Makindo Medical Notes

Related Subjects: | Hypercalcaemia | Neutropenic Sepsis | Pulmonary Embolism | Superior Vena Cava Obstruction Syndrome | Cerebral Metastases | Metastatic Bone Disease | Oncological Emergencies | Neutropenia | Neutrophils

Neutropenic sepsis is a medical emergency commonly seen 7–14 days after chemotherapy, characterized by a neutrophil count of less than 0.5 x10⁹/L. The loss of innate immunity makes patients highly susceptible to life-threatening infections. Prompt administration of intravenous broad-spectrum antibiotics is crucial. Expert advice should be sought if fever persists, as mortality can be high in febrile neutropenic patients.

💉 When to Add Gentamicin in Neutropenic Sepsis

✅ Most patients: Use single-agent broad-spectrum β-lactam (e.g. Piperacillin–Tazobactam).

⚠️ Add a single dose of Gentamicin (or Amikacin) if:
• Patient is haemodynamically unstable (shock, severe sepsis)
• Concern for resistant Gram-negative infection (e.g. colonised with ESBL/CRE)
• Following local microbiology guidance

⛔ Risks: Nephrotoxicity, ototoxicity → avoid routine use unless justified.

📌 Summary: Stable → Pip-Taz alone. Unstable/shock → Pip-Taz + single-dose Gentamicin.

About Neutropenic Sepsis

• An oncological and haematological emergency requiring immediate attention.
• Prompt isolation, investigation, and treatment are critical to improve outcomes.

Severity of Neutropenia

• Mild Neutropenia: Neutrophil count 1.0–1.5 x10⁹/L.
• Moderate Neutropenia: Neutrophil count 0.5–1.0 x10⁹/L.
• Severe Neutropenia: Neutrophil count < 0.5 x10⁹/L.

Definition

• Neutropenic sepsis is defined as a neutrophil count < 0.5 x10⁹/L (or expected to fall below this level) and either a temperature > 38°C or signs of sepsis.
• The absence of fever does not exclude infection; hypothermia may indicate severe infection.
• Patients with functional neutropenia (e.g., myelodysplastic syndrome) are also at risk.

Common Aetiology

• Cancer patients with bone marrow suppression due to chemotherapy or the disease itself.
• Drugs causing neutropenia: cytotoxic agents, carbimazole, some antiviral medications.
• Infections: Viral (e.g., HIV), bacterial, or fungal infections can contribute to neutropenia.

Background

• Common causative organisms include Gram-negative bacteria (e.g., Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (e.g., coagulase-negative Staphylococcus, Staphylococcus aureus).
• Fungal infections (e.g., Candida, Aspergillus) are more common in prolonged neutropenia or after broad-spectrum antibiotics.
• Viral infections (e.g., herpes simplex virus) can also occur.

Clinical Features

• Fever (> 38°C) or hypothermia.
• Chills, rigors, malaise, or unexplained deterioration.
• Signs of infection may be subtle due to impaired inflammatory response.
• Examine for sources of infection: skin, oral mucosa, catheter sites, lungs, abdomen, perianal area.
• Monitor vital signs: heart rate, blood pressure, respiratory rate, oxygen saturation.

Investigations

• Laboratory Tests:
  • Full Blood Count (FBC) with differential.
  • Urea and Electrolytes (U&E), creatinine.
  • Liver Function Tests (LFTs).
  • C-reactive protein (CRP).
  • Coagulation screen.
  • Lactate levels (venous or arterial blood gas).
• Microbiology:
  • Peripheral and central line blood cultures (at least two sets before antibiotics).
  • Urine culture and analysis.
  • Sputum culture if productive cough.
  • Swabs from any suspicious skin or mucosal lesions.
  • Stool culture if diarrhoea is present.
• Imaging:
  • Chest X-ray (CXR) to evaluate for pneumonia.
  • Consider CT scans if focal symptoms or signs are present.

Management

• Immediate Empirical Antibiotic Therapy:
  • Administer intravenous antibiotics within 1 hour of presentation.
  • First-line: Piperacillin/Tazobactam 4.5 g IV every 6–8 hours .
  • If allergic to penicillin: consider alternatives such as meropenem or discuss with microbiology.
  • Add vancomycin or teicoplanin if central line infection or MRSA is suspected.
  • Consider adding gentamicin for additional Gram-negative cover if indicated.
• Supportive Care:
  • Fluid resuscitation to maintain blood pressure and perfusion.
  • Oxygen therapy to maintain adequate oxygenation.
  • Monitor vital signs closely.
  • Isolate the patient if neutrophil count is very low to minimize infection risk.
• Consultation:
  • Involve haematology or oncology specialists promptly.
  • Consult microbiology for antibiotic guidance, especially in complex cases or allergies.
• Monitoring and Follow-up:
  • Reassess the patient regularly for response to treatment.
  • Adjust antibiotics based on culture results and clinical progress.
  • Consider antifungal therapy if fever persists after 4–7 days of antibiotics and neutropenia is ongoing.
• Growth Factors:
  • Consider granulocyte colony-stimulating factor (G-CSF) in selected patients to hasten neutrophil recovery.

Sepsis Criteria Requiring Urgent Attention

• Systolic blood pressure < 90 mmHg or mean arterial pressure < 65 mmHg.
• New requirement for oxygen to maintain saturation > 90%.
• Lactate > 2 mmol/L after fluid resuscitation.
• Reduced urine output (< 0.5 mL/kg/hour for 2 hours despite fluids).
• Altered mental status.
• Other organ dysfunction indicators (e.g., elevated creatinine, bilirubin).

References

• NICE Guideline CG151: Neutropenic sepsis: prevention and management in people with cancer
• American Society of Hematology: Neutropenia Guidelines
• Management of Neutropenic Fever in Adults with Cancer