Ell Children S Medical Center Evidence-based Outcomes Center

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Ell Children S Medical Center Evidence-based Outcomes Center

Transcript Of Ell Children S Medical Center Evidence-based Outcomes Center

ELL CHILDREN’S MEDICAL CENTER EVIDENCE-BASED OUTCOMES CENTER

ONCOLOGY MANAGEMENT OF FEBRILE NEUTROPENIA GUIDELINE PRIMARY USE: HEMATOLOGY/ONCOLOGY & INFECTIOUS DISESASES

LEGAL DISCLAIMER: The information provided by Dell Children’s Medical Center of Texas (DCMCT), including but not limited to Clinical Pathways and Guidelines, protocols and outcome data, (collectively the "Information") is presented for the purpose of educating patients and providers on various medical treatment and management. The Information should not be relied upon as complete or accurate; nor should it be relied on to suggest a course of treatment for a particular patient. The Clinical Pathways and Guidelines are intended to assist physicians and other health care providers in clinical decision-making by describing a range of generally acceptable approaches for the diagnosis, management, or prevention of specific diseases or conditions. These guidelines should not be considered inclusive of all proper methods of care or exclusive of other methods of care reasonably directed at obtaining the same results. The ultimate judgment regarding care of a particular patient must be made by the physician in light of the individual circumstances presented by the patient. DCMCT shall not be liable for direct, indirect, special, incidental or consequential damages related to the user's decision to use this information contained herein.

Definition: Febrile neutropenia (FN) is defined as a period in which a patient with cancer is at increased risk of infectious complications and antimicrobial therapy is necessary. Neutropenia is defined as an absolute neutrophil count (ANC) less than 500/mm3 or expected decline to less than 500/mm3 in 48 hours. Fever is defined as a single oral or axillary temperature greater than 38.3°C (101°F) or two oral or axillary temperatures greater than 38.0°C (100.4°F) in one hour.1-4
Incidence: FN remains a frequent cause of hospitalization in children treated for cancer. With good supportive care, mortality during FN is now of the order 1–3%. Less than 50% of children show a clinical or microbiological focus of infection during FN and the incidence of severe adverse outcomes such as intensive care admission and death is low. Thus the focus of care has shifted to management by risk stratification, potentially allowing a reduction in the intensity and/or duration of therapy in low risk patients.5
Etiology: The etiology of febrile neutropenia episodes may be noninfectious, bacterial, viral, or fungal. The most common gram positive bacterial pathogens include staphylococci spp., viridans streptococci, and enterococci spp.. The most common gram negative bacterial pathogens include E. coli and P. aeruginosa. Anaerobic bacteria are less commonly isolated. The most common fungal pathogens are Candida spp. and Aspergillus spp.. Mucormycosis group are other fungal pathogen isolated less frequently. The most common viral pathogens include respiratory pathogens and those causing gastroenteritis.3,6

Guideline Inclusion Criteria: Patients with a cancer diagnosis presenting in an outpatient clinic, emergency department, or hospitalized with the following symptoms:
1) Fever is defined as a single oral or axillary temperature greater than 38.3°C (101°F) OR two oral or axillary temperatures greater than 38.0°C (100.4°F) in one hour.
2) Neutropenia defined as ANC < 500/mm3 or expected decline to < 500/mm3 in the next 48 hours as determined by the treating oncologist.
3) Actively receiving treatment or within 6 months of completing treatment for the cancer diagnosis
Guideline Exclusion Criteria: • Patients with diagnosis of aplastic anemia due to no expected bone marrow recovery within a reasonable time period. • Acquired or congenital bone marrow failure syndrome (e.g. Diamond-Blackfan anemia, congenital neutropenia including Kostmann syndrome, Fanconi anemia, Shwachman-Diamond syndrome). • Lack of oncology diagnosis (i.e. viral suppression)

Diagnostic Evaluation:1-4

The evaluation of children with fever and neutropenia needs to be complete and completed as quickly as possible.

