Antibiotic Guidelines

CLINICAL GUIDELINE For use in (clinical areas): For use by (staff groups): For use for (patients): Document owner: Status: All clinical areas All clinicians For use for all patients Consultant Microbiologists Approved Purpose of the Guideline This document provides comprehensive guidelines concerning the use of empiric antibiotics to treat commonly encountered infections. National guidance and local sensitivity/resistance patterns are taken into account. The guideline is intended to help clinicians provide the best treatment, reduce the incidence of side effects, prevent the emergence of antibiotic resistant organisms, and reduce the incidence of Clostridium difficile associated diarrhoea 1,2. Guidelines covering antibiotic prophylaxis for surgical procedures are found in CG10049. Contents 1. INTRODUCTION 2. TABLE OF EMPIRIC ANTIBIOTIC THERAPY 3. ANTIBIOTIC COURSES: DURATION AND ROUTE OF ADMINISTRATION 3.1. Intravenous to oral switch 4. ALLERGIES 4.1. Penicillin allergy 5. ANTIBIOTIC ASSAYS 5.1. Once daily gentamicin protocol for adults with sepsis 5.2. Other gentamicin dosing regimes 5.3. Vancomycin dosing 5.4. Estimating creatinine clearance 6. ANTIBIOTIC GUIDELINES FOR PATIENTS REQUIRING CRITICAL CARE 7. DEVELOPMENT OF THIS GUIDELINE Source: Consultant Microbiologists Issue date: May 2009 Page 1 of 24

1. INTRODUCTION These guidelines are empiric, to be used at the start of treatment. Doses mentioned are for adults unless otherwise specified and assume normal renal and hepatic function. Antibiotics are NOT harmless. Serious side effects include Clostridium difficile diarrhoea, which may be fatal. Inappropriate antibiotic use leads to the development of resistant strains of bacteria. Principles of antibiotic prescribing Before using any antibiotic it is essential to determine whether it is 1) necessary and 2) appropriate. The clinical indication for antibiotics must be stated on the drug chart and in the medical notes. (Note: this may need updating as the clinical picture progresses). All antibiotic therapy must be reviewed on a daily basis, to ensure it remains appropriate to continue, taking account of culture and sensitivity results, clinical response and microbiological advice. Most conditions do not require more than 7 days antibiotic treatment and may need less. Course length should be documented on the drug chart and in the notes. Narrow-spectrum antibiotics should replace empirical broad-spectrum antibiotics at the earliest opportunity and in conjunction with microbiology results. Oral antibiotics should be given in place of IV antibiotics within 72 hours at the latest, EXCEPT in the following circumstances or on Consultant Microbiologist advice: Meningitis Continuing sepsis: Endocarditis i.e: 2 or more of: temperature >38 c or <36 c Necrotising fasciitis heart rate >90 beats/min Acute osteomyelitis respiratory rate >20/min Septic arthritis WBC count <4 or >12 x 10 9 /L Epidural abscess Critical care patients Discitis Paediatric patients Epiglottitis Nil by mouth / not absorbing Febrile neutropenia No suitable oral antibiotic available Nursing staff have been instructed not to administer IV antibiotics beyond 72 hours UNLESS the patient s consultant has documented reasons for this in the patient s notes or a valid condition, as above, is recorded on the drug chart. The team will be asked to review any IV antibiotic prescriptions that do not fit these criteria as a matter of urgency. This will require appropriate review & planning by the team ahead of weekends and bank holiday periods. This practice will be audited. Where this practice is not followed appropriately an incident form will be submitted. Source: consultant microbiologistsconsultant Microbiologists Issue date: May 2009 Page 2 of 24

Certain antibiotics are only available on recommendation from a consultant microbiologist, or for specified infections. These include: 2 nd and 3 rd generation cephalosporins quinolones e.g. ciprofloxacin carbapenems e.g. meropenem & ertapenem tigecycline daptomycin clindamycin systemic antivirals and antifungals. Guidance on taking specimens can be found in the Pathology Services Handbook. Remember that some antibiotics have significant interactions with other medication e.g. warfarin, cyclosporin, methotrexate, oral contraceptives etc. Please refer to the BNF for information. 2. TABLE OF EMPIRIC ANTIBIOTIC THERAPY The following table outlines suitable antibiotic treatment for a range of commonly encountered clinical conditions. Always consider first line treatments. Only substitute these with second line treatments if the patient is allergic or has failed to respond to first line treatment. For septicaemic patients, consider the likely source and prescribe according to the table. See also section 6 guidelines for critical care patients. For haematology and oncology patients, see also: Treatment of febrile/septic neutropaenic patients: CG10066-5 Treatment of febrile non-neutropaenic patients CG10070-5 Antifungal therapy: CG10061-2 Neutropaenic prophylaxis: CG10087-2 PCP prophylaxis: CG10083-2 If in doubt, please contact the consultant microbiologists (available 24 hours a day, 7 days a week via the hospital switchboard). Source: consultant microbiologistsconsultant Microbiologists Issue date: May 2009 Page 3 of 24

