Outline. Pharmacists Improving Outcomes in the Management of. of Infectious Diseases. Threats Against Desired Outcomes 7/11/2010

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1 Pharmacists Improving Outcomes in the Management of Infectious Diseases Christine Teng, MSc(Clin Pharm) BCPS Assistant Professor Dept of Pharmacy, National University of Singapore Principal Pharmacist (Clinical) Tan Tock Seng Hospital, Singapore Outline Desired outcomes in the management of infectious diseases Threats against desired outcomes Principles of antimicrobial use to achieve better patient outcomes How pharmacists have contributed and achieved better outcomes Scope antimicrobial use in hospitalised patients Desired Outcomes in the Management of Infectious Diseases Complex Interactions in the Use of Antimicrobial Agents Positive Clinical Outcomes Resistance Toxicity, ADR Eur J Clin Microbiol Infect Dis (2004) 23: Threats Against Desired Outcomes Pakyz AL,Oinonen M,Polk RE. Antimicrobial Agents and Chemotherapy 2009;53(5):

2 Consequences of Antimicrobial Resistance Infections becomes more difficult to treat Require use of more expensive (and toxic) antibiotics Increase length of hospital stay Increase health care costs Increase morbidity and mortality WHO Global Strategy for Containment of Antimicrobial Resistance, 2001 Principles of Antimicrobial Use to Achieve Better Patient Outcomes 1. Timely initiation of appropriate agents 3. Timely & appropriate alteration in response to clinical responses and microbiological data Principles of Antimicrobial Use to Achieve Better Patient Outcomes 1. Timely initiation of appropriate agents The choice of initial therapy depends on host factors, includingthe risk for infection with antibiotic resistant pathogens, with guidance from local susceptibility patterns Deresinski S. Clinical Infectious Diseases 2007; 45:S Higher mortality with delayed effective antimicrobial Higher mortality with initial (empiric) inadequate therapy Kumar A, et al. Crit Care Med 2006; 34(6): Burgess DS, Rapp RP. Am J Health Syst Pharm 2008; 65(Suppl 2):S4 15 Alvarez Lerma F et al. Intensive Care Med 1996;22: Ibrahim EH et al. Chest 2000;118: Valles J, et al. Chest 2003;123: Khatib R, et al. Eur J Clin Microbiol Infect Dis 2006;25:

3 Principles of Antimicrobial Use to Achieve Improved Patient Outcomes Apply PK/PD principles to maximise optimal antimicrobial effect, minimise likelihood of resistance emergence, minimise potential adverse effects Eur J Clin Microbiol Infect Dis (2004) 23: Pharmacists improving outcomes Provision of Therapeutic Drug Monitoring by Pharmacists has been shown to: Decrease toxicity Faster attainment of target drug concentrations Faster time to clinical response Decrease excessive use of resources (eg drug, laboratory monitoring etc) Decrease length of hospital stay Destache CJ, et al. Ther Drug Monit. 1990;12: Destache CJ, et al. DICP. 1989;23:33 38 Welty TE, et al. Ann Pharmacother. 1994;28: Burton ME, et al. Clin Pharmacol Ther. 1991;49: Winter ME, et al. Am J Hosp Pharm. 1986;43: Leehey DJ, et al. J Am Soc Nephrol. 1993;4:81 90 Principles of Antimicrobial Use to Achieve Better Patient Outcomes 3. Timely & appropriate alteration of antimicrobial in response to clinical responses and microbiological data consider escalation, de escalation or stopping antimicrobial * * * * P= Singh N, et al. Am J Respir Crit Care Med 2000;162: Singh N, et al. Am J Respir Crit Care Med 2000;162:

4 3. Timely & appropriate alteration of antimicrobial Singh N, et al. Am J Respir Crit Care Med 2000;162: Kollef MH, Micek ST. Crit Care Med 2005;33: Principles of Antimicrobial Use to Achieve Improved Patient Outcomes 1. Timely initiation of appropriate agents 3. Timely & appropriate alteration in response to clinical responses and microbiological data Formalised systemic approach required Antimicrobial Stewardship Programme Antimicrobial Stewardship Programme (ASP) ASP adopts a multi faceted approach to optimise the selection, dosing, route and duration of antibiotic therapy so as to Optimising clinical outcome Minimising toxicity, selection of pathogenic organisms and emergence of resistance Reducing healthcare cost without adversely impacting quality of care Deresinski S. Clinical Infectious Diseases 2007; 45:S Dellit TH, et al. Clin Infect Dis 2007;44: Pharmacist vital part of an ASP Pharmacists Improving Outcomes as part of a Multidisciplinary ASP Hospital Epidemiologist Infectious Diseases Physician Antimicrobial Stewardship Team Clinical Pharmacist Tan Tock Seng Hospital SINGAPORE IT specialist Clinical Microbiologist Infection Control Officer 4

5 ASP in Tan Tock Seng Hospital 1440 bed acute care hospital ASP formally approved in January 2009 Hospital wide implementation in March 2009 Multidisciplinary team Strategies Prospective review and feedback of antibiotics Dissemination of hospital antibiotic guidelines Formulary restriction Electronic Clinical Decision Support (from Oct 2009) ASP Workflow Prospective review and Feedback of Carbapenem Use Retrieve list of carbapenem prescribed daily Ward pharmacists to review all cases Ward pharmacists intervene if use is deemed inappropriate according to hospital guidelines Case escalated to ID pharmacists if intervention not accepted / complicated ID pharmacists review referred cases, call primary team consultant Case escalated to ID physicians if recommendations not accepted / complicated Criteria for Carbapenem Use in TTSH De escalation Criteria for Prospective Carbapenem review Must fulfill all of criteria 1 to 5 1. Afebrile (temperature <38 o C for >24 hours) 2. Off inotropes 3. Systolic blood pressure normal or >100 mmhg 4. Off mechanical ventilation OR FiO 2 <= Respiratory rate <25 breaths/minute and SaO 2 >92% 6. Reduction in white cell count ( if available) 7. Reduction in C reactive protein (if available) Pharmacists Empowered with Hospital Guidelines 5