Blood cultures obtained during the evaluation of fever and

neutropenia are important. Most pediatric patients

Urinalysis and urine culture should be considered if able to

undergoing chemotherapy treatment have indwelling

obtain a clean catch specimen (non-catheterized), before

intravenous catheters; it is essential to obtain a blood culture

initiation of antibiotics. However, urine collection should not

from every lumen of the central venous line (CVL). Consider

delay treatment.

obtaining a peripheral blood culture at the same time. Blood

cultures should be obtained at the time of presentation and

Chest radiography should be considered for children with

approximately every 24 hours with persistent fever and/or positive blood cultures.7,8

fever and neutropenia who have respiratory symptoms.

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ELL CHILDREN’S MEDICAL CENTER EVIDENCE-BASED OUTCOMES CENTER
Viral swabs, stool tests and wound cultures should be guided by presenting symptoms.
Comprehensive metabolic panel (CMP) and complete blood count (CBC) should be obtained, at the time of presentation for every patient. Antibiotic therapy should not be delayed while awaiting results.

History: Assess for1-4 • Date of last chemotherapy treatment and details of therapy. • Onset of fever and highest temperature, history of preceding low grade fever. Use of antipyretics. • Other symptoms as diarrhea, nausea, vomiting, pain (oral, abdominal, rectal), rash, drainage, cough, rhinorrhea. • Prior history of infections, organism cultured and site of infection. • Previous history of infection methicillin-resistant staphylococcus aureus (MRSA) or multi-drug resistant organism (MDRO).
Physical Examination:1-4 • Assess for signs and symptoms of shock. Review vital signs. • Detailed exam of entire body looking for signs and symptoms of local infection. • Examine CVL site for evidence of redness or drainage.
Imaging Tests: On admission:1-4
• Obtain chest radiography (CXR) in patient with respiratory symptoms.
• Obtain abdominal ultrasound (US) in patient with abdominal pain.
Persistent fever (fever duration ≥ 96 hours) or recurrent fever (new fever after 24-48 afebrile period) while recovering from neutropenia:15-19
• Consider chest computed tomographic scan (CT) after one week (7 days) of empiric antimicrobial therapy with persistent daily fevers.5
• Consider abdominal CT scan in patient with recurrent fever when recovering from neutropenia.5
• Do not recommend pelvic CT scan as it is not generally valuable diagnostically given the risks associated with additional radiation exposure.

Laboratory Tests:1-4 • If CVL in place, obtain blood culture at onset of fever from all lumens. • Consider peripheral-blood cultures concurrent with obtaining CVL cultures. • Obtain a CMP and CBC. • Consider urinalysis and urine culture, if able to obtain clean catch (non-catheterized specimen). • Consider respiratory studies in symptomatic patients: nasal wash for respiratory studies by rapid antigen, DFA, and/or PCR, throat swab. • Consider stool studies in symptomatic patients: bacterial, viral studies or clostridium difficile testing. • Do not use β-D Glucan assay (Fungitell®) for prospective monitoring of invasive fungal disease.13,14 • If completed, obtain galactomannan testing in bronchoalveolar lavage (BAL) and cerebrospinal fluid in patients at high risk for invasive fungal disease in symptomatic patients.

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Critical Points of Evidence

Evidence Supports Blood cultures obtained during the evaluation of fever and neutropenia. If an indwelling intravenous catheter is present it is essential to obtain a blood culture from every lumen of the CVL.1-4
Use of antipseudomonal B-lactam monotherapy as empiric therapy in febrile neutropenic patients.1-4, 20
No change to empiric antibiotics in patients who are clinically stable with persistent fever.1-4,21,22
Initiation of empiric antifungal therapy in patients at high risk of invasive fungal disease experiencing persistent or recurrent fever ≥ 96 hours despite broad spectrum antibiotic therapy with an unclear etiology.1-4

Evidence Lacking/Inconclusive Consider not using serum Galactomannan.3
Optimal timing of imaging of chest or abdomen in patients with persistent or recurrent fever with neutropenia.1-4, 15-19
Optimal timing to discontinue or de-escalate empiric antibiotics in high risk febrile neutropenia episode patients.33-
40
When to initiate antifungal therapy and which antifungal agent to select in patients at low risk of invasive fungal disease.1-4,41-42
Optimal timing to discontinue empiric antifungal therapy.1-4,41-
42