Table 1 Empiric antibiotic treatment for common infections in adults INFECTION 1 st LINE ANTIBIOTICS 2 nd LINE ANTIBIOTICS COMMENTS RESPIRATORY TRACT INFECTIONS Tonsillitis/Quinsy Oral penicillin V 500mg q.d.s. or i.v. benzyl penicillin 1.2g q.d.s. for 10 days Oral Clarithromycin 250mg b.d. or i.v. clarithromycin 500mg b.d. If anaerobic infection including Lemierre s disease (Fusobacterium necrophorum suppurative thrombophlebitis) or Ludwig s angina suspected, add metronidazole 400mg t.d.s. Discuss with microbiologists Epiglottitis Ceftriaxone 2g od IV Sinusitis Acute Oral Co-amoxiclav 625mg t.d.s. Oral Clarithromycin 250mg b.d. i.v. treatment with 1.2g coamoxiclav t.d.s. or clarithromycin 500mg b.d. may be given if required change to oral treatment as soon as possible Chronic Oral doxycycline 200mg (day 1) then 100mg o.d.(days 2 to 7) Oral Clarithromycin 250mg b.d. Add oral metronidazole 400mg t.d.s. if anaerobes suspected. Source: Consultant Microbiologists Issue date: May 2009 Page 4 of 24

INFECTION 1 st LINE ANTIBIOTICS 2 nd LINE ANTIBIOTICS COMMENTS Acute otitis media Oral Co-amoxiclav 625mg t.d.s. Oral Clarithromycin 250mg b.d. If recurrent, consider anaerobes. Infective exacerbation COPD (no signs of pneumonia on CXR, purulent sputum) Oral doxycycline 200mg (day 1) then 100mg o.d.(days 2 to 7) Oral clarithromycin 250 b.d. for 7 days Send sputum for culture. Failed antibiotic therapy discuss with microbiologists Severe infective exacerbation COPD (incl. Bronchiectasis) (no signs of pneumonia, purulent sputum, ph <7.35) Oral clarithromycin 500mg b.d. If severe, piperacillin/tazobactam 4.5g t.d.s. + gentamicin Send sputum. Discuss with microbiologists Community acquired pneumonia C - Confusion Mild (CURB 65 = 0-2) N.B. need for frequent review to identify deterioration Oral clarithromycin 500mg b.d. for 7 days Oral amoxycillin 500mg tds Only following consultant advice U - Urea >7mmols/l R - Resp 30/min Severe (CURB 65 3) i.v. clarithromycin 500mg b.d. + i.v. benzyl penicillin 1.2g q.d.s. Switch to oral clarithromycin 500mg b.d. at 2 days unless no improvement No response to 1 st line or probable aspiration consider piperacillin/tazobactam 4.5g t.d.s. to cover gram negatives Penicillin allergy discuss with microbiologists B - BP diastolic <60mmHg Age > 65 years (score 1 point for each of the above) Risk of atypical infection e.g. Legionella, psittacosis discuss with microbiologists Source: Consultant Microbiologists Issue date: May 2009 Page 5 of 24

INFECTION 1 st LINE ANTIBIOTICS 2 nd LINE ANTIBIOTICS COMMENTS Post-influenzal pneumonia Hospital acquired chest infection(>3 days from admission) No evidence of consolidation on CXR i.v. flucloxacillin 2g qds + i.v. gentamicin 5mg/kg once daily (monitor according to gentamicin guidelines) Oral doxycycline 200mg (day 1) then 100mg o.d.(days 2 to 7) Penicillin allergy discuss with microbiologists Discuss with microbiologists Document clinical findings Sputum for culture Blood cultures if pyrexial Evidence of new consolidation on CXR i.v. piperacillin/tazobactam 4.5g t.d.s. (+ i.v. gentamicin 5mg/kg o.d. if severe) for 5-7 days. Penicillin allergy discuss with microbiologists. Source: Consultant Microbiologists Issue date: May 2009 Page 6 of 24

