This letter authorises the extended use of the following guidance until 1st December 2018:

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1 NHS Grampian Westholme Woodend Hospital Queens Road ABERDEEN AB15 6LS NHS Grampian Date 29 1h May 2018 Our Ref FApenicillin/hype/MGPG/May 18 Enquiries to Frances Adamson Extension Direct Line f.adamsonnhs.net Dear Colleague This letter authorises the extended use of the following guidance until 1st December 2018: Guidance For NHS Grampian Staff On Antibiotic Choice For Patients With Penicillin Hypersensitivity This guidance remains clinically accurate and relevant, and the review of this guidance will commence shortly. If you have any queries regarding this please do not hesitate to contact the Pharmacy and Medicines Directorate. Yours sincerely -7 - Sandy Thomson Interim Chair of Medicines Guidelines and Policies Group

2 NHS Grampian Guidance For NHS Grampian Staff On Antibiotic Choice For Patients With Penicillin Hypersensitivity Lead Author/Coordinator: Gillian Macartney / Fiona McDonald Specialist Antibiotic Pharmacists Reviewer: Dr Alexander Mackenzie Consultant Infectious Diseases, Chair of Antimicrobial Group Approver: Dr Caroline Hind Chair of Medicines Guidelines and Policies Group Signature: Signature: Signature: SS/ a / ) Apils.c...4fria.ye 1-c_CN S a Identifier: NHSG/Guid/PenA/ MGPG754 ' Review Date: July 2017 Approval Date: July 2015 UNCONTROLLED WHEN PRINTED Version 4 Executive Sign-Off This document has been endorsed by the Director of Pharmacy and Medicines Management Signature:

3 This document is also available in large print and other formats and languages, upon request. Please call NHS Grampian Corporate Communications on (01224) or (01224) This controlled document shall not be copied in part or whole without the express permission of the author or the author s representative. Title: Unique Identifier: Guidance For NHS Grampian Staff On Antibiotic Choice For Patients With Penicillin Hypersensitivity NHSG/Guid/PenA/MGPG754 Replaces: NHSG/Guid/PenA/MGPG 593, Version 3 Lead Author/Coordinator: Subject Key word(s): Policy, Protocol, Procedure or Process Document: Document application: Purpose/description: Group/Individual responsible for this document: Policy statement: Specialist Antibiotic Pharmacists Prescribing and Prescription Antibiotic, Antibiotics, Antimicrobial, Antimicrobials, Penicillin, Beta-lactams, Allergy, Hypersensitivity Guidance (Antimicrobial Prescribing Guidance) NHS Grampian To define penicillin or beta-lactam allergy and direct to guidelines for treatment options. Specialist Antibiotic Pharmacists It is the responsibility of all staff to ensure that they are working to the most up-to-date and relevant policies, protocols and procedures. It is the responsibility of individual prescribers to ensure the management of infections in primary care patients is within the guidance laid down in this document. By doing so, the quality of the services offered will be maintained, and the chances of staff making erroneous decisions which may affect patient, staff or visitor safety and comfort will be reduced. UNCONTROLLED WHEN PRINTED Review Date: July 2017 Identifier: NHSG/Guid/PenA/MGPG754 - i -

4 Responsibilities for ensuring registration of this document on the NHS Grampian Information/Document Silo: Physical location of the original of this document: Job title of creator of this document: Job/group title of those who have control over this document: Responsibilities for disseminating document as per distribution list: Development Pharmacist Medicines Management Pharmacy and Medicines Directorate, Westholme Specialist Antibiotic Pharmacists Specialist Antibiotic Pharmacists Specialist Antibiotic Pharmacists Responsibilities for implementation: Organisational: Sector Departmental: Area: Review frequency and date of next review: Operational Management Team and Chief Executive General Managers, Medical Leads and Nursing Leads Clinical Leads Line Manager Every two years (or sooner if required); next review July 2017 Responsibilities for review of this document: Lead Author/Co-ordinator: Specialist Antibiotic Pharmacists Revision History: Revision Date Previous Revision Date Summary of Changes (Descriptive summary of the changes made) June 2015 June 2013 Aztreonam cross-sensitivity added. June 2015 June 2013 References 2, 10 and 11 added. June 2015 June 2013 Ampicillin, ticarcillin, ceftobiprole, fosfomycin added to chart. Changes Marked* (Identify page numbers and section heading ) Page 3 Page 4 Page 6 * Changes marked should detail the section(s) of the document that have been amended i.e. page number and section heading. UNCONTROLLED WHEN PRINTED Review Date: July 2017 Identifier: NHSG/Guid/PenA/MGPG754 - ii -