Management of patients experiencing low risk febrile
neutropenia episodes in the outpatient setting without evidence of bone marrow recovery with oral antibiotics.23-32

Evidence Against
Routine use of pelvic CT in patients with persistent and recurrent fever with neutropenia.1-4,15-19

Routine use β-D Glucan assay (Fungitell®) for prospective monitoring of invasive fungal disease in all patients.1-4,13,14

Practice Recommendations and Clinical Management
ADMISSION AND DISCHARGE CRITERIA FOR LOW AND HIGH RISK FEBRILE NEUTROPENIA EPISODES
1) Any cancer patient experiencing a febrile neutropenia episode will be admitted to the hospital for intravenous antibiotics for a minimum of 36 hours. If already admitted, intravenous antibiotics will be continued for a minimum of 36-48 hours.5 (Strong recommendation, moderate-quality evidence)
2) Utilize a risk stratification strategy to identify patients at low and high risk of infectious complications (i.e. bacteremia, significant bacterial infection) that includes patient-specific factors, treatment-specific factors, and episode-specific factors which can be assessed by providers at the time of presentation. Patients with one or more patient-specific factors, treatment-specific factors, and/or episode-specific factors are considered a high risk febrile neutropenia episode. Patients without any patient-specific factors, treatment-specific factors, and/or episode-specific factors are considered to be a low risk febrile neutropenia episode.1-5 (Strong recommendation, low-quality evidence) • Patient-specific factors include age and diagnosis of Trisomy 21. • Treatment-specific factors include cancer associated co-morbidities that put patients at a higher risk of prolonged neutropenia and risk of infection. • Episode-specific factors include medical conditions at the time of presentation or signs/symptoms of a focal infection that put patients at a higher risk of infection.
3) All patients/families must meet the eligibility criteria prior to being discharged, demonstrate understanding of outpatient followup instructions, and have antibiotic prescriptions in-hand prior to discharge, if applicable.1-4 (Strong recommendation, low-quality evidence)

Low Risk Febrile Neutropenia Episode1-5,23-40

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4) Patients meeting low risk criteria and without evidence of a focal infection can be considered for early discharge with or without oral antibiotics if well-appearing, resolution of fever for ≥ 24 hours, and blood culture is negative for minimum 36-48 hours. • If patients have evidence of bone marrow recovery defined as an ANC > 500/mm3 or at least two consecutive increasing ANC values with last ANC > 100/mm3 then upon discharge no oral antibiotic is necessary. Studies have shown an acceptable low risk of fever reoccurrence and bacterial infection (less than 5%) when utilizing an ANC cutoff of 100/mm3 and/or criteria to define a rise in ANC; however this relies heavily on careful selection of factors considered as low risk febrile neutropenia episodes • If there is no evidence of bone marrow recovery then patients should receive an oral antibiotic upon discharge to be taken until there is evidence of bone marrow recovery. (Strong recommendation, moderate-quality evidence)
5) Patients meeting low risk criteria that do not meet criteria for early discharge (i.e. clinically deteriorate/ill-appearing, remain febrile, and/or blood cultures become positive) and/or are found to have a focal infection no longer meet criteria for low risk and should be managed as a high risk patient. (Weak recommendation, very low-quality evidence)
High Risk Febrile Neutropenia Episode 6) Patients meeting high risk criteria should be assessed at admission for signs and symptoms of focal infection or medical conditions
that may require an additional or alternative antimicrobial therapy. (Strong recommendation, moderate-quality evidence)
7) Patients meeting high risk criteria and experience resolution of fever in less than 96 hours should continue intravenous antibiotics until evidence of bone marrow recovery, negative blood cultures at 48 hours, afebrile for at least 24 hours, and/or completion of defined duration of therapy, if focal infection documented. (Strong recommendation, low-quality evidence)
8) Patients meeting high risk criteria who do not experience resolution of fever in less than 96 hours should expand antimicrobial coverage to include fungal pathogens and antibiotic therapy be assessed for any necessary changes. (Strong recommendation, moderate-quality evidence)

LABORATORY TESTING1-5
1) Obtain blood cultures at the onset of fever from all lumens of a CVL.

