EMPIRICAL ANTIBIOTIC GUIDELINES FOR THE MANAGEMENT OF COMMON INFECTIONS IN ADULT INPATIENTS

EMPIRICAL ANTIBIOTIC GUIDELINES FOR THE MANAGEMENT OF COMMON INFECTIONS IN ADULT INPATIENTS Useful contacts: Consultant Clinical Microbiologist via switchboard Antimicrobial Pharmacist Bleep 294 Medicines Information Ext 2092 Topic/ Heading: Empirical antibiotic guideline for the management of common infections in adult inpatients Lead Clinician for Guideline: Dr. S N Patel, Consultant Microbiologist & Nicola Robinson, Senior Pharmacist Antimicrobials/ ICU Discipline: Medicines Management / Microbiology / Pharmacy Date of Guideline: September 2017 Version: 4.0 Approved By: Drugs & Therapeutics Committee and Antibiotic Stewardship Group Date: 26/7/16 Audit Date: Monthly and as indicated in annual antibiotic audit plan Guideline Review Date: September 2018 Review Completed By: Dr. S N Patel Consultant Microbiologist, Emma Guthrie Senior Pharmacist, Agnieszka Fryer Senior Pharmacist. Rationale for Development: To support prudent use of antimicrobials across the Trust Aims and Objectives: To ensure appropriate antibiotic treatment of common infections in adult inpatients Method of Guideline Development: In accordance with Trust policy Equality Impact Assessment: n/a Roles & Responsibilities: refer to Antimicrobial Prescribing policy in PIMS Guideline: Empirical antibiotic guidelines for the management of common infections in adult inpatients Evidence Base: See reference list Consultation: 2013 Blue Book with changes approved by relevant clinicians Implementation: Available via PIMS Monitoring: Antibiotic Stewardship Group annual audit plan Training Plan: Incorporated into induction training of new doctors and into regular training of medical, pharmacy and nursing staff. Outcome Measures and Audit Criteria: Regular antibiotic audits in medicine and surgery and antibiotic ward rounds Assessment of Competence to Carry Out the Procedure n/a Version 4.2 Review Date: September 2018 Page 1 of 57

CONTENTS 1 INTRODUCTION... 3 2 RECOMMENDATIONS FOR THE PRUDENT USE OF ANTIMICROBIALS... 4 2.1 PRINCIPLES OF GOOD ANTIBIOTIC PRESCRIBING... 4 2.2 REDUCING/PREVENTING C.DIFFICILE INFECTIONS... 5 2.3 IV TO ORAL SWITCH GUIDANCE... 5 2.4 CLINICAL ADVICE... 5 2.5 RESTRICTED ANTIBIOTICS... 5 2.6 PENICILLIN ALLERGY OR NOT?... 6 2.7 SPECIMENS... 6 3 BONE AND JOINT INFECTIONS... 7 4 CARDIOVASCULAR SYSTEM INFECTIONS... 8 4.1 BACTERIAL ENDOCARDITIS EMPIRICAL THERAPY... 8 4.2 BACTERIAL ENDOCARDITIS ORGANISM KNOWN... 9 5 CENTRAL NERVOUS SYSTEM INFECTIONS... 11 5.1 BACTERIAL MENINGITIS... 11 5.2 OTHER CNS INFECTIONS... 12 5.3 PROPHYLAXIS FOR CONTACTS OF HAEMOPHILUS AND MENINGOCOCCUS MENINGITIS... 13 6 GASTROINTESTINAL INFECTIONS (INCLUDING CLOSTRIDIUM DIFFICILE INFECTION)... 14 6.1 GASTROINTESTINAL INFECTIONS... 14 6.2 CLOSTRIDIUM DIFFICILE INFECTION (CDI)... 16 7 RESPIRATORY SYSTEM INFECTIONS... 18 8 SEPSIS... 22 9 SKIN AND SOFT TISSUE INFECTIONS... 23 10 UROGENITAL INFECTIONS... 24 APPENDIX A THERAPEUTIC DRUG MONITORING (TDM)... 27 A.1 ONCE DAILY GENTAMICIN PROTOCOL... 28 A.2 LOW DOSE GENTAMICIN FOR BACTERIAL ENDOCARDITIS... 30 A.3 ROLES AND RESPONSIBILITIES FOR GENTAMICIN PRESCRIBING AND MONITORING... 31 A.4 AMIKACIN... 32 A.5 VANCOMYCIN... 33 A.6 TEICOPLANIN... 35 APPENDIX B SURGICAL ANTIBIOTIC PROPHYLAXIS... 36 APPENDIX C SPLENECTOMY PATIENTS: PREVENTION OF INFECTION... 42 APPENDIX D NEUTROPENIA: MANAGEMENT OF NEUTROPENIC FEVER... 44 APPENDIX E DIABETIC FOOT INFECTION... 47 APPENDIX F SPECTRUM OF ACTIVITY OF ANTIBIOTICS... 49 APPENDIX G DOSE ADJUSTMENT IN RENAL IMPAIRMENT... 52 Version 4.0 Review Date: August 2018 Page 2 of 57

1 Introduction All NHS bodies are legally responsible for having antimicrobial prescribing policies in place as summarised in the following publications from the Department of Health (DH): The Health and Social Care Act, Code of Practice for health and adult social care on the prevention and control of infections and related guidance. 2008 (Updated 2010.); The Health Act 2006 Code of Practice for the Prevention and Control of Healthcare Associated Infections. The DH issued specific recommendations in the supporting document, Saving Lives: reducing infection, delivering clean and safe care: Antimicrobial Prescribing, including regular audit of antimicrobial prescribing to determine compliance with local guidelines. Further guidance provided an outline of evidence based antimicrobial stewardship in the secondary care setting: Antimicrobial Stewardship Start Smart - then Focus DH November 2011(updated 2015). The purpose of empirical antibiotic guidelines is to: Guide prescribers on the use of antibiotics in an evidence-based manner. Reduce the incidence of Healthcare Associated Infections (HCAIs) Reduce the emergence of antimicrobial resistance Minimise adverse effects Make the Trust compliant with the Health and Social Care Act. This guideline is not all encompassing. It aims to include the common infections seen at Kingston Hospital. This guideline is adapted from the Blue Book Guideline for the Management of Common Medical Emergencies and for the use of Antimicrobial Drugs 2013 edition and revised. Every attempt has been made to ensure that statements are fully compatible with the advice given by the British National Formulary, various professional bodies, the Royal Colleges, NICE guidelines, data from published clinical trials and national consensus statements. This is a dynamic document and if there are any comments, please direct them to the lead author so that comments can be used to modify subsequent versions. Prescribers should note that the antibiotics advised here are for EMPIRICAL purposes (unless otherwise specified) commenced before the causative organism is identified. Once culture and sensitivities are available, the choice of antibiotic should be changed to one with the narrowest spectrum to which the organism is sensitive. The guidelines are not applicable to pregnant patients (except where stated) or paediatric patients. References Department of Health, Health and Social Care Act. Code of Practice for health and adult social care on the prevention and control of infections and related guidance. 2008 (Updated 2009.) Department of Health, Health Act. Code of Practice for the Prevention and Control of Healthcare Associated Infections. 2006 Department of Health, Saving Lives: reducing infection, delivering clean and safe care: Antimicrobial Prescribing, 2007. Department of Health, Antimicrobial Stewardship - Start Smart then Focus, 2011. (2015 update) https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/417032/start_smart_then_focus_final. PDF British National Formulary 73 March 2017 September 2017 Version 4.0 Review Date: August 2018 Page 3 of 57

