Neutropenic fever
Background
Neutropenia
- ANC = (total WBC) x (%segs + %bands)
- Nadir usually occurs 5-10 days after chemotherapy
- Duration of neutropenia depends on type of cancer treatment
Common Causes
Definitive cause only found in 30%
- Endogenous flora 80%
- Skin
- Respiratory tract
- Other
High-Risk/Special Infections
- Neutropenic enterocolitis (typhlitis)
- Mucormycosis
- Hepatosplenic Candidiasis
- Occurs after neutropenic fever resolves and ANC has come up allowing abscess formation
- Treat with amphotericin B
Clinical Features
- Fever
- Classic manifestations of infection are frequently NOT seen
- Check skin, oral cavity, perianal area, entry sites of indwelling cath sites
Differential Diagnosis
- Transfusion reaction
- Medication allergies and toxicities
- Tumor-related fever
Oncologic Emergencies
Related to Local Tumor Effects
- Malignant airway obstruction
- Bone metastases and pathologic fractures
- Malignant spinal cord compression
- Malignant Pericardial Effusion and Tamponade
- Superior vena cava syndrome
Related to Biochemical Derangement
- Hypercalcemia of malignancy
- Hyponatremia due to SIADH
- Adrenal insufficiency
- Tumor lysis syndrome
- Carcinoid syndrome
Related to Hematologic Derangement
Related to Therapy
- Chemotherapy-induced nausea and vomiting
- Cytokine release syndrome
- Chemotherapeutic drug extravasation
- Differentiation syndrome (retinoic acid syndrome) in APML
- Stem cell transplant complications
- Catheter-related complications
- Tunnel infection
- Exit site infection
- CVC obstruction (intraluminal or catheter tip thrombosis)
- Catheter-related venous thrombosis
- Fracture of catheter lumen
- Oncologic therapy related adverse events
Evaluation
Patient should be placed and maintained on neutropenic isolation precautions during there stay in the ED and while in the hospital
Workup
AVOID rectal temp or digital rectal exam
- CBC
- Chemistry
- LFTs
- Urinalysis/Urine culture
- May not show WBCs or leuk esterase given neutropenia
- Sputum studies
- Gram stain
- Culture
- Blood culture x 2
- Take at least one sample from central line, if present
- Culture any indwelling catheters
- LP
- If neuro findings or suspicious
- Site-specific specimens
- Stool (if indicated)
- C dif
- O&P
- Cultures
- CXR
- CT (not required in all patients)
- Sinuses
- Chest
- Abdomen/Pelvis
- Should have high suspicion, given risk of typhlitis
Diagnosis
Neutropenic fever definition
- ANC <500 OR <1000 with predicted nadir of <500 in 48h AND
- Fever ≥ 38.3˚C (100.9˚F) once OR sustained temperature ≥38 (100.4) for >1hr
- Oral temperature (do not obtain rectal temp; risk of inducing bacteremia[1])
Management
Therapy is aimed at treating multiple flora that include Gram Negatives, Gram Positive Bacteria, Pseudomonas and if there is an indwelling catheter or high risk, then MRSA.
Inpatient
- Monotherapy appears to be as good as dual-drug therapy[2]
- Cefepime 2g IV q8hr or Ceftazidime 2g IV q8hr OR
- Imipenem/Cilastin 1gm IV q8hr or Meropenem 1gm IV q8hr OR
- Piperacillin/Tazobactam 4.5gm IV q 6hr
- Consider adding Vancomycin to above regimen for:[3]
- Severe mucositis
- Signs of catheter site infection
- Fluoroquinolone prophylaxis was recently used against gram-negative bacteremia
- Hypotension is present
- Institutions with hospital-associated MRSA
- Patient has known colonization with resistant gram-positive organisms
Outpatient
- Ciprofloxacin 750mg PO q12hrs AND Amoxicillin/Clavulanate 875mg PO q12hrs x7d OR[2]
- Ciprofloxacin 750mg PO q12hrs AND Clindamycin 450mg PO q8hrs
Disposition
- Low risk patients
- Brief (<7d duration) of neutropenia with few comorbidities[4]
- Consider discharge it patient scores ≥21 using the MASCC risk index scoring system
- Score ≥21 associated with <5% risk for severe complications and mortality <1%
MASCC Risk Index
- The MASCC study was an international collaboration to derive and validate a scoring system to identify low-risk patients for complications of febrile neutropenia.[5]
| 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 requiring IV fluids | 3 |
| Outpatient status at fever onset | 3 |
| Age <60yr | 2 |
CISNE
- Clinical Index of Stable febrile Neutropenia
- 230 febrile neutropenia, chemo-therapy induced, retrospective analysis of MASCC vs. CISNE[6]
- MASCC was ~55% specific and CISNE was ~98% specific with PPV ~98%
See Also
External Links
- https://www.mdcalc.com/calc/3913/mascc-risk-index-febrile-neutropenia
- https://www.mdcalc.com/calc/3997/clinical-index-stable-febrile-neutropenia-cisne
References
- ↑ Fleischman RJ. Emergency Complications of Malignancy. In: Cydulka RK, Fitch MT, Joing SA, Wang VJ, Cline DM, Ma O. eds. Tintinalli's Emergency Medicine Manual, 8e. McGraw-Hill; Accessed December 09, 2020. https://accessemergencymedicine.mhmedical.com/content.aspx?bookid=2158§ionid=162273381
- ↑ 2.0 2.1 Friefeld AG et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the IDSA. Clin Infect Dis. 2011; 52(4):e56-93 fulltext
- ↑ 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
- ↑ Freifeld AG et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the IDSA. Clin Infect Dis. 2011; 52(4):e56-93.
- ↑ Klatersky et al. The Multinational Association for Supportive Care in Cancer Risk Index: A Multinational Scoring System for Identifying Low-Risk Febrile Neutropenic Cancer Patients. J Clin Onc 18:3038-3051.
- ↑ Coyne et al. Application of the MASCC and CISNE Risk-stratification Scores to Identify Low-Risk Febrile Neutropenic Patients in the Emergency Department. Ann Emerg Med. 2016 Dec 29. pii: S0196-0644(16)31352-X. doi: 10.1016/j.annemergmed.2016.11.007.