All prescribers, charge nurses, clinical pharmacists. NHS Borders Antimicrobial Management Team

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1 Title Document Type Issue no Antimicrobial Guidelines for Hospitals Guideline Clinical Governance Support Team Use Issue date Jan 2014 Review date Jan 2016 Distribution All prescribers, charge nurses, clinical pharmacists Prepared by Developed by Anne Duguid NHS Borders Antimicrobial Management Team Equality & Diversity Impact Assessed Approved By NHS Borders Antimicrobial Management Team Document Addition/Amendments App iv Surgical Prophylaxis Guidelines Apr 14 Approved Date File Location: Clin_Pharm_Antimicrobial_Guidelines

2 Antimicrobial Guidelines for Hospitals January 2014 Produced by: NHS Borders Antimicrobial Management Team Review date January 2016 You can access the most recent version of the Guidelines on the NHS Borders Intranet Antimicrobials microsite. 2

3 CONTENTS PAGE 1 INTRODUCTION. 1.1 Penicillin Allergy. 1.2 Prudent Antimicrobial Prescribing Antimicrobial Categories for Prescribers. 2 SEPSIS AND BLOOD STREAM INFECTIONS Sepsis and Sepsis Sepsis of Unknown Source Sepsis in Neutropenic Patients (see Appendix viii) 2.4 Central Catheter Related Blood Stream Infection Yeast / Candida Blood Stream Infection Secondary to Long or Central Intravascular Lines Blood Stream Infection due to Staphylococcus aureus.. 3 BONE AND JOINT INFECTIONS. 3.1 Septic Arthritis / Osteomyelitis Prosthetic Joint Infections.. 4 CENTRAL NERVOUS SYSTEM INFECTIONS. 4.1 Bacterial Meningitis ( Notifiable Disease) 4.2 Viral Meningitis Brain Abscess Herpes Simplex Encephalitis. 5 CARDIOVASCULAR SYSTEM INFECTIONS 5.1 Infective Endocarditis.. 6 EAR, NOSE & THROAT INFECTIONS 6.1 Dental Abscess Otitis Externa Otitis Media or Sinusitis Tonsillitis / Quinsy. 7 GASTROINTESTINAL TRACT INFECTIONS 7.1 Intra-Abdominal Sepsis including Bacterial Peritonitis Hepatobiliary Sepsis Antibiotic Associated Diarrhoea Gastroenteritis / Food Poisoning ( Notifiable Disease) 7.5 Oral Candidiasis Systemic Candidiasis Helicobacter Eradication. 7.8 Spontaneous Bacterial Peritonitis. 8 URO-GENITAL SYSTEM INFECTIONS Pelvic Inflammatory Disease (PID) Gonorrhoea and/or contact with Gonorrhoea Chlamydia Epididymo-orchitis Genital Herpes Vaginal Candidiasis Penile Candidiasis. 9 URINARY TRACT INFECTIONS Simple Urinary Tract Infections Catheter specimen Urinary Tract Infections in Pregnancy. 9.4 Complicated Urinary Tract Infections Prostatitis

4 CONTENTS PAGE 10 RESPIRATORY TRACT INFECTIONS Acute Exacerbations of Chronic Obstructive Pulmonary. Disease 10.2 Community Acquired Pneumonia Legionella Pneumonia post influenza 10.3 Hospital Acquired Pneumonia Aspiration Pneumonia Ventilator Acquired pneumonia Tuberculosis SKIN AND SOFT TISSUE INFECTIONS Cellulitis (not perineum) Diabetic Foot Necrotising Fasciitis / Streptococcal Toxic Shock Syndrome Surgical Wound Infection Traumatic Wounds / Lacerations MRSA Skin and Soft Tissue Infections Multiple injuries and/or compound fractures of long bones Bites Herpes Leg Ulcers / Pressure Sores / PEG sites APPENDIX i MONITORING ANTIMICROBIAL DOSAGE Gentamicin... Vancomycin. APPENDIX ii PREGNANCY AND ANTIMICROBIALS APPENDIX iii.. ANTICOAGULANTS AND ANTIMICROBIALS APPENDIX iv.. SURGICAL PROPHYLAXIS GUIDELINES APPENDIX v GUIDELINES FOR THE PROTECTION OF THE ASPLENIC PATIENT APPENDIX vi.. PROPHYLAXIS OF INFECTIVE ENDOCARDITIS APPENDIX vii. GENERAL GUIDANCE FOR IV TO ORAL SWITCH Appendix viii PROTOCOL FOR MANAGEMENT OF PATIENTS WITH. NEUTROPENIC SEPSIS AT BORDERS GENERAL HOSPITAL APPENDIX ix.. RENAL IMPAIRMENT AND ANTIBIOTICS

5 1 INTRODUCTION This guidance is intended to assist medical staff to make a rational choice of an antimicrobial before drug sensitivities are known. It takes into account national and local guidelines and local sensitivities. Reference should also be made to guidelines for specific areas such as critical care. Unless otherwise stated, the guidance refers to the treatment of adult patients. Doses quoted are for patients with normal renal function. Please feel free to discuss infection problems with the Consultant Microbiologist. Telephone Numbers: Consultant Microbiologist Extension Microbiology Laboratory. Extension Microbiology Secretary Extension Advice is also available from Pharmacy: Antimicrobial pharmacist Extension Dispensary Extension 26609/10 Antimicrobial therapy should be reviewed daily, in the light of: Culture results Allergy or adverse reaction None-response Microbiology consultation 1.1 Penicillin Allergy The BNF has clear guidance on penicillin hypersensitivity. In this guideline, alternatives to penicillins are given as appropriate to the clinical scenario. Cephalosporins or other betalactam antibiotics (including piperacillin / tazobactam and meropenem) should NOT be given to patients with a history of anaphylaxis, angio-oedema, bronchospasm, urticaria or rash occurring immediately after penicillin administration. Please speak to a Consultant Microbiologist in such cases. NHS Borders Infection Control Manual contains policies related to the management of patient with infection and infectious disease and the control and prevention of cross infection (found in all wards / departments or on the NHS Borders intranet). Other useful websites: British Society for Antimicrobial Chemotherapy: Treatment of Hospital Infections.. British National Formulary Health Protection Scotland.. 5