2 Recommendations for the prudent use of antimicrobials 2.1 Principles of good antibiotic prescribing Only prescribe antimicrobials when there is clear benefit to the patient. Always take appropriate cultures before antibiotic administration where clinically feasible. Consider individual patient factors in all cases: Allergies/previous antibiotic history/previous infection with multi-resistant organism (such as MRSA or ESBL producing E.coli) / availability of oral route/renal &hepatic dysfunction/pregnancy or breast feeding/immunocompromised, predisposition to C.difficile infection. Review therapy at least every 48hrs Follow up all investigations (radiology, microbiology and serology) and rationalise antibiotics according to results. Review need for IV therapy at least every 24 hours and switch to oral alternative as soon as possible (ideally before 48hrs). Total duration (IV and PO) should not exceed 5 days unless recommended by a microbiologist or stated in this guideline. Longer duration of antibiotics are required for endocarditis, meningitis, osteomyelitis, septic arthritis, Staphylococcus aureus bacteraemia, septicaemia, severe cellulitis, serious deep seated infection or abscess. Therapeutic Drug Monitoring (TDM) is required for patients on Gentamicin, Vancomycin, Amikacin. Please refer to TDM guidance in Appendix A. TDM may also be required for other antimicrobial such as Teicoplanin but this will be on the advice of a Consultant Microbiologist. Version 4.0 Review Date: August 2018 Page 4 of 57

2.2 Reducing/preventing C.difficile infections AVOID all cephalosporins, Co-amoxiclav, quinolones (Ciprofloxacin etc) and Clindamycin especially in patients over 65 years of age. Prescribe narrow spectrum antibiotic for the shortest duration when clinical evidence of infection present. Review laxative and PPI use in elderly patients and consider stopping. 2.3 IV to Oral Switch Guidance Review need for IV therapy daily and switch to oral alternative as soon as possible (ideally before 48hrs). Clarithromycin, Metronidazole, Rifampicin, Ciprofloxacin, Clindamycin, Coamoxiclav, and Fluconazole have excellent tissue and cell penetration when taken orally. There is no advantage in using any of these drugs IV unless the patient cannot absorb them from the gut or is nil by mouth. The following features indicate a response to initial IV therapy and need for oral switch: o o o o o o o o Absence of positive blood cultures in the past 48 hours Temperature <38 O C for more than 48 hours Oral fluids tolerated (by mouth, NG or PEG tube) No ongoing or potential problems with GI absorption, diarrhoea or vomiting White cell count and/ or CRP are returning to normal Pulse Rate <100 beats/min Patient is not immunocompromised (HIV positive, neutropenic, on steroids, azathioprine, ciclosporin or cytotoxics) A suitable oral antimicrobial is available Oral switch options in this guidance are based on empirical choice. Eventual choice should be based on microbiology results and likely focus of infection. 2.4 Clinical advice Advice from a Consultant Microbiologist is available via switchboard. This is a consultant referral. Ensure that you have reviewed the patient s notes and drug chart and examined the patient before the call. Out of hours, a Consultant Microbiologist is available for emergency specialist advice if you cannot find it elsewhere (i.e. in this book, full antibiotic policy, the patient s notes, or from your senior colleagues). Document the clinical advice in the patient s notes. 2.5 Restricted antibiotics Piperacillin -Tazobactam (Tazocin), Temocillin, Meropenem, Teicoplanin, Ciprofloxacin, Clindamycin, Amikacin, Linezolid, Fosfomycin, Ertapenem, IV Vancomycin, Daptomycin, Ceftazidime and Fidaxomicin are restricted antibiotics. They can only be prescribed on Consultant Microbiologist advice when used outside of these guidelines. Please document in the patient s notes that the drug has been approved and by whom and complete the restricted antibiotics form on CRS. Out of hours restricted antibiotics may be prescribed by the Specialty trainee or above but must be discussed with the Consultant Microbiologist within 24 hours. All antifungals except Fluconazole and Nystatin are restricted except for use in ITU, Paediatrics and Haematology/Oncology. Version 4.0 Review Date: August 2018 Page 5 of 57

2.6 Penicillin allergy or NOT? True allergy is often confused with drug side effects i.e. nausea, vomiting and diarrhoea. 80-90% of patients who say they are allergic to penicillin are not. An accurate history and nature of the allergy should be taken and documented on the drug chart and in the notes. The following symptoms which have occurred during or immediately after a penicillin, indicate a true allergy: Bronchospasm causing breathlessness Urticaria/ rash/ erythema/ angioedema/ pruritis Oedema of the face, pharynx and larynx Profound hypotension and pulmonary oedema Patients with a history of a minor rash restricted to a small area of the body, or a rash that occurs more than 72 hours after penicillin administration are unlikely to have a true penicillin allergy. In these patients, penicillin should not be withheld unnecessarily for serious infections. A traffic light system is used in this document to facilitate drug choice in those patients with a true allergy to penicillin: RED penicillin based drugs contra-indicated in true penicillin allergy (e.g Flucloxacillin, Co-amoxiclav, Piperacillin-Tazobactam (Tazocin)) AMBER drugs structurally related to penicillin - upto10% of penicillin-allergic patients may exhibit cross-reactivity to these agents. If history of anaphylaxis, angioedema (blistering or swelling), erythroderma / Stevens-Johnson syndrome or bronchospasm, to a penicillin, these drugs should be avoided cephalosporins (e.g. Cefuroxime, Ceftriaxone) carbapenems (e.g. Meropenem, Ertapenem) GREEN considered safe in penicillin allergy e.g. Clarithromycin, Gentamicin, Teicoplanin, Vancomycin, Metronidazole. 2.7 Specimens Before starting antibiotics, take appropriate specimens to aide/confirm diagnosis. Specimens should be of good quality ie. Tissue or pus in sterile container rather than a swab, purulent sputum rather than saliva, faeces rather than rectal swab. Take blood for culture in accordance with the Trust Blood Culture policy on PIMS. Out of hours specimens that need to processed urgently: the oncall Biomedical Scientist should be contacted via Kingston or St George s switchboard 020 8672 1255 and air-call SG394. The requestor must give the air call switchboard their full contact telephone number and name. Version 4.0 Review Date: August 2018 Page 6 of 57

