NEUTROPENIC SEPSIS (Febrile Neutropenia with Sepsis)

Definition

Neutropenic sepsis refers to life-threatening organ dysfunction caused by a dysregulated host response to infection in a neutropenic patient.

• Neutropenia:
• ANC <1500 cells/µL
• Severe neutropenia: ANC <500/µL
• Profound neutropenia: ANC <100/µL
• Fever:
• Single oral temp ≥38.3°C
• Or ≥38.0°C sustained for ≥1 hour

Neutropenic sepsis: fever in a neutropenic patient with signs of sepsis or septic shock.

Pathophysiology

• Neutrophils are first-line defense against bacterial and fungal pathogens.
• When count <500/µL, translocation of microbes across mucosal barriers (gut, oropharynx, perineum) occurs.
• The immune response is blunted → minimal inflammatory signs, no pus formation, muted CXR changes.
• Endothelial injury and cytokine storm (IL-6, TNF-α) drive sepsis and multiorgan dysfunction once infection is established.

Etiology / Microbiology

Shift over time:
Gram-negatives historically dominant → Gram-positives increased due to catheters, prophylaxis, mucositis → recent trend again toward resistant Gram-negatives (ESBL, CRE, Pseudomonas).

Risk Factors

• Chemotherapy (especially cytotoxic, AML induction)
• Hematopoietic stem cell transplant
• Radiation therapy
• Hematologic malignancy (AML, ALL, lymphoma)
• Indwelling central venous catheters
• Mucositis, GI translocation
• Broad-spectrum antibiotic use (selects resistant flora)

Clinical Features

• Fever (may be the only sign)
• Minimal localizing symptoms due to blunted inflammatory response
• Hypotension, tachycardia, altered sensorium → suggest sepsis
• No pus or abscess formation
• Mucosal ulcers, perianal pain, cough, diarrhea, dysuria, or catheter site erythema may be clues

Diagnosis

1. Clinical Suspicion

• Any febrile neutropenic patient is an infection until proven otherwise.

2. Laboratory Tests

Risk Stratification

By MASCC (Multinational Association for Supportive Care in Cancer) Score:

• Score ≥21: Low risk → may be outpatient or oral therapy
• Score <21: High risk → inpatient, IV broad-spectrum therapy

ICU setting: almost all are high-risk.

Management

Initial Steps (Time-critical)

• Treat as emergency – initiate empirical antibiotics within 60 minutes (“Golden Hour”).
• Take blood cultures before antibiotics, but do not delay therapy.

Empirical Antibiotic Therapy (as per IDSA 2020, ESMO, NCCN)

First-line monotherapy (broad Gram-negative coverage including Pseudomonas):

• Piperacillin–tazobactam 4.5 g IV q6–8h
• Cefepime 2 g IV q8h
• Meropenem 1 g IV q8h
• Imipenem–cilastatin 500 mg IV q6h

If septic shock or suspected resistant organisms:

• Add aminoglycoside (amikacin/gentamicin) or colistin if CRE/ESBL suspected.
• If MRSA risk (e.g., catheter, skin lesion, colonized patient):
• Add vancomycin or linezolid.
• If VRE suspected: linezolid or daptomycin.

If anaerobic source (gut, perianal):

Add metronidazole.

If prolonged neutropenia (>7 days) or persistent fever (>4–5 days):

Add empirical antifungal therapy:

• Echinocandin (caspofungin) or liposomal amphotericin B
• Voriconazole if Aspergillus suspected.

Targeted Therapy (after culture results)

De-escalate antibiotics based on:

• Culture and sensitivity
• Site of infection
• Clinical response

Duration:

• Until neutrophil recovery (ANC >500/µL)
  and patient afebrile ≥48 hours.

Adjuvant Therapy

Source Control

• Remove or replace infected central lines
• Drain abscesses (rare)
• Evaluate for typhlitis (neutropenic enterocolitis) via CT abdomen

Typhlitis (Neutropenic Enterocolitis)

• Fever, abdominal pain, diarrhea, GI bleed in neutropenic patient.
• CT: cecal wall thickening (>4 mm), pneumatosis.
• Management: Bowel rest, IV fluids, broad-spectrum antibiotics (covering anaerobes), surgery if perforation.

Prevention

Prognosis

• Mortality: up to 30–50% in septic shock, <10% in early-treated febrile neutropenia.
• Poor prognostic factors:
• Profound or prolonged neutropenia (>10 days)
• Hypotension or multi-organ dysfunction
• MDR infection
• Delay in antibiotic initiation

Summary Table

References 

• Harrison’s Principles of Internal Medicine, 21st ed., Ch. 90
• IDSA Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients (2020)
• ESMO Guidelines: Management of Febrile Neutropenia (Ann Oncol 2021)
• Surviving Sepsis Campaign (2021 update)
• NCCN Guidelines: Prevention and Treatment of Cancer-Related Infections (v3.2024)