(Strong recommendation, low-quality evidence)

2) Consider obtaining peripheral blood cultures when obtaining cultures from a CVL. (Weak recommendation, low-quality evidence)

3) Consider obtaining a urinalysis (UA) and urine culture in patients in which a clean-catch or midstream specimen is possible. No in/out catheter specimens should be obtained. (Weak recommendation, low-quality evidence)

4) Do not use β-D Glucan (Fungitell®) testing for prospective monitoring of invasive fungal disease.13,14 (Strong recommendation, low-quality evidence)

5) If completed, obtain galactomannan testing in BAL and cerebrospinal fluid in patients at high risk for invasive fungal disease in symptomatic patients. (Weak recommendation, low-quality evidence)

IMAGING1-5
1) Consider obtaining a CXR in symptomatic patients. It has been shown that a CXR in asymptomatic children will show pneumonia in less than 5% of the cases. (Strong recommendation, moderate-quality evidence)

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2) Consider CT of the lungs and/or targeted imaging (CT or US of abdomen) of other suspected areas in patients with persistent fever for ≥ 96 hours despite broad spectrum antibiotic therapy or new fever in the context of persistent neutropenia for evaluation of invasive fungal disease.15-19 (Strong recommendation, moderate-quality evidence)
3) Consider obtaining ENT consultation for nasal endoscopy in patients with persistent fever for ≥ 96 hours despite broad spectrum antibiotic therapy for evaluation of invasive fungal disease.15-19 (Weak recommendation, low-quality evidence)
ANTIBIOTIC MANAGEMENT1-4, 20,45-54
1) Cefepime monotherapy is the recommended first line agent for empiric antibiotic therapy in patients experiencing a febrile neutropenia episode because it provides the most optimal coverage of common and virulent pathogens such gram negative organisms (i.e. Pseudomonas aeruginosa) and viridans group streptococci based on local resistance data. ➢ A retrospective review of DCMCCT oncology patients with blood cultures positive for viridans group streptococci identified 8 patients and 5 of the 8 isolates were resistant to piperacillin-tazobactam whereas only 2 of the 8 isolates were resistant to cefepime. Viridans group streptococci shows more favorable susceptibility to cefepime. ➢ Overall based on 2013-2014 antibiogram data cefepime shows more favorable susceptibility than piperacillintazobactam for common gram negative pathogens. • E. coli: cefepime 100% susceptible and piperacillin-tazobactam 98% • Klebsiella spp.: cefepime 100% susceptible and piperacillin-tazobactam 93-95% • Serratia marcescens: cefepime 89% susceptible and piperacillin-tazobactam 70% • Enterobacter spp.: cefepime 99% susceptible and piperacillin-tazobactam 85% • Pseudomonas aeruginosa: cefepime 85% susceptible and piperacillin-tazobactam 91%. Cefepime is more favorable when comparing blood isolates, 22 patients identified and only 95% susceptible to piperacillintazobactam whereas 100% susceptible to cefepime. ➢ Vancomycin is not recommended as part of empiric therapy if patient is hemodynamically stable/well-appearing and gram positive bacteria is not documented or strongly suspected. No benefit (i.e. mortality, time to defervescence) has been identified if no microbiologically or clinically defined gram positive infection at time of vancomycin initiation. Additionally local data does not suggest a high prevalence of pathogens requiring vancomycin (e.g. MRSA, viridans group streptococci) to warrant inclusion in empiric regimens at this time. The risks of unnecessary vancomycin therapy include emergence of vancomycin resistant enterococcus and toxicity. (Strong recommendation, high-quality evidence)
2) Consider adding metronidazole for any patient (low or high risk) experiencing abdominal pain, mucositis, perirectal abscess, colitis, and/or signs and/or symptoms consistent with typhlitis for anaerobic activity is recommended; unless patient is already receiving an antibiotic with anaerobic activity such as meropenem or piperacillin-tazobactam. Recommend enteral route for suspected C. difficile infection. (Strong recommendation, low-quality evidence)
3) If at any time a patient experiences hemodynamic instability the addition of vancomycin for gram positive organism coverage and tobramycin for gram negative organism coverage is recommended. Tobramycin is preferred over gentamicin based on local resistance data among gram negative organisms (e.g. Pseudomonas aeruginosa, E. coli, Serratia spp.). (Strong recommendation, low-quality evidence)
4) If at any time a patient’s blood cultures becomes positive for a gram positive organism the addition of vancomycin is recommended. (Strong recommendation, low-quality evidence)
5) If at any time a patient’s blood cultures becomes positive for a gram negative organism the addition of tobramycin is recommended. Tobramycin is preferred over gentamicin based on local resistance data among gram negative organisms (e.g. Pseudomonas aeruginosa, E. coli, Serratia spp.). (Strong recommendation, low-quality evidence)

