Neutropenic fever: Difference between revisions

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==Definition==
==Background==
{{Neutropenia background}}


===Common Causes===
''Definitive cause only found in 30%''
*Endogenous flora 80%
**[[E. Coli]], [[Enterobacter]], [[anaerobes]]
*Skin
**[[Staph]], [[strep]]
*Respiratory tract
**[[Step pneumonia]], [[klebsiella]], [[corynebacterium]], [[pseudomonas]]
*Other
**[[C. diff]], [[mycobacterium]], [[candida]], [[Aspergillosis|Aspergillus]]


ANC < 500 cells/µL (severe)
===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]]


OR
==Clinical Features==
*[[Fever]]
*Classic manifestations of infection are frequently NOT seen
*Check skin, oral cavity, perianal area, entry sites of indwelling cath sites


ANC < 1000 cells/µL (moderate) with a predicted nadir of ANC < 500 cells/µL in 48h
==Differential Diagnosis==
*[[Transfusion reaction]]
*Medication allergies and toxicities
*Tumor-related fever


&
{{Oncologic emergencies DDX}}


Fever ≥ 38.3˚C (101˚F) once
==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
**Nasopharyngeal wash (in patients with URI)
***[[RSV]], [[influenza]]
*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]]


OR
===Diagnosis===
{{Neutropenic fever definition}}


Sustained temp ≥ 38˚C (100.4˚F) for > 1h
==Management==
 
{{Neutropenic fever treatment}}
 
==Pathophysiology==
 
 
Nadir usually occurs 7-10d after chemo
 
Duration of neutropenia depends on type of cancer treatment
 
-Solid tumor Rx: ~<5d
 
-Hematologic malignancies: ~14d or longer
 
Leukemias, lymphomas + chemo most commonly associated with neutropenia
 
 
Common CausesDefinitive cause only found in 30%
 
Endogenous Flora 80%
 
-E Coli, Enterobacter, anaerobes
 
Skin
 
-Staph, strep
 
Respiratory tract
 
-Step pneumo, Klebsiella, Corynebacterium, Pseudomonas
 
Other
 
-C dif, Mycobacterium, Candida, Aspergillus
 
 
==Presentation/Exam==
 
 
Classic manifestations of infxn NOT seen
 
Check skin, mucosa, sinuses, indwelling cath sites CAREFULLY
 
-mild erythema, slight erosion in oropharynx or perianal area
 
-AVOID DRE
 
 
==DDx==
 
 
Transfusion reaction
 
Medication allergies and toxicities
 
Tumor-related fever
 
 
==W/U==
 
 
AVOID rectal temp
 
CBC with dif
 
Chem 10
 
LFTs
 
UA (may not show WBCs or leuk esterase given neutropenia), UCx
 
Sputum gram stain and Cx
 
BCx x 2 (20-30cc blood (adult) or 1-5cc (child); may take both samples from central venous catheter)
 
Cx any indwelling catheters
 
LP (if neuro abnl or suspicious)
 
Site-specific specimens
 
-nasopharyngeal wash in pts with UR (RSV, influenza)
 
Stool (if indicated)
 
-C dif
 
-O&P
 
-Cx
 
CXR
 
CT if necessary
 
-Sinuses
 
-Chest
 
-A/P
 
 
High-Risk/Special InfectionsNeutropenic Enterocolitis (Typhlitis)
 
Zygomycosis (see Mucormycosis)
 
Hepatosplenocandidiasis
 
-after neutropenic fever resolves and ANC has come up allowing abcess formation
 
--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)
 
-hypotension
 
-Grm + Bcx
 
-Hx of MRSA or Bactrim resistant pneumococci
 
-Prior ppx with fluoroquinolone or Bactrim
 
-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==
==Disposition==
*Low risk patients
**Brief (<7d duration) of neutropenia with few comorbidities<ref>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.</ref>
**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.<ref>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.</ref>
{| class="wikitable"
| '''Characteristic '''
| '''Points'''
|-
|
No or Mild Symptoms


Low Risk patients can be safely d/c'd home using the Multinational Association for Supportive Care in Cancer (MASCC) risk index:
Moderate Symptoms
 
 
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
≥21 pt = low risk for SBI
 
Home with close onc f/u and abx:
 
Cipro 500 Q8H
 
&
 
Augmentin 500 Q8H
 


Severe Symptoms


ADMIT all other patients (majority)
|
5


3


0


Pani 6/09, DeBonis 3/10
|-
| 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
|}


Reference: LLSA 2009; Halfdanarson Onc Emergencies Mayo Clin Proc June 2006; EMP
===CISNE===
*Clinical Index of Stable febrile Neutropenia
*230 febrile neutropenia, chemo-therapy induced, retrospective analysis of MASCC vs. CISNE<ref>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.</ref>
**MASCC was ~55% specific and CISNE was ~98% specific with PPV ~98%


==See Also==
*[[Neutropenia]]


==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==
<references/>


[[Category:Heme/Onc]]
[[Category:Heme/Onc]]
[[Category:ID]]

Latest revision as of 21:36, 11 September 2024

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
    • Solid tumor treatments: <5 days
    • Hematologic malignancies: 14 days or longer

Common Causes

Definitive cause only found in 30%

High-Risk/Special Infections

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

Oncologic Emergencies

Related to Local Tumor Effects

Related to Biochemical Derangement

Related to Hematologic Derangement

Related to Therapy

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
  • 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)
  • 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

Outpatient

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

References

  1. ↑ 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&sectionid=162273381
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
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