6 1.2 Prudent Antimicrobial Prescribing When choosing Antimicrobials consider: 1. Choice The likely organisms causing the infection Allergies and contra-indications Previous antimicrobial therapy Antimicrobial likely to achieve adequate concentrations at site of infection? Change according to culture and sensitivities Site of infection Severity. Age, weight, renal and hepatic function of the patient Consider oral route if appropriate for the patient Reassess IV route within 48 hours (see Appendix vii, General Guidance on IV to Oral Switch Guidelines). Choose oral antibiotic according to guideline or according to sensitivities. 2. Duration According to guidelines. Otherwise keep to 5 days and then review Always indicate a stop date or course length in the drug kardex and patient case notes Remember antimicrobials must be given regularly, e.g. every 6 hours or 8 hours When writing prescriptions for Antimicrobials Please refer to the British National Formulary for general guidance on prescribing and prescription writing. British National Formulary. 6

7 1.3 ANTIMICROBIAL CATEGORIES FOR PRESCRIBERS To assist in the management of antimicrobial prescribing, and minimise the emergence of resistance amongst bacteria, the antimicrobials stocked in Pharmacy are grouped into three categories. Group I Antimicrobial agents, which can be prescribed by all doctors when appropriate: Amoxicillin Benzylpencillin Cefalexin Cefotaxime (for CNS infections) Chloramphenical (eye preparations) Clarithromycin IV Clarithromycin oral Doxycycline oral Flucloxacillin Fluconazole oral Gentamicin * Metronidazole Nystatin suspension Phenoxymethylpenicillin Rifampicin (meningococcal prophylaxis) Trimethoprim Group II Antimicrobial agents that can only be prescribed for specific conditions, or infections as per antimicrobial guideline, or when indicated by culture and sensitivity results. Azithromycin (STI only) Fluconazole IV Cefixime (STI only) Mupirocin nasal ointment Ceftazidime Naseptin Ceftriaxone (STI only) Ofloxacin (STI only) Chlorampenicol Rifampicin (TB & Meningococcal Prophylaxis) Ciprofloxacin Sodium Fusidate oral Clindamycin *piperacillin/tazobactam *Co-amoxiclav Teicoplanin Co-trimoxazole Vancomycin Group III** Antimicrobials that can only be prescribed on the advice of a Consultant Microbiologist. Amphotericin IV Caspofungin Ceftriaxone (except for STI) Flucytosine 5FC (Flucytosine) * Meropenem Rifampicin Sodium Fusidate IV Voriconazole * Do not prescribe metronidazole with co-amoxiclav (amoxicillin / clavulanic acid), piperacillin/ tazobactam or meropenem ** In extreme circumstances, the critically ill patient may require antimicrobials out of Group III prior to discussion with the Consultant Microbiologist. The Consultant Microbiologist should be contacted as soon as possible in such circumstances. 7

8 2.0 SEPSIS AND BLOOD STREAM INFECTIONS 2.1 SEPSIS AND SEPSIS 6 Sepsis is important: it kills more people than acute myocardial infarction! Prompt management of sepsis saves lives. The goal of the Sepsis 6 is to reduce mortality by 25% What is the Sepsis 6? A bundle of interventions to be achieved within 1 hour (see below). What triggers the Sepsis 6? Any patient with a SIRS score of 2 or more (2 or more yellow boxes) and a suspicion of infection driving this inflammatory response. What do you do? All of the actions below. To make it easier, there is a sticker to document all of it in the notes. Use this as it helps us to audit the patients with sepsis. SEPSIS 6 1. Give high flow oxygen 2. Take blood cultures (ideally before antibiotics start) 3. Give iv antibiotics 4. Start iv fluid resuscitation 5. Check lactate (needs a yellow tube) and FBC (use sepsis order set) 6. Monitor hourly urine output. and refer patient to critical care outreach Easy. 3 things to check (lactate, blood cultures and urine output) and 3 things to do (give oxygen, fluids and antibiotics). The blood tests are part of the Sepsis 6 order set on Trak. IMPORTANT: the patient has to actually receive the antibiotics to get any benefit from them. If this means administering them yourself then that is a good use of anybody s time! Treatment of Sepsis There are three key features of the management of the patient with sepsis: 1. Recognition: early recognition is crucial to improvement of mortality from this important condition. In the BGH the SIRS chart will capture these patients early, and with a confirmed or suspected source of infection the diagnosis is made. 2. Prompt diagnosis and treatment: Sepsis 6: complete the bundle within 1 hour. Administration of appropriate IV antibiotics to the septic patient is essential: for every hour you delay the mortality can increase by 7%. 8

9 3. Organ support: if required the patient may need organ support in the ITU. Referral of all patients with sepsis to Critical Care Outreach will make this process easier. Your goal is to break the chain of progression from infection to sepsis to septic shock to multiple organ failure to death. With the Sepsis 6 bundle we can do that and reduce the chances of patients dying. Infection SIRS Definition Organisms at a normally sterile site with some inflammation. Systemic Inflammatory Response Syndrome Host inflammatory response May or may not be caused by infection 2 or more of: Temperature >38 o C or < 36 o C Heart Rate >90 beats/min Respiratory rate >20 White Cell Count >12,000 cell/mm 3 or < 4,000 cell/mm 3 Mortality Sepsis Suspected or confirmed infection SIRS 10-15% Severe Sepsis 20-30% Sepsis with dysfunction of one or more organs Elevated Lactate Altered mental state Oliguria Hypotension Septic Shock Multiple Organ Failure Sepsis induced hypotension (<80mmmHg or 30% less than normal) despite adequate fluid resuscitation Failure of more than two organ systems requiring acute support as a result of sepsis % 60-80% 9

10 2.2 SEPSIS OF UNKNOWN SOURCE If the source of infection is known, antimicrobial therapy can be based on the most suitable empirical therapy for the infection, pending results of culture and susceptibility tests. If source is unknown, take appropriate samples of specific body fluids, e.g. urine, sputum to determine the source of infection. Sepsis of unknown source Initial Treatment Co-amoxiclav 1.2g IV 8 hourly Gentamicin extended interval dosing See Appendix i, Monitoring Antimicrobial Dosage If MRSA suspected add Vancomycin IV (see Appendix i, Monitoring Antimicrobial Dosage) If intra-abdominal source suspected see Section 7.1. Penicillin allergy Vancomycin (see Appendix I, Monitoring Antimicrobial Dosage) Plus Ciprofloxacin 400mg IV 12 hourly ( IV for first dose then review if appropriate to switch patient to oral) Plus Metronidazole 500mg IV 8 hourly Change according to results of sensitivities. Switch to oral as soon as appropriate. 2.3 Sepsis in Neutropenic Patients (see Appendix viii) Take initial sets of blood culture samples, up to 2 sets advised (one from peripheral site and one from line, if in-situ). Patients receiving nephrotoxic chemotherapy, e.g carboplatin or cisplatin should not receive Gentamicin: contact Consultant Microbiologist or Haematologist for advice. Initial Treatment Piperacillin / tazobactam 4.5g IV 6 hourly Gentamicin extended interval dosing. See Appendix i, Monitoring Antimicrobial Dosage. Penicillin Allergy See Appendix viii Modify treatment on result of culture and discuss with Microbiologist and/or Haematologist if no improvement. 2.4 Central Catheter Related Blood Stream Infection The priority is prevention of infection from these lines. Adhere rigidly to the care bundles for these lines. Review the need for the line daily and if not required remove it. The rate of 10

