1. Antimicrobial therapy Laura Whitney Sept 2010

2. Limitations of this session Prescribing practice only – not micro teaching Not covering why prudent prescribing is a key Trust and national priority or principles of good prescribing Adults only Prescribing principles apply to paediatrics, just not drug choices/doses

3. What this session will cover Prescribing in allergies Reviewing antimicrobials IV to Oral Switch Gentamicin and Vancomycin prescribing and monitoring

4. Review of Anitbiotic Therapy Patient referred to the ward from MAU 67 year old male with CAP CURB-65 score = 2

5. On the Drug chart LW CC LW CC LW CC 10/10 11/10 12/10 October 2010 LW

6. Penicillin allergy Hx of allergy given by 5% to 20% of pts reactions range from mild rashes to life-threatening anaphylaxis Anaphylactic reactions rare (< 0.05%) BUT penicillins are the most common form of drug induced anaphylaxis (5-10% of cases are fatal) Up to 10% of patients with a true penicillin allergy will also be allergic to cephalosporins and carbapenems. Patients who have experienced side-effects e.g. nausea, diarrhoea etc. should not be labelled penicillin allergic the medical notes, drug chart and patient wrist band should be corrected to reflect this. A detailed clinical history is important to identify patients with TRUE penicillin allergy. Salkind AR et al. Is this patient Allergic to Penicillin? An Evidence-Based Analysis of the Likelihood of Penicillin Allergy. JAMA 2001; 285: 2498-2505.

7. Taking a history What was the patient’s age at the time of the reaction? Does the patient remember what happened? If not, who informed them of it? How long after beginning penicillin did the reaction begin? What were the characteristics of the reaction? What was the route of administration? Why was the patient taking the penicillin? What other medications was the patient taking? Why and when were they prescribed? What happened when the penicillin was stopped? Has the patient taken antibiotics similar to penicillin after the reaction? If so, what happened? Salkind AR et al. Is this patient Allergic to Penicillin? An Evidence-Based Analysis of the Likelihood of Penicillin Allergy. JAMA 2001; 285: 2498-2505.

8. Allergies – what to do Allergy Reaction Document Sign

9. Determining the nature of the allergy Immediate (<1hours) or accelerated (<72hours) reactions Often associated with systemic manifestations of anaphylaxis diffuse erythema, pruritis, urticaria, angioedema, laryngeal oedema, bronchospasm, hypotension or cardiac arrhthymias Patients reporting such reactions must not receive any β-lactam antibiotics. The use of cephalosporins and carbapenems should be avoided, where possible. Delayed reactions (>72hours) Patients with a history of minor rash (i.e. non-confluent rash restricted to a small area of the body) or a rash that occurs more than 72 hours after penicillin are probably not hypersensitive to penicillin. Avoid β-lactams Reasonable to administer a cephalosporin or carbapenem Salkind AR et al. Is this patient Allergic to Penicillin? An Evidence-Based Analysis of the Likelihood of Penicillin Allergy. JAMA 2001; 285: 2498-2505.

10. Common mistakes in allergic pts Side-effect not allergy Appropriate history not taken Drug, Reaction, Timeframe, Rechallenges? Unsure what is safe Betalactams Carbapenems/Cephalosporins Other classes Use of brand names Augmentin® and Tazocin® Augmentin = Co-amoxiclav Tazocin = Piperacillin-Tazobactam

11. Fatal mistakes in penicillin- allergic patients

12. Local Audit data 2009 Audit of penicillin allergy 9% in-patients labelled penicillin-allergic Endorsement complete (drug and reaction) in only 45% charts Allergies Angiodema/anaphylaxis = 15% Rash = 31% Side-effects only = 10% Unsure = 40%

13. Amend the Drug chart LW CC LW CC LW CC 10/10 11/10 12/10 October 2010 LW

14. Reviewing Antibiotics

15. When to review ≤ 48 hrs Was the diagnosis substantiated? Response to therapy? Any side effects of treatment? Any positive cultures? Continued treatment required? De-escalate Narrower spectrum possible? IV to oral switch? How to review

16. IV to oral switch criteria Temp <38°C for 48hours No unexplained tachycardia (HR<90bpm for 48 hrs) Tolerates oral foods/fluids with no malabsorption Patient is clinically stable Improving clinical parameters WCC, CRP Not treating conditions requiring high tissue penetration such as meningitis or endocarditis

17. Can we switch Mr DB to orals? Day 3 of admission for CAP Clinical improvement seen. IV fluids discontinued, pt eating and drinking. BCs negative so far Urinary legionella and pneumococcal antigens = negative

18. Can we switch Mr DB to orals? 8/99/910/9 WCC14.213.513.2 Neut12.812.112.2 CRP1026248

19. IV to oral switch criteria Temp <38°C for 48hours No unexplained tachycardia (HR<90bpm for 48 hrs) Tolerates oral foods/fluids with no malabsorption Patient is clinically stable Improving clinical parameters WCC, CRP Not treating conditions requiring high tissue penetration such as meningitis or endocarditis

20. What did you prescribe?

21. Why? ↓ adverse effects associated with IV therapy Phlebitis, administration errors, nosocomial infections ↑ Ease of administration Patient preference, ↓ nursing time, ↓ LOS ↓ Cost ↓ acquisition costs, ↓ LOS, ↓ costs associated with HCAIs Studies have demonstrated that PO therapy can be as effective as IV in the treatment of infections ranging from mild to severe

22. Local Audit data – June 2010 18-21% of in-patients on IV antibiotics 16% of patients on IV abx met the criteria for an IV to oral switch No patients who met the switch criteria had microbiology results indicating that an oral treatment option was unavailable 61% of patients who met the switch criteria were not on any other IV medicines or fluids at the time of the audit

