FEBRILE NEUTROPENIA

Dr MOHD SHAFI MOONA

KING ABDULLAH MEDICAL CITY

DEFINITION OF NEUTROPENIA

• Neutropenia: absolute neutrophil count (ANC) <1000 per μL

• Severe neutropenia: ANC <500 per μL • Profound neutropenia: ANC <100 per μL

DEFINITION OF FEBRILE NEUTROPENIA

• Fever: Single oral temperature ≥38.3°C or persistent temperature ≥38.0 °C for >1 hour.

RISK ASSESSMENT

• High Risk patients: Anticipated prolonged neutropenia (>7 days) ANC <500 cells/mm3 Significant medical comorbidities.Low risk patients are eligible for oral empirical therapy

• Can use Multinational Association for Supportive Care in Cancer (MASCC) score: MASCC >21 = low risk; may be eligible for oral/outpatient empirical antibiotic treatment MASCC<21= high risk; need inpatient hospitalization

MULTINATIONAL ASSOCIATION FOR SUPPORTIVE CARE IN CANCER (MASCC) SCORING SYSTEM

• To Identify Patients with Cancer and Febrile Neutropenia at Low Risk of Medical Complications.

• Maximum score is 26.• Scores ≥21 indicate a low risk for medical

complications.

THE MULTINATIONAL ASSOCIATION FOR SUPPORTIVE CARE IN CANCER INDEX SCORE

• Characteristic Point score

• Burden of illness: • No or mild symptoms 5• Moderate symptoms 3• No hypotension 5• No chronic obstructive pulmonary disease 4• Solid tumor or no previous fungal infection in hematologic• tumor 4• No dehydration 3 • Aged < 60 years 2

DEFINITION OF HIGH RISK PATIENTS•MASCC score < 21 •Severe neutropenia (ANC ≤ 500 cells/mm3) anticipated to extend > 7 days •Presence of any co-morbid medical problem including but not limited to: Hemodynamic instability Oral or GI mucositis that interferes with swallowing or causes severe

diarrhea. GI symptoms, including abdominal pain, nausea and vomiting, or diarrhea. Neurologic or mental status changes of new onset. Intravascular catheter infection, especially catheter tunnel infection. New pulmonary infiltrate or hypoxemia, or underlying chronic lung.

disease •Evidence of hepatic insufficiency : Aminotransferase levels > 5 x ULN •Evidence of renal insufficiency: Creatinine clearance of < 30 mL/min

TALCOTT’S GROUPS FOR STRATIFYING RISK OF MEDICAL COMPLICATIONS FROM FN

•Group 1: inpatients at onset of FN •Group 2: outpatients with a serious acute comorbidity

(defined as a medical condition other than FN requiring inpatient observation or therapy)

•Group 3: outpatients with uncontrolled cancer (defined as leukemia not in CR or, for other malignancies, progressive disease despite chemotherapy or other evidence of treatment failure)

•Group 4: outpatients without serious comorbidity or uncontrolled cancer (thus at low risk for medical complications from FN)

DURATION OF ANTIBIOTIC THERAPY

• Minimum 1 week of therapy if• Afebrile by day 3• Neutrophils >500/mm3 (2 consecutive days)• Cultures negative• Low risk patient, uncomplicated course

• > 1 week of therapy based if• Temps slow to settle (>3 days)• Continue for 4-5 days after neutrophil recovery (>500/mm3 )

• Minimum 2 weeks• Bacteraemia, deep tissue infection• After 2 weeks if remains neutropenic (< 500/mm3), but afebrile, no disease

focus, skin intact, no catheter site infection, no invasive procedures or ablative therapy planned. Stop antibiotics and observe.

ANTIBIOTIC SELECTION

• INITIAL REGIMEN: First line treatment is gram negative antibiotic that covers pseudomonas.Antipseudomonal monotherapy: cefepime,

meropenem, imipenem.

EMPIRIC GRAM (+) COVERAGE

• Vancomycin is not recommended as part of initial therapy unless you suspect:

• Catheter related infection• Soft tissue/skin infection• Pneumonia• Hemodynamic instability• Positive blood cultures• MRSA colonization

ANAEROBIC TREATMENT

• Specific anaerobic coverage not included in initial empiric therapy unless you suspect:• necrotizing mucositis• Sinusitis• periodontal cellulitis• perirectal cellulitis• intraabdominal infection• pelvic infection

ANTI-FUNGAL TREATMENT

• Not included in initial empiric coverage• Persistent fevers after 4-7 days in high risk patients

without clearly defined source.• Candida is most common organism.• Amphotericin, caspofungi, voriconazole,

itraconazole

MODIFYING YOUR ANTIBIOTIC REGIMEN

• No need to modify initial coverage if only persistent fever in a patient who is hemodynamically stable

• If vancomycin or empiric gram positive was started, may be stopped after 2-3 days if no evidence of gram positive infection

• If patient is hemodynamically unstable after initial empiric treatment, increase to cover gram positive, anaerobes, and fungi.

WHEN TEMPERATURES DO NOT GO AWAY

• Non-bacterial infection (eg fungal, viral)• Bacterial resistance to first line therapy (MRSA)• Slow response to drug in use• Superinfection• Inadequate dose• Drug fever• Abscess or catether related infectiona.• Disease-related fever

HOW LONG TO GIVE ANTIBIOTICS

• With clinically or microbiologically diagnosed infection, treat for full course of the infection

• In unexplained fever, continue antibiotics for the duration of neutropenia until ANC >500.

ASCO’S GUIDELINE

• ASCO’s guideline on hematopoietic colony-stimulating factors recommends primary prophylaxis for patients receiving chemotherapy regimens associated with ≥20% risk for fever & neutropenia (FN).

OUTPATIENT MANAGEMENT OF FEVER AND NEUTROPENIA

All of the following should apply for patients with cancer to receive empiric therapy for fever and neutropenia as outpatients: A) Residence ≤1 hour or ≤30 miles (48 km) from hospital; B) Patient’s primary care physician agrees to outpatient management; C) Able to comply with logistical requirements, including frequent clinic visits; D) Family member or other care giver at home 24 hours each day; E) 24-hour a day access to a telephone and transportation; F) No prior history of non-compliance with treatment protocols.

OUTPATIENT MANAGEMENT SHOULD INCLUDE

A) Frequent evaluation for at least 3 days, in clinic or at home; B) Daily or frequent telephone contact to verify (by home thermometry) that fever resolves. C) Monitoring of ANC and platelet count. D) Frequent return visits to clinic. E) Patients should be evaluated for admission to the hospital if any of the following occur: Persistent neutropenic fever. Fever recurs. New signs or symptoms of infection appear. Oral medications are no longer possible or tolerable. Change in the empiric regimen or an additional antimicrobial drug becomes necessary. Microbiologic tests identify species not susceptible to initial regimen.

KEY RECOMMENDATIONS(ASCO’S GUIDELINE)

• Administer the first dose of empiric therapy within 1 hr after triage from initial presentation after fever has been documented in a patient with neutropenia and pre-treatment blood samples have been drawn.

• Observe patients identified as low risk and selected for outpatient management for at least 4 hours to verify they are stable and can tolerate the regimen they will receive .

CONCLUSION• Febrile neutropenia is considered as oncological

emergency.• Febrile Neutropenia is a serious complication of

chemotherapy.• Be vigilant for febrile neutropenia in chemotherapy

patients.• Be vigilant for infection even when no fever.• Initiate EMPIRIC antibiotics immediately.• Several treatment options depending on risk

stratification.

• THANK YOU