Antimicrobial Pharmacist Experience South of the Border Dr Kieran Hand Consultant Pharmacist Anti-infectives infectives On behalf of the Antimicrobial Management Team Southampton University Hospitals NHS Trust SIRN Meeting Glasgow 19 th January 2009
C diff outbreak in your second week in the job! Use of key antibiotics in Medicine, Elderly Care and ED during Clostridium difficile outbreak versus new cases of C diff 700 16 Vials 600 500 400 300 200 100 14 12 10 8 6 4 2 New C diff toxin +ve case Augmentin 1.2g vials Clarithromycin 500mg vial Chloramphenicol 1.2g vial New CDT+ve 0 1 2 3 4 5 6 7 8 9 10 11 12 Week (2007) 0
Context for England & Wales Winning Ways 2005 Acute Hospitals Portfolio 2006 C diff Letter from CMO 2006 The Health Act 2006 Saving Lives 2007 Clostridium difficile infection: how to deal with the problem. 2009
Government reports 1 DH Winning Ways 2005 Abx Rx justified Abx Rx reflects local resistance Correct dose/duration Support for prudent Rx Prophylaxis justified Narrow spectrum > broad spectrum Healthcare Commission Acute Hospitals Portfolio 2006 Guidelines in place for each clinical indication Guidelines for surgical prophylaxis Number of feedback reports to prescribers Audits of cost, consumption and point prevalence Audit Rx against local resistance patterns.
Government reports 2 C diff letter from CMO 2006 Abx policy in place Control of broad spectrum agents IV 48 hour automatic stop IV switch policy Oral 5-day 5 course Surgical prophylaxis usually 1 dose Regular policy audits Training for prescribers Health Act 2006 Abx policy in place approved by D&T Audit program to show policies implemented Rx harmonised with BNF Choice, regimen and duration specified Procedures in place to ensure prudent Rx MRSA and C diff policies.
Government reports 3 Saving Lives 2007 Abx policy, compliance- audited Strategy for implementation, clinical pharmacist with infection training Formulary & guidelines Justified decision to prescribe Oral therapy preferred over IV, review IV at 48 hours Daily review, de- escalation, IV switch, course lengths 7 days Restrict broad spectrums Single dose surgical prophylaxis
Government reports 4 Clostridium difficile infection: how to deal with the problem. DH 2009 Antimicrobial management team: Micro/ID doctor Pharmacist IT analyst Automatic stops Doctor to prescribe Prescribing audits Monthly feedback to wards Mandatory training
Governance & Communication Trust Executive Committee DIPC Trust Board Executive Directors Non-Executive Directors Drugs Commitee Chief Pharmacist Consultant Pharmacist AM Senior Physician Senior Surgeon Infection Control Team Consultant Nurse IC ICNs Antimicrobial Pharmacists Consultant Pharmacist AM Teacher-Practitioner HCAI Pharmacist Infection Prevention Committee DIPC Consultant Medical Microbiologists Consultant Pharmacist Consultant Nurse IC Antimicrobial Management Team Consultant Medical Microbiologists Consultant Pharmacist AM Data Analyst Stakeholder Groups Microbiologists Physicians & Surgeons Pharmacists University PCTs Clinical Audit Teams SpRs FY Doctors Pharmacists
Policy Principles of prudent Rx Staff responsibility Standards Implementation strategy Framework Formulary New agent control-of-entry Cost-effectiveness Restricted access Department of Infection Website Evidence of infection Investigations Treatment Ongoing review Pocket Guide Guidelines Suite Choice, Dose, Route, Duration Switch
SUHT Am Rx Policy Approved Aug-07 Contents: Objectives Responsibilities of staff Principles of good Rx Standards required Strategy for containment of resistance Standards Justification for Rx Documentation of indication and duration Guideline adherence Formulary Restricted agents Narrow spectrum Review of empirical Rx IV / oral Rx
Guidelines: SUHT Infection website
Physician rating of usefulness of guideline formats for accessibility Computer database of major CPGs Workshop National directory Systematic review Table comparing CPGs on a topic Flow chart or clinical algorithm Pocket card summarising guidelines Journal article describing new guidelines Official manual with several recent CPGs Short pamphlet summarising guidelines Most useful Somewhat useful Least useful 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Hayward RSA et al 1997 (n=1878)
Guidelines pocket guide (Apr08)
e-referral system (Pharmacist Pilot) Electronic Systems Support MC&S Results Censored e-reporting & Interpretive Comments Development Work Antibiotic Pharmacists Bleep / Telephone Medical Student Teaching (Preparation for Practice, Year 5) Medical Microbiologist Telephone Advice & On-call service Telephone reporting of positive blood / CSF cultures Microbiology ward rounds Speciality: Weekly ICU: Daily Specialist advice Doctors & Ward Pharmacists (& NMPs) Expert support for Abx Rx Induction Training (Pocket Guide & Policy) Mandatory annual update Training Web-based training Web-based competency assessment Education & Training
Assurance Point Prevalence Audit (Trust-wide) Prescribing (DDD) Trends Audit Programme Clinical Audits Speciality-specific Clinical Audits Speciality-specific Surgical Prophylaxis Clinical Audits Speciality-specific IV-to-Oral Switch Antimicrobials
Is it possible to audit the quality of antibiotic prescribing?