6) In patients whose coverage was expanded to include vancomycin and/or tobramycin for double coverage and the patient is hemodynamically stable/well-appearing with no microbiologic resistance documented to justify continuation and/or blood

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cultures negative at least 36-48 hours, may consider discontinuing vancomycin and/or tobramycin. Continuation of double gram negative coverage or vancomycin has not demonstrated improved clinical outcomes, whereas increased adverse effects have been documented.
(Strong recommendation, moderate-quality evidence)
7) Empiric antibiotics should not be modified in clinically stable patients (i.e. no respiratory distress, hemodynamically stable, no focal findings on physical exam, normal neurologic status) based solely on persistent fever. (Strong recommendation, low-quality evidence)
8) If a patient has a serious allergy to cephalosporins AND anaphylaxis to penicillin ➢ If a patient has a serious allergy to cephalosporins AND anaphylaxis to penicillin • If a patient is hemodynamically stable/well-appearing then aztreonam and vancomycin are recommended for adequate coverage of gram negative and gram positive pathogens. The addition of vancomycin is necessary because aztreonam only provides coverage for gram negative pathogens. • If a patient is hemodynamically unstable/ill-appearing then meropenem and vancomycin are recommended. ➢ If a patient has a Cephalosporin allergy only, then (Zosyn) piperacillin/tazobactam. Add vancomycin if hemodynamically unstable ➢ If a patient has anaphylaxis to penicillin only then Cefepime. Add vancomycin if hemodynamically unstable
(Strong recommendation, moderate-quality evidence)
9) Low risk febrile neutropenia episode patients that meet criteria for early discharge with no evidence of bone marrow recovery may be discharged on oral ciprofloxacin to be taken until evidence of bone marrow recovery. (Strong recommendation, moderate-quality evidence)
10) High risk febrile neutropenia episode patients should continue antibiotic therapy until evidence of bone marrow recovery (ANC > 500/mm3 or at least 2 consecutive increasing ANC values and last ANC > 100/mm3). Antibiotics may be adjusted for focal infection. (Strong recommendation, moderate-quality evidence)
ANTIFUNGAL MANAGEMENT1-4,41,42
1) Patients experiencing persistent or recurrent fever for ≥ 96 hours despite broad spectrum antibiotic therapy with an unclear etiology should receive empiric antifungal therapy based on their antifungal risk category. ➢ High risk of invasive fungal disease: AML, relapsed AML/ALL, receiving intensive chemotherapy regimens likely to cause prolonged neutropenia (i.e. >7-10 days), or allogenic HSCT ➢ Low risk of invasive fungal disease: all other patients not meeting the high risk criteria (i.e. standard risk ALL, lymphoma, solid tumors) (Strong recommendation, moderate-quality evidence)
2) High risk of invasive fungal disease patients experiencing persistent or recurrent fever ≥ 96 hours despite broad spectrum antibiotic therapy with an unclear etiology should initiate liposomal amphotericin B. (Strong recommendation, low-quality evidence)
3) Low risk of invasive fungal disease patients experiencing persistent or recurrent fever ≥ 96 hours despite broad spectrum antibiotic therapy with an unclear etiology should consider initiation of micafungin. (Weak recommendation, low-quality evidence)
4) Empiric antifungal therapy should be continued in the absence of documented or suspected invasive fungal diseases until patient experiences bone marrow recovery. (Weak recommendation, low-quality evidence)

