Adult Antibiotic Guidelines. Secondary Care

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Adult Antibiotic Guidelines Secondary Care Please note: The Antibiotic Prophylaxis Guideline full document is available on the intranet N.B. Staff should be discouraged from printing this document. This is to avoid the risk of out of date printed versions of the document. The Intranet should be referred to for the current version of the document. Owner: Antimicrobial Working Group Policy Number:

1 Executive Summary These guidelines provide an overview of recommended antibiotics for empirical use within the organisation. 1.1 Scope of guidelines These guidelines apply to adult in-patients prescribed antibiotics. 2 Aims These guidelines aim to provide prescribers with guidance to ensure that empiric antibiotic prescribing is appropriate and cost effective. 3 Policy Statement These guidelines aim to improve the quality of prescribing of antibiotics within the organisation. 4 Responsibilities It is the prescriber s responsibility to check appropriateness of agents used taking into account co-existing conditions or medication. All prescribers and pharmacists have a responsibility to ensure empiric antibiotic prescribing is guided by the health board s antibiotic guidelines. 5 Training No formal training is required on these guidelines. New members of medical and pharmacy staff and other prescribers within the organisation will be advised on how to access the guidelines on their induction. 6 Audit The guidelines will be audited by the antibiotic working group or pharmacy annually. The results will be fed back to the antibiotic working group, which will agree an appropriate strategy dependant on audit results. 7 Further Information Further information can be obtained from the Antimicrobial Pharmacist based in the pharmacy department. Page 1 of 26

Contents Condition 1 Community-acquired pneumonia 2 Infective exacerbations of COPD 2 Infective exacerbation of asthma 3 Aspiration pneumonia 3 Hospital-acquired pneumonia 4 Clostridium difficile-associated diarrhoea 5 Intra-abdominal infections (cholecystitis, peritonitis, hepato-bilary) 6 Hepatic abscess 7 Spontaneous bacterial peritonitis 8 Gastroenteritis 9 Cellulitis 10 Diabetic foot ulcer 11 Infected human or animal bite 12 Breast lactational mastitis 13 Non lactational breast sepsis 14 Suspected necrotising fasciitis 15 Urinary tract infections Community acquired, uncomplicated 16 Urinary tract infections Hospital-acquired 17 Pyelonephritis (includes patients with an indwelling catheter) 18 Acute bacterial prostatitis 19 Epididymo-orchitis 20 Meningitis 21 Endocarditis 22 Sepsis (unknown origin) 23 Neutropenic sepsis 24 Osteomyelitis 24 Septic arthritis 25 Prosthetic joint infection 26 Open fracture 26 Dirty wound 27 Aminoglycosides & Vancomycin dosing information 28 Antimicrobial prophylaxis summary 29 Antimicrobial dosing guidelines in adults with renal impairment and failure 30 Gentamicin administration charts Page 2 of 26

Antibiotic Prescribing These guidelines have been revised in response to concerns nationally and locally over the rates of Clostridium difficile infection. Cephalosporins and fluoroquinolones have been particularly associated with a higher risk of C. difficile, but all broad-spectrum antibiotics are potentially hazardous for this infection. The routine use of cefuroxime, cefalexin and ciprofloxacin is not recommended. The use of these antibiotics should be limited to treating conditions where there are no alternatives that provide adequate cover or when their use is explicitly recommended in this guide. Whenever possible, relevant specimens for culture must be taken from in-patients before starting antibiotics. ALL antibiotics prescribed on a chart must have the intended DURATION or date for review specified in the special instructions section of the drug chart. Antibiotics should be given for the complete course prescribed and doses should not be omitted. Restricted antibiotics should be approved by microbiology before prescribing (See below). Oral antibiotics prescribed for 5 days will be stopped according to the criteria in the antibiotic automatic stop policy unless the duration is specified. All recommended doses are for ADULT in-patients with normal renal and liver function. Restricted antimicrobials The following antimicrobials are restricted within the organisation according to the restricted antimicrobial policy. If they are prescribed for an indication or patient group that is not listed in the exemptions in the restricted antimicrobial policy please contact microbiology to obtain approval for their use. Amphotericin, Caspofungin, Ciprofloxacin (IV), Doripenem, Ertapenem, Fidaxomicin*, Fluconazole (IV), Imipenem/Cilastatin, Levofloxacin, Linezolid, Meropenem, Pivmecillinam, Teicoplanin, Tigecycline, Voriconazole The restricted antimicrobial policy does NOT apply to: paediatric, haematology, critical care or neutropenic patients * Fidaxomicin requires approval by consultant microbiologist in all cases Page 3 of 26

1. Community-acquired pneumonia Mild (CURB-65 < 1) Amoxicillin PO 500mg tds Advised Total 7 days Mild (CURB-65 < 1) Doxycycline PO 200mg loading dose then PO 100mg od, or clarithromycin PO 500mg bd Moderate (CURB-65 = 2) Amoxicillin PO 500mg to 1g tds plus clarithromycin PO 500mg bd 7 days Moderate (CURB-65 = 2) Doxycycline PO 200mg loading dose then PO 100mg od, or clarithromycin PO 500mg bd Or if oral administration not possible: Amoxicillin IV 500mg tds plus clarithromycin IV 500mg bd If oral administration is not possible and cephalosporins are considered satisfactory having considered the nature of the allergy: Cefuroxime IV 1.5g tds plus clarithromycin IV 500mg bd In severe anaphylaxis: Levofloxacin IV 500mg bd Severe (C URB-65 > 3) Benzylpenicillin IV 1.2g qds plus clarithromycin IV/PO 500mg bd. Review IV need daily. If life-threatening infection, significant comorbidities, risk of Gram negative infection or care home resident: Co-amoxiclav IV 1.2g tds and Clarithromycin IV/PO 500mg bd. Review IV need daily. 7 to 10 days May extend to 14 to 21 days if Staphyloco ccal or Gram-neg infection Severe (CURB-65 > 3) Contact microbiology Page 4 of 26