11 infection from these lines has been significantly reduced by following these rules and very careful insertion in the first place. If infection from a central line is suspected (Catheter Related Blood Stream Infection) the default position should be to remove the line. For tunnelled lines (Hickman lines) this is difficult, so discuss with a Consultant Haematologist. The tip of the removed central line should be sent for culture along with peripheral blood cultures. For removal of central lines, advice and guidelines are available from ITU. If antibiotics are required As most line infections are due to coagulase-negative staphylococci, initial therapy should be directed against these organisms. Vancomycin seeappendix i Monitoring Antimicrobial Dosage. or Teicoplanin 400mg IV 12 hourly for 3 doses then 400mg 24 hourly Review Daily (Check dose with Microbiologist as in some cases 10mg/kg required). If sensitivities show methicillin sensitive Staphylococcus aureus change to Flucloxacillin 1g IV 6 hourly for 14 days total. CSM advice (hepatic disorders) see BNF. Antibiotics should be reviewed after 48 hours when cultures results are available and if necessary de-escalated. They may no longer be required after removal of the line, or could be changed to match the sensitivities of any organisms detected. Clinical judgement and discussion with Consultant microbiologist is required. 2.5 Yeast / Candida Blood Stream Infection Secondary to Long or Central Intravascular Lines Always discuss with Consultant Microbiologist. Early removal or change of line(s) is fundamental to management. Initial Treatment Fluconazole 400mg IV stat, then 200mg to 400mg IV / oral once daily. 2.6 Blood Stream Infection due to Staphylococcus aureus. Staphylococcus aureus sepsis is a serious condition and can be associated with deep seated infections and severe sequelae. Any patient with blood cultures positive for Staphylococcus aurues must be treated with a minimum of 2 weeks IV antibiotic therapy. If investigations show a deep seated source, longer treatment will be required, please discuss with microbiology. If Staphylococcus aureus is flucloxacillin sensitive, treat with IV flucloxacillin 1-2 grams 6 hourly. If flucloxacillin resistant, use vancomycin (See Appendix i Monitoring Antimicrobial Dosage) 11

12 3 BONE AND JOINT INFECTIONS 3.1 Septic Arthritis / Osteomyelitis (Native joint, not diabetic ulcer associated) Blood cultures, joint aspirates and other appropriate samples from potential source of infection MUST be taken prior to therapy. Discuss with Consultant Microbiologist if risk of Methicillin resistant Staphylococcus aureus or Staphylococcus epidermidis or if gonococcal septic arthritis is suspected. All therapy should be modified with culture results. Initial Treatment First 2 weeks Flucloxacillin 1g to 2g IV 6 hourly CSM advice (hepatic disorders) see BNF Third week Flucloxacillin 500mg to 1g IV or oral 6 hourly onward, if infection confirmed If infection not confirmed discuss with microbiology Penicillin Allergy First two Weeks Vancomycin, (see Appendix i, monitoring antimicrobial dosage) Third week Doxycycline 200mg daily onward, if infection confirmed If infection not confirmed discuss with microbiology If risk factors for gram negative infection (for example UTI, prostate symptoms, recent intraabdominal surgery), add Gentamicin as single daily dosing. See Appendix i, Monitoring Antimicrobial Dosage Effectiveness of therapy can be monitored using CRP estimation once or twice each week. Duration Treatment: Septic arthritis: 4 to 6 weeks Osteomyelitis: up to 6 months 3.2 Prosthetic Joint Infections Establish the microbiology of the infection. If occurring within 6 months of surgery, the organism is commonly Staphylococcus aureus. If the infection is late onset, it is usually coagulase-negative staphylococci or Gram-negative bacilli. Discuss all cases with Consultant Microbiologist as a variety of antibiotic combinations may be appropriate. 12

13 4 CENTRAL NERVOUS SYSTEM INFECTIONS 4.1 Bacterial Meningitis ( Notifiable Disease) On admission (adults) Cefotaxime 2g IV 6-8 hourly change to Benzylpenicillin 2.4g IV 4 hourly if culture shows meningococcal disease or sensitivities indicate In all patients over 55 years or immunocompromised, and in all other cases where Listeria is suspected, add amoxicillin 2g IV every 4 hours. Penicillin Allergy If history of anaphylaxis or bronchospasm with Penicillin, discuss with Consultant Microbiologist Chloramphenicol 25mg/kg IV 6 hourly Duration of Treatment Meningitis caused by meningococci Treatment for 5-10 days may suffice Meningitis caused by pneumococci Treatment for days Seek advice from Consultant Microbiologist if isolates unusual, in the immunocompromised, post neurosurgery or when the aetiology is in doubt. Chemoprophylaxis of Meningococcal Disease First choice Ciprofloxacin for most age groups and in pregnancy (rifampicin if <1 month) Given on advice of Public Health Doctor, contact through switchboard. Doses (all oral) Adults and Children over 12 years Ciprofloxacin 500mg as a single dose Children aged 5 12 years Ciprofloxacin 250mg as a single dose Children 1 month to 4 years Ciprofloxacin 125mg as a single dose Children under 1 month Rifampicin 5mg/kg every 12 hours for 2 days The administration of ciprofloxacin may be followed by anaphylactic reactions. Healthcare staff should give out information sheets that include the risk of side effects and be prepared to deal with allergic reactions. It can also interact with other drugs but a single dose is unlikely to have a significant effect. It has an unpredictable effect on epilepsy. Further information including alternative regimens and information sheets can be found at in the section on meningococcal disease. 13