Evaluating appropriateness: what factors influence choice / dose / route / duration of therapy? Presenting complaint / signs & Recent or previous microbiology / symptoms serology investigations Evidence of infection (SIRS) Previous antibiotics Past medical history (e.g. Biochemistry / haematology prosthetic valve, epilepsy) results / urine dipstick Immune status / Allergy / intolerance immunosuppressant drugs Pregnancy / breastfeeding Family / social contacts Organ dysfunction Occupation / hobbies GI absorption / swallowing Travel history Expert advice Pets / animal contact Source control DIAGNOSIS and likely pathogens Local pathogen epidemiology and Severity of infection resistance Prescriber s s training / experience Antibiotic spectrum Peer advice / consultant Site of infection (penetration) preference Interacting drugs (e.g. iron and Local guidelines / policy doxycycline) Recent contact with healthcare. Ethnicity (e.g. G6PD deficiency).
Antimicrobial prescribing on one day n=198 London H n=2165 Italy n=195 London A n=368 London E n=414 London J n=115 London B n=581 London D n=537 London C n=904 SUHT n=354 London G n=652 Sw eden n=517 London F n=745 Estonia n=927 Latvia n=198 London I n=938 Croatia n=684 Holland n=876 Lithuania 0 10 20 30 40 50 % of patients on antimicrobials
Standard 1 st line therapy or in line with guidelines (SUHT) First line therapy? No Guideline 4% Don't Know 10% Unspecified 11% Yes 57% No 18%
Auditing quality of prescribing Appropriateness of antimicrobrial prescribing by Care Group at SUHT (February 2007) 100% Unable to Assess 80% Inappropriate: Too narrow spectrum Inappropriate: Route inapropriate Inappropriate: Redundant agent 60% Inappropriate: No evidence of infection Inappropriate: More effective alternative 40% Inappropriate: Limited evidence of infection Inappropriate: Less toxic alternative Inappropriate: Less broad spectrum alternative 20% Inappropriate: Duration too long Inappropriate: Divergence from guidelines Appropriate 0% Cancer Care (n=23) Cardiothoracic (n=38) Child Health (n=18) Intensive Care (n=11) Medicine & Elderly Care (n=127) Neurosciences (n=7) Obstetrics & Gynaecology (n=14) Surgery (n=39) Trauma & Orthopaedics (n=32)
There has to be an easier way Quality improvement methodology
Indicators of quality in Abx Rx Antimicrobial indicated Evidence of infection documented?? AND Indication documented? Choice of agent First-line / alternative from local guidelines OR Rationale for guideline deviation documented? Duration Total course length <7 days? IV duration <3 days? Surgical prophylaxis <24 hours? Ultra-broad spectrum antibiotics? Approved indication documented OR Discussion with micro/id documented?