ALWAYS check and record the CURB-65 score Recent onset Confusion Urea >7 Resp Rate>30 BP systolic <90 or diastolic <60 Age>65 years Advised Total BTS Guidelines: Thorax 2009; v64 (Suppl III); iii1-iii55. doi:10.1136/thx.2009.121434 2. Infective exacerbations of COPD and asthm a with no signs of pneumonia on X-ray Amoxicillin PO 500mg tds Mild or Moderate exacerbation: 5 days Severe exacerbation: 7 days has had an anaphylactic Doxycycline PO 200mg stat then 100mg od Page 5 of 26

3. Hospital-acquired pneumonia and aspiration pneumonia Aspiration pneumonia Co-amoxiclav IV/PO (IV 1.2g tds/ PO 625mg tds) Contact microbiology if patient does not respond in 24 hours 7 days Doxycycline PO 200mg stat then doxycycline PO 100mg bd Hospital-acquired pneumonia that presents < 5 days after admission, and has not received antibiotics in last 10 days Co-amoxiclav IV/PO (IV 1.2g tds/ PO 625mg tds) Contact microbiology if patient does not respond in 24 hours 7 days Doxycycline PO 200mg stat then doxycycline PO 100mg bd Hospital-acquired pneumonia that presents > 5days after admission, or has received antibiotics within last 10 days, or has co-morbidities Piperacillin/tazobactam IV 4.5g tds. Switch to oral treatment with co-amoxiclav PO 625mg tds or according to culture and sensitivities has had an anaphylactic Please discuss with microbiology Always review previous microbiology results. Check organisms and sensitivities if known MRSA, Pseudomonas or multi-resistant gram organisms different antibiotics likely to be required.. Guidelines for the management of hospital-acquired pneumonia in the UK: Report of the Working Party on Hospital-Acquired Pneumonia of the British Society for Antimicrobial Chemotherapy J. Antimicrob. Chemother. 2008 62: 5-34 Page 6 of 26

4. Clostridium difficile-associated diarrhoea Where possible STOP all other antibiotics and PPIs Non-severe Metronidazole PO 400mg tds May be repeated once more if a non-severe relapse occurs. If symptoms not improving or are worsening, or a third episode occurs, switch to the severe treatment course. Severe (WBC > 15x10 9 /L, acutely rising creatinine and/or signs or symptoms of colitis) Vancomycin PO 125mg qds If symptoms not improving or relapse occurs, contact Surgical/GI/Micro for consultation on use of high-dose vancomycin, tapering regimes, combination therapy or fidaxomicin. 10 days 10 days, may be extended according to response Daily assessment is required. Symptoms not improving or worsening should not be deemed a treatment failure until received a few days of treatment. Anti-motility agents should not be prescribed unless recommended by gastroenterologist. See also Clostridium difficile Policy (available on intranet) or Department of Health guidelines. 5. Intra-abdominal infections (cholecystitis, periton itis, hepato-bilary) Amoxicillin IV 1g tds and gentamicin IV 5mg/kg od (check levels) and metronidazole IV 500mg tds. Minimum of 5 days of IV treatment. Switch to oral treatment with co-amoxiclav PO 625mg tds. If gentamicin is contra-indicated use the following combination:- Piperacillin / tazobactam IV 4.5g tds and metronidazole IV 500mg tds Comments/Reference See section 27 (aminoglycosides). Maximum dose for once daily Gentamicin is 560mg. Teicoplanin IV 400mg 12 hourly for three doses then 400mg od and gentamicin IV 5mg/kg od (check levels) and metronidazole IV 500mg tds. Contact microbiology to discuss choice of oral treatment. If gentamicin is contraindicated please contact microbiology 6. Hepatic abscess Metronidazole IV 500mg tds and piperacillin / tazobactam IV 4.5g tds (switch to oral treatment with co-amoxiclav PO 625mg tds if sensitivities known otherwise contact microbiology) Discuss with microbiology Contact microbiology for advice Page 7 of 26

7. Spontaneous bacterial peritonitis Treatment of spontaneous bacterial peritonitis Piperacillin / tazobactam IV 4.5g tds Tigecycline IV 100mg stat then IV 50mg bd Prophylaxis of spontaneous bacterial peritonitis Co-trimoxazole PO 960mg od for 5 days per week If there is an issue with compliance then co-trimoxazole can be prescribed PO 960mg daily, without the two day break 8. Gastroenteritis Antibiotics not recommended unless a particular cause, e.g. Clostridium difficile suspected Page 8 of 26

9. Cellulitis Mild to moderate cellulitis Flucloxacillin IV 1g qds (treat intravenously for a minimum of 48 hours before considering a switch to oral treatment flucloxacillin PO 1g qds) NB Mild cases with no systemic toxicity and no uncontrolled co-morbidities can be treated orally as an outpatient. ) Clarithromycin IV 500mg bd. Minimum of 4 days of intravenous therapy. Switch to oral clarithromycin PO 500mg bd. Flucloxacillin alone provides adequate cover for streptococci in mild to moderate cases. Cellulitis in a patient with risk factors for MRSA Vancomycin IV (check levels) Comments/Reference See section 27 for vancomycin dosing. Severe cellulitis has had an anaphylactic Flucloxacillin IV 1g qds and benzylpenicillin IV 2.4g 4-6 Vancomycin IV (check h ourly levels) and clindamycin IV 300-600mg bd-qds (see comments ) Discontinue clindamycin immediately if diarrhoea or colitis develops. For classification of cellulitis see: Eron, L. J. 2003. The admission, discharge and oral switch decision processes in patients with skin and soft tissue infections. Current Treatment Options in Infectious Diseases, 5: 245-250. See section 27 for vancomycin dosing. Page 9 of 26