3 Bone and Joint Infections Infection First Line antibiotic Alternative or True penicillin allergy Oral Switch Total Duration (IV+PO) Septic arthritis Native joint Flucloxacillin IV 2g QDS If MRSA +ve *Teicoplanin 12mg/kg IV 12 hourly for 3 doses then 12mg/kg OD *Teicoplanin 12mg/kg IV 12 hourly for 3 doses then 12mg/kg OD Guided by culture and sensitivity results. Initially 2 weeks IV followed by 4 weeks oral therapy BUT confirm sensitivities with microbiology results Prosthetic Joint Discuss with Microbiology Consultant Osteomyelitis Flucloxacillin IV 2g QDS Consider addition of PO Rifampicin 600mg BD or Sodium Fusidate 500mg TDS for first two weeks *Teicoplanin 12mg/kg IV 12 hourly for 3 doses then 12mg/kg OD Consider addition of PO Rifampicin 600mg BD or Sodium Fusidate 500mg TDS for first two weeks Guided by culture and sensitivity results. 4 6 weeks minimum Total duration depends on success of debridement, organisms isolated, response to treatment. * Round Teicoplanin doses to the nearest 200mg. Maximum initial teicoplanin dose 1.200mg. Monitor Teicoplanin levels take a trough level between day 3 to 5 and repeat at least once a week thereafter. Adjust dose based on levels References C. Mathews et al, (on behalf of the British Society for Rheumatology Standards, Guidelines and Audit Working Group.) BSR & BHPR, BOA, RCGP and BSAC Guidelines for the management of the hot swollen joint in adults. Rheumatology 2006; 1-22. http://rheumatology.oxfordjournals.org/content/45/8/1039.full.pdf+html Version 4.0 Review Date: August 2018 Page 7 of 57

4 Cardiovascular System Infections See Appendix A for Gentamicin (low dose for bacterial endocarditis) & Vancomycin monitoring and dosing. 4.1 Bacterial Endocarditis Empirical Therapy Infection First Line Antibiotic Alternative or True penicillin allergy Total Duration (IV) Bacterial Endocarditis - Empirical therapy If non acute / chronic presentation, take three blood cultures at least 6 hours apart before starting antibiotic treatment. If severe sepsis, take two blood cultures at different times and give empirical treatment, all within one hour. Native valve or late prosthetic valve (>1 year post surgery) Amoxicillin 2g IV 4 hourly plus Flucloxacillin 2g 4 hourly plus *Gentamicin 3mg/kg IV 24 hourly, modified according to renal function Early prosthetic valve (<1 year post surgery) **Vancomycin IV, modified according to renal function plus Rifampicin 600mg PO 12 hourly plus *Gentamicin 3mg/kg IV 24 hourly, modified according to renal function **Vancomycin IV, modified according to renal function plus *Gentamicin 3mg/kg IV 24 hourly, modified according to renal function **Vancomycin IV, modified according to renal function plus Rifampicin 600mg PO 12 hourly plus *Gentamicin 3mg/kg IV 24 hourly, modified according to renal function 2 6 weeks Depending on likely causative organism * For guidance on Gentamicin prescribing in endocarditis refer to Appendix A.2 **For guidance on Vancomycin prescribing refer to Appendix A.5 Version 4.0 Review Date: August 2018 Page 8 of 57

4.2 Bacterial Endocarditis Organism known *MIC=minimum inhibitory concentration (as advised by microbiology sensitivity result) Routine switch to oral antimicrobials is not recommended. Infection First Line Antibiotic Alternative or True penicillin allergy Streptococci Amoxicillin 2g IV 4 hourly Duration: 2 weeks **Vancomycin IV, modified according to renal function (4 to 6 weeks) Streptococci (relatively penicillin resistant) Native valve: Staphylococci - Methicillin sensitive Native valve: Staphylococci - Methicillin resistant Amoxicillin 2g IV 4 hourly plus *Gentamicin 3mg/kg IV 24 hourly, modified according to renal function Duration: 4 6 weeks for both antibiotics Flucloxacillin 2g IV 4 hourly Duration: 4 weeks **Vancomycin IV, modified according to renal function (4 to 6 weeks) Duration: 4 weeks **Vancomycin IV, modified according to renal function (4 to 6 weeks) plus *Gentamicin 3mg/kg IV 24 hourly, modified according to renal function Discuss with Consultant Microbiologist before starting if high risk of nephrotoxicity **Vancomycin IV, modified according to renal function Duration: 4 weeks Prosthetic Valve: Staphylococci - Methicillin sensitive Prosthetic valve: taphylococci - Methicillin resistant Enterococcus Flucloxacillin 2g IV 4 hourly (Duration: 6 weeks) plus Rifampicin 600mg PO 12 hourly (Duration: 6 weeks) plus *Gentamicin 3mg/kg IV 24 hourly, modified according to renal function (Duration > 2 weeks) **Vancomycin IV, modified according to renal function plus Rifampicin 600mg PO 12 hourly plus *Gentamicin 3mg/kg IV 24 hourly, modified according to renal function Amoxicillin 2g IV 4 hourly plus *Gentamicin 3mg/kg IV 24 hourly, modified according to renal function Duration: 4 6 weeks for both antibiotics **Vancomycin IV, modified according to renal function plus Rifampicin 600mg PO 12 hourly plus *Gentamicin 3mg/kg IV 24 hourly, modified according to renal function Discuss with Consultant Microbiologist **Vancomycin IV, modified according to renal function plus *Gentamicin 3mg/kg IV 24 hourly, modified according to renal function for 2 weeks Duration: 4 6 weeks Discuss with Consultant Microbiologist before starting if high risk of nephrotoxicity * For guidance on Gentamicin prescribing in endocarditis refer to Appendix A.2 ** For guidance on Vancomycin prescribing refer to Appendix A.5 Version 4.0 Review Date: August 2018 Page 9 of 57

Reference 2015 ESC Guidelines for the Management of Infective Endocarditis European Heart Journal (2015) 36, 3075-3123 http://eurheartj.oxfordjournals.org/content/36/44/3075 Guidelines for the antibiotic treatment of endocarditis in adults: report of the Working Party of the British Society for Antimicrobial Chemotherapy. J. Antimicrob. Chemother., 2012; 67: 269 289 http://jac.oxfordjournals.org/content/67/2/269.full.pdf+html Version 4.0 Review Date: August 2018 Page 10 of 57