14 4.2 Viral Meningitis Antimicrobials not indicated unless Herpes viruses suspected. Take extra CSF sample for Enterovirus or Herpes Simplex virus (HSV) PCR, as appropriate, as well as throat swab in viral transport medium. 4.3 Brain Abscess Usually causative agents are: anaerobes, Streptococcus species or Enterobacteriacae Cefotaxime 2g IV 6-8 hourly Metronidazole 500mg IV 8 hourly 4.4 Herpes Simplex Encephalitis Take CSF sample for HSV PCR Aciclovir 10mg/kg IV 8 hourly for 10 days 14

15 5 CARDIOVASCULAR SYSTEM INFECTIONS 5.1 Infective Endocarditis Discussion of all cases of endocarditis (including culture negative) with a Consultant Microbiologist and Cardiologist is strongly advised. Send three sets of blood cultures, from separate sites, over a 24 hour period if possible. In the acutely ill, two sets should be taken within 1 hour before starting empirical therapy. Initial Empirical Treatment Native Valve Endocarditis (NVE) - Indolent presentation Amoxicillin 2g IV 4 hourly alone or Gentamicin see divided dosing protocol appendix i Monitoring Antimicrobial Dosage If genuine penicillin allergy, use regimen for severe sepsis, below. NVE severe sepsis In severe sepsis, Staphylococci spp. need to be covered. Patients at increased risk of staphylococcal endocarditis include iv drug abusers and patients with intravascular devices. Vancomycin for dosing regimen see Appendix i Monitoring Antimicrobial Dosage if egfr>30 ml/min Gentamicin. See divided dosing protocol Appendix i Monitoring Antimicrobial Dosage if egfr <30 ml/min use ciprofloxacin as alternative If patients have risk factors for multiresistant Enterobacteriaceae or Pseudomonas, eg. evidence of previous colonisation, use meropenem 2g 8 hourly in place of gentamicin. Prosthetic valve endocarditis (PVE) Vancomycin for dosing regimen see Appendix i Monitoring Antimicrobial Dosage Rifampicin oral 300mg to 600mg 12 hourly if egfr>30 ml/min Gentamicin. See divided dosing protocol Appendix i Monitoring Antimicrobial Dosage If egfr <30 ml/min use ciprofloxacin as alternative Once causative organisms are known antibiotics should be tailored to the organisms isolated following discussion with the Consultant Microbiologist. Treatment follows the British Society for Antimicrobial Chemotherapy (BSAC) Endocarditis Working Party recommendations. Reference: Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy. Journal of Antimicrobial Chemotherapy 2012, 67,

16 6 EAR, NOSE, MOUTH AND THROAT INFECTIONS 6.1 Dental Abscess Penicillin V 500 mg oral 6 hourly (some advocate Amoxicillin 250 mg oral 8 hourly but BEWARE side effects diarrhoea, candidiasis) Penicillin allergy Metronidazole 400 mg oral 8 hourly 6.2 Otitis Externa Refer to Borders Joint Formulary Infections section. 6.3 Otitis Media or Sinusitis Refer to Borders Joint Formulary Infections section. 6.4 Tonsillitis / Quinsy Refer to Borders Joint Formulary Infections section 16

17 7 Gastrointestinal Tract Infections 7.1 Intra-Abdominal Sepsis including Bacterial Peritonitis Initial Treatment Amoxicillin 1g IV 8 hourly Metronidazole 500mg IV 8 hourly Gentamicin (Extended Interval Dosing. See Appendix i Monitoring Antimicrobial Dosage) Penicillin or Cephalosporin allergy If B-lactam allergy, consider vancomycin ciprofloxacin metronidazole and discuss with Microbiologist 7.2 Hepatobiliary Sepsis Amoxicillin 1g IV 8 hourly Metronidazole 500mg IV 8 hourly Gentamicin (Extended Interval Dosing. See Appendix i Monitoring Antimicrobial Dosage Penicillin or Cephalosporin allergy If B-lactam allergy, consider vancomycin ciprofloxacin metronidazole, and discuss with Microbiologist. 7.3 Antibiotic Associated Diarrhoea Only 40% of cases are associated with Clostridium difficile toxin production. All are due to disruption of the normal bowel flora. There is no need to send repeat specimens from patients with previous positive results unless there is a recurrence after a full course of treatment. If possible, STOP all antimicrobials. Discuss continuation of therapy with Consultant Microbiologist. Diarrhoea will begin to settle in 2 to 3 days in the majority of patients. Consider oral rehydration therapy. Consider treating according to protocol below if C.difficile toxin found in stool and if diarrhoea is bloody, persists, is severe or patient has abdominal distension and fever. 17

18 NHS Borders Treatment of C.difficile-associated disease (CDAD): first and second episodes Treatment of CDAD should be initiated based on assessment of symptoms and severity of disease while taking into account individual risk factors of the patient. Consider treatment if C.difficile toxin found in stool and if diarrhoea is bloody, persists, is severe or patient has abdominal distension and fever Antibiotic treatment is not required if patient has C.difficile toxin and non or resolving diarrhoea Ensure infection prevention and control measures are in place as soon as symptoms occur (do not wait for lab result to confirm diagnosis before putting control measures in place) Stop any (non-c.difficile) antimicrobial treatment in patients with CDAD if possible. Discuss continuation of any therapy with microbiologist Stop gastric acid suppressive therapy if possible e.g. PPIs, H 2 antagonists. Severity markers: Temperature >38.5 C Patient has major risk factors (eg. immunosupression) Hypotension (systolic bp <90mm/Hg) Suspicion of pseudomembranous colitis, toxic megacolon, ileus Colonic dilatation in CT scan >6 cm (CT scan not routinely recommended) White blood cell count > 15x10 9 cells/l Creatinine>1.5 x baseline Albumin <25 g/l Patient has no severity markers: Treat with oral metronidazole 400mg 8 hourly for days Rehydrate patient Patient has one or more severity markers: Treat with oral vancomycin 125mg 6 hourly for days Rehydrate patient Daily assessment of patient with mild to moderate disease: Observe bowel movement, symptoms (WBC&hypotension) and fluid balance If condition doesn t improve after 5 days treatment with oral metronidazole, patient should be switched to treatment with oral vancomycin (125mg 6 hourly for days) Daily assessment of patient with severe disease: Observe bowel movement, symptoms (WBC&hypotension) and fluid balance. Surgery, gastroenterology and microbiology consultations. CT scanning: consider pseudomembranous colitis, toxic megacolon, ileus or perforation. Patients with severe CDAD with hypotension or ileus should receive IV metronidazole 500mg 8 hourly in addition to oral vancomycin for days or as recommended by Consultant Microbiologist. If diarrhoea continues, or is a third episode, or in severe disease, discuss further management with Consultant Microbiologist. Probiotics may be initiated by specialists in patients experiencing a third or subsequent episode. 18