10. Diabetic foot ulcer Note that many of the drugs used here have significant risks for diarrhoea, drug interactions, and renal, liver, ocular or bone marrow toxicity. Assiduous vigilance and monitoring is required. Good quality microbiological specimens are critical in managing these infections. A separate detailed Diabetic Foot Care Pathwa y is also available. No infection (Pedis Grade 1) None Use local dressings and regular podiatry Mild infection (Pedis Grade 2) mild infection, cellulitis <2 cm, infection confined to skin and subcutaneous tissues and NOT systemically unwell. Doxycycline PO 100mg bd or Clindamycin PO 300mg qds Flucloxacillin PO 1g qds 5 to 7 days, then adjust in light of culture results and clinical response Antimicrobial dressings are recommended, such as Inadine. Improve glycaemic control and non-weight bearing. Suitable to be treated in the community. Moderate infection (Pedis Grade 3) mild infection, cellulitis >2 cm, lymphatic streaking, deep tissue or bone infection and NOT systemically unwell. No antibiotic given within the last month: Flucloxacillin PO 1g qds plus (if anaerobes suspected) Metronidazole PO 400mg tds Antibiotic given within the last month: If suitable for oral therapy: Either Clindamycin PO 300mg qds plus Ciprofloxacin PO 500mg bd; or (if Pseudomonas not suspected): Co-amoxiclav PO 625mg tds +/ amoxicillin 500mg PO tds If IV therapy required: Either: (if Pseudomonas not suspected): Co-amoxiclav IV 1.2g tds, with switch to oral 625mg tds +/ amoxicillin 500mg tds after 5-7 days; Or: Vancomycin IV (measure levels) plus Ciprofloxacin IV 400mg tds plus Metronidazole IV 500mg tds, with switch to oral Linezolid PO 600mg bd plus Ciprofloxacin PO 500mg-750mg bd plus Metronidazole PO 400mg tds Minimum 10 to 14 days Osteomyelitis minimum 4-6 weeks allergic patients or other contra-indications Clindamycin PO 300mg- 600mg qds Linezolid PO 600mg bd plus Ciprofloxacin PO 500mg- 750mg bd plus Metronidazole PO 400mg tds Vancomycin IV (measure levels) plus Ciprofloxacin IV 400mg tds plus Metronidazole IV 500mg tds, with switch to oral Linezolid PO 600mg bd plus Ciprofloxacin PO 500mg- 750mg bd plus Metronidazole PO 400mg tds See section 27 for vancomycin dosing. Antimicrobial dressings, debridement, improved glucose control and non-weight bearing are also recommended. Page 10 of 26

Severe infection SYSTEMICALLY UNWELL / SEPSIS SYNDROME (Pedis Grade 4) No antibiotic given within the last 90 days: Co-amoxiclav IV 1.2g tds plus Gentamicin IV 5mg/kg Antibiotic given within the last 90 days: Vancomycin IV (substitute with Teicoplanin if renal function very poor) plus either Piperacillin / tazobactam IV 4.5g tds (if ESBL coliforms never documented), or plus Meropenem IV 1g tds. Oral switch when clinically appropriate: Ciprofloxacin PO 500mg-750mg bd plus Metronidazole PO 400mg tds plus either Linezolid PO 600mg bd or Rifampicin* PO 300mg bd with one of: Doxycycline PO 100mg bd, or with Fusidic acid* PO 500mg tds, or with Trimethoprim PO 200mg bd Minimum 10 to 14 days Osteomyelitis minimum 4-6 weeks Vancomycin IV (substitute with Teicoplanin if renal function very poor) plus Ciprofloxacin IV 400mg bd plus Metronidazole IV 500 mg tds Take blood cultures and cultures from deep curettage or debridement tissue rather than superficial swabs. Adjust antibiotic regime based on culture results. * Need for hepatic monitoring. Do not use Rifampicin or Fusidic acid al one for staphylococcal therapy as there is a high risk of resistance development. See section 27 (aminoglycosides and vancomycin) and section 29 (other drug s) for renal dose adjustments. Maximum dose for once daily Gentamicin is 560mg. Diabetic foot ulcers with suspected or proven MRSA Add Vancomycin IV (check levels) or (if renal function very poor) Teicoplanin IV/IM 400mg od after 3 doses 12 hours apart If MRSA osteomyelitis suspected, also add: Rifampicin* PO/IV 600mg bd or Fusidic acid* PO 500mg tds (check LFTs) Oral switch when clinically appropriate: either Doxycycline PO 100mg bd (possibly with Fusidic acid* PO 500mg tds if dual therapy required) or Linezolid PO 600mg bd or Rifampicin* 300mg PO bd plus one of: Doxycycline PO 100mg bd, or with Fusidic acid* PO 500mg tds, or with Trimethoprim PO 200mg bd Advised Total has had an anaphylactic * Need for hepatic monitoring. Do not use Rifampicin or Fusidic acid alone for staphylococcal therapy as there is a high risk of resistance development. See section 27 (vancomycin). Page 11 of 26

11. Infected human or animal bite Co-amoxiclav PO 625mg tds 5 days Consult microbiology 12. Breast - lactational mastitis 00 bd Flucloxacillin IV/PO 1g qds (if mild and treated as 7 days Clarithromycin PO 5 mg outpatient PO 500mg qds) 13. Non lactational breast sepsis Co-amoxiclav IV/PO (IV tds) has had an anaphylactic dose 1.2g tds/ PO dose 625mg 7 days Clarithromycin IV/PO 500mg bd and metronidazole IV/PO (IV 500mg tds/ PO 400mg tds) 14. Suspected necrotising fasciitis Discuss with surgeons and microbiology Page 12 of 26

