Makindo Medical Notes

Related Subjects: | Neutropenic Sepsis | Oncological emergencies

WRITTEN WARNING MUST BE GIVEN to patients prescribed Carbimazole so they are aware to seek immediate medical help if they experience any signs or symptoms of agranulocytosis, such as a sore throat or mouth ulcers. Agranulocytosis is a serious condition affecting about 0.3 in 1000 patients. It should be suspected in patients on high doses of Carbimazole who present with symptoms of infection, such as a sore throat or mouth ulcers. The patient should stop taking the drug immediately and seek medical help. The risk of agranulocytosis is lower with Carbimazole than with Propylthiouracil. Once agranulocytosis is confirmed, it is an absolute contraindication to further antithyroid drug treatment, and radio-iodine therapy should be considered.

About

• Agranulocytosis is a severe reduction in neutrophils (neutropenia) and is associated with risks of sepsis, often relevant to neutropenic sepsis cases.

Aetiology

• The risk of sepsis increases as neutrophil counts drop below 1.0 x 10⁹/L, highlighting the importance of monitoring in susceptible patients.

Causes

• Post-chemotherapy: Neutropenia typically develops 7-14 days after treatment.
• Physiological causes: Common in Black African individuals, where neutrophil levels of 0.8-1.5 x 10⁹/L (sometimes as low as 0.5 x 10⁹/L) may be normal.
• Infections: Severe infections like Brucella, Typhoid, Miliary TB, viral or protozoal infections.
• Immune causes: Conditions such as SLE, autoimmune disorders, rheumatoid arthritis (Felty’s syndrome).
• Endocrine causes: Conditions like hypopituitarism, hypothyroidism, familial neutropenia.

Common Drug Causes of Neutropenia

• Chemotherapeutic agents: Cyclophosphamide, Busulfan, Methotrexate, 5-flucytosine.
• Antithyroid drugs: Carbimazole, Propylthiouracil.
• Other drugs: ACE inhibitors, NSAIDs, antimalarials, anticonvulsants, antidiabetics, penicillins, trimethoprim-sulfamethoxazole, antidepressants, antihistamines.

Classification of Neutropenia

• Mild: 1-1.5 x 10⁹/L.
• Moderate: 0.5-1.0 x 10⁹/L.
• Severe: < 0.5 x 10⁹/L.

Management

• Use topical antiseptics, chlorhexidine mouthwashes, and ensure a clean diet during neutropenia.
• Consider human keratinocyte growth factor (Palifermin) to reduce mucositis risk.
• If fever arises, perform urgent investigations: FBC, CRP, U&E, urine and blood cultures, inspect any cannulas, and perform a chest X-ray.
• If fever persists for 48-72 hours despite broad-spectrum antibiotics, consider fungal infection and start antifungal treatment, such as Amphotericin.

Antibiotic Policy: Empiric Therapy Options

• Consult your hospital’s antibiotic policy for specific guidance, as resistance patterns can vary.

Standard Empiric Therapy for Febrile Neutropenia

• Piperacillin/Tazobactam (Tazocin): 4.5g tds IV, effective against gram-positive, gram-negative, and anaerobic bacteria.
• Gentamicin: IV once daily, often added to Tazocin in cases of severe infection or suspected gram-negative bacteria.

Alternative Regimens

• Meropenem: 1g tds IV, suitable for monotherapy where multidrug-resistant (MDR) organisms are suspected, or in patients with severe penicillin allergies.
• Cefepime: 2g bd IV, an alternative to Tazocin in patients with penicillin allergies.
• Ceftazidime: 2g tds IV, useful in centers with a high prevalence of gram-negative infections, especially Pseudomonas.

Additional Considerations for MRSA or Resistant Organisms

• Vancomycin: 1g bd IV, indicated if line-associated infections are suspected or if MRSA risk is high.
• Linezolid: 600 mg bd IV, an option for MRSA, especially if Vancomycin cannot be used.

Second-Line Considerations

• Antifungal Therapy: Initiate if no bacterial source is identified within 48-72 hours and fever persists. Options include:
  • Amphotericin B: particularly useful in severe infections.
  • Fluconazole: generally well-tolerated and effective for certain Candida infections.
  • Posaconazole or Voriconazole: broader spectrum against invasive Aspergillus and other molds.