5 Guidance For NHS Grampian Staff On Antibiotic Choice For Patients With Penicillin Hypersensitivity Contents Page No Introduction... 2 What is the True Incidence of Penicillin Allergy?... 2 Who is at risk?... 2 Recording Drug Allergies... 2 Who should not be prescribed or administered penicillins?... 3 Are there situations where cephalosporins or other beta-lactam antibiotics can be prescribed for patients with penicillin hypersensitivity?... 3 Which antibiotics can I use in a penicillin allergic patient?... 3 What should be prescribed empirically for truly penicillin allergic patients?... 3 References... 4 Consultation List... 4 Distribution list... 5 Appendix 1: Penicillin Allergy Poster... 6 UNCONTROLLED WHEN PRINTED Review Date: July 2017 Identifier: NHSG/Guid/PenA/MGPG

6 Guidance For NHS Grampian Staff On Antibiotic Choice For Patients With Penicillin Hypersensitivity Introduction The phrase allergic to penicillin is commonly seen in medical notes and on medicine charts. The diagnosis of penicillin allergy is often simply accepted without obtaining a detailed history of the reaction. It has been reported that a significant percentage (up to 90%) of patients labelled as penicillin allergic are not truly allergic to the drug (1, 2). As a result, penicillins are unnecessarily withheld as a treatment option for these patients, which may subsequently affect their clinical outcomes. Alternatives to penicillins may be broader spectrum, more costly, and have the potential for more adverse reactions (including Clostridium difficile), and induction of antimicrobial resistance (3,4). The in-patient antibiotic cost of managing a patient with an allergy to penicillin has been reported to be more than 60% higher than that of a patient who can tolerate a penicillin (5). What is the True Incidence of Penicillin Allergy? General hypersensitivity reactions (e.g. rashes) to penicillin occur in between 1% and 10% of exposed patients but true anaphylactic reactions (which can be fatal) occur in less than 0.05% of treated patients (6). Hypersensitivity to penicillin gives rise to immediate reactions including anaphylaxis, angioedema, urticaria, and some maculopapular rashes. Late reactions may include serum sickness-like reactions and haemolytic anaemia (7). Individuals with a history of a minor rash (i.e. non-confluent, non-pruritic rash restricted to a small area of the body) or a rash that occurs more than 72 hours after penicillin administration are probably not allergic to penicillin and in these individuals a penicillin should not be withheld unnecessarily for serious infections; the possibility of an allergic reaction should, however, be borne in mind. Other beta-lactam antibiotics (including cephalosporins) can be used in these patients (6). Please note that patients who have a vague history of symptoms or gastro-intestinal intolerance are probably not truly allergic to penicillins. Clinical judgement must be used if adequate information about a patient s history of penicillin allergy is difficult to obtain. Who is at risk? Patients with a history of atopic allergy (e.g. asthma, eczema, hay fever) are more likely to be allergic to penicillins (6). Recording Drug Allergies NHS Grampian policy states that any known drug/medicine sensitivity should be entered in the appropriate box on the prescription and administration record (PAR) at the time of admission or as this information becomes available. The information recorded should include the drug name and the nature of the reaction. UNCONTROLLED WHEN PRINTED Review Date: July 2017 Identifier: NHSG/Guid/PenA/MGPG

7 Who should not be prescribed or administered penicillins? Individuals with a history of immediate hypersensitivity following penicillin administration, clinically recognisable by features of urticaria, laryngeal oedema, bronchospasm, hypotension or local swelling within 72 hours of administration should NOT receive a penicillin. Patients who are allergic to one penicillin will be allergic to all because the hypersensitivity is related to the basic penicillin structure. In cases of intolerance to penicillins (e.g. gastrointestinal upset) or development of a rash 72 hours after administration, penicillins/related antibiotics should not be withheld unnecessarily in severe infection but the patient must be monitored closely after administration. Treatment options in these patients should be discussed with medical microbiology or an infection specialist. Are there situations where cephalosporins or other beta-lactam antibiotics can be prescribed for patients with penicillin hypersensitivity? The incidence of cross-reactivity to cephalosporins in penicillin-allergic patients is 0.5% - 6.5% (6). Second and third generation cephalosporins are less likely to be associated with cross reactivity as they have different side chains to penicillin. If a cephalosporin is essential (e.g. in life threatening infections) in these patients because a suitable alternative antibacterial is not available, then cefixime, cefotaxime, ceftazidime, ceftriaxone, or cefuroxime can be used with caution. Avoid cefalexin and cefradine (6). Carbapenems (e.g. meropenem, ertapenem) and monobactams (e.g. aztreonam) should also be used with caution in patients with a history of an immediate hypersensitivity reaction (6); very low rates of cross-sensitivity have been reported (9,11). Which antibiotics can I use in a penicillin allergic patient? Antibiotics which are unrelated to penicillins and safe to use include: Tetracyclines (e.g. doxycyline) Aminoglycosides (e.g. gentamicin) Macrolides (e.g. clarithromycin) Clindamycin Sulphonamides (e.g. co-trimoxazole) Trimethoprim Metronidazole Quinolones (e.g. ciprofloxacin) Vancomycin or teicoplanin Fosfomycin What should be prescribed empirically for truly penicillin allergic patients? See Grampian Joint Formulary for full guidelines. For information on which antibiotics should be avoided in penicillin allergy, those that should be used with caution, and those that are safe see Appendix 1. UNCONTROLLED WHEN PRINTED Review Date: July 2017 Identifier: NHSG/Guid/PenA/MGPG

