Neutropenic fever

Background

• ANC = (total WBC) x (%segs + %bands)
• Nadir usually occurs 5-10d after chemo
• Duration of neutropenia depends on type of cancer treatment
  • Solid tumor Rx: <5d
  • Hematologic malignancies: 14d or longer
• (Leukemia or lymphoma) + chemo most commonly associated with neutropenia

Definition

1. ANC <500 OR <1000 w/ predicted nadir of <500 in 48h AND
2. Fever ≥ 38.3˚C (100.9˚F) once OR sustained temp ≥38 (100.4) for >1hr
   1. Oral temp (do not obtain rectal temp)

Common Causes

• Definitive cause only found in 30%

1. Endogenous flora 80%
   1. E Coli, Enterobacter, anaerobes
2. Skin
   1. Staph, strep
3. Respiratory tract
   1. Step pneumo, klebsiella, corynebacterium, pseudomonas
4. Other
   1. C. diff, mycobacterium, candida, aspergillus

High-Risk/Special Infections

1. Neutropenic Enterocolitis (Typhlitis)
2. Mucormycosis
3. Hepatosplenic Candidiasis
   1. Occurs after neutropenic fever resolves and ANC has come up allowing abcess formation
   2. Treat w/ amphotericin B

Factors Favoring Low Risk Infection in Adults

1. Age < 60years
2. Absolute neutrophil and monocyte counts >100 cells/cc
3. Normal chest radiograph
4. Normal or near normal hepatic and renal function tests
5. Duration of neutropenia <7 days or exptected resolution in <10 days
6. No IV catheter site infection
7. Early evidence of bone marrow recovery
8. Malignancy in remission
9. Peak temperature < 39C
10. No prior history of fungal infection or treatment for fungal infections
11. Asymptomatic or non-ill appearing
12. Absence of neurologic or mental status changes
13. Absence of abdominal pain
14. No comorbid conditions or complications
    1. diabetes
    2. lung disease
    3. hypotension

Diagnosis

1. Classic manifestations of infection are frequently NOT seen
2. Check skin, oral cavity, perianal area, entry sites of indwelling cath sites

DDx

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

Work-Up

1. AVOID rectal temp
2. CBC
3. Chemistry
4. LFTs
5. UA/UCx
   1. May not show WBCs or leuk esterase given neutropenia
6. Sputum studies
   1. Gram stain
   2. Cx
7. BCx x 2
   1. 20-30cc blood (adult); 3-9cc (child)
   2. May take both samples from CVC (if present)
8. Cx any indwelling catheters
9. LP
   1. If neuro abnl or suspicious
10. Site-specific specimens
    1. Nasopharyngeal wash (in pts with URI)
       1. 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

Treatment

Inpatient

1. Monotherapy appears to be as good as dual-drug therapy
   1. Cefepime 2g IV q8hr or ceftazidime 2g IV q8hr OR
   2. Imipenem/cilastatin 1gm IV q8hr or meropenem 1gm IV q8hr OR
   3. Piperacillin/tazobactam 4.5gm IV q 6hr
2. Consider adding vancomycin to above regimen for:
   1. Severe mucositis
   2. Signs of catheter site infection
   3. Fluoroquinolone prophylaxis was recently used against gram-negative bacteremia
   4. Hypotension is present
   5. Institutions with hospital-associated MRSA
   6. Pt has known colonization with resistant gram-positive organisms

Outpatient

1. Ciprofloxacin 500mg PO q8hr AND amoxicillin/clavulanate 500mg PO q8hr x7d

Disposition

• Low risk patients
  • Consider discharge it pt scores ≥21 using the MASCC risk index scoring system
  • Score ≥21 associated w/ <5% risk for severe complications and mortality <1%

MASCC Risk Index

Characteristic	Points
No or Mild Symptoms Moderate Symptoms Severe Symptoms	5 3 0
No Hypotension (SBP<90)	5
No COPD	4
Solid tumor OR no previous fungal infection	4
No dehydration	3
Outpatient status	3
Age <60yr	2

Source

• LLSA 2009
• Halfdanarson, Onc Emergencies Mayo Clin Proc June 2006
• Tintinalli
• Hughes WT, Armstrong D, Bodey GP, et al. 2002 guidelines for the use of antimicrobial agents in neutropenic patients with cancer. Clinical Infectious Disease 2002; 34:730-751