Example of run chart Antibiotic prescribing indicators on Nightingale Ward % 100 80 60 40 20 Antibiotic necessary Recommended choice Short duration Approved ultra-broad spectrum 0 January February March April May June
IV-to to-oral oral switch What about unintended consequences? Medicines Act compliance
IVOST Validated criteria for switch University hospital Switzerland 2 General medical wards (n=162 control, 215 intervention) All patients on IV antibiotics for 48-72h evaluated regardless of indication Not surgical prophylaxis Not if transferred to wards after >3 days IV Not if transferred out before 72 hours IV Printed IVOST checklist placed in medical notes Results Median duration IV therapy reduced from 6 to 5 days (p=0.01) No significant difference control vs intervention in: Frequency of restarting IV therapy (8% vs 10.2%) Mortality rate (8% vs 7%) Readmission rate within 90 days (35.2% vs 31.6%) Mertz D 2009 JAC In Press
IVOST Validated criteria for switch Inclusion Intravenous antibiotics for >24 hours Afebrile for >24 hours (<38ºC C tympanic) Clinical improvement Oral administration of fluids is feasible Oral administration of tablets is feasible Exclusion Haematological malignancies or neutropenia Severe soft tissue infection; osteomyelitis; ; septic arthritis Abscess, no incision CNS infection Staphylococcus aureus bacteraemia Endocarditis or intravascular infection (e.g. suppurative thrombophlebitis) Impaired gastrointestinal absorption Other: Mertz D 2009 JAC In Press
e-referral
equest Pharmacist places request
Request details
Referral details
Ward round printout
Microbiologist worklists (HICCS)
Communicating ward round outcomes
Data from ward rounds Early days Identify common themes Monitor workload to support business cases Provide reassurance to risk management
30 25 20 15 10 5 0 Referrals by ward (Medicine & Elderly) Nov-Dec08 Total Count of Patient No Total AMU Admissions 1 (AM1) AMU Admissions 2 (AM2) AMU Admissions 3 (AM3) / [Old Short Stay (AMS)] D5 Managed Care (D5M) D6 Medical D7 Medical D8 D8 Medical F5 ENT F8 Acute Stroke Unit (F8A) G5 Elderly Care G6 Elderly Care G7 Elderly Care (G7C) G8 Elderly Care G9 Elderly Care Infectious Diseases Unit, SGH (IDU) Medical High Dependency Unit (MHDU) Total reviews found: 117 Ward
Recommendations Total Route - Recommend date for IV-to-oral switch Count of Patient No Route - Convert from IV to oral immediately Rejection - Referral rejected (patient not reviewed on ward round) Rejection - Referral rejected (inappropriate) Other - stop co-amox due to rise in LFTs. for stat gent Dose - Course length - Stop agent(s) Recommendation Course length - Recommend stop date Course length - Continue current treatment Total Clinical - Do further diagnostic tests and review Clinical - Continue as before and review Choice of antimicrobials - Streamline to narrow spectrum Choice of antimicrobials - Start new agent Choice of antimicrobials - Replace current ineffective agent with another effective agent Choice of antimicrobials - Replace agent with lower risk agent for C diff Choice of antimicrobials - Remove redundant agent 0 5 10 15 20 25 30
16 14 12 10 8 6 4 2 0 Referrals by date Total 04-Nov 06-Nov 07-Nov 10-Nov 11-Nov 13-Nov 18-Nov 20-Nov 21-Nov 25-Nov 27-Nov 28-Nov 02-Dec 04-Dec 05-Dec 08-Dec 09-Dec 11-Dec 15-Dec 16-Dec 17-Dec 18-Dec 19-Dec 29-Dec 30-Dec 31-Dec Count of Patient No Nov Dec Months Request Date Total