INFECTION 1 st LINE ANTIBIOTICS 2 nd LINE ANTIBIOTICS COMMENTS URINARY TRACT INFECTIONS ESBL INFECTIONS Always discuss with microbiologists prior to commencing treatment Uncomplicated UTI Trimethoprim 200mg b.d. orally Nitrofurantoin 50mg 6 hourly Send mid-stream or clean catch urine sample for culture. Await results if no systemic symptoms and treat according to results. 3 day course adequate for most adults. Asymptomatic bacteriuria Do not treat even if >65 yrs or diabetic unless pre-op. Only treat if pregnant or before instrumentation or surgery. Treat according to culture results. Acute pyelonephritis / complicated urosepsis Age <40, otherwise well Age >40, otherwise well Co-amoxyclav 1.2g tds i.v Piperacillin/tazobactam 4.5g tds iv i.v. gentamicin 5mg/kg o.d. Send MSU & blood cultures prior to starting empiric antibiotics. Review with culture results at 48 hours and switch to oral if possible see table 2, section 3.1 Source: Consultant Microbiologists Issue date: May 2009 Page 7 of 24

INFECTION 1 st LINE ANTIBIOTICS 2 nd LINE ANTIBIOTICS COMMENTS Catheter associated bacteriuria Antibiotics do not eradicate bacteria from urinary catheters. Results of dipstick testing are not helpful in diagnosing catheter related infections send a CSU if systemically unwell, or pre-operatively. Treat according to culture report. Consider change or removal of catheter. GENITAL TRACT INFECTIONS If in doubt, discuss with microbiologists Prostatitis/epididymo-orchitis oral ofloxacin 400mg b.d. for 28 days Pelvic inflammatory disease Oral metronidazole 400mg t.d.s. + oral ofloxacin 400mg bd for 14 days oral doxycycline 200mg on day 1 then 100mg b.d. for a total of 28 days Oral doxycycline 100mg b.d. + oral metronidazole 400mg t.d.s.for 14 days Or Refer to GUM if a sexuallytransmitted infection is suspected Genital chlamydiosis Refer to GU Medicine Oral erythromycin 500mg b.d. + metronidazole 400mg t.d.s. for 14 days. Vaginal candidiasis Clotrimazole pessary 500mg stat Oral fluconazole 150 mg stat Alternative topical preparations available if no response discuss with microbiologists. Source: Consultant Microbiologists Issue date: May 2009 Page 8 of 24

INFECTION 1 st LINE ANTIBIOTICS 2 nd LINE ANTIBIOTICS COMMENTS GASTROINTESTINAL INFECTIONS Community acquired gastroenteritis Antibiotics not usually indicated Severe campylobacter infections oral clarithromycin 250mg b.d. for 5-7 days (but check sensitivities as some are resistant) Patient to be admitted to side room. Notify Infection Control/oncall microbiologist Send faeces for culture Helicobacter pylori Amoxycillin 1g bd Lansoprazole 30mg bd Clarithromycin 500mg bd Metronidazole 400mg bd Lansoprazole 30mg bd Clarithromycin 250mg bd Bacteraemic infections may require antibiotic therapy discuss with microbiologists All 7 days All 7 days Source: Consultant Microbiologists Issue date: May 2009 Page 9 of 24

INFECTION 1 st LINE ANTIBIOTICS 2 nd LINE ANTIBIOTICS COMMENTS Clostridium difficile Only treat if symptomatic diarrhoea with green, foul smelling stool with history of antibiotic use Review drug chart. Stop antibiotics where possible Mild may respond to stopping concurrent antibiotic treatment. Oral metronidazole 400mg t.d.s. for 10 days Oral vancomycin 125mg qds for 10 days if failed to respond to metronidazole Severe Fever, leucocytosis, sepsis, hypoalbuminaemia, abdominal tenderness/distension Oral vancomycin 125-500 mg qds for 10-14 days discuss with microbiologists If pseudo membranous colitis suspected commence oral and i.v. vancomycin and get URGENT SURGICAL REVIEW Pancreatic and biliary sepsis i.v. Piperacillin/tazobactam 4.5g t.d.s. Add i.v. gentamicin 5mg/kg if severe Severe intra-abdominal sepsis i.v. Piperacillin/tazobactam 4.5g t.d.s. Add i.v. gentamicin 5mg/kg if severe Discuss with microbiologists Discuss with microbiologists DISCUSS WITH MICROBIOLOGISTS Source: Consultant Microbiologists Issue date: May 2009 Page 10 of 24