5 Central Nervous System Infections 5.1 Bacterial Meningitis Take blood cultures. Perform lumbar puncture (LP) if no contraindications. If LP or blood culture delayed, first dose of antibiotics should be given. Notify Public Health: 0344 326 2052. Contact tracing is necessary for cases of Haemophilus influenzae, meningococcal meningitis and TB meningitis see also prophylaxis table in Section 5.3 Give dexamethasone 10mg IV 6 hourly before or up to 12 hours after administration of first dose of antibiotic (esp. if suspecting pneumococcal meningitis) - AVOID in septic shock, meningococcal septicaemia, immunosuppression and following neurosurgery. If pneumococcal meningitis confirmed, continue for 4 days. If other pathogen confirmed, stop dexamethasone. Organism First line Antibiotic Alternative or True penicillin allergy Total Duration (IV) Empiric / organism not known Consider adding treatment for Listeria (see below) if 60 years old or immunocompromised Ceftriaxone 2g IV BD Ceftriaxone may still be suitable in patients with mild penicillin allergy 10 days Haemophilus influenzae Ceftriaxone 2g IV BD 10 days Meningococcus Benzylpenicillin 2.4g IV every 4 hours followed by Ciprofloxacin 500 mg PO as a single dose (not required if patient has received at least one dose of Ceftriaxone) Chloramphenicol 25mg/kg IV QDS decrease dose as soon as clinically indicated carries a risk of aplastic anaemia monitor full blood count 5-7 days Pneumococcus Consider dexamethasone (see above) Ceftriaxone 2g IV BD If travelled in last 6 months to country with high rate of resistant pneumococci**: Add *Vancomycin IV or Rifampicin 600mg PO/IV BD 10-14 days Listeria consider in 60 years old or immunocompromised Tuberculosis Amoxicillin 2g IV 4 hourly Co-trimoxazole 5mg/kg QDS IV 21 days Contact Consultant Microbiologist and Respiratory physicians. *For guidance on Vancomycin prescribing refer to Appendix A.5 ** Canada, China, Croatia, Greece, Italy, Mexico, Pakistan, Poland, Spain, Turkey, USA. Full list: http://bit.ly/1kosckx and http://bit.ly/1rob3cx Version 4.0 Review Date: August 2018 Page 11 of 57

5.2 Other CNS Infections Organism First Line Antibiotic Alternative Total Duration (IV) Brain Abscess Discuss with neurosurgical team re: surgical drainage *Vancomycin IV 12 hourly, modified according to renal function + Metronidazole 400mg PO TDS plus Ceftriaxone 2g IV BD ** Chloramphenicol 25mg/kg IV QDS (decrease dose as soon as clinically indicated) plus * Vancomycin IV 12 hourly, modified according to renal function Clinical review at 6 weeks Viral meningoencephalitis (suspected or confirmed HSV and VZV) Aciclovir 10mg/kg IV TDS (based on ideal body weight if obese) Oral Aciclovir is NOT effective 14-21 days Enteroviruses are the commonest cause of viral meningitis. Antivirals are not indicated and no antibiotics necessary, remember to take stool sample and viral throat swab to aid diagnosis *For guidance on Vancomycin prescribing refer to Appendix A.5 **Chloramphenicol carries a risk of aplastic anaemia monitor full blood count at least twice weekly Version 4.0 Review Date: August 2018 Page 12 of 57

5.3 Prophylaxis for Contacts of Haemophilus and Meningococcus Meningitis Prophylaxis with Ciprofloxacin should be given to all household contacts. This includes all children below 4 years of age, regardless of their immunisation status. Infection First Line antibiotic Alternative if contra-indication to First Line Prophylaxis of meningococcal and Haemophilus influenzae meningitis Pregnant and breast-feeding women should be counselled about the risks/benefits of receiving antibiotic prophylaxis Adults and children over 12years: Ciprofloxacin 500 mg PO as a single dose Child 5-12years: Ciprofloxacin 250mg PO as a single dose Child 1month 4years: Ciprofloxacin 30mg/kg PO as a single dose (maximum 125mg) Adults and children over 12years: Rifampicin 600 mg PO BD for 2 days Child 1-12 years Rifampicin 10 mg/kg PO BD for 2 days Child under 1year Rifampicin 5 mg/kg PO BD for 2 days Pregnancy Azithromycin 500mg as a single dose. References McGill F, et al.,the UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults, J Infection (2016), Volume 72, Issue 4, 405 438 http://www.journalofinfection.com/article/s0163-4453(16)00024-4/fulltext Heyderman RS et al (on Behalf of British Infection Society). Early management of suspected meningitis and meningococcal septicaemia in adults. Journal of Infection. 2003; 46: 75-77 Fitch MT et al. Emergency diagnosis and treatment of adult meningitis. Lancet Infectious Diseases. 2007; 7: 191-200 Tunkel AR et al (On behalf of the Infectious Diseases Society of America). Practice guidelines for the management of bacterial meningitis. Clinical Infectious Diseases 2004; 39: 1267-84 http://www.idsociety.org/uploadedfiles/idsa/guidelines-patient_care/pdf_library/bacterial%20meningitis(1).pdf Guidelines for public health management of meningococcal disease in the UK (2011) updated August 2015 Solomon T, Michael BD, Smith PE, Sanderson F, Davies NWS, Hart I, et al. National ABN/BIA guideline for the management of encephalitis for adults. J Infect 2012;64(4):347-73 http://www.encephalitis.info/files/2613/5480/9792/yjinf_2823.pdf Version 4.0 Review Date: August 2018 Page 13 of 57

6 Gastrointestinal Infections (including Clostridium difficile infection) Note: Cefalexin should NOT be used. It does not have as broad a spectrum of activity as IV cephalosporins. *For guidance on Gentamicin prescribing refer to the online Gentamicin Calculator and Appendix A. 6.1 Gastrointestinal Infections Infection Campylobacter Usually no antibiotic required. First Line Antibiotic If severe, recurrent or persistent Clarithromycin 500mg PO BD If septicaemia Clarithromycin 500mg PO BD plus *Gentamicin IV OD Alternative or True penicillin allergy Oral switch Total Duration (IV+PO) Seek advice Clarithromycin 500mg PO BD 5 days Cholecystitis / biliary sepsis Amoxicillin 1g IV TDS + Metronidazole 500mg IV TDS plus *Gentamicin IV OD If Jaundice with suspected ascending cholangitis Piperacillin-Tazobactam (Tazocin) 4.5 g IV TDS Metronidazole 500mg IV TDS plus *Gentamicin IV OD Patients <65 years: Co-amoxiclav 625mg PO TDS Patients >65years or otherwise at risk of C.difficile: Amoxicillin 500mg PO TDS plus Metronidazole 400mg PO TDS 5 days Diverticulitis Cefuroxime 1.5g IV TDS plus Metronidazole 500mg IV TDS Metronidazole 500mg IV TDS plus *Gentamicin IV OD Penicillin Allergy: Trimethoprim 200mg PO BD plus Metronidazole 400mg PO TDS 5 days Gastroenteritis (Enteropathic E.coli, Salmonella spp, Shigella) Generally avoid antibiotics: antibiotics prolong carriage of organism. First Line Antibiotic Alternative or True penicillin allergy Oral switch Total Duration (IV+PO) Version 4.0 Review Date: August 2018 Page 14 of 57