15. Urinary tract infections- Male and female community acquired (w ithout systemic symptoms) 1 st Line: Trimethoprim po 200mg bd, unless elderly (over 65) or have had antibiotics within the last 3 months, when the risk of a resistant organism is higher. 2 nd Line: Nitrofurantoin PO 50mg qds (see comments) Female: 3 days Male: 7 days Alternatives Nitrofurantoin is contra-indicated in patients with CrCl <20mL/min, and not generally recommended if CrCl <50 ml/min. Consider use of Co-amoxiclav or Pivmecillinam if Trimethoprim is also contra-indicated. Calculator for creatinine clearance can be found in the renal dose section (section 29) and on the Clinical Portal. If patients are showing systemic symptoms then treat as hospital-acquired urinary tract infection. 16. Hospital-acquired urinary tract infection Gentamicin IV 5mg/kg stat then antibiotic choice based on urine sensitivities, available within 24 hours. Alternatives Comments/Reference If patient unable to have Gentamicin contact microbiology to discuss. See section 27 (aminoglycosides). Maximum dose for once daily Gentamicin is 560mg. 17. Pyelonephritis (includes patients with an indwelling catheter) Co-amoxiclav IV/PO (IV dose 1.2g tds/ PO dose 625mg tds). Continue IV until temperature resolves. If no response after 24 hours or sepsis add gentamicin IV 5mg/kg od (check levels). 14 days Gentamicin IV 5mg/kg od (check levels) If patient unable to have gentamicin please contact microbiology to discuss. Once sensitivities are reported switch to oral antibiotics according to sensitivities. For patients with chronic urinary conditions please review previous sensitivities. Ensure all patients with a UTI are well hydrated. See section 27 (aminoglycosides). Maximum dose for once daily Gentamicin is 560mg.. 18. Acute bacterial prostatitis Ciprofloxacin PO 500mg bd 14 days More severe cases 2 4 weeks Page 13 of 26

19. Epididymo-orchitis in adults If risk of STD: Ceftriaxone 500mg IM single dose and doxycycline PO 100mg bd If STD not suspected: Ciprofloxacin PO 500mg bd 14 days Azithromycin 1g PO single dose plus Ciprofloxacin PO 500mg bd 21 days 20. Meningitis Ceftriaxone IV 2g bd For patients with other risk factors: >55 years, alcohol, Pregnant - please discuss with microbiology 7-21 days depending on organism grown Consult microbiology It is statutory requirement to notify the Health Protection Team (Public Health) on 01495 332219 or via ambulance control out of hours. Page 14 of 26

21. Endocarditis Blood cultures are a cornerstone of diagnosis and should be taken prior to starting treatment in all cases. In sub-acute presentation, three sets of blood cultures should be taken over 12 hours from peripheral sites prior to commencing antimicrobial therapy. In acute presentation take two sets one hour apart and start antibiotics. Key Reference: Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults. Journal of Antimicrobial Chemotherapy, 2012, v67, pp269-289. Native Valve indolent presentation Amoxicillin IV 2g 4 hourly and (optional) gentamicin IV 1mg/kg bd. (check gentamicin levels) Advised Total has had an anaphylactic Vancomycin IV and gentamicin IV 1mg/kg bd (check vancomycin & gentamicin levels) Comments/Reference See section 27 (aminoglycosides & vancomycin dosing). The use of gentamicin is optional before culture results are available. If patient is stable, ideally wait for blood culture results. Native Valve, severe shock but no risk factors for Enterobacteriaceae, Pseudomonas. Vancomycin IV and gentamicin IV 1mg/kg bd (check vancomycin and gentamicin levels) Comments/Reference See section 27 (aminoglycosides & vancomycin dosing). Advised Total Alternatives Consult microbiology if vancomycin allergy or gentamicin is contraindicated Native Valve, severe shock with risk factors for Enterobacteriaceae, Pseudomonas. Vancomycin IV and Meropenem IV 2g 8 hourly (check vancomycin levels) Advised Total has had an anaphylactic Consultant microbiology Comments/Reference See section 27 (vancomycin dosing) See section 29 (meropenem in renal impairment). Prosthetic valve endocarditis pending blood cultures or if negative blood cultures Vancomycin IV and gentamicin IV 1mg/kg bd and rifampicin IV or PO 300mg-600mg bd (use the lower rifampicin dose if severe renal impairment) (check LFTs, vancomycin and gentamicin levels) See section 27 (aminoglycosides & vancomycin dosing). Advised Total Alternatives Consult microbiology if vancomycin allergy or gentamicin is contraindicated Patient with additional risk factors for staphylococcus (IV drug user, dialysis) Vancomycin IV and gentamicin IV 80mg tds (If patient <60kg reduce dose to 60mg) (check vancomycin and gentamicin levels) See section 27 (aminoglycosides & vancomycin dosing). Advised Total Alternatives Consult microbiology if vancomycin allergy or gentamicin is contraindicated Page 15 of 26

22. Sepsis Unknown origin Co-amoxiclav IV 1.2g tds and gentamicin IV 5mg/kg od (monitor levels) If patient is renally impaired (CrCl < 30mL/min): Piperacillin / tazobactam IV. Please refer to section 29 for dosing in renal impairment. Contact microbiology If patient has neutropenic sepsis then refer to neutropenic sepsis guidelines. Blood cultures should be taken prior to first dose given and results should be reviewed within 24 hours. See section 27 (aminoglycosides). Maximum dose for once daily Gentamicin is 560mg. Unknown origin with history of ESBL coliform infection 1 st Line: Imipenem/cilastatin IV 500mg/500mg qds Take cultures prior to first dose. Review antibiotic choice once cultures are available. Tigecycline IV initially 100mg stat then 50mg every 12 hours. 23. Neutropenic sepsis Refer to Integrated Care Pathway Neutropenic Fever Contact microbiology Page 16 of 26