8 References 1. Yates AB. Management of patients with a history of allergy to beta-lactam antibiotics. The American Journal of Medicine 2008; 121(7); NICE Clinical guideline 183 Sept 2014: Drug allergy: diagnosis and management of drug allergy in adults, children and young people 3. Borch JE, Andersen KE, Bindslev-Jensen C. The prevalence of suspected and challenge-verified penicillin allergy in a University Hospital population. Basic & Clinical Pharmacology & Toxicology 2006;98: MacLaughlin EJ, Saseen JJ, Malone DC. Costs of b-lactam allergies: Selection & costs of antibiotics for patients with a reported b-lactam allergy. Archives of Family Medicine 2000;9: Sade K, Holtzer I, Levo Y, Kivity S. The economic burden of antibiotic treatment of penicillin-allergic patients in internal medicine wards of a general tertiary care hospital. Clin Exp Allergy 2003; 33(4): British National Formulary 65 March 2013 at 7. Martindale: The Complete Drug Reference [accessed via 8. UKMI Medicines Q&A Is there a 10% cross-sensitivity between penicillins and cephalosporins? [accessed via ergy 9. Hawkey PM, Livermore DM. Carbapenem antibiotics for serious infections. BMJ 2012;344:e3236 doi: /bmj.e3236 (Published 31 May 2012) 10. Saxon A, et al. Immediate hypersensitivity reactions to beta-lactam antibiotics. Ann. Inter. Med. 1987;107(2): Gaeta F, et al. Tolerability of aztreonam and carbapenems in patientswith IgEmediated hypersensitivity to penicillins J. Allergy Clin. Immunol. Article in press 2014 ( Consultation List The document (including summary guide) was originally developed in consultation with: All Consultants Group Pharmacy HSCP Pharmacists HSCP Clinical Hospital Leads Medical Microbiology Registrars Non-Medical Prescribers Unit Nurse Managers Review consultation list (for 2015 update): All acute sector pharmacists Medical Microbiology UNCONTROLLED WHEN PRINTED Review Date: July 2017 Identifier: NHSG/Guid/PenA/MGPG

9 This policy has been reviewed and agreed by; NHS Grampian Antimicrobial Management Team July 2015 NHS Grampian Medicines and Guidelines Group July 2015 Distribution list All Consultants Group Pharmacy HSCP Clinical Hospital Leads HSCP Pharmacists Medical Microbiology Registrars Non-Medical Prescribers Unit Nurse Managers GP Practices UNCONTROLLED WHEN PRINTED Review Date: July 2017 Identifier: NHSG/Guid/PenA/MGPG

10 Penicillin Allergy All drug-allergies must be specified on medication charts (with the patient s reaction) In TRUE penicillin allergy* ALL penicillins, cephalosporins and other beta-lactam antibiotics should be avoided Appendix 1: Penicillin Allergy Poster CONTRA- INDICATED Antibiotics to be avoided in penicillin allergy Amoxicillin Benzylpenicillin Co-amoxiclav (Augmentin ) Flucloxacillin Penicillin V (phenoxymethylpenicillin) Piperacillin / Tazobactam (Tazocin ) Pivmecillinam Temocillin Ticarcillin (Timentin ) 1 st generation Cephalosporins Cefradine, Cefalexin CAUTION Use with caution if non-severe allergy (e.g. minor rash or rash after 72 hours) CONSIDERED SAFE Antibiotics to be used with caution in non-severe penicillin allergy Other Cephalosporins: Cefixime, Cefotaxime, Ceftazidime, Ceftriaxone, Ceftobiprole, Cefuroxime Other beta-lactam antibiotics Aztreonam, Ertapenem, Imipenem, Meropenem Antibiotics safe in penicillin allergy (not an exhaustive list) Amikacin Azithromycin Ciprofloxacin Clarithromycin Clindamycin Colistin Co-trimoxazole Daptomycin Doxycycline Erythromycin Fosfomycin Gentamicin Levofloxacin Linezolid Metronidazole Nitrofurantoin Ofloxacin Rifampicin Sodium Fusidate Teicoplanin Tetracycline Tigecycline Tobramycin Trimethoprim Vancomycin *TRUE penicillin allergy includes anaphylaxis, urticaria or rash immediately after penicillin administration. In cases of INTOLERANCE to penicillins (e.g. gastrointestinal upset) or a rash occurring >72 hours after administration, penicillins/ related antibiotics should not be withheld unnecessarily in severe infection but the patient must be monitored closely after administration. The full guidance on antibiotic choice for patients with penicillin hypersensitivity is available at - Chapter 5 Infections NHS Grampian Antimicrobial Management Team (with thanks to NHS Tayside) June 2015 Review: June 2017 UNCONTROLLED WHEN PRINTED Review Date: July 2017 Identifier: NHSG/Guid/PenA/MGPG

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