Neutropenia and Neutropenic Fever

Background

  • Neutropenia: absolute neutrophil count (ANC) < 1500
    • Severe neutropenia: absolute neutrophil count (ANC) <500 [Use manual count if available]
    • Typically requires immediate evaluation and often hospitalization
    • >500 is threshold for allowing pt’s to return home after chemo-induced neutropenia

 

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 & sequestration

Congenital

Genetics

Benign ethnic neutropenia, familial neutropenia

Immune destruction

Autoimmune disorders

RA, SLE

Other

Autoimmune neutropenia

 

Management

  • 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 & Complications – see below
    • Evaluate for indications for prophylaxis – see below
    • Provide Neutropenic Precautions:
      • Neutropenic diet: low microbial diet
      • Idea is to prevent food-borne illness, however has not been shown to decrease infection risk in meta-analyses
      • No raw, or undercooked foods
      • No deli meats, seafood, salad bars, unpasteurized products or raw sprouts
      • 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

 

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
  • If abdominal pain, get CT A/P with IV contrast

 

Management

  • 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

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 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 Regimen

Alternatives

Bacterial

Levofloxacin 500mg PO daily

Cefdinir 300mg PO BID

Viral

Valacyclovir 500mg PO BID

Acyclovir 400mg PO BID (adjust for renal dysfunction)

Fungal

Fluconazole 400mg PO daily

Posaconazole 300 PO BID x2 days

300 daily (AML induction for aspergillus)

Micafungin 50mg IV daily

PJP

(if steroids)

Inhaled pentamidine 300 mg monthly

Dapsone (check G6PD)

Avoid Bactrim (risk of myelosuppression)

 

Filgrastim (G-CSF – Neupogen/Zarxio)

  • Induces bone marrow production of Neutrophils
  • Can be given for chemo-induced neutropenia in non-AML malignancies
  • Sometimes given in AML in certain regimens like CLAG-M
  • 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 outpatient