Neutropenic Sepsis

Immediate Assessment

1. Assess all patients with suspected neutropenic sepsis within 15 minutes of presentation to hospital and start resuscitation following the Sepsis 6 care bundle.
2. Use sepsis severity and NEWS to assign patients to Standard Risk or High Risk as shown in flow chart
3. Identify specific risks such as central venous catheters, previous MRSA colonisation or possible atypical respiratory pathogens.
4. In line with current standards for management of sepsis, all patients should be assessed within 15 minutes of presentation to hospital and managed using the Sepsis 6 Care Bundle.
5. Advice that follows is also applicable to cancer patients who are clinically septic with normal neutrophil count but known to be immunocompromised eg recent stem cell transplant, high dose steroid therapy

Investigations Should Include

1. A meticulous and well documented physical examination including mouth and perineum.
2. Peripheral blood cultures and central blood cultures if a central line is present. Always take blood cultures before giving antibiotics.
3. Urine culture and CXR, but do not delay antibiotic therapy for trips to radiology or if micturition is not immediately possible.
4. Stool cultures and C Diff toxin testing if diarrhoea present.
5. Urgent FBC, U&E, LFTs, CRP, albumin, lactate on admission.
6. Daily FBC, U&E, LFTs, CRP during therapy

Management

1. Aim to give first antibiotic dose within 1 hour of presentation by following flowchart below
2. Cover specific infection risks by giving IV Vancomycin or Teicoplanin if recent infection with MRSA, current or previous MRSA colonisation, suspected central line infection or signs of skinsoft tissue infection
3. Rx IV Clarithromycin 500mg 12 hourly if community acquired pneumonia suspected and atypical cover required (check drug interactions)
4. Previous ESBL infection or known ESBL carrier – Meropenem 1g tds IV in place of Tazosin
5. Review IV therapy daily.  Consider IVOST as per local guidance and stop if infection excluded. Maximum Gentamicin duration without review – 3 days.

First Line Antibiotic Therapy in Neutropenic Sepsis

Penicillin Allergy

1. If there is a clear cut history of severe reaction to any β-lactam drugs e.g. anaphylaxis, angioedema, bronchospasm then all β -lactam drugs carry risk, including the penicillins co-amoxiclav and Tazosin, all the cephalosporins, meropenem and aztreonam.
2. If severe β -lactam reaction replace Tazosin with a combination of vancomycin IV with ciprofloxacin 750mg bd orally
3. If severe β -lactam reaction replace oral coamoxiclav with oral clarithromycin 500 mg bd and oral metronidazole 400 mg tds throughout the guideline.
4. If the β -lactam reaction consists of a rash only it should be safe to replace Tazosin with vancomycin plus either Ciproxin or Aztreonam.

Cautions

1. Suggested antibiotic dosages based on normal renal function
2. If using Gentamicin/Vancomycin combination – potential for additive adverse renal effects.  Consider Teicoplanin in place of Vancomycin.  Monitor renal function closely.
3. Seek early appropriate senior specialist advice and refer patient to specialist haemato-oncology transplant unit if indicated.
4. Seek senior specialist advice before using Gentamicin in myeloma patients due to risk of renal toxicity.

Standard Risk Patients After 48 Hours

1. Treat any positive cultures while continuing broad spectrum cover.
2. Once afebrile and well with neutrophils recovering >500/mm³ for 24 hours then switch to coamoxyclav and ciprofloxacin orally and consider discharge. Complete total of 7 days antibiotics
3. If still febrile or unwell then move to high risk algorithm

High Risk Patients After 48 Hours

1. Treat any positive cultures while continuing broad spectrum cover.
2. If well continue Tazosin but stop gentamicin. Once afebrile with neutrophils recovering >500/mm³ for 24 hours then switch to coamoxyclav and ciprofloxacin orally and consider discharge. Complete total of 7 days antibiotics
3. If remains unwell then move to second line therapy with meropenem 1g tds IV and vancomycin IV. Consider changing IV access devices.
4. Reassess after 72 hours on second line therapy or earlier if concerned. Treat any positive cultures.
5. If remains unwell, request CT chest/abdo to exclude fungal sepsis and start antifungal therapy empirically if there is likely to be a delay in having the scan.
6. Consider GCSF therapy if neutrophils are not beginning to recover.

Links

• Guidance on Initial Antibiotic Management of Neutropenic Sepsis/Febrile Neutropenia in Adult Cancer Patients (including Hemato-oncology) – May 2019 [pdf]