24. Osteomyelitis and Septic arthritis Flucloxacillin IV 1-2g qds and sodium fusidate PO 500mg tds 4-6 weeks Contact microbiology Consider alternatives once cultures available High risk patients (see comments) or confirmed Gram-negative infection Contact microbiology Contact microbiology High risk cases: prostheses, immuno-compromised, diabetic, IVDU, catheter related bloodstream infection. 25. Prosthetic joint infection Vancomycin IV (check levels) and rifampicin IV 300-600mg bd (check LFTs are normal) See section 27 (vancomycin dosing). (IV and oral) Consult orthopaedic surgeon Alternatives 26. Open fracture or dirty wound Co-amoxiclav IV/PO (IV dose 1.2g tds/ PO dose 625mg tds) Consult medical microbiologist Comment:: Give Tetanus prophylaxis. Infections often polymicrobial. Page 17 of 26

27. Aminoglycosides & Vancomycin Guidelines for dosing Calculations required for determining ideal body weight and creatinine clearance: Ideal body weight: Males: Females: IBW = 50kg + 0.9kg for every cm over 152cm IBW = 45.5kg + 0.9kg for every cm over 152cm If patient s actual body weight is 30% more than IBW: Adjusted body weight = IBW + 0.4(Actual body weight IBW) C reatinine clearance: Aminoglycoside and vancomycin dosing is dependent on a patient s renal function. This can be approximated by calculating the creatinine clearance using the Cockcroft Gault equation: Creatinine clearance (ml/min) = (140 age in y ears) x weight (kg) x (1.25 for men) Serum creatinine (micromoles per litre) Gentamicin The majority of patients should receive gentamicin once daily. Exclusion criteria for once daily dosing include: severe renal impairment, pregnancy and post-partum women, endocarditis, dialysis, ascites, cystic fibrosis and major burns (more than 20% of body). Gentamicin once daily dosing In patients with normal renal function give 5mg/kg ideal body weight (maximum of 560mg) to the nearest 40mg increment. Neutropenic policy exempt: states 6mg/kg od. Appropriate dosing is given in the table below: Creatinine clearance (ml/min) Gentamicin >70 30-70 10-30 5-10 5mg/kg OD and monitor levels 3-5mg/kg OD and monitor levels 2-3mg/kg OD and monitor levels 2mg/kg every 48-72 hours according to levels Page 18 of 26

Serum level measurement for once daily dosing: All levels should be taken prior to next dose (pre-dose levels). Peak dose levels are not required. First level should be taken prior to the third dose at the latest unless the patient is acutely unwell where the level should be taken prior to the second dose. Sample creatinine should be checked every other day and increase frequency of levels if renal function worsens. If patient is renally stable and the dose was not altered then assay every 5-7 days. Adjust dose depending on gentamicin level as shown in table below. Gentamicin Once daily dosing Pre-dose (mg/l) (Trough level) Ideal range <1 Level too high Reduce frequency Gentamicin mu ltiple daily dosing To be used by patients excluded from once daily dosing Dose: 3 to 5mg/kg IBW (Ideal Body Weight) per day in divided doses, every 8 or 12 hours usually 120mg loading dose, then 80mg or 120mg every 8 to 12 hours. Dose to nearest 40mg increment. Serum level measurement for multiple daily dosing: Check both pre-dose and post-dose levels after the third dose. If patient is renally stable and no adjustments were required, assays should be taken every 3-5 days. Levels will need to be taken more regularly in renal impairment and in deteriorating patients. Adjust dose depending on gentamicin level as shown in table below. Gentamicin Multiple daily dosing Pre-dose (mg/l) Prior to next dose Post-dose (mg/l) 1hr after last dose Ideal range <2 5 10 (other than Streptococcal & Staphylococcal endocarditis) Streptococcal & <1 3 5 Staphylococcal endocarditis Level too high Reduce frequency Reduce dose Level too low Increase dose Page 19 of 26

Vancomycin These dosing guidelines are for intra-venous dosing. For information dosing in the treatment Clostridium difficile, please see section 4. for oral Intravenous vancomycin: Initially, the size of dose is determined by the patient s weight, and the frequency of dosing by the renal function. Doses should then be adjusted according to serum levels. Dilute vancomycin in 250mL of 0.9% sodium chloride given over 2 hours. 50 60kg patient: 750mg doses 60 80kg patient: 1g doses Other weights: 15mg/kg to a max of 2g per dose. Creatinine clearance (ml/min) Vancomycin dosing >80 60-80 40-60 30-40 20-30 10-20 <10 or on dialysis every every every every every every every 12 18 24 36 48 60 96 hours interval hours hours hours hours hours hours Serum level measurement Levels are required for every patient before the third dose. If the patient is renally stable and no adjustments were required after the first level then assays should be taken every 3 to 5 days. Levels need to be taken more regularly in renal impairment and in deteriorating patients. Adjust dose depending on vancomycin level as shown in table below. Peak levels are not routinely required, but may be performed if there is concern a bout clinical response to therapy. Vancomycin Pre-dose (mg/l) Prior to next dose Post-dose (mg/l) 1hr after last dose Ideal range for 10 15 20 40 uncomplicated infections Range for Bacteraemia, 15 20 20 40 Endocarditis, Osteomyelitis, Pneumonia, less susceptible (VISA) strains of MRSA Level too high Reduce frequency Reduce dose Level too low Increase frequency Increase dose (max 12 hourly) Ref: Cardiff and Vale University Health Board. Good Prescribing Guide. Prescribing Guidelines for Medical Staff. Sixth Edition. Januar y 2011 Page 20 of 26

