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) Variable 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 ❑ 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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