saline and/or sodium bicarbonate
      • Magic mouthwash for symptomatic relief (or viscous lidocaine at the VA)
      • Typically recovers quickly when ANC > 500

Neutropenic enterocolitis (typhlitis)

  • Life-threatening bacterial translocation due to breakdown of gut-mucosal barrier
  • Presentation: Abdominal pain + fever
    • ± abdominal distension, nausea, vomiting, watery and/or bloody diarrhea
  • Diagnosis: CT A/P with contrast, consider C. diff PCR if diarrhea
  • Treatment
    • Cefepime/Flagyl OR Zosyn
    • If no perforation/abscess on CT scan, typically continue until 14 days after ANC recovers >500 and abdominal pain resolves
    • Can change to cipro/flagyl once ANC >500
    • If perforation/abscess: will need imaging to confirm resolution, and longer duration of abx

Neutropenic Prophylaxis

  • Used if ANC is expected to be < 500 for > 7 days
Most Common Regimens Alternatives
Bacterial levofloxacin 500mg daily (renally dosed) cefdinir 300mg BID
Viral valacyclovir 500mg BID acyclovir 400mg BID (renally dosed)
Fungal fluconazole 400mg daily Posaconazole 300mg BID x2 days -> 300mg daily (AML induction for aspergillus)

micafungin 50mg IV daily
PJP (if steroids) inhaled pentamidine 300mg qmonthly dapsone (check G6PD)
Avoid Bactrim (risk of myelosuppression)

Filgrastim (G-CSF – Neupogen/Zarxio /Granix)

  • Induces bone marrow production of neutrophils
  • Dose: either 300mcg or 480mcg (rounded from 5 mcg/kg/day)
  • Common side effects: fatigue, nausea
  • PEG-filgrastim (Neulasta): long-acting version that is only given as an outpt