Secondary Care Adult Antibiotic Guidelines 28. Antimicrobial Prophy laxis Summary Table Please refer to the full Antimicrobial Prophylaxis Guidelines for further information. MRSA If a patient has been known to have MRSA colonisation or infection in the past, its pre-operative eradication and the addition of specific anti- MRSA prophylaxis is reco mmended, particularly for major invasive p rocedures. This is in addition to the routine prophylactic antibiotics if t hey will not themselves cover MRSA. A single dose of Teicoplanin 400mg IV is advised for adults. Vancomycin IV 1g infused over 100 minutes is a less practical alternative. It is intended that antibiotic pr ophylaxis is given as a single dose. Although t here has been a tradition of repeat doses for 24 hours or more for some procedures, the supporting evidence is weak and this is no longer recommended in all but the most exceptional circumstances. If during the procedure it is appar ent that there is infection at the operative site, it is appropriate to extend the prophylactic dose into a thera peutic course of an antibiotic. An additional dose of the prophylactic agent intra-operatively or post- loss of 1500mL during surgery or haemodilution of up to 15mL/kg. Post-operative doses of antibiotic for prophylaxis should not operatively is not indicated in adults unless the procedure lasts for more than 4 hours, or there is blood o therwise be given for any oper ation. Any decision to prolong prophylaxis beyond a single dose should be explicit and supported by an evidence base. If patients have contra-indi cations to any of the recommended antibiotics, please contact microbiology. Procedure First line Alternative Upper GI Oesophageal, Gentamicin 120mg IV Gastric, Duodenal Uncomplicated Small bowel Gentamicin 120mg IV & Appendicectomy Metronidazole 500mg IV Colo-rectal Perforated or Gangrenous Gentamicin 120mg IV & Appenicectomy or Colo-rectal Metronidazole 500mg IV Biliary laparoscopic Nil, unless converted to cholecystectomy open procedure Biliary Open but Gentamicin IV 120mg uncomplicated Biliary Open procedure, Gentamicin 120mg IV & Complicated / Infected ERCP Endoscopic Retrograde Cholangiopancreatography Metronidazole 500mg IV Gentamicin 120mg IV Breast Flucloxacillin IV 1g Clindamycin 600mg IV Page 21 of 26

Secondary Care Adult Antibiotic Guidelines Gynaecology Hysterectomy Gentamicin 120mg IV & & other procedures involving Metronidazole 500mg IV or vaginal or uterine incision 1g PR Caesarean Section Cefuroxime 1.5g IV & Clindamycin 600mg Metronidazole IV 500mg IV Termination of Pregnancy Metronidazole 400 mg PO Add treatment for genital Chlamydia if not ruled out, e.g. Doxycycline ENT Head and Neck & Clarithromycin 500mg IV & Otological Procedures Metronidazole 500mg IV Hernia repair with mesh (Open Amoxicillin 1g IV, Clindamycin 600 mg or laparoscopic) Gentamicin IV 120mg IV, IV & Gentamicin 120 Metronidazole IV 500mg mg IV Urology see also Prostate Choose cover from pre- If results negative below operative culture result then gentamicin IV 120mg Prostate Resection Gentamic in 120mg IV (Transurethral) TURP Prostate Biopsy ( Transrectal) Vascular arterial surgery in Ciprofloxacin 750mg oral & Metronidazole 400 mg oral Flucloxacillin 1g IV& Teicoplanin IV abdomen, pelvis or legs Gentamicin 120mg IV 400mg Add Metronidazole if diabetic or gangrene or amputation Antibiotic is sometimes also incorporated into vascular grafts Orthopaedics clean Teicoplanin 400 mg IV & Gentamicin120mg IV Arthroplasty, Internal fixation of Antibiotic e.g. Gentamicin may also be incorporated fractures into cement, etc., if used Orthopaedics contaminated wound, complex open fractures with extensive tissue damage Teicoplanin 400 mg IV & Gentamicin120mg IV & Metronidazole 500mg IV or 1g PR Lower limb amputation or after Benzyl penicillin 600mg IV Metronidazole IV major trauma QDS/ Amoxicillin 500mg PO TDS for 5 days 400-500mg TDS for 5 days Closed clean orthopaedic procedures without prosthesis No prophylaxis recommended Urinary Catheter Change only Choose cover from pre- If negative then for patients at exceptional risk e.g. with prosthetic implants culture result if procedure available Gentamicin 120mg IV Page 22 of 26