Infection H. pylori eradication First Line Antibiotic Omeprazole 20mg PO BD plus Clarithromycin 500mg PO BD plus Amoxicillin 1g PO BD if appropriate, continue Omeprazole 20mg PO OD (refer to BNF) Alternative or True penicillin allergy Omeprazole 20mg PO BD plus Clarithromycin 500mg PO BD plus Metronidazole 400mg PO BD Oral switch See left columns Total Duration (IV+PO) 7 days Prophylaxis in Cirrhosis with GI Bleed Piperacillin-Tazobactam (Tazocin) 4.5g IV TDS Meropenem 1g IV TDS Seek advice from Consultant Microbiologist 5 days Pancreatitis Antibiotics routinely not indicated. If CT evidence of >30% necrosis Piperacillin-Tazobactam (Tazocin) 4.5g IV TDS If CT evidence of >30% necrosis: Meropenem 1g IV TDS Oral antibiotics may not be appropriate in severe sepsis 5 days (longer if abscess/cyst present) Spontaneous Bacterial Peritonitis If WBC >250/ml (mainly neutrophils) or >300/ml (mainly lymphocytes) Piperacillin-Tazobactam (Tazocin) 4.5g IV TDS Meropenem 1g IV TDS Guided by culture and sensitivity result 5 days Prophylaxis following SBP Refer to Gastroenterology Team Localised or generalised peritonitis e.g. after perforation of the appendix or colon Amoxicillin 1g IV TDS plus Metronidazole 500mg IV TDS plus *Gentamicin IV OD Metronidazole 500mg IV TDS plus *Gentamicin IV OD If < 65 years old Co-amoxiclav 625mg PO TDS Patients >65years or otherwise at risk of C.difficile Amoxicillin 500mg PO TDS plus Metronidazole 400mg PO TDS 5 days References Test and treat for Helicobacter pylori (HP) in Dyspepsia, Quick Reference Guide for Primary Care, For consultation and local adaptation. PHI and BIA. July 2012 https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/346305/helicobacter_guidance_update_post_maastricht_iv_24_10.pdf UK guidelines for the management of acute pancreatitis. UK Working Party on Acute Pancreatitis. Gut 2005; 54;1-9. http://www.bsg.org.uk/pdf_word_docs/pancreatic.pdf Soares-Weiser K, Brezis M, Tur-Kaspa R, Leibovici L. Antibiotic prophylaxis for cirrhotic patients with gastrointestinal bleeding. Cochrane Database of Systematic Reviews 2002, Issue 2. Art. No.: CD002907. DOI: 10.1002/14651858.CD002907. Cohen MJ, Sahar T, Benenson S, Elinav E, Brezis M, Soares-Weiser K. Antibiotic prophylaxis for spontaneous bacterial peritonitis in cirrhotic patients with ascites, without gastrointestinal bleeding. Cochrane Database of Systematic Reviews 2009, Issue 2. Art. No.: CD004791. DOI: 10.1002/14651858.CD004791.pub2. Version 4.0 Review Date: August 2018 Page 15 of 57

6.2 Clostridium difficile infection (CDI) The full policy is available on the hospital intranet Policies Information Management System (PIMS) Prevention Use the narrowest spectrum antibiotic for the shortest time possible AVOID all cephalosporins, Co-amoxiclav, quinolones (Ciprofloxacin etc) and Clindamycin especially in patients over 65 years of age. Always review and restrict the use of proton pump inhibitors e.g. omeprazole Do not use Metronidazole to prevent infection in patients receiving antibiotics Management of suspected or confirmed C. difficile infection Send a stool sample if clinically indicated: request C. difficile testing and state antibiotic history Stop precipitating antibiotic if possible and substitute with an agent less likely to induce CDI Apply general infection control measures Refer to the diarrhoea care bundle Avoid antiperistaltic agents in acute infection (they may precipitate toxic megacolon); STOP laxatives, Review the need for proton pump inhibitors (PPIs) which are a risk factor for CDI Consider prescribing barrier agents to prevent skin excoriation: Cavilon spray and/or Hydromol ointment Version 4.0 Review Date: August 2018 Page 16 of 57

Severity Mild disease Moderate disease Severe disease Any of the following indicate severe CDI: WCC > 15 10 9 /L; Acutely rising blood creatinine (e.g. >50% increase above baseline); Temperature >38.5ºC; or Evidence of severe colitis (abdominal signs, radiology) Recurrent infection Intractable infection Action May not require treatment. If treatment is required use oral Metronidazole* 400 mg TDS for 10 days. Oral Metronidazole* 400mg TDS for 10 days. 1 st line: **Oral Vancomycin 125 mg QDS for 10 days 2 nd line: **Oral Vancomycin 250 mg QDS for 10 days plus IV Metronidazole 500 mg TDS for 10 days 3 rd line: consider Fidaxomicin** 200 mg BD for those with severe CDI who are at high risk of recurrence, including elderly patients with multiple comorbidities who are receiving concomitant antibiotics. The addition of PO Rifampicin 300 mg BD or IV immunoglobulin 0.40 g/kg may also be considered after discussion with microbiology consultant. ***Oral Vancomycin 125 mg QDS for 10 days Discuss Fidaxomicin** 200 mg BD with Consultant microbiologist if fails to respond to Vancomycin Tapering doses of oral Vancomycin : Discuss with Consultant Microbiologist before commencing 125 mg QDS for one week, 125 mg BD for one week, 125 mg od for one week, 125 mg on alternate days for one week, 125 mg every third day for one week (six weeks in total). *For patients with a nasogastric tube contact pharmacy as metronidazole liquid cannot be used. **Fidaxomicin is a restricted antibiotic please discuss with Consultant Microbiologist before commencing. *** Vancomycin vials for parenteral administration may be used orally if patient has a nasogastric tube or swallowing difficulties. Reconstitute a 500mg vial with 10ml water for injections. Dilute the required dose in 20-30 ml of water. Reconstituted solution can used for up to 24 hours if stored in the fridge Reference Updated guidance on the management and treatment of Clostridium difficile infection. Public Health England, 2013. http://www.hpa.org.uk/webc/hpawebfile/hpaweb_c/1317138914904 Version 4.0 Review Date: August 2018 Page 17 of 57