19 7.4 Gastroenteritis / Food Poisoning ( Notifiable Disease) In general, antimicrobial therapy should be avoided, as most bacterial infections are self-limiting. Generally antibiotics only reduce diarrhoea by 1-2 days, can cause resistance and are contraindicated in E. coli 0157 infection where they may enhance toxin release and increase the risk of haemolytic uraemic syndrome. If patient is immunocompromised, or has signs/symptoms suggestive of deep seated or invasive infection, please discuss treatment options with a Microbiologist. Stool and, where appropriate, blood cultures should be taken and clearly labelled with relevant history, including travel history. 7.5 Oral Candidiasis First choice Fluconazole 50mg to 100mg oral 24 hourly for 7 to 14 days Second choice Nystatin suspension units per ml, 1ml 6 hourly after food usually for 7 days (continue for 48 hours after lesions have resolved) 7.6 Systemic Candidiasis Discuss with Consultant Microbiologist Fluconazole 400mg oral initially then mg daily (IV only if oral route not possible) 7.7 Helicobacter Eradication First line treatment Omeprazole 20mg 12 hourly for 7 days Clarithromycin 500mg oral 12 hourly for 7 days Amoxicillin 1g oral 12 hourly for 7 days or Omeprazole 20mg 12 hourly for 7 days Clarithromycin 250mg oral 12 hourly for 7 days Metronidazole 400mg oral 12 hourly for 7 days Second line treatment See BNF for alternative regimes. Refer patient to specialist if eradication has failed with ONE of the above regimens. Any antibiotic used recently should be avoided in the eradication regime. 19

20 7.8 Spontaneous Bacterial Peritonitis First line treatment Co-amoxiclav 1.2g IV 8 hourly Second line treatment Cefotaxime 2g IV 8 hourly Or, in immediate (type 1) beta-lactam sensitivity, Vancomycin IV (see appendix i: monitoring antimicrobial dosage) Ciprofloxacin 500mg oral 12 hourly (IV if enteral route unavailable). Consult Microbiologist if patient has been receiving a quinolone as SBP prophylaxis. Prophylaxis Norfloxacin 400mg oral daily 20

21 8 URO-GENITAL SYSTEM INFECTIONS It is essential that Sexually Transmitted Infections especially Chlamydia, Gonorrhoea, and Syphillis are reported to GUM Clinic for follow-up and contact tracing. Also see Failure to refer carries a high risk of re-infection. GUM Health Advisors should be contacted on the following numbers: GU Clinic, Galashiels Health Centre Pelvic Inflammatory Disease (PID) Treatment follows NHS Borders STI Management Protocol. Antimicrobial treatment should be commenced as soon as diagnosis is suspected. Women with suspected PID should be screened for Gonorrhoea and Chlamydia. Out-Patient or non-severe Ofloxacin 400mg oral 12 hourly for 14 days CSM advice (tendon damage) see BNF Metronidazole 400mg oral 12 hourly for 14 days Inpatient and severe Ofloxacin 400mg IV 12 hourly (infused over at least 1 hour) Metronidazole 500mg IV 8 hourly Switch to oral to complete course as soon as clinically appropriate. 8.2 Gonorrhoea and/or contact with Gonorrhoea 1 st Line: Ceftriaxone 500mg IM single dose or 2 nd Line: Cefixime 400mg oral single dose. azithromycin 1g as a single dose for possible Chlamydia co-infection 8.3 Chlamydia Treatment follows NHS Borders STI Management Protocol. Treatment should be initiated without waiting for laboratory information. Suitable samples In men, a first void urine In women, undergoing a vaginal examination, a cervical swab In women not undergoing a vaginal examination, a first void urine A self-taken swab is an alternative for women not undergoing a vaginal examination Uncomplicated men and women Azithromycin 1g oral single dose or Doxycycline 200mg oral stat then 100mg 12 hourly for 6 days 21

22 Pregnant women OR risk of pregnancy Azithromycin is not licensed for use in pregnancy but is very widely used. (Discuss with GUM) Caution: Erythromycin and amoxicillin have a recognised failure rate hence careful follow-up necessary. Ofloxacin and doxycycline are contra-indicated in pregnancy. Erythromycin 500mg oral 12 hourly for 14 days or, if intolerant to erythromycin Amoxicillin 500mg oral 8 hourly for 14 days Treatment of Neonatal chlamydial eye infection Erythromycin 12.5mg/kg oral 6 hourly for 14 days 8.4 Epididymo-orchitis All sexually active men should be tested for Chlamydia prior to treatment Sexual transmission suspected or men under 35, cause unknown 1 st line Doxycycline 100mg oral 12 hourly for 14 days or 2 nd line Erythromycin 500mg oral 12 hourly for 14 days Ceftriaxone 500mg IM single dose No suggestion of sexual transmission or men over 35, cause unknown 1st line Ofloxacin 400mg oral 12 hourly for 14 days or 2 nd line Ciprofloxacin 500mg oral 12 hourly for 10 days CSM advice (tendon damage) see BNF Review at 14 days. If symptoms persist, for further course of antimicrobial treatment. 8.5 Genital Herpes First Episode Aciclovir 200mg oral x 5 times a day for 5 days or Valaciclovir 500mg oral 12 hourly for 5 days If symptoms are very severe consider a 10 day course If frequent recurrences seek advice from GUM ( ) 8.6 Vaginal Candidiasis Fluconazole 150mg oral single dose (not in pregnancy) or Clotrimazole pessary 500mg single dose If frequent recurrences (defined as four episodes of mycologically proven candidiasis in 12 months) see NHS Borders STI Management Protocol available on the intranet. 8.7 Penile Candidiasis Clotrimazole cream 1% 8 hourly for 7 days 22