INFECTION 1 st LINE ANTIBIOTICS 2 nd LINE ANTIBIOTICS COMMENTS CARDIOVASCULAR SYSTEM Bacterial endocarditis Take 3 sets of blood cultures and discuss URGENTLY with microbiologists CENTRAL NERVOUS SYTEM Bacterial meningitis i.v. Ceftriaxone 2g b.d. for 10-14 days (discuss with micro) SKIN, SOFT TISSUE, BONE AND JOINT INFECTIONS Immunocompromised add i.v. amoxycillin 2g q.d.s. to cover Listeria Penicillin allergy - Chloramphenicol 25 mg/ Kg 6hrly IV Always discuss with microbiologists. Send CSF for microscopy and culture only if safe to do so. Take blood cultures. Consider EDTA blood sample for meningococcal PCR, throat swab and skin aspirate if? meningococcaemia with Rash. Cellulitis IV benzylpenicillin 1.2 qds & IV flucloxacillin 2g qds IV clarithromycin 500mg bd or vancomycin 1g bd Oral flucloxacillin if not severe. If severe (e.g. necrotising fasciitis, burns) discuss with microbiologists. If MRSA D/W microbiologists. Source: Consultant Microbiologists Issue date: May 2009 Page 11 of 24

INFECTION 1 st LINE ANTIBIOTICS 2 nd LINE ANTIBIOTICS COMMENTS Chronic leg ulcers Diabetic ulcers Bacteria are ALWAYS present. Take diagnostic swabs ONLY if inflamed (i.e. red/hot/increasing pain, rapid deterioration). Swab from around the inflamed edge, do not take swabs from exudates. Treat according to culture results. Take swabs and discuss with microbiologists. Post-operative wound infection Send wound swab for culture Discuss with microbiologists Osteomyelitis i.v. flucloxacillin 2g q.d.s. Add oral fusidic acid 500mg tds Discuss with microbiologists, particularly if MRSA positive. Septic arthritis history of trauma/intervention/ skin lesions i.v. flucloxacillin 2g q.d.s. Add oral fusidic acid 500mg tds Discuss with microbiologists, particularly if MRSA positive. community acquired, presumed haematogenous infection i.v. ceftriaxone 2g o.d. On microbiologist advice Prosthetic joint infection Discuss with microbiologists Source: Consultant Microbiologists Issue date: May 2009 Page 12 of 24

INFECTION 1 st LINE ANTIBIOTICS 2 nd LINE ANTIBIOTICS COMMENTS Compound fracture/badly soiled wounds Co-amoxiclav 1.2g t.d.s. i.v. Discuss with microbiologists Bites (human or animal) Oral Co-amoxiclav 625mg t.d.s. Discuss with microbiologists MRSA INFECTIONS Refer to blood borne virus policy for human bites Antibiotics not required for colonisation. If intravenous treatment clinically indicated, commence i.v. vancomycin 1g b.d. and discuss with microbiologists. If oral treatment required, treat according to the results of laboratory antibiotic susceptibility testing. N.B. oral vancomycin is NOT absorbed and CANNOT be used to treat MRSA infections. SEPSIS IN THE IMMUNOCOMPROMISED PATIENT No central line i.v. Piperacillin/tazobactam 4.5g t.d.s. + gentamicin 5mg/kg o.d. Central line in situ As above but add i.v. vancomycin Send full septic screen. Contact relevant specialist (haematologist, oncologist, GUM physician) and microbiologist to discuss. Source: Consultant Microbiologists Issue date: May 2009 Page 13 of 24