7 Respiratory System Infections *For guidance on Gentamicin prescribing refer to the online Gentamicin Calculator and Appendix A Infection First Line Antibiotic Alternative or True penicillin allergy Community acquired pneumonia (CAP) CURB-65 Score: 0-1 Amoxicillin PO 500mg TDS CURB-65 Score: 0-1 Clarithromycin PO 500mg BD Oral Switch See left columns Total Duration (IV+PO) Also refer to the Community Acquired Pneumonia Pathway bundle below Clinical signs of consolidation +/- Evidence of consolidation on CXR Assess severity using the CURB-65 score below (1 point for each feature present): new Confusion Urea > 7 mmol/l Respiratory rate > 30/min Blood pressure (SBP <90mmHg or DBP < 60 mmhg) Age > 65 years CXR findings and CURB-65 score MUST be documented CURB-65 Score: 2 Amoxicillin PO 500mg TDS plus Clarithromycin PO 500mg BD CURB-65 Score: 3 to 5 (not requiring HDU/ITU care) Amoxicillin IV 1g TDS plus Clarithromycin PO/IV 500mg BD CURB-65 Score: 2 Doxycycline 200 mg PO STAT on day 1 followed by 100mg OD PO from day 2-5 CURB-65 Score: 3 to 5 (not HDU/ITU) Teicoplanin IV refer to dosing table in Appendix A + Clarithromycin PO/IV 500mg BD Clarithromycin Mycoplasma infection is uncommon in patients aged > 65 years. Stop Clarithromycin as soon as clinically indicated. See left columns CURB-65 Score: 3 to 5 (not requiring HDU/ITU) care Amoxicillin PO 500mg TDS +/- Clarithromycin PO 500mg BD 5 days Suspected atypical pneumonia (excludes patients known or strongly suspected to be HIV positive) If HIV risk seek advice from GUM Consultants Clarithromycin PO 500 mg BD Clarithromycin PO 500 mg BD See left columns Minimum 7 days Hospital Acquired Pneumonia (Infection occurring 5 days hospital stay) Evidence of new consolidation on CXR. Clinical findings must be documented Send sputum Mild Doxycycline 200 mg PO STAT on day 1 followed by 100mg OD PO from day 2-5 Severe Amoxicillin 1g IV TDS plus *Gentamicin IV OD Seek advice Teicoplanin IV refer to dosing table in Appendix A plus *Gentamicin IV OD Doxycycline 200 mg PO STAT on day 1 followed by 100mg OD PO from day 2-5 5 days Version 4.0 Review Date: August 2018 Page 18 of 57

Infection First Line Antibiotic Alternative or True penicillin allergy Oral switch Total Duration (IV+PO) Aspiration pneumonia only indicated if pneumonic signs present not indicated on day of aspiration Send sputum. Document CXR changes 48-72 hours after aspiration Amoxicillin 1g IV TDS plus *Gentamicin IV OD plus Metronidazole PO 400mg TDS / IV 500mg TDS Teicoplanin IV refer to dosing table in Appendix A plus Metronidazole PO 400mg TDS / IV 500mg TDS plus *Gentamicin IV OD Clarithromycin PO 500mg BD plus Metronidazole PO 400mg TDS 5 days Mycobacterium TB Notifiable Refer to Respiratory physician Send three sputum samples ( taken on three separate days) for AFB investigation Infection control precautions until initial two weeks of effective therapy completed 6 9 months Determined by site of disease and response to therapy Infective exacerbation of COPD Only needs treating with antibiotics if increasing purulence of sputum or CXR changes. A sputum sample should be sent for culture. Review appropriateness of antibiotics when sensitivities become available. Doxycycline 200 mg PO STAT on day 1 followed by 100mg OD PO from day 2-5 If CXR changes of pneumonia Use CAP / HAP protocol above as appropriate Clarithromycin PO 500 mg BD If CXR changes Use CAP / HAP protocol accordingly See left columns 5 days Version 4.0 Review Date: August 2018 Page 19 of 57

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Infection First Line Antibiotic Alternative if true allergy to First Line Total Duration (IV+PO) Acute sore throat Viral - No antibiotic required Majority are viral If fever, purulent tonsils, cervical lymphadenopathy and absence of cough then may benefit from antibiotics Streptococci Penicillin V 500mg PO QDS (Avoid Amoxicillin as it causes rash in EBV/glandular fever) Clarithromycin PO 500mg BD 10 days Penicillin V 5 days Clarithromycin Acute otitis media 60% resolve without antibiotics Sinusitis Majority are viral Amoxicillin PO 500mg TDS Clarithromycin PO 500mg BD 5 days Amoxicillin PO 500mg TDS Doxycycline 200 mg PO STAT on day 1 followed by 100mg OD PO from day 2-5 7 days Acute epiglottitis Ceftriaxone 2g IV OD Not appropriate 7-10 days Diphtheria Notifiable: Contact Consultant Microbiologist References Lim WS, Baudouin SV, George RC et al. British Thoracic Society guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax 2009;64(Suppl III):iii1 iii55. http://www.brit-thoracic.org.uk/portals/0/clinical%20information/pneumonia/guidelines/capguidelinefull.pdf National Institute for Health and Clinical Excellence. (2010). Chronic obstructive pulmonary disease in over 16s: diagnosis and management (CG101) https://www.nice.org.uk/guidance/cg101/resources/chronic-obstructive-pulmonary-disease-in-over-16s-diagnosis-and-management-35109323931589 National Institute for Health and Clinical Excellence(2014). Pneumonia in adults: diagnosis and management (CG191) https://www.nice.org.uk/guidance/cg191/resources/pneumonia-in-adults-diagnosis-and-management-35109868127173 HPA: Management of Infection guidance for Primary care- for consultation & local adaptation, May 2016 https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/524984/management_of_infection_guidance_for_primary_care_for_consultation_and_local_adaptatio n.pdf Version 4.0 Review Date: August 2018 Page 21 of 57

8 Sepsis Also refer to severe sepsis guidelines in the Blue Book. In suspected sepsis, take blood cultures and start broad spectrum antibiotics within one hour. The Surviving Sepsis Campaign recommends that intravenous antibiotic therapy be started as early as possible and within the first hour of recognition of septic shock. Consider oral switch at 48 hours. Oral choice depends on the subsequent identification of the focus of infection. *For guidance on Gentamicin prescribing refer to the online Gentamicin Calculator and Appendix A. Likely source of infection First Line Antibiotic Alternative or True penicillin allergy Total Duration (IV+PO) Severe Sepsis of UNKNOWN SOURCE Efforts should be made to find source Request chest x-ray, send urine, blood cultures and other relevant samples as part of septic screen; check any previous culture results for resistant organisms Intra-abdominal or pelvis IV catheter - peripheral or central (Remove line if possible) Soft tissue/skin e.g. cellulitis Urinary Tract Amoxicillin 1g IV TDS plus *Gentamicin IV OD If high risk for MRSA or colonised: Teicoplanin IV refer to dosing table in Appendix A plus *Gentamicin IV OD Amoxicillin 1g IV TDS plus *Gentamicin IV OD plus Metronidazole 400mg PO TDS Flucloxacillin 1g IV QDS. If >85kg 2g IV QDS If MRSA colonised Teicoplanin IV refer to dosing table in Appendix A Flucloxacillin 2g IV QDS If high risk for MRSA or colonised Teicoplanin IV refer to dosing table in Appendix A *Gentamicin IV OD plus Amoxicillin 1g IV TDS Teicoplanin IV refer to dosing table in Appendix A plus *Gentamicin IV OD Teicoplanin IV refer to dosing table in Appendix A plus *Gentamicin IV OD plus Metronidazole 400mg PO TDS Teicoplanin IV refer to dosing table in Appendix A Teicoplanin IV refer to dosing table in Appendix A *Gentamicin IV OD alone 5 14 days depending on focus and clinical response Version 4.0 Review Date: August 2018 Page 22 of 57