23 9 URINARY TRACT INFECTIONS Reference SIGN 88: Whenever possible, a specimen of urine should be collected for culture and sensitivity testing before starting antibacterial therapy. The therapy should reflect current local antibacterial sensitivity patterns. In general asymptomatic bacteriuria in the elderly should not be treated with antibiotics. Dipstick results are only helpful in MSU. Remember genital tract sites e.g. vagina, prostate, may give rise to WBC on specimen microscopy. Please contact a Nephrologist immediately if a kidney transplant patient is found to have a urinary tract infection. 9.1 Simple Urinary Tract Infections Excludes pregnancy and children Women and Men First line: Trimethoprim 200mg oral 12 hourly or Second line: Nitrofurantoin 50mg oral 6 hourly. Avoid nitrofurantoin in renal failure (egfr less than 60ml/min) due to toxicity & lack of efficacy. Duration of treatment: Women. 3 days Men....7 days Further therapy should be based on sensitivity results 9.2 Catheter specimen In catheterised patients, the bladder quickly becomes colonised. Microscopy and/or dip-stick testing is unhelpful as WBC, rbc, nitrate and protein may all be positive when the bladder is colonised. Catheter urine samples should be sent for culture and sensitivities only if patient is febrile or systemically unwell and bladder is the likely source. If possible, remove catheter. Treat only if there is clinical suspicion of bacteraemia and, if appropriate, after consultation with microbiologist. If treating, the catheter should be changed. Changing of long term urinary catheter: Where patients have developed sepsis related to changing a long-term urinary catheter, prophylaxis may be considered. Previously documented antimicrobial resistance should be considered when choosing an appropriate antimicrobial. The following suggestions are made for empirical use in the absence of antimicrobial resistance information. 23

24 First choice GENTAMICIN Dose: 3 mg/kg (lean body weight) up to a maximum of 320 mg IV single dose Second choice TRIMETHOPRIM Dose: 200mg orally single dose 9.3 Urinary Tract Infections in Pregnancy Mid-stream urine sample must be taken. Always treat asymptomatic bacteriuria. A post-treatment specimen should always be sent. Initial treatment Cefalexin 250mg oral 6 hourly for 7 days 9.4 Complicated Urinary Tract Infections Principally pyelonephritis. Also includes patients with abnormal renal tract, immunocompromised patients, or history of recurrent UTI's. Appropriate urine samples should be taken before commencing antimicrobials. Initial Treatment Ciprofloxacin 500mg 12 hourly PO If nil by mouth, use co-amoxiclav IV first line with or without Gentamicin as below. Second line Co-amoxiclav 625 mg 8 hourly PO (1.2g 8 hourly IV if pyelonephritis, nil by mouth or nausea / vomiting - change to PO once able to tolerate), if severe add Gentamicin (Extended Interval Dosing - see Appendix i Monitoring Antimicrobial Dosage) to either ciprofloxacin or co-amoxiclav, above Treat for 7-14 days Change treatment, according to sensitivities. Switch to oral, according to sensitivities, when no nausea, vomiting, fever or sepsis. 24

25 9.5 Prostatitis Acute Prostatitis requires immediate treatment. Chronic Prostatitis requires investigation before antimicrobials are started; only 10% of cases are caused by infection. Initial treatment First line Ciprofloxacin 500mg oral 12 hourly CSM advice (tendon damage) see BNF Second line Trimethoprim 200mg oral 12 hourly Duration of treatment: Acute and Chronic Bacterial Prostatitis. 4 to 6 weeks 25

26 10 RESPIRATORY TRACT INFECTIONS General ref: NICE Respiratory Tract Infectionhttp:// Acute Exacerbations of Chronic Obstructive Pulmonary Disease* Patients with two or more of the three cardinal signs may benefit from treatment with antimicrobials Increased shortness of breath Increased sputum volume Purulent sputum Most patients who have persistent purulent sputum between exacerbations are colonised with Haemophilus, Streptococcus, Staphylococcus, Moraxella or Pseudomonas species. Antimicrobials should be tailored against previous isolates where possible, otherwise start treatment with - Amoxicillin 500mg oral 8 hourly for 5 to 7 days Penicillin allergy Doxycycline 200mg oral on first day then 100mg daily for a total of 7 days For treatment failures: Co-amoxiclav (Amoxicillin/clavulanic acid) 625mg oral 8 hourly for 7 days If severe Co-amoxiclav 1.2g IV 8 hourly Plus Clarythromycin 500mg IV 12 hourly (Clarithromycin IV should only rarely be necessary in COPD) Pseudomonal infections Ciprofloxacin 750mg oral 12 hourly (use IV route (400mg) only if oral not possible) CSM advice (tendon damage) see BNF Note: It is important to distinguish between colonisation/overgrowth and actual infection in patients with sputum culture positive for Pseudomonas. The patient s clinical condition should always be included in the assessment for anti-pseudomonal antibiotics. Heavy growth of pure Pseudomonas, repeated positive culture, significant purulence of sputum and presence of systemic symptoms indicate a greater likelihood of infection as opposed to colonisation / overgrowth. When colonisation / overgrowth is suspected it is appropriate to delay antibiotics and continue to review the patient s clinical progress and/or repeat sputum cultures after an interval. Resistance to CIPROFLOXACIN is a significant risk in Pseudomonas respiratory tract infection *NICE COPD Guideline. Bronchiectasis: See protocol in Borders Joint Formulary Immunosuppressed Patients: Consult other relevant protocols, e.g. neutropenic sepsis, HIV. 26

27 10.2 Community Acquired Pneumonia CURB-65 Severity Scores for Community Acquired Pneumonia CURB-65 score Any of: Confusion Urea >7 mmol/l Respiratory rate 30/min Blood pressure (SBP <90mm Hg or DBP 60mm Hg) Age 65 years 0 or or more GROUP 1 Mortality low (1.5%) GROUP 2 Mortality intermediate (9.2%) GROUP 3 Mortality high (22%) Treatment options Likely suitable for home treatment Consider hospital supervised treatment Options may include: (a) short stay inpatient (b) hospital supervised outpatient Manage in hospital as severe pneumonia Assess for ICU admission especially if CURB-65 score = 4 or 5 Antibacterials Amoxicillin 500mg to 1g oral 8 hourly for 7 days Penicillin allergy Clarithromycin 500mg oral 12 hourly for 7 days Amoxicillin 500mg to 1g orally 8 hourly Clarithromycin 500mg oral 12 hourly for 7 days or, if IV required Amoxicillin 1g IV 8 hourly Clarithromycin 500mg IV 12 hourly Switch to oral antibiotics as soon as clinically appropriate Penicillin allergy or intolerance to Clarithromycin Discuss with Consultant Microbiologist Suggest doxycycline 200mg daily Co-amoxiclav 1.2g 8 hourly IV Clarithromycin 500mg IV 12 hourly Alternative in penicillin allergy Clarithromycin 500mg IV 12 hourly Vancomycin See appendix 1 Monitoring Antibiotic Dosage Switch to oral equivalents as soon as Clinically appropriate (vancomycin switches to doxycyline) REMEMBER: Switch from IV oral therapy when clinically stable and by 3 days if RR <25/min, haemodynamically stable and able to take oral agents. 27

