280FM.2 MANAGEMENT OF PATIENTS ON IMMUNOSUPPRESSANTS ADMITTED WITH SUSPECTED INFECTIONS

Consider immunosuppression in patients with cancer, haematological disorders, rheumatoid arthritis, ulcerative colitis, Crohn’s disease, polymyalgia rheumatica, patients with transplants, severe atopic eczema or dermatitis, severe psoriasis, patients on long-term steroids (list not exhaustive)

Which immunosuppressant(s) was the patient taking prior to admission?

List not exhaustive Biologic therapies, including monoclonal Oral cytotoxic, including - Azathioprine antibodies (list not exhaustive) protein kinase inhibitors - Ciclosporin - Abatacept - Cyclophosphamide - Anakinra - Hydroxycarbamide - Anti-TNF- alpha** (infliximab, - Leflunomide adalimumab, certolizumab pegol, - Methotrexate* etanercept, golimumab) - Mycophenolate - Alemtuzumab - Sirolimus (non-formulary) - Basiliximab (non-formulary) Refer to Haematology/ - Tacrolimus - Belimumab Oncology - 6-mercaptopurine - Rituximab within the last 6 months - Tocilizumab*** - Secukinumab - Ustekinumab Steroids: Prednisolone >10 mg OD is considered to be immunosuppressive. In patients with sepsis on long term steroids, double the dose, unless already on a very high dose (40 mg), when advice should be sought.

What is the indication?

Immunosuppressants to be Transplant Non-transplant indication stopped include: - Methotrexate* ↓ ↓ - Leflunomide CONTINUE STOP - Azathioprine IMMUNOSUPPRESSANTS IMMUNOSUPPRESSANTS - Mycophenolate mofetil (Unless specified by specialist The team who are usually - Cyclophosphamide team). responsible for the patient must - Biologic therapies, Contact team responsible for be informed as soon as including monoclonal patient as soon as possible. possible. antibodies Renal Transplant. Contact the - Rheumatology Team on These immunosuppressants on-call team at the Churchill 01296 316664 or should be withheld until the Hospital on 01865 741841. Rheumatology SpR bleep course of antibiotics has been Other Transplant. Contact the 905 or 907. completed. team who usually look after the - Respiratory Team. Liaise with the patient’s usual patient. - Dermatology Team. team about this. - Gastroenterology Team.

 Consider drug interactions – therapeutic drug monitoring may be required for some immunosuppressants.  If the source of the sepsis is unknown, treat as for neutropenic sepsis – see Guideline 36.  If the source of infection is known, the appropriate empirical guideline for treatment of that infection should be followed but consider treating as severe.  If no response, unusual or atypical pathogens a possibility (e.g. pneumocystis carinii pneumonia (PCP), mycobacterium) or foreign travel, discuss with Microbiology.  Treat according to culture and sensitivity results if/when known.  Treatment durations may need to be extended.

If an infection has occurred as a result of an immunosuppressant, a Yellow Card should be completed and the specialist team informed (if not done so already) so that the continued use of immunosuppressants can be reviewed, e.g. for patients with repeated infections.

Guideline 280FM.2 1 of 2 Uncontrolled if printed *Methotrexate  In addition to stopping methotrexate in patients on antibiotics, intravenous (IV) folinic acid rescue 15 mg IV, repeated every 6 hours for 24 hours (may be continued by mouth) should be considered in patients with neutropenia, dehydration and renal impairment or pneumonitis due to methotrexate.  Patients on methotrexate (and rheumatoid arthritis patients in general) are at increased risk of severe varicella infection. If this is suspected, aciclovir 10 mg/kg (use ideal body weight for obese patients; maximum 800 mg per dose) intravenous (every 8 hours) should be given immediately. If there has been a history of contact with varicella or shingles, advice from a Consultant Microbiologist should be sought urgently.

**Infliximab  Is particularly associated with serious infections.  Mycobacterial infections need to be considered in any patient on biologics.

***Tocilizumab  Is associated with an increased risk of bowel perforation (especially in patients with inflammatory bowel disease (IBD) or diverticular disease) and this needs to be considered in patients presenting with abdominal pain and sepsis.

See also: Guideline 36 Care of Adult Patients with Suspected Neutropenic Sepsis (BHT users only) Guideline 222 Adult and Paediatrics Injectables Guide (BHT users only)

Title of Guideline Management of Patients on Immunosuppressants with Suspected Infections Guideline Number 280FM Version 2 Effective Date November 2019 Review Date November 2022 Original Version Published June 2016 Approvals: Antimicrobial Stewardship Group 1st October 2019 Clinical Guidelines Subgroup 5th November 2019 Author/s Claire Brandish, Anti-Infectives Pharmacist SDU(s)/Department(s) responsible Microbiology, Dermatology, Gastroenterology, Pharmacy, for updating the guideline Respiratory Medicine, Rheumatology Uploaded to Intranet 7th November 2019 Buckinghamshire Healthcare NHS Trust

Guideline 280FM.2 2 of 2 Uncontrolled if printed