3. ANTIBIOTIC COURSES: DURATION AND ROUTE OF ADMINISTRATION The duration of antibiotic treatment must be stated on the drug chart. All prescriptions for intravenous antibiotic treatment must be reviewed within 48 hours to determine whether a change to oral therapy is appropriate. Where a course length is not stated, ward based pharmacists will contact the prescriber to review the prescription. 3.1. INTRAVENOUS TO ORAL SWITCH For patients on i.v. antibiotics, it is essential that medical staff ensure that oral antibiotic therapy is introduced as soon as practicable. This is important for patient safety as intravascular devices are associated with infection including fatal septicaemia. Please discuss the case with a consultant microbiologist if you think that stepping down is inappropriate or you are unclear as to the best oral agent to use. Long courses of i.v. antibiotics are indicated for some infections e.g. endocarditis and some bone/joint infections. The prescription chart should be annotated to indicate that a long course is indicated, with a stop or review date added. Check culture and antibiotic susceptibility results to ensure that the chosen oral antibiotic is likely to be effective. See Table 2 Source: Consultant Microbiologists Issue date: May 2009 Page 14 of 24

Table 2 Antibiotic Options when switching from IV to oral treatment A direct switch can occur where possible e.g. clarithromycin IV clarithromycin PO. Condition Firstly, Secondly, if no positive microbiology to guide you and antibiotics need to continue: Respiratory COPD Community-acquired pneumonia - Post-influenza pneumonia Hospital-acquired pneumonia Check & be guided by microbiology results Check & be guided by microbiology results Check & be guided by microbiology results Check & be guided by microbiology results Co-amoxiclav but discuss with microbiologist if Pseudomonas thought likely. Refer to section 4.1 if penicillin allergy. Amoxicillin, co-amoxiclav, clarithromycin, or doxycycline. If atypical respiratory pathogen suspected use clarithromycin or doxycycline. Flucloxacillin or clarithromycin. Doxycycline if MRSA positive. Co-amoxiclav but discuss with microbiologist if Pseudomonas thought likely. Refer to section 4.1 if penicillin allergy. Urinary Infections All Check & be guided by microbiology results Gastro-intestinal infections Pancreatic, biliary & severe abdominal sepsis Check & be guided by microbiology results Co-amoxiclav. Refer to section 4.1 if penicillin allergy. Skin & soft tissue infections Cellulitis Check & be guided by microbiology results Direct switch e.g. flucloxacillin IV flucloxacillin PO If on vancomycin for MRSA use doxycycline PO. If on vancomycin for penicillin allergy use clarithromycin PO and refer to section 4.1. Source: Consultant Microbiologists Issue date: May 2009 Page 15 of 24

4. ALLERGIES It is important to realise that allergic reactions are responsible for a number of deaths each year in National Health Service hospitals. To prevent these happening, and to ensure that appropriate antibiotics are not withheld due to an inaccurate history, medical staff must establish the true allergy status of each patient. 4.1 PENICILLIN ALLERGY The most important side-effect of the penicillins is hypersensitivity which causes rashes and anaphylaxis and can be fatal. Allergic reactions to penicillins occur in 1 10% of exposed individuals; anaphylactic reactions occur in fewer than 0.05% of treated patients. Check the history of the reported allergy; it is often inaccurate. Patients commonly report minor skin reactions and stomach upset as penicillin allergy. There is no test for allergy. Allergic or anaphylactic response is not dose related. Individuals with a history of anaphylaxis, urticaria, or rash immediately after penicillin administration are at risk of immediate hypersensitivity to a penicillin; these individuals should not receive a penicillin, a cephalosporin or another beta-lactam antibiotic. Individuals with a history of a minor rash (i.e. non-confluent 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 but the possibility of an allergic reaction should be borne in mind. Cephalosporins and carbapenems should be used with caution in penicillin allergic patients since there is a quoted incidence of 10% cross-allergenicity. Substitutes: (where other allergies do not contra-indicate) if uncertain please discuss with a consultant microbiologist For penicillin use oral clarithromycin or i.v. cefuroxime/ceftriaxone following discussion with microbiologist For flucloxacillin use i.v. cefuroxime/ceftriaxone following discussion with microbiologist or oral cefradine or clarithromycin For amoxicillin the substitute is dependent upon the indication. Discuss with consultant microbiologist. Source: Consultant Microbiologists Issue date: May 2009 Page 16 of 24