9 Skin and Soft Tissue Infections Cellulitis - CONSIDER IV TO ORAL SWITCH AT 48 HOURS Ideally send tissue/pus in sterile container (rather than wound swab). Infection First Line Antibiotic Alternative or True penicillin allergy Oral switch Total Duration (IV+PO) Breast abscess/mastitis Flucloxacillin 1g IV/PO QDS If septic, rapidly spreading cellulitis or systemic features consider increasing to Flucloxacillin 2g IV QDS Breast abscess - Clarithromycin 500mg PO BD Mastitis Erythromycin 500mg IV/PO QDS See left columns 5 10 days Cellulitis/ Phlebitis (including peri-orbital cellulitis) Draw demarcation lines to follow progress Send wound swab if broken skin Check for previous MRSA results Non Severe Flucloxacillin PO 1g QDS Severe Cellulitis Flucloxacillin IV 2g QDS MRSA colonisation or infection: Teicoplanin IV refer to dosing table in Appendix A Non Severe Clarithromycin 500mg PO BD Severe Cellulitis Teicoplanin IV refer to dosing table in Appendix A Flucloxacillin PO 1g QDS 5 14 days depending on clinical response Diabetic foot infection SEE APPENDIX E Human or animal bites Leg ulcers and pressure sores Necrotising fasciitis Wound infections Co-amoxiclav 625mg PO/ 1.2g IV TDS Cat/dog bite- Doxycycline PO 100 mg BD plus Metronidazole PO 400mg TDS Human bite Clarithromycin PO 500mg BD (or Doxycycline PO 100 mg BD) plus Metronidazole PO 400mg TDS See left columns 7 days. Review at 24 and 48 hours Chronic ulcers will always be colonised with organisms. Swabbing of the site and antibiotics are only indicated if there is evidence of acute infection: increased pain, cellulitis, pyrexia, raised WCC. Medical / Surgical emergency: Discuss with Consultant Microbiologist and on call surgical team. Send blood culture, tissue sample, or swab from broken or weeping site. Should be drained and only treated with antibiotics if the patient is septicaemic or has spreading cellulitis. Version 4.0 Review Date: August 2018 Page 23 of 57

10 Urogenital Infections Take specimen(s) for culture and sensitivities and then start treatment. Therapy must be changed later in the light of the results. Clearly state specimen type: MSU or CSU. In young sexually active men consider urethritis in the differential diagnosis. If there is a discharge present refer to the Wolverton Centre for Sexual Health. Check previous urine results including those sent by GP surgeries for multiresistant organisms eg ESBL producing E coli/klebsiella (any site) in the previous 24 months. Asymptomatic bacteriuria: Should only be treated before urological procedures or in pregnancy Asymptomatic bacteruria in the elderly should not be treated: treatment does not reduce mortality or symptoms but increases the risk of adverse events. Catheterised patients: All catheters will become colonised with organisms within 24 to 48 hours of insertion. Do not treat a positive CSU culture unless there are clinical signs and symptoms of infection Only send urine samples for laboratory culture if the patient has clinical sepsis, not because of the appearance or smell of the urine In catheterised patients who present with fever: o look for associated localising (loin or supra-pubic tenderness) or systemic features o exclude other potential sources of infection o send an appropriately taken CSU sample for culture to determine the infecting organism and susceptibility to antibiotics o consider antibiotic therapy taking into account the severity of the presentation and any comorbid factors. CONSIDER IV TO ORAL SWITCH AT 48 HOURS For guidance on Gentamicin prescribing refer to the online Gentamicin Calculator and Appendix A. Version 4.0 Review Date: August 2018 Page 24 of 57

Infection First Line Antibiotic Alternative or True penicillin allergy Uncomplicated UTI Dysuria, urgency, frequency, suprapubic tenderness +/-low grade fever 37.9 o C) and no back pain. Nitrofurantoin 50mg PO QDS (Avoid if CrCl less than 45ml/min) Trimethoprim 200mg PO BD Review when sensitivities are known Oral switch Total Duration (IV+PO) Men: 7 days Women: 3 days Acute Pyelonephritis Mild: loin pain, flank tenderness, +/- low grade fever 37.9 o C Severe: Fever >38 C, rigors, loin pain, flank tenderness, nausea, vomiting, tachypnoea, tachycardia, hypotension, confusion Mild Trimethoprim 200mg PO BD Severe: Amoxicillin 1g IV TDS plus *Gentamicin IV OD *Gentamicin IV OD alone Guided by sensitivities. Do not switch to oral amoxicillin as monotherapy without sensitivity data 10 Days Catheter UTI Catheter urine specimens are usually dipstick and culture positive. Treat with antibiotics only if the patient is symptomatic. Remove catheter if possible. Be guided by sensitivities. Catheter change/insertion: antibiotic prophylaxis not routinely required - see surgical prophylaxis Appendix B for details. 7 days UTI in pregnancy For pyelonephritis in pregnancy see separate guideline on PIMS Amoxicillin 500mg PO TDS (if susceptible) or Cefalexin 500mg PO TDS Nitrofurantoin 50mg PO QDS (avoid at term and if CrCl less than 45ml/min) 7 days Endometritis Send HVS and ECS for chlamydia Cefuroxime 1.5g IV TDS plus Metronidazole 500mg IV TDS Seek advice Co-amoxiclav 625mg PO TDS Add Erythromycin 500mg QDS if Chlamydia positive 7 days Epididymo-orchitis Send urethral swabs and urine for culture and sensitivity and urine sample for Chlamydia NAAT testing Ceftriaxone 500mg IM immediately (single dose) plus Ciprofloxacin 500mg PO BD Patients who are sexually active Add Doxycycline 100mg BD Seek advice Ciprofloxacin for 14 days Doxycycline for 10 days Version 4.0 Review Date: August 2018 Page 25 of 57

Infection First Line Antibiotic Alternative or True penicillin allergy Pelvic inflammatory disease (PID) Mild PID Ceftriaxone 500mg IM immediately If NIL by mouth (single dose) Followed by : Ceftriaxone dosed as in left column Doxycycline 100mg PO BD plus Metronidazole 400mg PO BD Acute Prostatitis Severe PID Ceftriaxone 2g IV OD plus Doxycycline 100mg PO BD plus Metronidazole 400mg PO BD Stop Ceftriaxone when apyrexial for 48 hrs, Take blood cultures Cefuroxime 1.5g IV TDS plus *Gentamicin IV OD Followed by: Ciprofloxacin 400 mg IV BD plus Metronidazole 500mg IV BD (change to oral as soon as tolerated) Oral switch Doxycycline 100mg PO BD plus Metronidazole 400mg PO BD Patients <65 years old: Ciprofloxacin 500mg PO BD Patients >65 years old: Trimethoprim 200mg PO BD Total Duration (IV+PO) 14 days IV 48 hours plus PO 28 days References SIGN Management of suspected bacterial urinary tract infection in adults: A national clinical guideline. Scottish Intercollegiate Guidelines Network. July 2012 http://www.sign.ac.uk/pdf/sign88.pdf PHE: Management of Infection guidance for Primary care- for consultation & local adaptation, May 2016 https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/524984/management_of_infection_guidance_for_primary_care_for_consultation_and_local_adaptatio n.pdf BASHH (2011). United Kingdom guidelines for the management of epididymo-orchitis. British Association for Sexual Health and HIV. Accessed at: www.bashh.org BASHH (2011). United Kingdom National guideline for the management of pelvic inflammatory disease. British Association for Sexual Health and HIV. Accessed at: www.bashh.org Version 4.0 Review Date: August 2018 Page 26 of 57

