Can Infections Cause Neutropenia?
Yes, infections can cause neutropenia—viral infections are well-recognized causes of transient neutropenia, and patients presenting with low absolute neutrophil counts during acute infection require immediate evaluation for both the infection and the underlying cause of neutropenia. 1, 2
Mechanisms by Which Infections Cause Neutropenia
Viral infections are the primary infectious cause of transient neutropenia, with specific pathogens including CMV, EBV, HIV, parvovirus, and hepatitis B/C causing temporary drops in neutrophil counts 1. The mechanism involves either direct viral suppression of bone marrow production, accelerated neutrophil consumption at sites of infection, or redistribution of neutrophils from the circulating pool 3, 4.
Bacterial infections typically cause neutrophilia (elevated neutrophil counts) rather than neutropenia, though severe overwhelming bacterial sepsis can paradoxically deplete neutrophil reserves and cause neutropenia 5. This occurs when neutrophil consumption exceeds production capacity during severe septicemia 6.
Immediate Evaluation of Neutropenic Patients with Acute Infection
Severity Assessment
Determine the absolute neutrophil count (ANC) immediately, as this dictates management urgency 1:
- Mild to moderate neutropenia (ANC >500 cells/µL): Lower infection risk, can be managed with observation and monitoring 1
- Severe neutropenia (ANC <500 cells/µL): High infection risk requiring immediate intervention 1, 7
- Profound neutropenia (ANC <200 cells/µL): Extremely high risk with significantly increased morbidity and mortality 8, 3
Critical Diagnostic Steps
Perform a comprehensive medication review first, as drugs are a common reversible cause of neutropenia, including chemotherapy agents, immunosuppressants, antibiotics (particularly beta-lactams and sulfonamides), and anticonvulsants 1. This is the highest-yield initial step.
Obtain viral serologies for CMV, EBV, HIV, parvovirus B19, and hepatitis B/C to identify treatable viral causes of transient neutropenia 1. These infections are reversible causes that resolve with treatment or spontaneously.
Check nutritional markers including vitamin B12, folate, and copper levels, as deficiencies can cause neutropenia that mimics infection-related causes 1.
Examine the peripheral blood smear to distinguish true neutropenia from pseudo-neutropenia and identify morphologic abnormalities suggesting specific etiologies 6.
Treatment Algorithm Based on Clinical Presentation
Febrile Neutropenia (Fever + ANC <500 cells/µL)
Initiate empiric broad-spectrum antibiotics immediately covering gram-negative bacteria (especially Pseudomonas aeruginosa) and gram-positive organisms, as infections can become rapidly fatal in this population 8, 2. The Infectious Diseases Society of America guidelines should direct specific antibiotic selection 8.
Add antimicrobial prophylaxis for severe neutropenia including fluoroquinolones with streptococcal coverage (or fluoroquinolone plus penicillin), acyclovir (or congeners), and fluconazole 8, 1. Continue until ANC recovers to ≥500 cells/µL 8.
Non-Febrile Neutropenia with Infection
For patients with severe neutropenia (ANC <500 cells/µL) without fever, implement prophylactic antimicrobials including antibacterial, antiviral, and antifungal agents to prevent infections 1. This is critical even in asymptomatic patients.
Consider G-CSF (filgrastim) for severe, prolonged neutropenia, particularly in congenital or idiopathic cases, at doses of 5-10 mcg/kg/day subcutaneously 1, 9, 7. Monitor weekly complete blood counts during treatment 1.
Mild Neutropenia (ANC >500 cells/µL)
Manage with observation and regular monitoring with repeat complete blood counts every 3 months initially 1. Educate patients on signs of infection requiring urgent evaluation including fever, chills, and sore throat 1.
Critical Pitfalls to Avoid
Do not confuse relative lymphocytosis with absolute lymphocytosis—a low ANC with high lymphocyte percentage but normal absolute lymphocyte count indicates neutropenia causing a relative shift, not a lymphoproliferative disorder like CLL 1. This is a common source of unnecessary workup.
Recognize benign ethnic neutropenia in individuals of African descent, which does not increase infection risk and should not trigger extensive evaluation 1. These patients have chronically lower baseline ANCs (often 1000-1500 cells/µL) without clinical consequences.
Do not empirically administer gut prophylaxis with anaerobic coverage unless clinically indicated (abdominal wound, C. difficile), as altering anaerobic gut flora may worsen outcomes in neutropenic patients 8.
In immunocompromised patients, fever may be the only sign of infection—do not wait for localizing symptoms before initiating broad-spectrum antibiotics 8. Immunosuppressed patients demonstrate minimal other evidence of infection even with serious bacterial or fungal disease.
Special Populations
AIDS patients have neutropenia in 20-25% of cases due to HIV itself, medications, or opportunistic infections, and require empiric broad-spectrum antibiotics including staphylococcal prophylaxis when presenting with fever 8.
Oncology patients receiving chemotherapy develop neutropenia lasting 4-58 days, with over 60% of catheter-related sepsis occurring during neutropenic periods (ANC <500/mm³) 8. These patients require aggressive antimicrobial prophylaxis and may benefit from catheter salvage strategies rather than removal 8.