Alerts

• In any patient with neutropenic fever, obtain appropriate blood culture(s) and administer appropriate antimicrobials as soon as possible and certainly WITHIN ONE HOUR of presentation
• Even if other causes possible, always treat fever in neutropenic sepsis as if caused by infection 
• Consider infection in any unwell neutropenic patient even if no fever
• This guideline does NOT discuss COVID. Be very alert to the possibility of COVID. Refer to COVID care pathway

Symptoms and signs

• Fever or abnormally low temperature
• Oral or tympanic membrane temperature ≥38°C with neutrophil count <0.5 x 10⁹/L (or likely to fall to this level within days)
• Significant deterioration in clinical state [e.g. development of rigors, shock (systolic BP <90 mmHg) or falls of normal blood pressure by >50 mmHg]
• Signs consistent with infection of respiratory tract, urinary tract, or central venous catheter/Hickman line/PICC line
• Severely ill patient with no obvious other explanation for clinical state
• If suspicion of infection (even in the absence of a fever), start treatment for sepsis
  • if there is a suspicion of sepsis and patient is at risk from neutropenia (e.g. has had recent chemotherapy), treat for neutropenic sepsis without waiting for blood results, and adapt treatment later if necessary

Possible sites of infection

• Enquire about, and look for, inflammation/infection at following sites and sample as appropriate:
  • teeth, gums, pharynx
  • ears, nose, sinuses
  • eyes, including fundi
  • lungs - cough, shortness of breath, sputum
  • upper gastrointestinal tract
  • lower gastrointestinal tract - if diarrhoea present, consider isolation and discuss with infection prevention team
  • perineum, especially anal area (avoid PR examination)
  • skin - consider fungal, pseudomonas, generalised herpes and varicella zoster infections
  • genito-urinary tract
  • vascular access sites, especially central venous line insertion sites, bone marrow aspiration sites, nail margins, skin tunnels and surgical incision sites
• Enquire whether central venous line used or flushed within preceding 24 hr

Timing of chemotherapy

• Risk of infection is proportional to duration of neutropenia and how far and how fast neutrophil count falls
• Establish type of chemotherapy administered and date of last dose (refer to patient alert card)
• Estimate expected onset and anticipated duration of neutropenia by establishing time elapsed since first day of current cycle of chemotherapy
• Assume that any patient who has received chemotherapy within the last month, or whose last recorded blood counts show neutropenia may be neutropenic
• If a subsequent blood count result shows no neutropenia, choice of antimicrobial can be revised at that time if necessary in discussion with the appropriate specialist team
• If any of this information not available, do not delay start of antimicrobial therapy and revise later

Investigations

General

• FBC including differential WBC
• CRP
• U&E
• LFT
• Lactate
• Blood cultures - peripheral and central (through IV catheter lumens) (take blood through each lumen of Hickman/PICC line)
  • do not access Hickman/PICC line unless trained to do so
• Review any recent microbiology culture results
• Coagulation screen
• MSU/CSU

Specific

• If varicella zoster suspected, consider swabs for viral culture and PCR
• Appropriate swabs e.g. throat, mouth, wound, skin/peri-anal area (do not perform PR), Hickman line/central venous catheter/PICC line exit site
• If chest signs and/or SpO₂ <92% on air, chest X-ray
• If GI symptoms (e.g. diarrhoea and abdominal pain), send stool sample for culture/sensitivity and Clostridium difficile toxins
• If urinary symptoms or patient catheterised, urinalysis and culture
• Respiratory secretions for rapid testing for viral antigens by immunofluorescence, viral cultures or PCR (e.g. throat swab)
• Complete MASCC score https://www.qxmd.com/calculate-online/hematology/febrile-neutropenia-mascc

• Discuss management of patients admitted with neutropenic fever with acute oncology specialist nurse, haematologist or on-call oncologist
• If a patient who has had an allogeneic stem cell transplant is admitted febrile or unwell, contact on-call consultant haematologist immediately after initial assessment

Penicillin Allergy

• True penicillin allergy is rare
• Ask the patient and record what happened when they were given penicillin
• If any doubt about whether patient is truly allergic to penicillin, seek advice from a microbiologist or consultant in infectious diseases

Infection Control alerts

• Check for IC alert
• If IC alert not available, check previous 12 months of microbiology reports
• If MRSA present, treat as tagged for MRSA. See MRSA management
• if ESBL, MGNB, CARB present, treat as tagged for ESBL. See ESBL/MGNB/CARB management

Use of piperacillin/tazobactam

• Give piperacillin/tazobactam (Tazocin^®) diluted in 50 mL as an extended infusion over 2-4 hr
  
  • in patients with serum albumin <20 g/L, use 4 hr infusion 
  • if patient is required to leave the ward i.e. scan, then bolus the remaining dose to prevent omitting part or all of the dose

Viral infections

• In cases of varicella zoster, adopt infection prevention precautions to protect staff and other patients - discuss with infection prevention team
• Be alert to possibility of COVID and refer to COVID care pathway
• If influenza appears likely on clinical grounds, ensure viral throat swab taken for extended viral panel
  
  • consider immediate treatment with antiviral medication in addition to the antimicrobial treatment recommended above
  • choice of antivirals determined by national guidance. If uncertainty, seek advice of on-call microbiologist.
  • isolate patient to reduce risk of spread to others
  • if viral swab subsequently reveals no evidence of influenza infection, discontinue empirical treatment 

Colony-stimulating factors

• Discuss use of colony-stimulating factors (filgrastim 300 microgram SC daily) with consultant oncologist or haematologist

• Subsequent management 24-72 hr after initiating antimicrobial treatment depends on blood culture results and clinical condition
• Always discuss subsequent management plan with consultant haematologist/oncologist

• FBC, U&E and CRP daily until recovery
• LFT 2-3 times weekly until recovery (more often if significant abnormalities discovered on admission sample)
• Coagulation screen on admission
  • if normal, no further routine repeats necessary
  • if abnormal, seek advice from consultant haematologist/consultant oncologist
• If fever persists, repeat blood cultures based on clinical assessment
• If clinically indicated, repeat chest X-ray
• If fever not resolved after 72-96 hr, urgent high-resolution chest CT - discuss with consultant radiologist
• Infections in neutropenic patients typically take 2-7 days to respond to antimicrobial therapy

• Discharge patients only after consultation with acute oncology specialist nurse, haematology or oncology team