All patients

Blood cultures (take prior to administering antibiotics but this should not delay treatment) - minimum 2 sets

• Paired (same volume, same time from peripheral vein and all lumens) if central/tunnelled line in situ
• If no CVC, sample from two peripheral veins

FBC, U&E, CRP, LFT, Lactate

Selected patients

Please consider if clinically appropriate:

• Urine sample - state ‘immunosuppression’ on request, otherwise sample may not be cultured   
• Swab skin lesions, vascular catheter exit site, throat, mouth - for MC&S 
• Consider viral swab for skin lesions, oral ulceration 
• If diarrhoea present, send stool for viral PCR, enteric pathogen screen and C difficile testing 
• Chest X-ray 
  • If respiratory symptoms/signs present 
  • For all haematology patients with neutropenia 
  • For all patients with lung cancer, or known lung metastases 
• If community acquired pneumonia present 
  • Send sputum for MC&S 
  • Consider sending urine for legionella Ag 
  • Consider sending respiratory viral throat swab (includes mycoplasma PCR) 
• If upper respiratory tract infection, please send respiratory viral throat swab  
• See trust guidance re: COVID-19 testing, remember atypical presentation may occur in immune-compromised patients 

Patients at risk of fungal infection (e.g. prolonged immunosuppression, post haemopoeitic stem cell transplant)

If known history or strong clinical suspicion (e.g. sinusitis or pleuritic chest pain), please send Aspergillus antigen and beta-D-glucan tests and consider further investigation (e.g. high resolution CT chest, or sinus CT)

See LTHT guidance on anti-fungal treatment in haematology patients

Empirical antimicrobials for adult neutropenic sepsis  

Always check previous microbiology results before prescribing, antibiotic regimens may need to be modified if multi-drug resistant organisms are present

(e.g. CPE, MRSA, MR Pseudomonas aeruginosa) 

First-line therapy

History of penicillin allergy or patient has received high-dose methotrexate

Haematology patients

Piperacillin/tazobactam 
IV 4.5g 6-hourly 

+/- ³

Amikacin ⁴
IV 15mg/kg^* over 24 hours
See LTHT Amikacin  guidance for dosage and monitoring advice (essential if renal impairment with eGFR <60 mL/min)

Teicoplanin  IV 12mg/kg¹
(see LTHT guidance)

AND

Aztreonam ² 2g IV 8-hourly

+/- ³

Amikacin ⁴
IV 15* mg/kg over 24 hours
See LTHT Amikacin  guidance for dosage and monitoring advice (essential if renal impairment with eGFR <60 mL/min)

*In confirmed multi-resistant Pseudomonas infection, higher doses of Amikacin  may be indicated <22.5mg/kg/day a switch to cefiderocol but only in consultation with microbiology 

Oncology patients

Piperacillin/tazobactam  4.5g IV 6-hourly

+/-³

Gentamicin IV as per Hartford nomogram
(only if eGFR ≥30 ml/min if patient specific or microbiological indication)

Teicoplanin  IV 12mg/kg¹
(see LTHT guidance)

AND

Aztreonam ² 2g IV 8-hourly

All patients

Do not switch initial empiric antibiotics in patients with unresponsive fever unless there is clinical deterioration or a microbiological indication

Second line therapy if deterioration on first-line therapy

• Consider suitability of addition of Gentamicin/Amikacin  (as listed above)
  OR
• Switch toMeropenem 1g IV 8 hourly (see note below)
• Please note, the multi-resistant Pseudomonas aeruginosa seen previously in LTHT haematology patients is resistant to Meropenem , sensitive to Amikacin .

Meropenem  resistance is increasing in haematology/oncology patients at LTHT, this agent should be used only when alternatives are unsuitable:

• If antibiotic regimens above are unsuitable due to hypersensitivity reactions
• If a patient has an eGFR <30 ml/min and Piperacillin/tazobactam  or Teicoplanin /Aztreonam  alone thought not to be appropriate (or not responding to first-line regimen at 72 hours).
• If patient has recently completed a course of Piperacillin/tazobactam  AND is on Levofloxacin  prophylaxis (increasingly likelihood of multi-drug resistant Gram-negative infection)
• Patient has recent ESBL/AmpC reported in microbiology sample
• Please commence antibiotic course within 1 hour, all patients commencing Meropenem  should be discussed with haematology/oncology or consultant/microbiology (next morning if commenced overnight)
• Please contact microbiology if previous meropenem-resistant organism reported

All patients

Add Clarithromycin 500mg PO 12-hourly for 5 days

• If patient has community acquired pneumonia

Add Teicoplanin  IV 12mg/kg¹ (see LTHT guidance)

• If intra-vascular catheter related infection is suspected (and teicoplanin is not part of the empiric regimen). Symptoms include exit site infection, fever after line-use or sepsis in the absence of any other clinical source
• If recent MRSA
• NB If Teicoplanin  is added to a regimen with Gentamicin/Amikacin . Discuss with microbiology as combined risk of nephrotoxicity.

Add Metronidazole  500mg IV or 400mg PO 8-hourly if

• Peri-anal infection, intra-abdominal infection or necrotising oral ulceration is present and patient is receiving a regimen without anaerobic coverage e.g. Teicoplanin /Aztreonam  or Teicoplanin /Ciprofloxacin 
• Peri-anal infection, intra-abdominal infection or necrotising oral ulceration is present and fever/symptoms are not improved after 48 hours of a regimen with anaerobic coverage e.g. Piperacillin/tazobactam  or Meropenem 

Add anti-viral agents if clinically indicated e.g. encephalitis, varicella zoster infection, influenza, COVID-19 etc.

Table 3: Recommendations on the duration of therapy - review IV antibiotics daily

1

Patient has neutrophils >0.5  x 10⁹/L but was started on antibiotic treatment for suspected neutropenic sepsis on admission 

• If ‘functional’ neutropenia is excluded, treat as per general LTHT guidelines for non-neutropenic adult patients.
• De-escalate antibiotics where possible as per guidance.

2

Blood cultures positive

• All cases will be liaised by microbiology team
• Usually minimum 7 days duration from date of blood culture, but longer may be required

3

Culture-negative neutropenic sepsis - Haematology patients

• Duration of therapy is dependent on source of infection and response to therapy
• Oral switch at 24 hours is not appropriate
• Intra-venous antibiotics should be continued until minimum 48 hours after patient becomes apyrexial/CRP improves
• Stop Amikacin /Gentamicin as soon as patient is afebrial/clinically improving and blood cultures negative at 48 hours (i.e. most patients will receive just one or two doses)

4

Culture-negative neutropenic sepsis - Oncology patients

• If low risk as determined by MASCC score and assessment (see below), oral switch may be suitable at 24 hours
• If high risk as determined by MASCC score and assessment (see below), patient requires a minimum of 48 hours IV antibiotics

5

Oral switch appropriate

• Discuss with microbiology if culture negative 

Table 4. MASCC risk score: NB a higher score denotes a lower risk.  

Characteristic

Score

Burden of illness (including cancer, co-morbidities and infection)         

No or mild symptoms
Moderate symptoms
Severe or moribund

5
3
0

Systolic BP > 90 mm Hg

5

No chronic obstructive pulmonary disease

4

Solid tumour

4

Haematological malignancy with no previous invasive fungal infection

4

Adequately hydrated & NOT requiring parenteral fluids

3

Outpatient at onset of this FNE

3

Age <60 years

2

Maximum theoretical score possible

26