Neutropenic fever: Difference between revisions
 
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==Background==
==Background==
*ANC = (total WBC) x (%segs + %bands)
{{Neutropenia background}}
*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===
{{Neutropenic fever definition}}
#ANC <500 OR <1000 w/ predicted nadir of <500 in 48h AND
#Fever ≥ 38.3˚C (100.9˚F) once OR sustained temp ≥38 (100.4) for >1hr
##Oral temp (do not obtain rectal temp)


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


===High-Risk/Special Infections===
===High-Risk/Special Infections===
#[[Neutropenic Enterocolitis (Typhlitis)]]  
*[[Neutropenic Enterocolitis (Typhlitis)]]  
#[[Mucormycosis]]
*[[Mucormycosis]]
#Hepatosplenic Candidiasis
*Hepatosplenic [[Candidiasis]]
##Occurs after neutropenic fever resolves and ANC has come up allowing abcess formation
**Occurs after neutropenic fever resolves and ANC has come up allowing abscess formation
##Treat w/ amphotericin B
**Treat with [[amphotericin B]]


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


==Differential Diagnosis==
==Differential Diagnosis==
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*Tumor-related fever
*Tumor-related fever


==Work-Up==
{{Oncologic emergencies DDX}}
#AVOID rectal temp
#CBC
#Chemistry
#LFTs
#UA/UCx
##May not show WBCs or leuk esterase given neutropenia
#Sputum studies
##Gram stain
##Cx
#[[BCx]] x 2
##20-30cc blood (adult); 3-9cc (child)
##May take both samples from CVC (if present)
#Cx any indwelling catheters
#[[LP]]
##If neuro abnl or suspicious
#Site-specific specimens
##Nasopharyngeal wash (in pts with URI)
###[[RSV]], [[influenza]]
#Stool (if indicated)
##[[C dif]]
##O&P
##Cx
#CXR
#CT (if necessary)
##Sinuses
##Chest
##A/P


==Treatment==
==Evaluation==
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]].
'''AVOID rectal temp or digital rectal exam'''
===Inpatient===
*CBC
*Monotherapy appears to be as good as dual-drug therapy<ref name="antibiotics">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</ref>
*Chemistry
**[[Cefepime]] 2g IV q8hr or [[Ceftazidime]] 2g IV q8hr OR
*[[LFTs]]
**[[Imipenem/Cilastin]] 1gm IV q8hr or [[Meropenem]] 1gm IV q8hr OR
*[[Urinalysis]]/Urine culture
**[[Piperacillin/Tazobactam]] 4.5gm IV q 6hr
**May not show WBCs or leuk esterase given neutropenia
*Consider adding [[Vancomycin]] to above regimen for:<ref>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</ref>
*Sputum studies
**Severe mucositis
**[[Gram stain]]
**Signs of catheter site infection
**Culture
**[[Fluoroquinolones|Fluoroquinolone]] prophylaxis was recently used against [[gram-negative bacteremia]]
*[[Blood culture]] x 2
**[[Hypotension]] is present
**20-30cc blood (adult); 3-9cc (child)
**Institutions with hospital-associated [[MRSA]]
**May take both samples from CVC (if present)
**Patient has known colonization with resistant [[gram-positive organisms]]
*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 (if necessary)
**Sinuses
**Chest
**A/P
*Patient should be placed and maintained on neutropenic isolation precautions during there stay in the ED and while in the hospital


===Outpatient===
==Management==
#[[Ciprofloxacin]] 500mg PO q8hr AND [[Amoxicillin/Clavulanate]] 500mg PO q8hr x7d<ref name="antibiotics"></ref>
{{Neutropenic fever treatment}}
 
== Disposition  ==


==Disposition==
*Low risk patients  
*Low risk patients  
**Consider discharge it pt scores ≥21 using the MASCC risk index scoring system
**Brief (<7d duration) of neutropenia with few comorbidities<ref>Freifeld AG et al. Clinical practice guideline for the use of antimicrobial agents in
**Score ≥21 associated w/ &lt;5% risk for severe complications and mortality &lt;1%
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 ===
===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>
*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"
{| class="wikitable"
| Characteristic  
| '''Characteristic '''
| Points
| '''Points'''
|-
|-
|  
|  
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|-
|-
| No Hypotension (SBP&lt;90)  
| No [[Hypotension]](SBP<90)  
| 5
| 5
|-
|-
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| 4
| 4
|-
|-
| Solid tumor OR no previous fungal infection  
| Solid tumor '''OR''' no previous fungal infection  
| 4
| 4
|-
|-
| No dehydration  
| No dehydration requiring IV fluids
| 3
| 3
|-
|-
| Outpatient status  
| Outpatient status at fever onset
| 3
| 3
|-
|-
| Age &lt;60yr  
| Age <60yr  
| 2
| 2
|}
|}


==Source==
===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]]
 
==References==
<references/>
<references/>


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

Latest revision as of 20:43, 1 February 2021

Background

Neutropenia

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

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])

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

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
    • 20-30cc blood (adult); 3-9cc (child)
    • May take both samples from CVC (if present)
  • Culture any indwelling catheters
  • LP
    • If neuro findings or suspicious
  • Site-specific specimens
  • Stool (if indicated)
  • CXR
  • CT (if necessary)
    • Sinuses
    • Chest
    • A/P
  • Patient should be placed and maintained on neutropenic isolation precautions during there stay in the ED and while in the hospital

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

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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