Secondary Care Adult Antibiotic Guidelines 29. Antimicrobia l dosing guidelines in adults with renal impairment and failure (Doses taken from The Renal Handbook, 3rd edition 2009, UK Renal Pharmacy Group, the Electronic Medicines Compendium www.emc. medicines.org.uk Summaries of Product Characteristics) CAPD = Continuous ambulatory peritoneal dialysis HD = Intermittent Haemodialysis N/A = Preparation not available or not used routinely within Health Board Dose for patients on CAPD or HD as per patients with a Creatinine Cl earance (CrCl) <10ml/min unless otherwise stated. CrCl may be calculated by: (140 age in years) x body weight (kg) (x1.25 for men) = ml/min Serum creatinine (micromoles per litre) If patient is a dialysis patient please contact your ward pharmacist for advice. Antibiotic CrCl Oral Dose Intravenous Dose (ml per minute) Aciclovir > 50 200mg 400mg 5 x /day 2 5mg/kg tds 3 Treatment of 25 50 200mg 400mg 5 x /day 2 5mg/kg bd Herpes 10 25 200mg 3 4x /day 5mg/kg od Simplex < 10 200mg bd 2.5mg/kg od Aciclovir Treatment of Varicella Zoster 1 Benzylpenicillin Note: Higher doses (>7.2g/day) should be reserved for the treatment of meningitis and severe cellulitis Cefalexin Cefotaxime Ceftriaxone Cefuroxime Ciprofloxacin Clarithromycin > 50 800mg 5 x /day 5-10mg/kg tds 3 25 50 800mg 5 x /day 5-10mg/kg bd 3 10 25 800mg bd - tds 5-10mg/kg od 3 (some units use 3.5-7mg/kg od) < 10 400mg 800mg bd 2.5-5mg/kg od 3 > 20 N/A 2.4g 14.4g daily in 4 6 divided doses. 10 20 N/A 600mg 2.4g qds, depending on severity of infection < 10 N/A 600mg 1.2g qds, depending on severity of infection > 20 250mg qds or 500mg bd/tds N/A Recurrent UTI prophylaxis: 125mg at night 10 20 500mg bd/tds N/A < 10 250mg 500mg bd/tds N/A > 10 N/A Mild infection: 1g bd Moderate infection: 1g tds Severe infection: 2g qds Life-threatening infection: up to 12g daily in 3 4 divided doses. < 10 N/A 1g bd / tds >10 N/A 1g od; 2 4g daily in severe infections <10 N/A Dose as in normal renal function, maximum 2g daily >50 N/A 750mg 1.5g tds 20 50 N/A 750mg 1.5g tds 10 20 N/A 750mg 1.5g bd / tds <10 N/A 750mg 1.5g od/bd >20 250mg 750mg bd 100mg 400mg bd 10 20 50% - 100% of normal dose 50% 100% of normal dose <10 50% of normal dose 50% of normal dose CAPD /HD 250mg bd 200mg bd Up to 500mg bd in CAPD peritonitis >30 250mg 500mg bd 500mg bd <30 250mg 500mg bd 250mg 500mg bd Page 23 of 26

Secondary Care Adult Antibiotic Guidelines Antibiotic Co-amoxiclav Co-trimoxazole (N.B. Higher doses used for Pneumocystis) Doripenem Ertapenem Erythromycin Flucloxacillin Imipenem / cilastatin Gentamicin Levofloxacin CrCl (ml per minute) Oral Dose >30 375mg 625mg tds 10 30 Dose as in normal renal function <10 Dose as in normal renal function >30 960mg od for SBP prophylaxis 15 30 480mg od for SBP prophylaxis <15 480mg od for SBP prophylax is Intravenous Dose 1.2g tds. Up to qds in severe infections 1.2g bd 1.2g stat followed by either 600mg tds or 1. 2g bd >50 N/A 500mg tds 30 50 N/A 250mg tds <30 N/A 250mg bd >30 N/A 1g od 10 30 N/A Use 50% 100 % of dose <10 N/A Use 50% of dose or 1g three times per week >10 250mg 500mg qds or Mild to moderate infection, 500mg 1g bd 25mg/kg/day. Severe infection or immunocompromised, 50mg/kg/day (maximum 4g/day for adults) <10 50% 75% of normal dose, 50% 75% of normal dose, maximum 2g daily maximum 2g/day >10 250mg 1g qds 250mg 2g qds. Endocarditis: Maximum 2g every 4 hours (if weight >85kg) Osteomyelitis: 8g/day in divided doses <10 Dose as in normal renal Dose as in normal renal function. Maximum dose is 4g function. Maximum dose is 4g daily daily >70 N/A 500mg/500mg 1g/1g tds / qds (Max 4g/4g per day) 31 70 N/A 500mg/500mg tds qds 21 30 N/A 500mg/500mg bd tds <20 N/A 250mg/250mg 500mg/ 500mg bd or 3.5mg/3.5mg per kg bd, whichever is lower CAPD/HD N/A 250mg/250mg 500mg/500mg bd or 3.5mg/3.5mg per kg bd, whichever is lower >70 N/A 5mg/kg od. Monitor levels. 30 70 N/A 3-5mg/kg od. Monitor levels. 10 30 N/A 2-3mg/kg od. Monitor levels. 5 10 N/A 2mg/kg every 48 72 hours according to levels. CAPD N/A 2mg/kg every 48 72 hours according to levels. HD N/A 2mg/kg every 48 72 hours according to levels. Dose after dialysis. >50 500mg od/bd 500mg od/bd 20 50 Initial dose 250mg 500mg Initial dose 250mg 500mg then reduce dose by 50% then reduce dose by 50% 10 20 Initial dose 250mg 500mg Initial dose 250mg 500mg then 125mg 12 24 hourly then 125mg 12 24 hourly <10 Initial dose 250mg 500mg Initial dose 250mg 500mg then 125mg 24 48 hourly then 125mg 24 48 hourly Page 24 of 26