Reasons for referral Total Reason Count of Patient No Unknown (HICSS referral) Route (IV-to-oral switch eligibility) Dose (Toxic or subtherapeutic serum levels) Dose (Dosing query) Course length (Request plan for course length) Course length (Can treatment be stopped) Clinical (Need for antimicrobial) Clinical (Microbiology review) Clinical (Failure to document indication) Clinical (Bloodstream infection) Choice of antimicrobial(s) (Restricted antibiotic) Choice of antimicrobial(s) (Polypharmacy) Choice of antimicrobial(s) (No guideline) Choice of antimicrobial(s) (Narrower spectrum alternatives) Choice of antimicrobial(s) (Mismatch of treatment with microbiology results) Choice of antimicrobial(s) (Low risk agent for clostridium difficile) Choice of antimicrobial(s) (Guideline antimicrobial choice) Choice of antimicrobial(s) (Alternative in allergy/contraindication) Choice of antimicrobial(s) (Alternative if prior antimicrobial exposure) Choice of antimicrobial(s) (Alternative due to toxicity) Total 0 5 10 15 20 25 30 35 40 45 50
Monitoring consumption Cannot link to indication / appropriateness Very useful for monitoring prescribing trends over time Behaviour change through measurement Can demonstrate success/failure of policy/guideline change Keep it simple! (max 3 indicators)
5 4 3 2 1 0 Trends in Abx Rx at SUHT Trustwide Antimicrobial prescribing per admission (12-month rolling average) Standard treatment days per admission Oct-06 Nov-06 Dec-06 Jan-07 Feb-07 Mar-07 Apr-07 May-07 Jun-07 Jul-07 Aug-07 Sep-07 Oct-07 Nov-07 Dec-07 Jan-08 Feb-08 Mar-08 Apr-08 May-08 Jun-08 Jul-08 Aug-08 Sep-08 Oct-08
60% 50% 40% 30% 20% 10% 0% High-risk antimicrobials Trustwide Antimicrobial Use By Risk Classification (12 Month Rolling Average) Oct-06 Nov-06 Dec-06 Jan-07 Feb-07 Mar-07 Apr-07 May-07 Jun-07 Jul-07 Aug-07 Sep-07 Oct-07 Nov-07 Dec-07 Jan-08 Feb-08 Mar-08 Apr-08 May-08 Jun-08 Jul-08 Aug-08 Sep-08 Oct-08 Antifungal Antiviral High risk Intermediate risk Low risk Specialist Ultra broad spectrum
Infection control initiatives SUHT C.difficile 2007-2009 (All Cases) Correlation between No of C.diff Cases Immediate Patient Isolation 70 120 No. of Cases 60 50 40 30 20 10 42 50 35 49 45 65 48 67 60 73 83 62 59 67 57 75 81 91 94 86 100 100 80 60 40 20 "Patient Isolated Immediately Diarrhoea Apparent % Achieved 0 Apr- 07 May- 07 Jun- 07 Jul- 07 Aug- 07 Sep- 07 Oct- 07 Nov- 07 Dec- 07 Jan- 08 Feb- 08 Mar- 08 Apr- 08 May- 08 Jun- 08 Jul- 08 Aug- 08 Sep- 08 Oct- 08 Nov- 08 Dec- 08 0 No of Cases Immediate Isolation Linear (No of Cases)
70% 60% 50% 40% 30% 20% 10% 0% Horses for courses Horses for courses Antimicrobial Use By Risk Classification (12 Month Rolling Average) Med & EC 40% Antimicrobial Use By Risk Classification (12 Month Rolling Average) Critical Care 35% 30% Oct-06 Nov-06 Dec-06 Jan-07 Feb-07 Mar-07 Apr-07 May-07 Jun-07 Jul-07 Aug-07 Sep-07 Oct-07 Nov-07 Dec-07 Jan-08 Feb-08 Mar-08 Apr-08 May-08 Jun-08 Jul-08 Aug-08 Sep-08 Oct-08 Antifungal Antiviral High risk Intermediate risk Low risk Specialist Ultra broad spectrum 25% 20% 15% 10% 5% 0% Oct-06 Nov-06 Dec-06 Jan-07 Feb-07 Mar-07 Apr-07 May-07 Jun-07 Jul-07 Aug-07 Sep-07 Oct-07 Nov-07 Dec-07 Jan-08 Feb-08 Mar-08 Apr-08 May-08 Jun-08 Jul-08 Aug-08 Sep-08 Oct-08 Antifungal Antiviral High risk Intermediate risk Low risk Specialist Ultra broad spectrum
