C-05-07-60629 Fever And Neutropenia Clinical Practice ...
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FEVER AND NEUTROPENIA CLINICAL PRACTICE GUIDELINE
DOCUMENT TYPE: GUIDELINE
C-05-07-60629 Published Date: 18-Jun-2020 Page 1 of 5 Review Date: 09-Jun-2023
This is a controlled document for BCCH& BCW internal use only – see Disclaimer at the end of the document. Refer to online version as the print copy may not be current.
Site Applicability
Applicable in all BC Children’s Hospital areas where neutropenic oncology patients are cared for.
Guideline Statements
Fever with neutropenia is a medical emergency. Children with fever and neutropenia require urgent triage, evaluation and treatment. Blood cultures must be collected and antimicrobials must be administered STAT, prior to patient transfer to any other area, within one hour of patient presentation or fever if inpatient.
The clinical pathway below should be followed and the recommendations for empiric antibiotic use should be implemented. Subsequent treatment will also be dictated by the hospital’s infection diseases team and the antibiotic’s sensitivity profile.
The treating pediatric oncologist or (oncologist on call after hours) must be notified when a child on active oncology treatment develops a fever while neutropenic.
This is applicable to patients on antineoplastic agents, allogeneic stem cell transplant patients within 6 months of transplantation or still receiving immunosuppressive agents and patients who have completed cancer therapy but still have a central venous line (CVL) in situ.
Fever in non-neutropenic patients requires blood cultures. If patient is clinically well and there are no focal infections requiring treatment, empiric therapy is not required.
Definitions
In the oncology population, fever is defined as greater than or equal to 38.5ºC oral or temporal. If unable to obtain oral or temporal temperature, axillary temperature greater than or equal to 38ºC is considered a fever. There may be different fever guidelines in patient specific protocols and research studies.
Neutropenia is defined as an absolute neutrophil count (ANC) < 0.5x109 cells/L
ANC is the sum of neutrophils and bands.
FEVER AND NEUTROPENIA CLINICAL PRACTICE GUIDELINE
DOCUMENT TYPE: GUIDELINE
C-05-07-60629 Published Date: 18-Jun-2020 Page 2 of 5 Review Date: 09-Jun-2023
This is a controlled document for BCCH& BCW internal use only – see Disclaimer at the end of the document. Refer to online version as the print copy may not be current.
Guideline
Definition of High Risk Febrile Neutropenia (any of the following criteria):
High Risk Low risk
Diagnosis of :
Acute myeloid leukemia (AML)
Infant acute lymphoblastic leukemia (infantALL)
Relapsed leukemia
Burkitt
Infant brain tumor
Stage 4 neuroblastoma
Relapsed lymphoma/solid tumor with bonemarrow involvement
Aplastic anemia with neutropenia
Patient with Down Syndrome onchemotherapy
Within 6 months post allogeneic stem celltransplant
Chronic GVHD
High risk clinical features:
Hypotension
Respiratory distress or hypoxia or newinfiltrate on chest X-ray
Altered mental status
Suspected typhlitis
Severe mucositis
Previous sepsis in last three months
Evidence of significant local infection (e.g.central line infection, perianal abscess,cellulitis)
ANC < 0.1
Inpatient at the time of fever
There may be other patient specific factors or therapeutic protocols that may constitute high risk categorization
Absence of high risk features
FEVER AND NEUTROPENIA CLINICAL PRACTICE GUIDELINE
DOCUMENT TYPE: GUIDELINE
C-05-07-60629 Published Date: 18-Jun-2020 Page 3 of 5 Review Date: 09-Jun-2023
This is a controlled document for BCCH& BCW internal use only – see Disclaimer at the end of the document. Refer to online version as the print copy may not be current.
High Risk Stable, Low Risk
Init
ial M
an
ag
em
en
t
Evaluation:
Blood cultures from each lumen of central venous catheters
Other cultures as clinically indicated: urine and urinalysis, stool, throat swab, NP swab, CSF, mouth ulcer swab,other apparent sites of infection
CXR only if respiratory symptoms present
CBC and differential, electrolytes, urea, SCr, glucose, CRP
Screen for multi-resistant organisms as per Infection Control policies
Consider Group and Screen
In unstable patients, consider: venous gas, lactate, peripheral coagulation profile
Consider patient’s past medical history of previously cultured organisms, resistance patterns, and antimicrobial use within past three months
Treatment
Piperacillin/tazobactam [if penicillin allergy{anaphylaxis}: cefepime]
Septic shock or admission to ICU : vancomycin+ meropenem + gentamicin
Treatment
If able to reliably tolerate oral route: levofloxacin
Consider outpatient management
For patients who cannot tolerate oral route:Piperacillin/tazobactam [if penicillin allergy{anaphylaxis}: cefepime]
On
go
ing
Ma
na
ge
me
nt
≥2
4 t
o 7
2
hrs
If patient is stable
Do not modify empiric antibacterial regimen based solely on persistent fever in children who are clinically stable
In patients who remain febrile, draw CVL blood cultures no more than once daily
In patients responding to initial empiric antibiotic therapy, continue empiric regimen. In patients who started > 1antibiotic, consider narrowing empiric monotherapy antibiotic as suggested above.
