Neutropenic Sepsis

Question 1

What is neutropenic sepsis?

Answer 1

Neutropenic sepsis is a potentially life-threatening complication of neutropenia (low neutrophil count). It is defined as a temperature of greater than 38°C or any symptoms and/or signs of sepsis, in a person with an absolute neutrophil count of 0.5 x 109/L or lower.

Question 2

What can cause neutropenic sepsis?

Answer 2

There are multiple possible causes of neutropenia such as cytotoxic chemotherapy and other immunosuppressive drugs, stem cell transplantation, infections, bone marrow disorders such as aplastic anaemia and myelodysplastic syndromes, and nutritional deficiencies.

Question 3

Following chemotherapy, when does neutropenic sepsis commonly occur?

Answer 3

It most commonly occurs 7-14 days after chemotherapy.

Question 4

What are the risk factors for neutropenic sepsis?

Answer 4

• Characteristics of neutropenia
  
  • The risk of infection and/or sepsis increases with severe neutropenia (absolute neutrophil count of 0.5 x 109/L or lower) and prolonged neutropenia lasting more than 7 days
• Age (infants and people over 60 years of age)
• Chemotherapy
• Corticosteroids
• Co-morbidities such as diabetes mellitus, liver disease, renal disease and poor nutritional status

Question 5

Why does chemotherapy increase the risk of neutropenic sepsis?

Answer 5

Affects immune cellular function and may reduce mucosal barrier protection by causing mucositis and epithelial damage, which increases the risk of bacterial translocation across the gut wall.

Question 6

What pathogens can cause neutropenic sepsis?

Answer 6

• Gram-negatives:
  
  • E.coli
  • Klebsiella
  • Enterobacter spp. - can get carbapenem-resistent strains (CRE)
  • Pseudomonas aeruginosa
  • Acinetobacter
• Gram-positives:
  
  • Coagulase-negative staphylococci (e.g. staph epidermidis)
  • Staphylococcus aureus (including MRSA)
  • Enterococcus (including VRE)
  • Viridans group strep
  • Strep pneumo
  • Group A streptococci
• Fungal:
  
  • Candida
  • Aspergillus

Question 7

What investigations should be ordered for neutropenic sepsis?

Answer 7

• Blood gas including glucose and lactate measurement
• Blood culture
• Full blood count
• C-reactive protein (CRP)
• Creatinine, urea and electrolytes
• Liver function tests
• Clotting screen
• Urine analysis and culture, sputum microscopy and culture, chest X-ray, and additional investigations such as chest CT or bronchoalveolar lavage may be indicated if there is severe or prolonged neutropenia

Question 8

Why investigate using blood gas including glucose and lactate measurement?

Answer 8

Hypoglycaemia may result from depleted glycogen stores; hyperglycaemia may result from the stress response to sepsis; hyperlactataemia is a non-specific indicator of cellular or metabolic stress and is a marker of illness severity, with a higher level predictive of higher mortality rates.

Question 9

Why investigate FBC?

Answer 9

White cell count may be high or low; thrombocytopenia may indicate disseminated intravascular coagulation (DIC), but may also be chemotherapy- or tumour-related.

Question 10

Why invstigate LFTs?

Answer 10

Increased bilirubin or alanine aminotransferase (ALT) levels may indicate cholestasis or other liver dysfunction, and may be chemotherapy-induced.

Question 11

Why investigate clotting screen?

Answer 11

If abnormal may indicate coagulopathy/DIC.

Question 12

Why investigate using urine analysis and culture, sputum microscopy and culture, chest X-ray, and additional investigations such as chest CT or bronchoalveolar lavage?

Answer 12

May be indicated if there is severe or prolonged neutropenia.

This may allow identification of the source of infection, pathogen(s) and sensitivities, and subsequent tailoring and/or de-escalation of antibiotic therapy if appropriate. Source control to eliminate a focus of infection may be possible, such as abscess drainage, debridement of infected tissue, removal of infected devices or foreign bodies, or surgery.

Question 13

Briefly describe the treatment for neutropenic sepsis

Answer 13

Specialist assessment and management in an acute hospital setting involves implementation of the UK Sepsis Trust ‘Sepsis Six’ bundle within the first hour following recognition of sepsis:

1. Give oxygen therapy to people with reduced oxygen saturation or with an increase in oxygen requirement over baseline, to maintain oxygen saturation above 94% unless contraindicated.
2. Take blood tests and microbiology samples.
3. Give an intravenous broad-spectrum antibiotic at the maximum recommended dose.
4. Give an intravenous fluid bolus to restore tissue perfusion.
5. Check serial lactate measurement.
6. Check urine output, monitor fluid balance hourly and monitor the person’s clinical condition.

Question 14

What is the antibiotic of choice in neutropenic sepsis?

Note: not penicillin allergic

Answer 14

IV tazobactam 4.5g TDS.

Question 15

What is the antibiotic of choice in neutropenic sepsis?

Note: penicillin allergic

Answer 15

IV meropenam 1g TDS.

Question 16

When treating neutropenic sepsis, if a hickman line is insitu and evidence of a line/ tunnel infection what antibiotic should be added to treatment?

Answer 16

Add in IV vancomycin.

Question 17

What antibiotic can be given prophylactically against neutropenic sepsis?

Answer 17

Prophylaxis with a fluoroquinolone can be offered.