Initial management of febrile neutropenia or sepsis of unknown source in immunocompromised adults (Antimicrobial)

TAM (Treatments and Medicines) NHS Highland
NHS Highland

Patient definition

All patients who have received RECENT CHEMOTHERAPY (<3 weeks) that have ANY of the following signs/symptoms MUST be assumed to be neutropenic and septic:

  • Fever >38.0°C OR > 37.5°C on 2 occasions 30 minutes apart (measured at home, by ambulance or in hospital) or
  • Hypothermia <36.0°C or
  • Chills, shivers or sweats or
  • Other symptoms suggestive of an infection

All patients with: Neutrophil count of 0.5 x 109/L or less , OR 1.0 x 109/L or less if recent chemotherapy (usually within 10 days but can be up to 28 days) PLUS fever / hypothermia or SIRS or sepsis / septic shock.

All OTHER Immunocompromised patient groups clinically unwell with UNDIFFERENTIATED infection with normal neutrophil count eg previous transplant (solid organ or stem cell), high dose corticosteroid therapy (e.g. prednisolone > 15 mg/ day for > 2 weeks), other immunosuppressive agents (eg anti-TNF, cyclophosphamide) or primary immunodeficiency disease.

Immediate clinical management

Neutropenic sepsis is a life-threatening medical emergency. Patients should not remain untreated whilst awaiting confirmation of neutropenia. ALL patients should be assessed by experienced clinical staff within 15 minutes of presentation to hospital and resuscitation should be commenced following the Sepsis 6 care bundle below.

1. Blood cultures (& any other relevant samples) 2. Antibiotic administration 3. Oxygen to maintain target saturation
4. Bloods; FBC, U&Es, LFTs, Lactate and CRP 5. IV fluids 6. Monitor urine output

Notify relevant speciality at the next available in-hours opportunity.
Haematology are available on call 24 hours. 

Empirical antibiotics

Start IV antibiotics as soon as possible.
Authorisation codes for protected antibiotics are not required in the first 24 hours. Admission areas should hold these drugs as stock.

Note: Neutropenia in the absence of signs of infection does NOT require treatment

ADDITIONAL antimicrobials and advice for specific infection risks:

  • See Antimicrobial Guidance on TAM for management of other anatomically defined infections.
  • Check previous microbiology culture & sensitivity results as may modify antibiotic choice (eg history of resistant Gram negatives).
  • Consider the possibility of respiratory viral infection, fungal infection or opportunistic infections such as PJP or reactivation of previous infection eg CMV, VZV. Discuss with appropriate specialist/ Microbiologist/ Infectious Disease physician.
  • * IV Gentamicin and IV Vancomycin dosing as per NHS Highland policies on TAM. All other doses based on normal renal/ hepatic function. See BNF or Renal Drug Database for dose adjustments.

Ensure review within 48 hours and consider:

  • escalation (if insufficient/poor response)
  • continuation of current therapy
  • de-escalation (with positive microbiology or suitable for IV to oral switch)

If clinical concerns, seek advice from infection specialist

Drug details

Standard risk                                                                                                                            

IV piperacillin/tazobactam 4·5g every 6 hours (in critical care, administer dose over 3 hours)

If recent/ current infection/ colonisation with MRSA or suspected line or skin/ soft tissue infection: ADD IV vancomycin*

If true penicillin/ beta-lactam allergy: IV aztreonam 2 grams every 6 hours PLUS IV vancomycin* 

If previous ESBL infection/ known carrier: SWITCH piperacillin/tazobactam or aztreonam TO meropenem 1g every 8 hours (in critical care, administer dose over 3 hours)

High risk:

Patient has had a stem cell transplant (in the last 100 days) OR is receiving chemotherapy for acute leukaemia and has septic shock or NEWS ≥ 5

IV piperacillin/tazobactam 4.5g every 6 hours (in critical care, administer dose over 3 hours) PLUS IV gentamicin* (max 4 days)

If recent/ current infection/ colonisation with MRSA or suspected line or skin/ soft tissue infection: ADD IV vancomycin*

If true penicillin/ beta-lactam allergy: IV aztreonam 2g every 6 hours PLUS IV vancomycin PLUS IV ciprofloxacin 400mg every 8 hours

If previous ESBL infection/known carrier: SWITCH piperacillin/tazobactam or aztreonam TO meropenem 1g every 8 hours (in critical care, administer dose over 3 hours)

Editorial Information

Last reviewed: 05/01/2026

Next review date: 05/01/2029

Author(s): Antimicrobial Management Team.

Version: 4.1

Approved By: TAM Subgroup of ADTC

Reviewer name(s): A Macdonald, Area Antimicrobial Pharmacist.

Document Id: AMT176