Initial Workup for Neutropenia
The initial workup for a patient presenting with neutropenia should include a thorough clinical evaluation, blood cultures, chest radiograph, and appropriate laboratory tests to determine the etiology, with aggressive determination of any skin or soft tissue infections through aspiration and/or biopsy of suspicious lesions. 1
Definition and Risk Assessment
- Neutropenia is defined as an absolute neutrophil count (ANC) <500 cells/µL, or a neutrophil count expected to decrease to <500 cells/µL within 48 hours 1
- Risk stratification is essential:
- High-risk patients: those with anticipated prolonged (>7 days) and profound neutropenia (ANC <100 cells/µL) or with a Multinational Association for Supportive Care (MASCC) score of <21 1
- Low-risk patients: those with anticipated brief (<7 days) periods of neutropenia and few comorbidities or with a MASCC score of ≥21 1
Initial Clinical Evaluation
- Carefully examine sites most commonly infected in neutropenic patients:
- Periodontium, pharynx, lower esophagus, lung, perineum (including anus), eyes, and skin (including bone marrow aspiration sites, vascular catheter access sites, and tissue around nails) 1
- Evaluate all skin lesions, no matter how small or innocuous, as signs and symptoms of inflammation may be diminished in neutropenic patients 1
- Assess for fever (≥38.3°C), which is a critical sign requiring immediate intervention 1
- Look for clinical signs such as hypotension and headache, which are associated with severe neutropenia 2
Laboratory and Diagnostic Testing
- Obtain at least 2 sets of blood cultures (from central venous catheter if present and peripheral vein) 1
- Consider quantitative blood cultures for suspected catheter-related infections 1
- Complete blood count with differential to confirm neutropenia 3
- Examination of peripheral blood smear 3
- Basic metabolic panel including blood urea nitrogen and transaminases 1
- For skin and soft tissue lesions: perform aspiration and/or biopsy for cytological/histological assessment, microbial staining, and cultures 1
- Chest radiograph for all patients, especially those with respiratory signs/symptoms or if outpatient management is planned 1
Additional Imaging
- Additional imaging (including chest CT) as indicated by clinical signs and symptoms 1
- Radiologic imaging of chest/sinuses may identify silent or subtle pulmonary sites of infection that have resulted in dissemination to skin or soft tissues 1
Management Considerations
- Empirical antibiotic therapy should be administered promptly to all neutropenic patients at the onset of fever 1
- For high-risk patients: hospitalization and empiric antibacterial therapy with vancomycin plus antipseudomonal antibiotics such as cefepime, a carbapenem (imipenem-cilastatin or meropenem or doripenem), or piperacillin-tazobactam 1
- For low-risk patients: initial oral or IV empirical antibiotic doses in a clinic or hospital setting; may be transitioned to outpatient oral or IV treatment if they meet specific clinical criteria 1
- Afebrile neutropenic patients who have new signs or symptoms suggestive of infection should be evaluated and treated as high-risk patients 1
Special Considerations
- Early involvement of infectious diseases specialists, surgeons, and dermatologists familiar with neutropenic patients may improve outcomes 1
- For patients with recurrent or persistent fever after 4-7 days of antibiotics and expected neutropenia >7 days, consider empirical antifungal therapy and investigation for invasive fungal infections 1
- Consider bone marrow examination (aspirate and/or biopsy) and cytogenetic testing for diagnostic evaluation, particularly in cases of severe chronic neutropenia 3
Common Pitfalls to Avoid
- Delaying empirical antibiotic therapy in febrile neutropenic patients 1
- Failing to obtain appropriate cultures before initiating antibiotics 1
- Overlooking subtle signs of infection due to diminished inflammatory response in neutropenic patients 1
- Not considering non-infectious causes of fever in neutropenic patients (drug-related fever, thrombophlebitis, underlying cancer, blood resorption) 1
- Changing antibiotics based solely on persistent fever without clinical deterioration or positive cultures 1