6 Evaluation of Prospective Carbapenem Review & Feedback From 1 April 2009 to 30 June 2009, 498 cases of carbapenem orders were reviewed Ward pharmacists/ ID Pharmacists/ ID Physicians suggested 226 recommendations in 183 cases Types of Recommendations made by ASP (Apr June 2009) Type of Recommendation All cases N = 226 Accepted N = 134 (59.3) De escalation 123 (54.4) 81 (65.9) Antibiotic optimization 27 (11.9) 18 (66.7) Stop antibiotics 26 (11.5) 7 (26.9) Meropenem to Imipenem 26 (11.5) 15 (57.7) conversion Convert to oral antibiotics 13 (5.7) 8 (61.5) Dose optimization 5 (2.2) 3 (60.0) Suggest ID referral 3 (1.3) 1 (33.3) Others 3 (1.3) 1 (33.3) 31 75% of ASP recommendations were made by Pharmacists ASP Team No of Accepted recommendations N(%) Total (59.3) ID physician (57.9) ID pharmacist (56.1) Ward (62.8) Pharmacist Baseline Characteristics of Cases with ASP Recommendations Baseline parameters Not accepted (n = 53) Accepted (n = 130) P value Median age, years (range) 70 (34-94) 74 (17-98) 0.31 Male, n (%) 26 (49.1) 63 (48.5) 0.94 Median Charlson s score (range) 5 (0-12) 5 (0-12) 0.89 Median Pitt bacteraemia score (range) 0 (0-5) 0 (0-12) 0.78 Cases with and without acceptance of ASP recommendations were comparable in demographic data, co morbidity and acute illness severity 34 Better Outcomes in Cases that Implemented ASP Recommendations Outcome Not accepted (n = 53) Accepted (n =130) P value Median days of index carbapenem (range) 6 (0-35) 2 (0-46) < day clinical response, n (%) 36 (67.9) 98 (75.4) 0.30 End of ftherapy clinical i l response, n (%) 41 (77.4) 116 (89.2) day microbiological response, n (%) 10/14 (71.4) 19 /27(70.4) 0.99 Survival at discharge, n (%) 37 (69.8) 106 (81.5) day mortality, n (%) 14 (26.4) 15 (11.5) Median days of hospitalisation (range) 27 (1-356) 23 (3-356)

7 Impact of Pharmacist Prospective Review and Feedback on Carbapenem Use Objective: To evaluate impact in terms of appropriateness of carbapenem prescriptions and patient outcomes Design: A retrospective before and after study Subjects: A total of 211 randomly selected patients receiving imipenem, i meropenem or ertapenem pre ASP = 110 (Jan Mar 09) vs. post ASP =101 (Apr Jun 09) Outcome assessment: Primary: Proportion of appropriate carbapenem prescriptions Secondary: Length of hospitalisation, 7 day and end oftreatment clinical response, in hospital mortality, 30 day mortality and microbiological clearance 37 Impact of Pharmacist Prospective Review and Feedback on Carbapenem Use: 1. Improved appropriateness of carbapenem use Impact of Pharmacist Prospective Review and Feedback on Carbapenem Use: 2. Shorter duration of carbapenem use 3. Shorter length of hospital stay Impact of Pharmacist Prospective Review and Feedback on Carbapenem Use: 4. Better patient outcomes in terms of improved clinical response reduced mortality In Conclusion Pharmacist has a vital role to play in promoting rational use of antimicrobials by ensuring: 1. Timely initiation of appropriate agents 3. Timely & appropriate alteration in response to clinical responses and microbiological data Thus leading to improve patient outcomes in the management of infectious diseases. 7

8 Acknowledgement ASP core team: Dr David Lye, Dr Brenda Ang, Dr Ling Li Min, Mr Ng Tat Ming All ward pharmacists in Tan Tock Seng Hospital Project team: ASP core team, Ms Lim Shu Fang and Ms Mindy Tay. Supportive and receptive culture in TTSH Pharmacists improving outcomes 3. Timely & appropriate alteration in response to clinical responses and microbiological data Pharmacist managed proactive program for IV to oral conversion of Levofloxacin Clinical and economic outcomes of critically ill patients with sepsis in ICUs Presence of Clinical Pharmacist associated with better patient outcomes Kuti JL et al. Am J Health Syst Pharm 2002;59(22): MacLaren R, et al. Crit Care Med 2008; 36: Segmented regression of interrupted time series Antibiotic use, January 2008 February 2010 Baseline trend (denotes if there was any sig incr+ or decr trend before ASP) Change in level (denotes change in use immediately after ASP) Change in slope (denotes if there is a sig change in trend post vs. pre ASP) mean LCI UCI P value mean LCI UCI P value mean LCI UCI P value All carbapenems Ertapenem Imipenem Meropenem < Pip Tazo Ceftriaxone Ceftazidime Cefepime Ciprofloxacin PO Levofloxacin PO Amox Clav Pre ASP: Sig incr trend for carbapenems, piptazo; sig decr trend for ceftriaxone Post ASP: Sig immediate decr in meropenem + levofloxacin; sig immediate incr in ceftaz, cefepime and amox clav Post ASP: Decr trend for all antibiotics, except cefepime, amoxclav; sig decr for all carbapenems, pip taz, cefriaxone and ceftaz 47 8