Antibiotic management of neutropenic sepsis or febrile neutropenia in adult oncology patients in the Edinburgh Cancer Centre pathway

Important notes on additional infection risks and initial choice of antibiotics

Give first dose of antibiotics within 1 hour and cover any specific infection risks identified, e.g:

• If MRSA infection/colonised, suspected intravenous catheter infection, or signs of skin/soft tissue infection, consider adding IV vancomycin (as per dosing calculator). Note increased nephrotoxicity when given with IV gentamicin.
• If CAP, consider adding oral doxycycline 200mg od on day 1 then 100mg od, or if abnormal absorption IV clarithromycin 500mg BD
• If previous VRE infection/carriage, replace IV vancomycin with linezolid^$ 600mg BD or daptomycin^$ 6mg/kg.
• Caution prescribing ciprofloxacin if at increased risk of C. difficile: refer to NHS Lothian Antimicrobial Companion – found on Scottish Antimicrobial Prescribing Group app /intranet site.

$ Denotes a reserve antibiotic: refer to restricted antibiotic policy on AMT site on NHS Lothian intranet for more information (only accessible when connected to intranet)

Notes to accompany Guidelines for antibiotic management of neutropenic sepsis or febrile neutropenia in adult oncology patients in the ECC

1. Prompt antibiotic therapy is essential in neutropenic sepsis. The first dose of gentamicin (if required) can be given without knowledge of current renal function (at a dose of 5mg/kg or dose as per guidelines below) based on last documented eGFR. If there is a clear history of prior renal impairment then refer to NHS Lothian Antimicrobial Management Team (AMT) Gentamicin guideline (only accessible when connected to intranet) for first dose. Doses should be calculated on the online calculator, which should be printed off and kept in the patient’s notes. After the first dose gentamicin levels should be monitored, entered onto the printed sheet, and doses adjusted as specified in the guidelines. The gentamicin guideline and dosage calculator is available on the NHS Lothian Antimicrobial Management Team (AMT) Gentamicin guideline  (only accessible when connected to intranet)

2. Duration of treatment with gentamicin should be limited to minimise toxicity. All prescriptions should be reviewed daily in conjunction with microbiology results. Renal toxicity is more likely in those who are septic, hypotensive or who are also on other potentially nephrotoxic drugs such as NSAIDs, ACE inhibitors or diuretics, regardless of initial eGFR. If possible these drugs should be withheld when septic.

3. The first dose of piperacillin/tazobactam 4.5g IV is safe whatever the renal function. Thereafter, if eGFR is less than 40ml/min, dosing frequency should be adjusted according to renal function as specified below:

4. Use of vancomycin requires assessment of renal function and monitoring of drug levels, as per NHS Lothian AMT Antibiotic Prescribing Guidelines in Adults (only accessible when connected to intranet) Doses should be calculated on the online calculator, which should be printed off and kept in the patient’s notes. After 3 days on vancomycin, consider stopping the drug if no relevant culture isolates obtained (discuss with Microbiology).

5. 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 piperacillintazobactam, and all the cephalosporins.

6. Avoid ciproflocaxin if previous cipro resistant Gram negative cultures, recent exposure to cipro as prophylaxis, C. difficile carriage or infection in the past 12 weeks (equivocal or toxin positive stool), suspected MRSA or VRE, and only use with extreme caution in the frail elderly.

7. In the case of piperacillin-tazobactam or ceftazidime shortage, replace these antibiotics with IV aztreonam^$ 2g 6 hourly + IV vancomycin + IV metronidazole 500mg 8 hourly (+ consider adding IV gentamicin if high risk).

8. Document indication for antibiotics and length of treatment on Hepma and in patient notes wherever possible.

$ Denotes a reserve antibiotic: refer to restricted antibiotic policy on AMT site on NHS Lothian intranet for more information (only accessible when connected to intranet)