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 CONTRA -INDICATED Antibiotics to be avoided in penicillin allergy Amoxicillin (in Co-amoxiclav/Augmentin, Heliclear) Ampicillin (in Co-fluampicil/Magnapen) Benzylpenicillin / Penicillin G Flucloxacillin (in Co-fluampicil / Magnapen) Phenoxymethylpenicillin / Penicillin V Piperacillin (in Tazocin) Ticarcillin (in Timentin) CAUTION Avoid if serious penicillin allergy (e.g. anaphylaxis / angioedema). Use with caution if non-severe allergy (e.g. minor rash) only Antibiotics to be avoided or used with caution in penicillin allergy (not a complete list) Cephalosporins: Cefixime, Cefotaxime, Cefradine, Ceftazidime, Ceftriaxone, Cefuroxime Other beta-lactam antibiotics: Aztreonam, Imipenem, Meropenem, Ertapenem CONSIDERED SAFE Antibiotics safe in penicillin allergy (not a complete list), Doxycycline Tigecycline Vancomycin Tobramycin Clarithromycin Erythromycin Sodium Fusidate Co-trimoxazole Rifampicin Metronidazole Ciprofloxacin (Oxy)Tetracycline Gentamicin Azithromycin Clindamycin Linezolid Trimethoprim Nitrofurantoin Ofloxacin *TRUE penicillin allergy includes anaphylaxis, urticaria or rash immediately after penicillin administration In cases of INTOLERANCE to penicillin (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 Source: Consultant Microbiologists Issue date: May 2009 Page 17 of 24

5. ANTIBIOTIC ASSAYS: GENTAMICIN AND VANCOMYCIN Assays for gentamicin and vancomycin are carried out at specific times each day. Assays will not be carried out during on-call periods except in exceptional circumstances (see Pathology Services Handbook) Other antibiotic assays may rarely be required. These are available by arrangement with Microbiology. 5.1 ONCE DAILY GENTAMICIN PROTOCOL FOR ADULTS WITH SEPSIS Once daily gentamicin dosing is used for most patients requiring gentamicin. Exceptions are listed below. Patients less than 16 years old Patients with rapidly changing renal function Patients receiving a single dose of gentamicin as prophylaxis Patients who are pregnant or in the immediate post-partum period Patients receiving dialysis Patients being treated for endocarditis Patients with ascites Patients with severe oedema Patients with major burns (>20%) Patients with cystic fibrosis Patients with renal impairment if creatinine clearance <20ml per minute, then discuss with Microbiologist or Ward Pharmacist. Full details about once-daily gentamicin dosing and monitoring are found in CG10100-2 available on the intranet. http://www.wsh.nhs.uk/secure/thepinkbook/newguidelines/docs/cg10100-2useofgentimicinasaoncedailydoseinadults.doc 5.2 OTHER GENTAMICIN DOSING REGIMES Always discuss alternative dosing regimes with a consultant microbiologist. Except in cases of severe renal impairment, there is no reason to check the levels within the first 48 hours of starting or stopping treatment or changing the dose. A pre-dose level taken immediately before the dose and a peak level taken 1 hour after i.m. or i.v. dose should be sent to the laboratory. Accurate timing of peak and trough levels is essential. State times on the request form. Pre-dose levels should be less than 2mg/l (ideally <1mg/l) Peak levels should be 6-10mg/l (exceptions include some cases of endocarditis discuss with microbiologist). 5.3 VANCOMYCIN Full details about Vancomycin dosing and monitoring are found in Vancomycin Prescribing and Monitoring Guideline (Excluding Paediatric Patients) available on the intranet. 5.4 ESTIMATING CREATININE CLEARANCE Please refer to the relevant page on the pharmacy section of the intranet Advice on renal function and dose changes - estimating creatinine clearance Source: Consultant Microbiologists Issue date: May 2009 Page 18 of 24

6. EMPIRIC ANTIBIOTIC GUIDELINES FOR PATIENTS REQUIRING CRITICAL CARE 6.1 Purpose of the Guideline These guidelines are solely for use for patients under Critical Care Services. Serious infections in critical care often require empirical antibiotic treatment prior to microbiological identification of the infectious organism and before antibiotic sensitivities are known. These guidelines describe the initial antibiotic treatment of common serious infections in patients admitted to critical care. The antibiotics must be reviewed once the results of microbiological tests are available. If there is uncertainty advice must be sought from the on-call Consultant Microbiologist. 6.2. Contents Intensive Care Unit antibiotic guidelines for: Respiratory Tract Infections Peritonitis Wound Infections Meningitis Urinary Tract Infections Cellulitis Necrotising Fasciitis Note that the dose of vancomycin and gentamicin will depend on renal function and should be given in accordance with guidance on critical care. Source: Consultant Microbiologists Issue date: May 2009 Page 19 of 24