28 Legionella Antimicrobial combinations which include clarithromycin will provide cover for Legionella. Samples for Legionella testing are acute and convalescent sera (clotted blood) and urine for Legionella antigen Pneumonia post influenza Ref. Thorax, 2007; 62: supp 1. Hospital treated, non-severe pneumonia, post influenza Co-amoxiclav 625mg oral tds or, if IV needed, co-amoxiclav 1.2g tds IV Penicillin allergy: clarithromycin 500mg oral bd or, if IV needed, clarithromycin 500mg bd IV Hospital treated, severe pneumonia, post influenza Co-amoxiclav 1.2g IV tds Plus clarithromycin 500mg IV bd Penicillin allergy: consult microbiologist 10.3 Hospital Acquired Pneumonia Obtain advice at an early stage. Contact a Consultant Microbiologist if Pseudomonas or MRSA present or if previously treated with antimicrobials Initial treatment Co-amoxiclav (Amoxicillin / clavulanic acid) 625mg oral 8 hourly If severe Co-amoxiclav 1.2g IV 8 hourly Gentamicin (Extended Interval Dosing See Appendix i Monitoring Antimicrobial Dosage) Penicillin allergy Vancomycin (see appendix i monitoring antimicrobial dosage) Ciprofloxacin 500mg oral 12 hourly 10.4 Aspiration Pneumonia Co-amoxiclav (Amoxicillin / clavulanic acid) 1.2g IV 8 hourly Penicillin allergy Discuss with microbiologist 10.5 Ventilator Acquired pneumonia Consult ITU protocol 10.6 Tuberculosis ALL cases of suspected Tuberculosis or other Mycobacterial disease must be referred to the Respiratory Physician responsible for TB care. 28

29 11 SKIN AND SOFT TISSUE INFECTIONS 11.1 Cellulitis (not perineum) Commonly caused by Streptococci, may occasionally involve Staphylococcus aureus. Non-severe Flucloxacillin 500mg oral 6 hourly CSM advice (hepatic disorders) see BNF alone, or Penicillin V 500mg oral 6 hourly Penicillin allergy Clarithromycin 500mg oral 12 hourly Severe Benzylpenicillin 1.2g IV 4 6 hourly Plus Flucloxacillin 1g to 2g IV 6 hourly CSM advice (hepatic disorders) see BNF and consider: Gentamicin (Extended Interval Dosing. See Appendix i Monitoring Antimicrobial Dosage) Penicillin allergy substitute Benzylpenicillin Flucloxacillin with: Vancomycin See Appendix i Monitoring Antimicrobial Dosage If severe unresponsive cellulitis, consider deeper infections, including necrotising fasciitis. If this is suspected please discuss with both surgery and microbiology urgently. If cellulitis is associated with lymphoedema, refer to NHS Borders Guideline Orbital Cellulitis Co-amoxiclav (Amoxicillin / clavulanic acid) 1.2g IV 8 hourly Penicillin allergy Cefuroxime 750mg to 1.5g IV 8 hourly Metronidazole 500mg IV 8 hourly Skin and soft tissue infections related to drug misuse Benzylpenicillin 1.2g IV 4 6 hourly Plus Flucloxacillin 1g to 2g IV 6 hourly CSM advice (hepatic disorders) see BNF Seek advice from Microbiology 11.2 Diabetic foot See diabetes protocol on hospital intranet 29

30 11.3 Necrotising Fasciitis / Streptococcal Toxic Shock Syndrome Discuss with Consultant Microbiologist Initial treatment (and for upper limb) Benzylpenicillin 1.2g to 2.4g IV 4 hourly Flucloxacillin 1-2g IV 6 hourly Clindamycin 600mg IV 6 hourly Initial treatment for lower limb Tazocin 4.5g IV 8 hourly Clindamycin 600mg IV 6 hourly 11.4 Surgical Wound Infection Wounds quickly become colonised, treat and swab only when there are clinical signs of infection. Initial treatment Flucloxacillin 500mg oral 6 hourly for 5 to 7 days CSM advice (hepatic disorders) see BNF Penicillin allergy Clarithromycin 500mg oral 12 hourly for 5 to 7 days 11.5 Traumatic Wounds / Lacerations Wound infection occurs in 1 12% of all non-bite wounds. Antibiotic prophylaxis or tetanus immunoglobulin is not usually required for simple, clean lacerations. For high risk tetanus prone wounds (heavily contaminated with soil / faeces or devitalised tissue) human tetanus immunoglobulin should be given, irrespective of the tetanus immunisation history of the patient. A tetanus containing vaccine is given if necessary, according to immunisation history. Ref: Green Book, Tetanus (chapter 30) Treatment of clean lacerations that become infected Flucloxacillin 500mg oral 6 hourly for 5 to 7 days CSM advice (hepatic disorders) see BNF Penicillin allergy Clarithromycin 500mg oral 12 hourly for 5 to 7 days Consider antimicrobial prophylaxis if patient is immunocompromised e.g. diabetic, asplenic, alcohol dependant or laceration is stellate, intra-oral or to the feet. Antibiotics are as for treatment. 30

31 Treatment of infected lacerations that were previously contaminated; puncture wounds or wounds with a significant amount of devitalised tissue Co-amoxiclav (Amoxicillin / Clavulanic acid) mg oral 8 hourly Penicillin allergy Clarithromycin 500mg oral 12 hourly Metronidazole 400mg oral 8 hourly for 5 to 7 days Consider antimicrobial prophylaxis in puncture wounds or wounds contaminated with soil, manure or faeces and wounds with a significant amount of devitalised tissue. Antibiotics are as for treatment MRSA Skin and Soft Tissue Infections Cellulitis / febrile but not unstable: First line Doxycycline 100mg oral 12 hourly on Day 1, then 100 mg oral 24 hourly Rifampicin 600mg oral 24 hourly or Second line Trimethoprim 200mg oral 12 hourly Sodium Fusidate 500mg oral 8 hourly For all MRSA infections, antibiotic monotherapy should not be given as this can cause rapid development of resistance. The only two exceptions to this are Vancomycin and Doxycycline, which in some circumstances may be prescribed as monotherapy. Toxic / unstable Vancomycin For dosing regimen see Appendix i Monitoring Antimicrobial Dosage 11.7 Multiple injuries and/or compound fractures of long bones Co-amoxiclav 1.2g IV 8 hourly Penicillin allergy Discuss with Consultant Microbiologist REMEMBER Tetanus prophylaxis 31