If patient clinically deteriorates, consider requesting an Infectious Diseases consult and modifying empiric regiment:
Add vancomycin (e.g. if suspect skin and skin structure infection, central line infection)
Add gentamicin (e.g. if suspect urosepsis)
Switch piperacillin/tazobactam to meropenem (e.g. if suspect intra-abdominal focus, unstable patients withunknown focus)
If an organism is identified, antibiotics may be tailored as necessary by adding an antibiotic or by changing to another broad-spectrum antibiotic. Broad spectrum coverage should not be narrowed to an organism-specific antibiotic alone in a
neutropenic patient.
≥96
ho
urs
aft
er
init
iati
on
of
em
pir
ic
an
tib
ac
teri
al
the
rap
y
Consider antifungal therapy for patients with persistent fever and/or deterioration Evaluation:
Serum galactomannan weekly
In patients who remain febrile, continue to draw CVL blood cultures no more than once daily. Send blood culturesfor dimorphic fungi (e.g. Histoplasma capsulatum, Blastomyces dermatitidis, Coccidiodes immitis) if clinicallysuspected.
CT chest
Abdominal ultrasound
Consider CT sinus for high risk patients with focal findings (e.g. facial pain)
If imaging features concerning for invasive fungal infection, attempt should be made to obtain BAL, FNA/tissuebiopsy
Empiric Treatment:
Initiate liposomal amphotericin B
If a fungus is identified or imaging results are suggestive of IFI, tailor antifungals as appropriate and refer to “Management of Invasive Fungal Infections in Oncology/HSCT Patients”. If investigations suggest aspergillus, consult ID and consider
starting voriconazole.
Dis
co
nti
nu
ati
on
of
an
tim
icro
bia
ls Discontinue empiric antibiotics in patients who have one negative blood culture at 48 hours, who have been afebrile ≥ 24
hours, and who have evidence of marrow recovery (e.g. ANC > 0.2 and rising, or increasing monocytes)
Consider discontinuing antibiotics after 7 to 14 days in patients with persistent neutropenia who are clinically
well with no focus of infection, and who have been afebrile ≥ 48 hours.
Consider discontinuing empiric antibiotics at 72 hours in patients with one negative blood culture and who have been
afebrile ≥ 24 hours, irrespective of marrow recovery status, as long as careful follow-up is ensured.
FEVER AND NEUTROPENIA CLINICAL PRACTICE GUIDELINE
DOCUMENT TYPE: GUIDELINE
C-05-07-60629 Published Date: 18-Jun-2020 Page 4 of 5 Review Date: 09-Jun-2023
This is a controlled document for BCCH& BCW internal use only – see Disclaimer at the end of the document. Refer to online version as the print copy may not be current.
Algorithm Algorithm
FEVER AND NEUTROPENIA CLINICAL PRACTICE GUIDELINE
DOCUMENT TYPE: GUIDELINE
C-05-07-60629 Published Date: 18-Jun-2020 Page 5 of 5 Review Date: 09-Jun-2023
This is a controlled document for BCCH& BCW internal use only – see Disclaimer at the end of the document. Refer to online version as the print copy may not be current.
References
Lehrnbecher T, Robinson P, Fisher B, Alexander S, Ammann RA, Beauchemin M, et al. Guideline for the Management of Fever and Neutropenia in Children With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: 2017 Update. J Clin Oncol. 2017 Jun 20;35(18):2082–94.
Manji A, Beyene J, Dupuis LL, Phillips R, Lehrnbecher T, Sung L. Outpatient and oral antibiotic management of low-risk febrile neutropenia are effective in children—a systematic review of prospective trials. Support Care Cancer. 2012 Jun;20(6):1135–45.
Robinson PD, Lehrnbecher T, Phillips R, Dupuis LL, Sung L. Strategies for Empiric Management of Pediatric Fever and Neutropenia in Patients With Cancer and Hematopoietic Stem-Cell Transplantation Recipients: A Systematic Review of Randomized Trials. J Clin Oncol. 2016 Jun 10;34(17):2054–60.
Sung L, Manji A, Beyene J, Dupuis LL, Alexander S, Phillips R, et al. Fluoroquinolones in Children With Fever and Neutropenia: A Systematic Review of Prospective Trials. Pediatr Infect Dis J. 2012 May;31(5):431–5.
Version History DATE DOCUMENT NUMBER and TITLE ACTION TAKEN
16-Jul-2020 C-05-07-60629 Fever And Neutropenia Clinical Practice Guideline
Approved at: Pharmacy Therapeutics & Nutrition Committee
09-Jun-2020 “ Approved at: Pharmacy, Therapeutics & Nutrition Committee
Disclaimer This document is intended for use within BC Children’s and BC Women’s Hospitals only. Any other use or reliance is at your sole risk. The content does not constitute and is not in substitution of professional medical advice. Provincial Health Services Authority (PHSA) assumes no liability arising from use or reliance on this document. This document is protected by copyright and may only be reprinted in whole or in part with the prior written approval of PHSA.
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