C-05-07-60629 Fever And Neutropenia Clinical Practice ...

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.