6.3 RESPIRATORY TRACT INFECTIONS 6.3.1.Community Acquired Pneumonia 1 st Choice 1 i.v. benzyl penicillin 1.2g q.d.s. i.v. clarithromycin 500mg b.d. 2 nd Choice i.v. piperacillin/tazobactam 4.5g t.d.s. i.v. clarithromycin 500mg b.d. Major Penicillin allergy Possible Aspiration If possible MRSA or PVL Staph aureus i.v./oral ciprofloxacin 200/250mg b.d. plus i.v. vancomycin 1g b.d. i.v. piperacillin/tazobactam 4.5g t.d.s. Add i.v. linezolid 600mg b.d. + i.v. clindamycin 1.2g b.d. Discuss with microbiologist Likely organisms 1. Strep pneumoniae 2. Mycoplasma 3. Haemophilus influenzae 4. Chlamydia 5. Legionella 1. If there is strong history suggestive of influenza, add flucloxacillin 2g iv qds Take urine sample for Legionella antigen and serum sample for atypical organism and viral serology. Remember to take blood and sputum cultures. 6.3.2. Exacerbation of COAD 1 st Choice As for community acquired pneumonia (6.3.1 above) Recently treated with doxycycline, penicillin or cephalosporin? Discuss with microbiologist Likely organisms 1. Above + 2. Coliform 3. Pseudomonas 6.3.3. Hospital Acquired Pneumonia 1 st Choice i.v. piperaciliin/tazobactam 4.5g t.d.s. plus i.v. gentamicin 2 nd Choice If penicillin allergic, i.v. ciprofloxacin 200mg b.d. plus i.v. vancomycin Likely organisms 1 Pseudomonas 2 Coliforms 3 MRSA 4 Anaerobes Possible Aspiration As above (piperacillin/tazobactam has good activity against anaerobes). Penicillin allergy add metronidazole Add gentamicin if known Pseudomonas aeruginosa. Source: Consultant Microbiologists Issue date: May 2009 Page 20 of 24

6.3.4. Upper Respiratory Tract Infections (Epiglottitis, Ludwig s Angina, Quinsy) 1 st Choice i.v. ceftriaxone 2 g o.d. plus i.v. metronidazole 500mg t.d.s. 2 nd Choice i.v. vancomycin plus i.v. ciprofloxacin 200mg b.d. Likely organisms 1 Strep pneumoniae 2 Strep group A 3 Staph aureus 4 Anaerobes 6.4 Peritonitis 1 st Choice i.v. piperaciliin/tazobactam 4.5g t.d.s. ± i.v. gentamicin 2 nd Choice i.v. tigecycline 100mg first dose then 50 mg b.d. plus i.v. gentamicin Likely organisms 1 Coliforms 2 Bacteroides 3 Enterococci 4 Pseudomonas 6.5 Wound Infections 6.5.1.Orthopaedic Trauma wounds 1 st Choice i.v. co-amoxyclav 1.2g t.d.s. Likely organisms 1. Staph aureus 2 nd Choice i.v. vancomycin plus i.v./oral 2. Streptococcus A (penicillin ciprofloxacin 200mg/250mg b.d. plus allergy) i.v. metronidazole 500mg t.d.s. (if 3. Coliform soiled) 4. Pseudomonas 5. Anaerobes in dirty wounds DO NOT FORGET TETANUS PROPHYLAXIS 6.5.2 Burns & Toxic epidermal necrolysis ( TEN) 1 st Choice i.v. piperaciliin/tazobactam 4.5g t.d.s. plus i.v. vancomycin 2 nd Choice (penicillin allergy) i.v. ciprofloxacin 200mg b.d. plus i.v. vancomycin1g b.d. plus i.v. metronidazole 500mg t.d.s. Likely organisms 1. Staph aureus 2. Streptococcus A 3. Coliform 4. Pseudomonas 5. Anaerobes in dirty wounds Source: Consultant Microbiologists Issue date: May 2009 Page 21 of 24