32 11.8 Bites Consider antimicrobial prophylaxis for the following: human bites, bites to the hand, foot or face, deep/puncture wounds, wounds requiring surgical debridement, bites to high risk patients e.g. diabetics, immunocompromised, prosthetic valve. The choice of antimicrobial for prophylaxis is the same as used for treatment. See Traumatic Wounds / Lacerations above for management of high risk tetanus prone wounds. Human, Dog or Cat bites Co-amoxiclav (Amoxicillin / clavulanic acid) 625mg oral 8 hourly for 5 days Penicillin allergy, excluding pregnancy and children Doxycycline 100mg every 12hours Metronidazole 400mg oral 8 hourly for 7 days Penicillin allergy in Pregnancy Erythromycin 500mg every 12 hours Metronidazole 400mg oral 8 hourly for 7 days Consult Microbiologist if animal species is other than a dog or a cat 11.9 Herpes Herpes Simplex (cold sores) Aciclovir cream 5% applied 5 times daily at onset of episode for 5 10 days Herpes zoster (shingles) Treatment beneficial if commenced within 72 hours of onset of rash Aciclovir 800mg oral fives times daily (every four hours) for 7 days Disseminated Herpes Infection Discuss with Consultant Microbiologist Aciclovir 5mg/kg IV 8 hourly Leg Ulcers / Pressure Sores / PEG sites Antimicrobial treatment is ONLY indicated if there is evidence of spreading cellulitis. Discuss with Consultant Microbiologist 32

33 Appendix i Monitoring Antimicrobial Dosage Gentamicin Extended Interval Dosing for Adults Intravenous Gentamicin Use in Adults (GGC Guidance Approved SAPG January 2013) Background This policy covers the use of intravenous (IV) gentamicin in adults using the Greater Glasgow and Clyde (GGC) dosing guidance. The policy is for the use of gentamicin for the treatment of infection only. SAPG recommendations on gentamicin dosing for surgical prophylaxis are provided elsewhere. The guidance does not apply to gentamicin use in the following: o synergistic treatment of endocarditis or Staphylococcal bone infection o patients treated in Renal units or receiving haemodialysis or haemofiltration o major burns o ascites o age < 16 years o cystic fibrosis (refer to local guidelines) o pregnancy (refer to local guidelines) Contra-indications and cautions Contra-indications to gentamicin therapy hypersensitivity, myasthenia gravis Cautions to gentamicin therapy: o o o Patients with decompensated liver disease - aminoglycosides are associated with an increased risk of renal failure. Concurrent administration of neurotoxic and / or nephrotoxic agents increases the risk of gentamicin toxicity. Review therapy and consider amending or withholding nephrotoxic drugs during gentamicin treatment. Avoid co-administration with the following: neuromuscular blockers other potentially nephrotoxic (e.g. NSAIDs and ACE Inhibitors) or ototoxic drugs potent diuretics other aminoglycosides This list is not exhaustive consult the Summary of Product Characteristics (espc) for a full list ( Chronic Kidney Disease (CKD) Stage 4 or more, known or suspected acute kidney injury in the previous 48 hours ( 50% increase in baseline serum creatinine or oliguria > 6 hours). If gentamicin is clinically indicated, give one dose as per guidance and check with microbiology or an infection specialist before giving a second dose. Prescribing and documentation To improve the prescribing of gentamicin, ensure consistency and reduce risk, standardised charts (agreed nationally) should be used to document the prescription, administration and monitoring of gentamicin. These should be used for prescribing treatment doses of gentamicin in conjunction with the existing inpatient prescribing chart (e.g. kardex) and medical / nursing documentation. These charts contain a step-wise approach to safe and effective prescribing and key points of advice on monitoring, interpreting and re-prescribing. 33

34 STEP 1: Calculate, prescribe and administer the first dose To reduce the risk of mortality, commence gentamicin administration within 1 hour of recognising sepsis. If creatinine is known use the online calculator (preferred method). The guidelines in Table 1 (below) can be used if the online calculator is not available. The dose amount and dosage interval are based on estimated creatinine clearance (Box 1) and actual body weight. If creatinine is not known give an initial dose of 5 mg/kg gentamicin (maximum 400 mg) or, if Chronic Kidney Disease (CKD) 5, give 2.5 mg/kg (maximum 180 mg) on advice of senior staff. Calculate the dose using actual body weight. Give the recommended dose by infusion in 100 ml sodium chloride 0.9% over 30 minutes and ensure the time of administration is noted on the medicine chart. Box 1: Estimation of creatinine clearance (CrCl) The following Cockcroft Gault equation can be used to estimate creatinine clearance (CrCl) [140 age (years)] x weight (kg) x 1.23 (male) OR x 1.04 (female) CrCl = (ml/min) serum creatinine (micromol/l) Cautions: Use actual body weight or maximum body weight whichever is lower. For maximum body weight table see In patients with low creatinine (< 60 micromol/l), use 60 micromol/l. Note: Use of estimated glomerular filtration rate (egfr) is not recommended. Table 1: Initial GENTAMICIN doses and dose intervals Actual body weight Creat Cl kg kg kg kg > 80 kg (ml/min) < mg/kg (max 180 mg) then take a sample after 24 hours mg 48 hourly 200 mg 48 hourly 240 mg 48 hourly 240 mg 48 hourly 260 mg 48 hourly mg 48 hourly 240 mg 48 hourly 280 mg 48 hourly 300 mg 48 hourly 320 mg 48 hourly mg 48 hourly 280 mg 48 hourly 320 mg 48 hourly 360 mg 48 hourly 400 mg 48 hourly mg 24 hourly 240 mg 24 hourly 280 mg 24 hourly 300 mg 24 hourly 320 mg 24 hourly > mg 24 hourly 280 mg 24 hourly 320 mg 24 hourly 360 mg 24 hourly 400 mg 24 hourly Caution: If the patient weighs < 40 kg and CrCl is 21 ml/min, give a single dose of 5 mg/kg then take a sample 6 14 hours after the dose and follow the instructions in Step 2. 34