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Consults/Referrals: • Consider Infectious Disease consultation in high risk febrile neutropenic patients with persistent symptoms/fever and patients with MDRO organisms. • Consider ENT consultation in high risk febrile neutropenic patients with signs or symptoms of sinusitis. • Consider surgical consultation if nodular lesions amendable to biopsy are present.
Patient Disposition Discharge Criteria for Low Risk Patients:23-40
• Patient and family must meet eligibility criteria: o Current admission is not a readmission after previous discharge as a “Low Risk” patient. o Family must live within 1 hour radius of Dell Children’s Medical Center of Central Texas. o Family is reliable and will call for recurrent fever, worsening condition, or with any concerns. o Family has telephone access. o Family has adequate transportation to return to clinic for appointments and for any new fever. o Age ≥ 1 year. o Afebrile ≥ 24 hours. o Blood cultures negative for at least 36-48 hours.7,8,43,44 o Patient is well appearing (i.e. normal vital signs for at least 12 hour prior to discharge). o No high risk cancer-associated co-morbidity, medical condition, or focal infection. Exclusion criteria as follows: ▪ Diagnosis of Trisomy 21 ▪ AML, Infant ALL, ALL at diagnosis/relapse < 28 days, ALL not in remission > 28 days, Intensive B-NHL/relapse Leukemia protocol, and Intensive chemotherapy regimens likely to cause prolonged neutropenia, > 7-10 days. ▪ Hypotension, shock, hemorrhage, dehydration, or organ failure. ▪ Changes in respiratory status (e.g. hypoxia, distress, compromise, pneumonitis). ▪ New onset abdominal pain, mucositis (requiring IV narcotics, unable to tolerate PO), or perirectal/other soft tissue abscess. ▪ Altered mental status, neurological changes, or irritability/meningism. ▪ Current or history of ICU admission with FN episode.
• Outpatient antibiotic therapy, ciprofloxacin, is recommended if patient does not have evidence of bone marrow recovery at time of discharge. Bone marrow recovery defined as an ANC > 500/mm3 or at least two consecutive increasing ANC values AND last ANC > 100/mm3. o If antibiotic therapy is necessary patient must be able to tolerate oral antibiotic(s). o If antibiotic therapy is necessary then family/caregiver must have the home antibiotics in hand prior to discharge. It is preferred to have the antibiotics filled at Seton Central Outpatient Pharmacy (SCOP). o Oral antibiotic is recommended to be taken until patient demonstrates evidence of bone marrow recovery.
• Parent information sheet must be given to family and reviewed with them. • Documentation by provider in the medical record that the parent information sheet was given and reviewed, that patient
meets eligibility criteria, and the antibiotics have been given to family. • First follow-up appointment must be scheduled and entered in patient’s depart plan. • Email must be sent to hemeonc.signout informing nursing and clinic staffs of patient’s discharge and plan for close outpatient
follow up.
Follow-Up Care for Low Risk Patients Meeting Early Discharge Criteria: • The patient should have daily telephone or clinic follow-up. Twice per week follow up should be planned in the Children’s Blood and Cancer Center (CBCC) clinic (with labs/exam). Remaining 5 days should include telephone follow-up. • Telephone follow up on weekdays will include call by clinic nurse during the weekday. Weekend telephone follow up with be from the on-call NP. All calls should be made prior to 2pm.