APPENDIX A Therapeutic Drug Monitoring (TDM) Gentamicin and Amikacin (restricted drug) are dosed once daily to minimise nephrotoxicity. Vancomycin (restricted drug outside of ITU) is dosed twice-daily in patients with normal renal function. TIMING OF DOSES Document the exact time of administration. It is recommended that doses are given at 06:00 and 18:00 hours for BD regimen, 12 noon or 18:00 hours for OD regimen. This ensures timely administration of antibiotic and collection of level. MONITORING All patients should have their serum creatinine, weight and height checked before starting treatment (unless a delay in treatment would be harmful). The creatinine should then be checked daily to monitor for nephrotoxicity and to allow dosage adjustment. Monitor for ototoxicity (new tinnitus, dizziness, hearing loss). All patients should have blood antibiotic levels checked except if prescribed for less than 24 hours only. Blood should be taken from the opposite arm to administration and from a peripheral vein (NOT through a line). TIMING OF SAMPLES FOR BLOOD LEVELS Drug concentrations are not readily interpretable unless the patient is at steady state and the blood drawn at the correct time pre/post dose. Current dose, time of administration and time of level should be clearly marked in request details on CRS. Gentamicin, Vancomycin and Amikacin assays will be performed when required by the Biochemistry department. These are the only levels performed at the hub lab. INTERPRETATION OF BLOOD LEVELS Accurate documentation of dose, time of administration and time of level is required for dose individualisation. Use the appropriate drug monitoring algorithm (below) to guide interpretation of level and further dosing. Version 4.0 Review Date: August 2018 Page 27 of 57

A.1 Once Daily Gentamicin Protocol (See also Once Daily Gentamicin Algorithm below and online Gentamicin Calculator) EXCLUSIONS: Bacterial endocarditis, burns >15% of the patient s body surface area,, patients allergic to Gentamicin or other aminoglycosides, myasthenia gravis, dialysis patients or patients with creatinine >300 µmol/l. Concurrent administration of nephrotoxic agents increases the risk of Gentamicin toxicity. Consider amending or withholding nephrotoxic drugs during Gentamicin treatment. Step Action 1 Use the Gentamicin Calculator to calculate the first dose (preferred method) - requires input of patient gender, age, weight, height and creatinine. Alternatively follow steps 2-4 below. 2 Calculate the ideal body weight (IBW) to determine if the patient is obese (>20% over IBW) for pregnant patients, use the pre-pregnancy weight if it is not >20% of IBW: Refer to IBW and maximum body weight tables on the hospital intranet Policies Information Management System (PIMS) if required. IBW male (kg) = 50 + (2.3 x number of inches over 5ft OR 0.9 x number of cms over 152cms) IBW female (kg) = 45 + (2.3 x number of inches over 5ft OR 0.9 x number of cms over 152cms). 3 Calculate creatinine clearance (CrCl) using the Cockroft-Gault equation*. *CrCl(ml/min) = N x (140-age) x wt (kg) Serum Cr (µmol/l) N= 1.23 for males or 1.04 for females IBW should be used for obese patients (see step 2). If creatinine is <60 µmol/l, use 60 µmol/l to avoid over estimating the CrCl 4 Calculate initial dose based on patient s age, weight and creatinine clearance as shown in table below. IBW should be used for obese patients (see step 2). Weight used should not exceed 100kg Creatinine Clearance >60ml/min >60ml/min 40 and 60ml/min 20 and <40ml/min < 20ml/min Patient age < 65 years 65 years All patients All patients All patients Dose 5mg/kg 4mg/kg 4mg/kg 3mg/kg 2mg/kg Round dose to the nearest 10mg and prescribe on the regular side of the drug chart 5 Administration: Give in 100ml Sodium Chloride 0.9% or Glucose 5% over 30 minutes. Record exact time of administration. 6 Take blood for level at 22-24 hours post dose (5ml yellow top vacutainer bottle) and send to Biochemistry Dept. Clearly document the sample time. Refer to Once daily Gentamicin algorithm below to interpret level. 7 Daily serum creatinine & urea is recommended for patients on IV Gentamicin. Consider an alternative agent if there is a significant rise in creatinine or the patient becomes oliguric 8 Stop Gentamicin if ototoxicity (new tinnitus, dizziness, hearing loss) develops. 9 Assess daily the ongoing need for Gentamicin 10 If CrCl significantly improves and levels are <1mg/l consider re-calculating the dose Version 4.0 Review Date: August 2018 Page 28 of 57

ONCE DAILY GENTAMICIN ALGORITHM Version 4.0 Review Date: August 2018 Page 29 of 57

A.2 Low Dose Gentamicin for Bacterial Endocarditis DOSE 3mg/kg OD (use ideal body weight if obese i.e. >20% over *IBW). If creatinine clearance is below 20ml/min, then dose is 1.5mg/kg OD STAT then dose as per levels. Round dose to the nearest 10mg ADMINISTRATION Administration: Give in 100ml Sodium Chloride 0.9% or Glucose 5% over 30 minutes WHEN TO TAKE 1 ST LEVEL HOW OFTEN TO TAKE LEVELS BLOOD BOTTLE LABELLING OF SAMPLE TARGET BLOOD LEVEL RENAL IMPAIRMENT DOSE ADJUSTMENT Take a level just before giving the 3 rd dose (trough level) Check pre dose levels TWICE weekly, if renal function is stable. Check more regularly if subsequent levels are > 1mg/L and /or renal function deteriorates 5 ml clotted-yellow top vacutainer bottle Dose, date, pre dose, and time sample taken TROUGH (PRE-DOSE) < 1 mg/l Discuss with microbiologist if creatinine clearance is <20ml/min. Note that elderly patients may have renal impairment without large changes in urea and creatinine See Algorithm: Low dose Gentamicin for endocarditis (below). Before adjusting the dose ensure that the level was taken at the correct time and that the initial dose was prescribed correctly *IBW formula in step 2 of once daily gentamicin protocol LOW DOSE GENTAMICIN FOR ENDOCARDITIS Version 4.0 Review Date: August 2018 Page 30 of 57