6.5.3. General Surgery/Gynaecological wound infections 1 st Choice* i.v. flucloxacillin 2g q.d.s. plus i.v. metronidazole 500mg t.d.s. plus i.v. gentamicin 2 nd Choice i.v. tigecycline 100mg first dose then 50 mg b.d. plus i.v. gentamicin Likely organisms 1. Above + 2. Bacteroides 3. Other haemolytic streptococci * substitute vancomycin for flucloxacillin if high risk of MRSA or MRSA carrier 6.6 Meningitis Discuss ALL cases with duty Microbiologist 1 st Choice Ceftriaxone 2g bd iv Likely organisms 2 nd Choice Chloramphenicol 25mg/kg qds iv 1. N meningitidis 2. Strep pneumoniae 3. H. Influenzae Patients may have already received benzylpenicillin Consider acyclovir in suspected viral meningitis Consider amoxicillin 2g tds iv if Listeria suspected, eg pregnant or immuno-compromised patient 6.7 Urinary Tract Infections 6.7.1. Community acquired UTI 1 st Choice i.v. co-amoxyclav 1.2g t.d.s. ± i.v. gentamicin 2 nd Choice Discuss with microbiologist Likely organisms 1. Coliform 2. Staphs and Streps post-instumentation 6.7.2. Risk of Hospital Acquired UTI 1 st Choice i.v. piperaciliin/tazobactam 4.5g t.d.s. plus i.v. vancomycin 2 nd Choice Discuss with microbiologist 6.7.3. Risk of ESBL coliform UTI 1 st Choice Meropenem 500mg iv tds or Ertapenem 1g od iv Source: Consultant Microbiologists Issue date: May 2009 Page 22 of 24

6.8 Cellulitis Clinical Notes Always look for an entry site and consider surgical opinion Use vancomycin if high risk of MRSA or MRSA carrier If immunocompromised or diabetic add i.v. piperaciliin/tazobactam 4.5g t.d.s. If trauma or bite add in i.v. metronidazole 500mg t.d.s. 1 st Choice Benzylpenicillin 2.4g 4 hourly and Flucloxacilin 2g iv qds 2 nd Choice Vancomycin 1g bd iv Likely organisms 1. Staph aureus 2. Streptococcus 3. Bacteroides 6.9. Necrotising Fasciitis Obtain an immediate senior surgical opinion Discuss ALL cases with microbiologist 1 st Choice i.v. ceftriaxone 2g b.d. plus i.v. gentamicin plus i.v. clindamycin 600-1200mg b.d. 2 nd Choice i.v. vancomycin 1g b.d. plus i.v. piperaciliin/tazobactam 4.5g t.d.s. plus i.v. clindamycin 600-1200mg bd Likely organisms 1. Streptococcus A 2. Enterobacteriaciae 3. Bacteroides 4. PVL Staph aureus References: 1. Wilcox MH et al. Long-term surveillance of cefotaxime and piperacillin-tazobactam prescribing and incidence of Clostridium difficile diarrhoea. Journal of Antimicrobial Chemotherapy 54 (1):168-72, 2004. 2. O Connor KA et al. Antibiotic prescribing policy and Clostridium difficile diarrhoea. Quarterly Journal of Medicine 97 (7):423-9, 2004. 3. Claxton A et al. Restrictive empirical antibiotic guidelines for common infections in HUH medical admissions and inpatients. Homerton University Hospital NHS Trust. October 2006. Source: Consultant Microbiologists Issue date: May 2009 Page 23 of 24

7. DEVELOPMENT OF THE GUIDELINE Changes compared to previous document This guideline replaces CG10118-4, issued in March 2008. Statement of clinical evidence See references above. Contributors and peer review The original guideline was written by the then Chief Pharmacist, John Anthistle, in collaboration with the consultant microbiologists, Dr Wright and Dr Tremlett. The changes in this fifth edition have been reviewed by the Chief Pharmacist, Simon Whitworth, and the consultant microbiologists Dr R. Tilley & Dr C. Barker. The section on treatment in Critical Care was originally contributed by Dr. N. Levy and Dr. A. Burns, with amendments for the subsequent editions by the consultant microbiologists. Distribution list/dissemination method These guidelines are available to all Trust staff in the electronic clinical guidelines (Pink Book) on the hospital intranet. The Electronic Clinical Information Editorial Group is responsible for dissemination and awareness of the guideline. These guidelines are promoted at junior and senior doctor inductions. Document configuration information Author(s): Chief Pharmacist and consultant microbiologists Other contributors: Dr. N Levy, Dr. A Burns and Dr C Laroche, Dr. R Bannon Approved by: Drugs and Therapeutics Committee Issue no: 5 File name: Supercedes: CG10118-4 Additional Information: Source: Consultant Microbiologists Issue date: May 2009 Page 24 of 24