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Discharge Criteria for High Risk Patients: • Must have evidence of bone marrow recovery. • Parent information sheet must be given to family and reviewed with them. • Family has telephone access. • Family has adequate transportation to return to clinic for appointments and for any new fever. • Afebrile ≥ 24 hours. • Blood cultures negative for at least 36-48 hours.7,8,43,44 • Patient is well appearing (i.e. normal vital signs for at least 12 hour prior to discharge). • If patient to be discharged on oral or intravenous antibiotics then family/caregiver(s) must receive the appropriate education and training. o If oral antibiotic therapy then patient must be able to tolerate oral antibiotic(s). o If oral antibiotic therapy is necessary then family/caregiver must have the home antibiotics in hand prior to discharge. It is preferred to have the antibiotics filled at Seton Central Outpatient Pharmacy (SCOP). • First follow-up appointment must be scheduled and entered in patient’s depart plan. • Email must be sent to hemeonc.signout informing nursing and clinic staffs of patient’s discharge.

Guidelines for Readmission: • Recurrent fever (Fever is defined as a single oral or axillary temperature greater than 38.3°C (101°F) or two oral or axillary temperatures greater than 38.0°C (100.4°F) in one hour). • New exam findings for focal infection. • Not tolerating or not adherent to oral antibiotics. • Respiratory distress. • Non-adherence to phone or clinic follow-up. • Blood culture turns positive. • Physician concern.

Prevention: • Parent information sheet to be provided at discharge which includes guidelines for when they should call, antibiotic administration guidelines, required outpatient follow up, and instructions for home temperature checks. • Family to be given thermometer at discharge. • Family to check temperature 2-3 times per day at home and any time they suspect a temperature. • If patient has a fever they will return immediately to CBCC outpatient clinic or ER for DCMCCT readmission.

Outcome Measures: • Readmission rate and reason for readmission (i.e. fever, documented infection) • Antimicrobial utilization (inpatient, outpatient) • Hospital duration and cost • Antibiotic-related adverse effects (i.e. superinfection, therapy limiting side effects, resistance)

Addendums: 1. Antimicrobial Dosing Guide for Febrile Neutropenia 2. Outpatient Management for Low Risk Febrile Neutropenia

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Criteria for High Risk Febrile Neutropenia Episode  Age < 1 year  Diagnosis of Trisomy 21 Cancer associated co-morbidities  AML  Infant ALL  ALL at diagnosis/relapse < 28 days or not yet in remission  ALL not yet in remission  Intensive B-NHL/relapse Leukemia protocol Medical conditions  Evidence of Focal Infection  Hypotension, shock, hemorrhage, dehydration, or organ failure  Changes in respiratory status (i.e. hypoxia, distress, compromise, pneumonitis)  New onset abdominal pain, mucositis (requiring IV narcotics, unable to tolerate PO), or perirectal/other soft tissue abscess  Altered mental status, neurological changes, or irritability/ meni ng ism Other  Readmission after discharge as “Low Risk” patient 1
High Risk of Invasive Fungal Disease  AML  High Risk ALL  High Dose Steroids  Relapsed ALL/AML  Allogenic HSCT
2

No Outpatient

Yes

Antibiotic Therapy

Early Discharge Criteria for Low Risk Patients  Caregivers demonstrate understanding of
outpatient follow-up instructions  Antibiotic prescription is filled and delivered
prior to discharge or easily accessible by caregivers immediately after discharge  Lives within 1 hour and no social concerns

Febrile Neutropenia Pathway Hematology & Oncology Patients Evidence Based Outcome Center
Inclusion Criteria (Clinic, Emergency Department, or Hospitalized patients)  Fever defined as oral or axillary temperature > 101°F (38.3ºC) once OR two temperatures > 100.4°F (38.0ºC) in a 1 hour period  Neutropenia defined as ANC < 500/mm3 or expected decline to < 500/mm3 in the next 48 hours  Actively receiving treatment or within 6 months of completing treatment for the cancer diagnosis
 Always admit patient and begin intravenous antibiotics for minimum 36-48 hours, initiate Cefepime Consider additional or alternative antibiotic if known history of resistant pathogen or allergy (Refer to Addendum 1 for additional antibiotic guidance)  Obtain blood culture from all lumens of central venous catheter (CVC)  Consider peripheral blood culture when obtaining culture from CVC
Sepsis Pathway