Secondary Care Adult Antibiotic Guidelines Antibiotic Meropenem Nitrofurantoin Piperacillin / Tazobactam Rifampicin Teicoplanin Vancomycin Cr Cl (ml per minute) Oral Dose Intravenous Dose >50 N/A 500mg 1g tds, up to 2g tds in meningitis / cystic fibrosis / endocarditis 20 50 N/A 500mg 2g bd 10 20 N/A 500mg 1g bd or 500mg tds <10 N/A 500mg 1g od >50 50mg 100mg qds (or once N/A nightly for prophylaxis) 20 50 50mg 100mg qds (or once N/A nightly for prophylaxis) Use with caution <20 and CAPD/HD Contra-indicated: drug N/A ineffective due to reaching inadequate urine conc. Toxic plasma concentrations can occur with adverse effects. >20 N/A 4.5g tds (qds for neutropenic sepsis) 10 20 N/A 4.5g bd/tds <10 N/A 4.5g bd >10 600mg 1200mg daily in 600mg 1200mg daily in divided doses divided doses <10 50-100% of normal dose 50-100% of normal dose >20 N/A Initially 400mg 12 hourly for 3 doses then subsequently 400mg od 10 20 N/A Give normal loading dose then 200mg 400mg every 24 48 hours <10 N/A Give normal loading dose then 200mg 400mg every 48 72 hours >50 125mg 500mg qds 1g bd. Take levels. depending on severity of Clostridium difficile 20 50 Dose as in normal renal 500mg 1g od/bd. Take function levels. 10 20 Dose as in norm al renal 500mg 1g every 24 48 function hours based on levels. <10 Dose as in norm al renal 500mg 1g every 48 96 function hours based on levels. Drugs that d o not usually require dose adjustments include: 4 Amoxicillin Doxycycline Moxifloxacin Tigecycline Azithromycin Linezolid 4 Penicillin V Trimethoprim 4 Clindamycin Metronidazole Sodium fusidate For drugs not listed please contact your Ward Pharmacist. 1 Where a dosage range is given the higher dose should be reserved for severely immunocompromised patients. These patie nts may require much higher doses than those quoted. 2 For prophylaxis of Herpes Simplex reduce dosing frequency to four times daily. 3 Treatment of Herpes Simplex Encephalitis use IV dose at higher range (10mg/kg) quoted. 4 Contact ward pharmacist if CrCl < 10mL/min or patient is on dialysis. Page 25 of 26

Secondary Care Adult Antibiotic Guidelines 30. Guidelines for ONCE daily gentamicin administration in adults Affix patient s addressograph here Exclusion criteria for once daily dosing is severe renal impairment, pregnancy and post-partum women, endocarditis, dialysis, ascites, cystic fibrosis and major burns (more than 20% of body). Ward: Diagnosis: Actual Body Weight: Height: REMEMBER TO WRITE GENTAMICIN ON PATIENT S REGULAR DRUG CHART WITH SEE GENTAMICIN CHART ALONG SIDE. Dose: In patients with normal renal function give 5mg/kg Ideal Body Weight (maximum of 560mg) to the nearest 40mg increment. (Neutropenic policy exempt: states 6mg/kg od) To calculate a patient s ideal body weight: Males: IBW = 50kg + 0.9kg for every cm over 152cm Females: IBW = 45.5kg + 0.9kg for every cm over 152cm If patient s actual body weight is 30% more than IBW: Adjusted body weight = IBW + 0.4(Actual body weight IBW) For patients with renal impairment contact microbiology or medicines information. Administration: The daily dose should be diluted in 100mL sodium chloride 0.9% or glucose 5% and administered over 60 minutes. Do not wait for level results before administering the next dose if patient has normal renal function. 1 2 3 4 5 6 7 Date Serum Creatinine Time gentamicin given Nurse s signature for administration Time blood taken for level* Next gentamicin dose due in 24 unless do ctor has otherwise specified Gentamicin level (m g/l). When next dose due. Signature *Levels: All levels should be taken prio r to next dose (pre-dose leve ls). Peak dose levels are not required First level should be taken prior to the third dose unless the patient is acutely unwell where the level may need to be taken sooner. Sample creatinine should be checked every other day and increase frequency of levels if renal functi on worsens. If patient is renally stable and the dose was not altered after the 3 rd dose then assay every 5-7 days. Adjust dose depending on gentamicin l evel as shown in table below. Pre-dose (mg/l) (Trough level) Ideal range <1 Level too high Reduce frequency Page 26 of 26

Secondary Care Adult Antibiotic Guidelines UGuidelines for MULTIPLE daily gentamicin administration in adults Affix patient s addressograph here Exclusion criteria for once daily dosing is severe renal impairment, pregnancy and post-partum women, endocarditis, dialysis, ascites, cystic fibrosis and major burns (more than (20% of body). Ward: Diagnosis: Actual Body Weight: Height: REMEMBER TO WRITE GENTAMICIN ON PATIENT S REGULAR DRUG CHART WITH SEE GENTAMICIN CHART ALONG SIDE. Dose: 3 to 5mg/kg Ideal Body Weight per day in divided doses, every 8 or 12 hours. Usually 120mg loading dose, then 80mg or 120mg every 8 to 12 hours. Dose to the nearest 40mg increment. To calculate a patient s ideal body weight: Males: IBW = 50kg + 0.9kg for every cm over 152cm Females: IBW = 45.5kg + 0.9kg for every cm over 152cm If patient s actual body weight is 30% more than IBW: Adjusted body weight = IBW + 0.4(Actual body weight IBW) For patients with renal impairment contact microbiology or medicines information. Administration: The daily dose should be diluted with 50-100mL sodium chloride 0.9% or glucose 5% and administered over 20-30 minutes. Do not wait for level results before administering the next dose if patient has normal renal function. Day 1 Date & time dose to be given (00:00hrs) Actual time given (00:00hrs) Nurse s signature of administration Time level taken Gentamicin levels mg/l Pre Post Pre Post Reviewed by doctor/ pharmacist 2 3 4 5 6 Levels will need to be taken more regularly in renal impairment or deteriorating patients. If patient is renally stable and no adjustments were required after the first levels (at the third dose), assays should be taken every 3-5 days. Adjust dose depending on gentamicin level as shown in table below. Pre-dose (mg/l) Prior to next dose Post-dose (mg/l) 1hr after last dose Ideal range (other than Streptococcal or <2 5-10 Staphylococcal endocarditis) Streptococcal or Staphylococcal endocarditis <1 3-5 Level too high Reduce frequency Reduce dose Level too low Increase dose Page 27 of 26