23. Did you remember to document indication and duration? Assists in regular review Ensures optimum treatment duration Prevents overuse of anti-infectives Remember to document in medical notes too

24. Local Audit data

25. Extended interval aminoglycosides AG of choice is Gentamicin @ 5mg/kg OD Amikacin 15-20mg/kg OD used in certain indications (neutropenic sepsis) or on micro advice Benefits of extended interval dosing Concentration-dependent killing Post antibiotic effect Drug free period reduces renal toxicity More convenient to administer and monitor But… Few trials included patients with pre-existing renal impairment No evidence for use in endocarditis Altered PK in ascities, pregnancy and burns These pts are excluded from policy – contact pharmacy for advice

26. Extended Interval AG

27. Gentamicin prescribing Seek advice if unsure Not very fat soluble - adjust dose in obese patients Use dose determining weight (DDW) if actual weight (ABW) >120% ideal body weight (IBW) IBW (kg) = 50/45kg + (2.3 x every inch over 5ft) 50 = male 45 = female DDW (kg) = IBW + 0.4 (ABW – IBW) Or just remember to cap pt wt at 100kg Dose = 5 mg/kg ↓ in renal impairment - See guidelines But not always necessary in severe sepsis

28. Miss LC 46 year old patient being treated for abdominal sepsis already on amoxicillin 1g IV tds and metronidazole 500mg IV tds. You are asked to Rx the gentamicin Weight = 95kg Height = 5ft 4” Serum Creatinine = 74mmol/L What do you prescribe?

29. Miss LC IBW (kg) = 45kg + 2.3 kg x 4 = 45 + 9.2  55kg >120% IBW DDW (kg) = 55 + 0.4 (95 – 55) = 55 + 16 = 71kg Renal function normal – Dose = 5mg/kg = 360mg If not adjusted 95 x 5 = 475 mg

30. What did you prescribe?

31. Gentamicin monitoring Aim for trough<1mg/L must be taken 18-24h post first dose Document sampling time on blood form Peak levels not required Only wait for levels to come back before giving 2 nd dose in Elderly patients Patients with renal impairment If previous levels were high If trough high reduce dose or increase dosing interval If trough within range and renal function normal monitor levels twice weekly More frequent monitoring may be required in elderly patients or those with renal impairment

32. Call from Staff nurse 9/9/10 2pm Answer?? Pt LC was off the ward when bloods were done this morning shall we give the 2pm dose? But take bloods before the dose – We’ll check the results later Pt is under 65 with good renal function

33. Vancomycin Glycopeptide antibiotic in use for  50yrs Early use associated with adverse effects as impure compound Standard practice in the UK is to monitor levels to assure efficacy and prevent toxicity evidence for this is lacking and this approach is controversial

34. IDSA guidelines 2009

35. Vancomycin blood concentrations

36. IDSA guidelines 2009 cont..

37. Vancomycin prescribing Therapeutic range = 10-15mg/L Higher levels may be required in severe infections on micro advice Give loading dose (LD) to ensure therapeutic concentrations achieved on day 1 If unsure about calculating CrCl/MD just give LD and contact pharmacy for advice You have at least 12 hrs to sort this out!

38. Pt MH – treatment with vancomycin is required cellulitis as pt is MRSA colonised.

39. Mr MH Age 76 Weight = 75kg Height = 5ft 10 Serum Creatinine = 105μmol/L (stable) CrCl = (140-76) x 1.23 x 75 = 56ml/min 105 What do you prescribe?

40. What did you prescribe?

41. Vancomycin monitoring Trough levels (0-60 minutes pre-dose) must be taken at steady state Document sampling time on blood form Peak levels not required Do not wait for levels to come back before giving dose unless dialysis pt Only need to check levels twice weekly if renal function stable

42. Call from Staff nurse 9/9/10 10pm What is your response? Pt MH had vanc levels taken this morning? The result came back at 36mg/L. I’m not going to give the dose When was the level taken? The phlebotomist was late this morning so they weren’t done till 11am

43. Local Audit data 2008 Audit of Vanc, gent & amikacin prescribing, administration and monitoring 14% doses inappropriately omitted 32% levels sent without sampling time 32% levels taken at incorrect time = 34% levels useful  Although some not needed 67% appropriately timed levels acted on appropriately  Inappropriate actions more common when levels taken at the wrong time

44. Top Tips Antibiotic Prescribing 1Documentation ensure that you record the indication for therapy on the prescription chart and in the medical notes, along with any specific monitoring parameters or plan for review 2Duration ensure that you record either a proposed review date (ideally within 72 hours of starting therapy) or a proposed stop date on the prescription chart at the time of prescribing 3De-escalation when further information on the causative organism or diagnosis becomes available, change therapy from broad-spectrum empiric antimicrobials to a more narrow-spectrum choice, if appropriate 4Dosing choose a dose and route of antimicrobial appropriate for the patient ’ s severity of illness – convert from IV therapy to oral as soon as is practical and appropriate 5Don’t don ’ t treat colonisation – treat infection; don ’ t treat contamination – treat infection; don ’ t routinely use ciprofloxacin empirically – it can predispose to MRSA and Clostridium difficile

45. Top Tips Antibiotic Therapeutic Drug Monitoring PK/PD properties of vanc and gent are very different – different prinicples apply to dosing and monitoring Vancomycin Therapy

46. Top Tips Antibiotic Therapeutic Drug Monitoring cont Samples must be taken at the correct time Always document sampling time on blood forms Avoid unnecessary dose omissions Interpret results carefully No need to do levels every day in every patient