No

Meets Criteria for High Risk? u Yes

Develops evidence focal Infection?

of

u

NO

Meets Criteria for Early Discharge? Criteria:  Well appearing  Afebrile ≥ 24 hours  Blood culture negative ≥ 36-48 hours
Yes

Evidence of Bone Marrow Recovery: ANC > 500/mm3 OR
At least 2 consecutive increasing ANC values AND last ANC > 100/mm3

No

Outpatient Oral Antibiotic Therapy First Line Antibiotic: Ciprofloxacin To be taken until evidence of bone marrow recovery

Febrile Neutropenia YES If clinicAanlltyibsitoabtilceM, eamnpaigreicmtehenrtaGpuyisdheoliunledsnot be
changed based on persistent fever alone

Fev Yes
Evidence of Bone Marrow Recovery: ANC > 500/mm3 OR
At least 2 consecutive increasing ANC values AND last ANC > 100/mm3
No Yes

Discontinue anti-infectives and/or
De-escalate for focal infection

Continue until evidence of bone marrow recovery

Discharge (Refer to Addendum 2 for
Outpatient Follow-up Instructions)

For questions concerning this pathway, Click Here
Last Updated August 1st, 2019

EXCLUSION CRITERIA  Aplastic Anemia (due to no expected
bone marrow recovery)  Bone Marrow Failure Syndrome
(acquired/congenital)  Lack of oncology diagnosis (i.e. viral
supression)

ALERT!
Refer to addendum 1 for antibiotic guid an ce if patien t experiences clinical deterioration, hemodynamic instability, new fever, diagnosed with focal infection, or blood cultu re becomes positive.
Febrile Neutropenia Antibiotic Management Guidelines

Clinically unstable or new findings:
Assess current Antibiotics Febrile Neutropenia Antibiotic
Management Guidelines

High Risk of Invasive
Fungal Disease? v

YES
ADD liposomal Yes amphotericin B
Or micafungin

No
Antifungals not routinely
recommended

Fever Resolves in < 96 hours?
No
Manage Off Pathway Consider ID Consult

ALERT!
Assess antibiotics if patient experiences clinical deterioration,
hemodynamic instability, diagnosed with focal infection, or blood culture becomes positive.

Start Meropenem

And

NO

Vancomycin

Febrile Neutropenia Antibiotic Management Guidelines Hematology & Oncology Patients

High Risk Febrile Neutropenia Episode OR
Low Risk Febrile Neutropenia Episode Not Meeting Criteria for Early Discharge

Is the Patient Hemodynamically
Stable?
YES
Start Aztreonam And
Vancomycin

Cephalosporin Allergy?

NO Continue Cefepime*

YES

YES

Anaphylactic Penicillin Allergy?

NO Piperacillin/ Tazobactam

Is abdominal pain, mucositis, perirectal abscess, colitis, and/or typhlitis present?

YES

NO

ADD Metronidazole *Not needed if on piperacillin/tazobactam*

Continue Current Therapy

Clinically Stable

 No respiratory distress

 Hemodynamicaly stable

 No focal findings on physical exam

 Normal neurologic status

1

Is the Patient Hemodynamically
Stable?

ADD Vancomycin

NO

And

ADD Tobramycin

YES

Culture Positive for

NO

Culture Positive for

YES

Gram Positive?

Gram Negative?

YES

YES

ADD Vancomycin (if not already receiving)

ADD Tobramycin (if not already receiving)

Blood Culture Positive?

If clinically stable, empiric therapy should not be
NO changed based on persistent fever alone u

De-escalate Therapy Based on Susceptibilities And
Complete Appropriate Duration of Therapy Based on Site/Source of Infection

Febrile Neutropenia Pathway

For questions concerning this pathway, Click Here
Last Updated August 1st, 2019

* if patient has penicillin allergy cefepime can be used*
EvidenceRiskFeverPatientsRecommendation