Neutropenia and Neutropenic Fever

Rachel Gorham

Background

  • 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
Malignancies Leukemias, MDS
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

Management

  • If ANC <500:
    • Check all lines/IVs for erythema and induration daily.
    • Check mouth for mucositis – see Neutropenic Fever.
    • Assess for need to prophylaxis, fever, and complications – see Neutropenic Fever.
    • No evidence to support use of neutropenic diet.
    • No digital rectal exams or enemas/suppositories (risk of bacterial translocation).

Neutropenic Fever

  • Definition: ANC < 500 and either a single oral temperature ≥ 38.3°C (100.9 °F) or a sustained temperature ≥ 38°C (100.4°F) for 1 hour. Neutropenic patients are unable to mount an adequate immune response and can become critically ill very quickly.
  • Start antibiotics immediately (within 1 hour of fever onset)-see below.

Evaluation

  • 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, Consider GIPP.
  • If abdominal pain, consider CT A/P with IV contrast to evaluate for typhlitis.

Management 

  • Empirically treat with cefepime (2g IV q8h) or zosyn (4.5g IV q 6h).
  • Indications for vancomycin:
    • Hemodynamic instability or other worrisome change in clinical status.
    • Skin/soft tissue infection (eg mucositis).
    • Pneumonia.
    • Suspected catheter-related infection (erythema/induration around port or IV).
    • Blood cultures + GPCs.
  • Additional Coverage:
    • If concern for C-diff can start PO vancomycin 125mg q6h.
    • Fungal coverage: consider if risk factors (TPN) or persistent fevers (>72hrs)(eg micafungin 100 mg IV daily).
    • If ESBL bacteria suspected, can page ID to start meropenem.

Neutropenic Complications

Mucositis

  • 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 Miracle mouthwash 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 oral and IV contrast.
  • Treatment o 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 oral regimen (eg cipro/flagyl) once ANC >500
    • If perforation/abscess: surgical treatment - consult EGS; 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

Bacteriallevofloxacin 500mg daily (renally dosed)Cefdinir 300mg q12 hrs ciprofloxacin 500mg BID
Viralvalacyclovir 500mg BIDacyclovir 400mg BID
Fungalfluconazole 400mg dailyposaconazole 300mg BID x2 days then 300mg daily (preferred if AML induction) Micafungin 50mg daily
PJP (if steroids, some ALL induction)inhaled pentamidine 300mg qmonthly
Bactrim DS 800-160 on MWF (theoretical risk of myelosuppression, renal toxicity)		dapsone (check G6PD)

Granulocyte-Colony Stimulating Factors (G-CSF)

(eg. Filgrastim aka Neupogen)

  • Induces bone marrow production of neutrophils, goal is to reduce duration of neutropenia, often used in ALL and AML induction
  • Dose: either 300mcg or 480mcg (rounded from 5 mcg/kg/day)
  • Pegfilgrastim (Neulasta): long-acting version that is only given as an outpt
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