70% 60% 50% 40% 30% 20% 10% 0% IV Abx Rx at SUHT Trustwide Antimicrobial Use By Administration Route (12-month rolling average) Oct-06 Nov-06 Dec-06 Jan-07 Feb-07 Mar-07 Apr-07 May-07 Jun-07 Jul-07 Aug-07 Sep-07 Oct-07 Nov-07 Dec-07 Jan-08 Feb-08 Mar-08 Apr-08 May-08 Jun-08 Jul-08 Aug-08 Sep-08 Oct-08 IV Oral
RAG ratings Care Group Surgery T&O Medicine & Elderly Care Antimicrobial prescribing per admission High risk antimicrobial prescribing Low risk antimicrobial prescribing Ultra-broad spectrum antimicrobial prescribing IV antimicrobial prescribing Cancer Care Child Health O&G Cardiothoracic Critical Care Neuroscience GREEN AMBER GREEN AMBER AMBER GREEN AMBER GREEN GREEN GREEN GREEN GREEN AMBER GREEN GREEN GREEN GREEN GREEN GREEN GREEN AMBER AMBER GREEN GREEN GREEN AMBER GREEN GREEN RED RED GREEN GREEN GREEN RED RED AMBER GREEN GREEN RED RED AMBER AMBER GREEN AMBER
16 14 12 10 8 6 4 2 0 MRSA and antibiotics? MRSA and antibiotics? SUHT: Number of avoidable MRSA bloodstream infections Number of Cases Apr-05 May-05 Jun-05 Jul-05 Aug-05 Sep-05 Oct-05 Nov-05 Dec-05 Jan-06 Feb-06 Mar-06 Apr-06 May-06 Jun-06 Jul-06 Aug-06 Sep-06 Oct-06 Nov-06 Dec-06 Jan-07 Feb-07 Mar-07 Apr-07 May-07 Jun-07 Jul-07 Aug-07 Sep-07 Oct-07 Nov-07 Dec-07 Jan-08 Feb-08 Mar-08 Apr-08 May-08 Jun-08 Jul-08 Aug-08 Sep-08 Oct-08 Nov-08 Dec-08
Peri-operative antibiotic prophylaxis in Trauma & Orthopaedics at SUHT in September 2008: Analysis of impact of new guidelines (flucloxacillin 1g x 4 plus gentamicin 160mg x 1) on renal function Dr Sarah Waldman FY1 Kieran Hand Consultant Pharmacist Anti-infectives Dr Ann Pallett Consultant Medical Microbiologist January 2009
Absolute changes in SCr N = 37 procedures Average SCr at baseline and post-op 120 Serum Creatinine (micromol/l 100 80 60 40 20 Baseline SCr Post-op SCr 0 No Gent (n=8) 80mg (n=1) 100mg (n=1) 120mg (n=6) 160mg (n=21) Gentamicin exposure
11 10 9 8 7 6 5 4 3 2 1 0 Relative changes in SCr N = 37 procedures Relative changes in SCr by gentamicin exposure Number of patients (-) 20-30% (-) 10-20% +/- 10% (+) 10-20% (+) 20-30% (+) 30-40% (+) 40-50% (+) 50-60% Relative change in SCr from baseline to post-op peak None 80mg 100mg 120mg 160mg
Baseline renal function: poor predictor of SCr rises Peri-operative change in SCr by baseline egfr 12 10 8 6 4 2 >90 ml/min 50-90 20-50 10-20 0 Number of patients (-) 20-30% (-) 10-20% +/- 10% (+) 10-20% (+) 20-30% (+) 30-40% (+) 40-50% (+) 50-60%
SCr changes by age group: poor predictor of SCr rises 100 SCr changes by age-group (n=37) SCr (micromol/l) 80 60 40 20 Pre-op SCr Post-op peak 0 30s (n=2) 40s (n=2) 50s (n=3) 60s (n=7) 70s (n=12) 80s (n=8) 90s (n=3)
Summary & Conclusions Around one third of 36 patients developed SCr rises >10% above baseline No patient developed an absolute SCr rise of >30μmol/L SCr increases of >30% above baseline were seen in: 2/8 patients who did not receive gentamicin 0/6 patients who received 120mg gentamicin 4/21 patients who received full-dose (160mg) gentamicin SCr increases of >50% above baseline were seen in: 2/21 patients who received 160mg gentamicin No patient had sustained elevation of SCr Baseline egfr, age group and vancomycin exposure were poor predictors of who would develop a SCr rise Recommendation: 2mg/kg gentamicin should be considered as the standard prophylactic dose providing no severe renal failure
Thank you for inviting me! Acknowledgements SUHT Antimicrobial Management Team Dr Adriana Basarab Dave Browning Antibiotic pharmacists Mike Vickers Sally Pearce