Neutropenic fever

Background

Definition

1. ANC
   1. < 500 cells/µL (severe)
2. OR, <1000 cells/µL (moderate) with a predicted nadir of ANC < 500 cells/µL in 48h
3. AND
   1. Fever ≥ 38.3˚C (101˚F) once
   2. OR, Sustained temp ≥ 38˚C (100.4˚F) for > 1h

Pathophysiology

1. Nadir usually occurs 7-10d after chemo
2. Duration of neutropenia depends on type of cancer treatment
   1. Solid tumor Rx: ~<5d
   2. Hematologic malignancies: ~14d or longer
3. Leukemias, lymphomas + chemo most commonly associated with neutropenia

Common Causes

1. Definitive cause only found in 30%
2. Endogenous Flora 80%
   1. E Coli, Enterobacter, anaerobes
3. Skin
   1. Staph, strep
4. Respiratory tract
   1. Step pneumo, Klebsiella, Corynebacterium, Pseudomonas
5. Other
   1. C dif, Mycobacterium, Candida, Aspergillus

Diagnosis

1. Classic manifestations of infxn NOT seen
2. Check skin, mucosa, sinuses, indwelling cath sites CAREFULLY
   1. mild erythema, slight erosion in oropharynx or perianal area
   2. AVOID DRE

DDx

1. Transfusion reaction
2. Medication allergies and toxicities
3. Tumor-related fever

Work-Up

1. AVOID rectal temp
2. CBC with dif
3. Chem 10
4. LFTs
5. UA (may not show WBCs or leuk esterase given neutropenia), UCx
6. Sputum gram stain and Cx
7. BCx x 2 (20-30cc blood (adult) or 1-5cc (child); may take both samples from central venous catheter)
8. Cx any indwelling catheters
9. LP (if neuro abnl or suspicious)
10. Site-specific specimens
    1. nasopharyngeal wash in pts with UR (RSV, influenza)
11. Stool (if indicated)
    1. C dif
    2. O&P
    3. Cx
12. CXR
13. CT if necessary
    1. Sinuses
    2. Chest
    3. A/P

High-Risk/Special Infections

1. Neutropenic Enterocolitis (Typhlitis)
2. Zygomycosis (see Mucormycosis)
3. Hepatosplenocandidiasis
   1. after neutropenic fever resolves and ANC has come up allowing abcess formation
   2. Rx ampho b

Treatment

Even if afebrile, if si/sy of infxn, TREAT

3rd or 4th gen cephalosporin (cefepime 2g or ceftazidime 2g)

OR

Carbapenem (imipenem 500mg or meropenem 1g)

OR

Zosyn 4.5g

+/-

Aminoglycoside (gent 2-5mg/kg, amikacin)

OR

Antipseudomonal fluoroquinolone (moxi, levo, cipro)

+/-

Vancomycin 1g (alternative: quinupristin/dalfopristin, daptomycin, linezolid)

1. hypotension
2. Grm + Bcx
3. Hx of MRSA or Bactrim resistant pneumococci
4. Prior ppx with fluoroquinolone or Bactrim
5. Catheter related infxn

Add Amphotericin B 0.5-1 mg/kg qd if fever >72 h or candida in esophagus, urine or stool

Add anaerobic coverage (clindamycin, flagyl) if peritonitis or abdominal symptomatology occurs

If PMNs expected to be ≤ 100/mm3 for one week, consider G-CSF/GM-CSF

-Unless pt has hx of leukemia, in which case G-CSF is generally contraindicated

^No current evidence supports antifungals or antivirals if fever alone; after 4-7 days may need to start either/both

Disposition

Low Risk patients can be safely d/c'd home using the Multinational Association for Supportive Care in Cancer (MASCC) risk index:

Patient Clinical Factor Score

Patient Clinical Factor	Score
Severity of illness: no symptoms or mild symptoms moderate symptoms	5 3
No hypotension	5
No chronic obstructive pulmonary disease	4
Solid tumor or no fungal infxn	4
No dehydration	3
Outpt at onset of fever	3
Age < 60yo	2

Severity of illness:

1. no symptoms or mild symptoms
2. moderate symptoms

5

3

No hypotension 5 No chronic obstructive pulmonary disease 4 Solid tumor or no fungal infxn 4 No dehydration 3 Outpt at onset of fever 3 Age < 60yo 2 ≥21 pt = low risk for SBI

Out Patient

Home with close onc f/u and abx:

1. Cipro 500 Q8H
2. AND, Augmentin 500 Q8H

In Patient

ADMIT all other patients (majority)

Source

Pani 6/09, DeBonis 3/10

Reference: LLSA 2009; Halfdanarson Onc Emergencies Mayo Clin Proc June 2006; EMP