Febrile neutropenia resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rim Halaby, M.D. [2]

Definition

Neutropenic fever is defined as one oral temperature of ≥38.3°C (101°F) or a temperature of ≥38.0°C (100.4°F) for over one hour. Neutropenia is defined as an absolute neutrophil count (ANC) <500 cells/mm³ or an ANC that is expected to become less than 500 cells/mm³ over the next 48 hours. Profound neutropenia is defined as an ANC <100 cells/mm³. Patients with functional neutropenia have a qualitative abnormality of neutrophil functions despite a normal or elevated ANC, as seen in hematological malignancy, and are at increased risk of infections similarly to patients with low ANC.

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

• Life threatening cause 1
• Life threatening cause 2
• Life threatening cause 3

Common Causes

• Common cause 1
• Common cause 2
• Common cause 3
• Common cause 4
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Management

Initial Management

In cancer patients on chemotherapy: Characterize the symptoms: ❑ Fever ❑ Single oral temperature ≥38.3° C (101° F) or ❑ Temperature ≥38° C (100.4°F) sustained for over one hour and ❑ Check Absolute Neutrophil Count (ANC) ❑ ANC <500 cells/mm3 or ❑ ANC that is expected to decrease to <500 cells/mm3 in the next 48 hours

Consider the diagnosis of febrile neutropenia

Obtain a detailed history: ❑ New site specific onset ❑ Exposure to infections ❑ Prior documented infections or pathogen colonization ❑ Non infectious causes of fever (example: administration of blood products) ❑ Recent surgical procedures ❑ Current antibiotic prophylaxis

Examine the patient: ❑ Site of previous procedures (entry and exit sites of catheters, bone marrow aspiration site) ❑ Oropharynx (perioduntum) ❑ Alimentary tract ❑ Lungs ❑ Perineum

Order lab tests and cultures: Labs every 3 days during the course of antibiotics: ❑ CBC ❑ Electrolytes ❑ Serum creatinine ❑ BUN Labs weekly during the course of antibiotics ❑ Transaminases Cultures: ❑ Blood culture (repeat every day for two days) Additional tests (not routine) ❑ Stool test for clostridium difficile toxin (if diarrhea is present) ❑ Urine culture ( if there are UTI symptoms, urinary cath, abnormal urinalysis) ❑ Skin aspiration or biopsy (if there is suspicion of an infected lesion) ❑ Respiratory specimen ❑ CXR ❑ CSF analysis

DO A RISK ASSESSMENT

LOW RISK ❑ MASCC score* ≥21 ❑ Expected brief neutropenia (≤ 7 days) ❑ Clinically stable patient ❑ No comorbidities

HIGH RISK ❑ MASCC score* <21, OR ❑ Expected prolonged neutropenia (> 7 days) AND profound neutropenia (ANC≤100 cells mm3), AND/OR ❑ Presence of comorbidities

Outpatient oral antibiotics (Urgent) ❑ Ability to tolerate oral medications ❑ Availabilty of telephone, transportation to hospital, caregiver

Inpatient IV antibiotics (Urgent) ❑ Inability to tolerate oral medications ❑ Unavailabilty of telephone, transportation to hospital, caregiver ❑ Identified infection necessitating IV antibiotics

Inpatient IV antibiotics (Urgent)

Administer oral antibiotics: ❑ ciprofloxacin + amoxicillin/clavulanate Observe and discharge: ❑ Observe for 4 hours following the initial dose of antibiotics and discharge for outpatient treatment after making sure the patient is stable and tolerating the treatment

Administer IV monotherapy with an antipseudomonal: ❑ Cefepime, OR ❑ Piperacillin/tazobactam, OR ❑ Carbapenem

Modify antibiotics if necessary: Add vancomycin if: ❑ Suspected catheter related infection ❑ Suspected skin or soft tissue infection ❑ Suspected pneumonia ❑ Hemodynamic instability Cover for organisms in case of previous infection, colonization, high endemicity: ❑ MRSA: Add vancomycin, or linezolid or daptomycin ❑ VRE: Add linezolid or daptomycin ❑ ESBL: Add carbapenem ❑ KPC: Add polymyxin, colistin or tigecycline

Do's

• Modify the antibiotic regimens depending on the clinical picture and the epidemiology of infections in the area and the hospital where the patient is being treated at.

Don'ts

• Don't measure the temperature of the patient in the axillary area because it is not as specific as if it was taken orally.
• Don't measure the temperature of the patient rectally to avoid contaminating the skin and soft tissues of the rectal area.

References

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