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]

Synonyms and keywords:

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
• Common cause 5

Management

Initial Management

Characterize the symptoms: Symptom suggestive of neutropenic fever: ❑ Fever in cancer patients who are on chemotherapy ❑ Single oral temperature ≥38.3° C (101° F) or ❑ Temperature ≥38° C (100.4°F) sustained for over one hour with ❑ Reduced 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 neutropenic fever POTENTIALLY LIFE THREATENING

Obtain a detailed history: ❑ History of any symptom of infections and inflammation of ❑ Skin and soft-tissues ❑ Respiratory system ❑ Central nervous system ❑ Urinary tract ❑ History of any co-morbid conditions ❑ Diabetes mellitus ❑ Chronic obstructive lung disease ❑ History of any recent exposure to infections ❑ History of any current antibiotic prophylaxis ❑ History of non infectious causes of fever (example: administration of blood products) ❑ History of recent surgical procedures ❑ History of prior documentation of infections or pathogen colonization

Examine the patient: ❑ Search for signs of infections at ❑ Entry and exit sites of catheters in skin ❑ Sites of previous procedures in skin (example: bone marrow aspiration site) ❑ Oropharynx (including perioduntum) ❑ Lungs ❑ Alimentary tract ❑ Perineum

Order laboratory tests (routine): ❑ CBC with ❑ Differential leukocyte count ❑ Platelet count ❑ BMP ❑ AST ❑ ALT ❑ Total bilirubin ❑ Blood cultures (at least 2 sets) Central catheter 1st set 2nd set ❑ Present ❑ From each lumen of existing central catheters ❑ From a peripheral vein site ❑ Absent ❑ From one separate venipuncture ❑ From another separate venipuncture ❑ Urinalysis Order additional tests (not routine and order if clinically indicated): Tests Clinical indications ❑ Urine culture ❑ Urinary tract infection ❑ Urinary catheter in place ❑ Abnormal findings on urinalysis ❑ Chest X-ray ❑ Respiratory tract infection ❑ CT head ❑ CNS infection ❑ CT sinuses ❑ Sinus infection ❑ CT abdomen ❑ Infection of abdominal organs ❑ CT pelvis ❑ Infection of pelvic organs ❑ Stool for clostridium difficile toxin assay ❑ Diarrhea ❑ Stool for bacterial pathogen cultures or for ova and parasite ❑ Diarrhea following a history of recent travel ❑ CSF analysis and culture ❑ Meningitis ❑ Skin aspiration or biopsy for cytological testing, gram staining, and culture ❑ Skin infection ❑ Sputum analysis ❑ Productive cough ❑ Bronchoalveolar lavage and analysis ❑ Infiltrations on chest imaging with an uncertain etiology ❑ Nasal wash or bronchoalveolar lavage and assays for viral detection ❑ Respiratory infection during an outbreak or during winter

Do a risk assessment: (MANDATORY) Characteristic Weight ❑ No or mild symptoms in patients following an episode of febrile neutropenia ❑ 5 ❑ Absence of hypotension with a systolic blood pressure >90 mmHg ❑ 5 ❑ No chronic obstructive pulmonary disease (active chronic bronchitis, emphysema, decrease in forced expiratory volumes, need for oxygen therapy and/or steroids and/or bronchodilators) ❑ 4 ❑ Solid tumor or hematologic malignancy with no previously demonstrated fungal infection or empirically treated suspected fungal infection ❑ 4 ❑ Absence of dehydration that requires parenteral fluids ❑ 3 ❑ Moderate symptoms in patients following an episode of febrile neutropenia ❑ 3 ❑ Outpatient status ❑ 3 ❑ Age <60 years ❑ 2

Low risk patients: ❑ MASCC score ≥21 or ❑ Expected brief neutropenia (≤7 days) and/or ❑ Clinically stable and/or ❑ Absence of comorbidities (neurological changes, gastrointestinal symptoms, underlying chronic lung disease, intravascular catheter infection, hemodynamic instability, hepatic insufficiency, or renal insufficiency)

High risk patients: ❑ MASCC score <21 or ❑ Expected prolonged neutropenia (>7 days) and ❑ Profound neutropenia (ANC≤100 cells mm3) and/or ❑ Clinically unstable (unbearable pain, altered mental status, or hypotension) and/or ❑ Presence of comorbidities (neurological changes, gastrointestinal symptoms, underlying chronic lung disease, intravascular catheter infection, hemodynamic instability, hepatic insufficiency, or renal insufficiency) Patients who do not strictly fulfill the criteria for being at low risk

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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