Session 13. The Role of the DTC in Containing Antimicrobial Resistance

1. Drug and Therapeutics Committee Session 13. The Role of the DTC in Containing Antimicrobial Resistance

2. The Threat of AMR HIV/AIDS ARI (pneumococci) Diarrhea (shigella) Avian influenza MRSA, VRSA, VRE, and other nosocomial infections Multidrug- resistant-TB Threat of Antimicrobial Resistance Extensively drug- resistant TB Community acquired-MRSA Multidrug-resistant gonorrhea Multidrug-resistant malaria

3. Understand the global situation of antimicrobial resistance Describe the role of the Drug and Therapeutics Committee (DTC) in containing AMR Discuss multifaceted strategies to contain AMR Objectives

4. Introduction and Background Global Situation and Impact of AMR Causes of AMR Role of DTC in Containing AMR Activity Summary Outline

5. Antimicrobials have greatly contributed to the decline in morbidity and mortality from infectious diseases. These achievements, however, are being undermined by the rapidly growing problem of AMR. If used well, DTCs can be a powerful mechanism to improve antimicrobial management and contain AMR, especially in institutional settings. Introduction

6. Pathogens causing TB, malaria, sexually transmitted infections, typhoid, bacterial dysentery, and pneumonia are now resistant or multidrug-resistant (MDR). Up to 17% of TB is MDR. And, extensively drug-resistant (XDR) TB is now being recorded in countries worldwide. In 81 of 92 malaria-prevalent countries, chloroquine is no longer effective. Source: WHO. 2004. Country Data 2000–03, Containing Antimicrobial Resistance, Policy Perspectives on Medicine, Nov 20. Geneva: WHO. Global Situation of AMR (1)

7. Salmonella typhi Multidrug resistance emerged as a public health problem in Asia. Shigella Resistance to ampicillin, tetracycline, co-trimoxazole, and chloramphenicol is widespread in Africa. Up to 90% resistance to ampicillin and co-trimoxazole has been found in parts of Asia. Resistance is emerging to fluoroquinolones, the only available option to left for treatment. Vibrio cholera Up to 90% of isolates are resistant to at least one antibiotic. Global Situation of AMR (2) Sources: Okeke, I.N., et al. 2005. Antimicrobial Resistance in Developing Countries. Part I: Recent Trends and Current Status. Lancet Infectious Diseases 5(8):481–93. WHO. 2004.Country Data 2000–03.

8. Streptococcus pneumonia Penicillin and erythromycin resistance is an emerging problem in community acquired pneumonia in Asia, Mexico, Argentina, Brazil, Kenya, and Uganda. MDR (penicillin + two other classes) in Africa is 25%; in the Far East, 63%; in the Middle East, 18%; in Latin America, 20%; in eastern Europe, 12%; in western Europe, 18%; and in the United States, 26%. Global Situation of AMR (3) Source: Okeke, I.N., et al. 2005. Antimicrobial Resistance in Developing Countries. Part I: Recent Trends and Current Status. Lancet Infectious Diseases 5(8):481–93.

9. Widespread resistance to penicillin and tetracycline resulted in replacement with more expensive first-line medicine. Penicillin resistance ranges from 9 to 90% across Asia and is over 35% in sub-Saharan Africa and the Caribbean. Replacement medicines also developed resistant problems, azithromycin resistance was found in 16%–72% in the Caribbean and South America and quinolone resistance is commonly reported in Asia and Africa. The only option remaining may be a very expensive third-generation cephalosporin. Global Situation of AMR (4): Running out of Options—Example of N. Gonorrhea Source: Okeke, I.N., et al. 2005. Antimicrobial Resistance in Developing Countries. Part I: Recent Trends and Current Status. Lancet Infectious Diseases 5(8):481–93.

10. Up to 10% of admitted patients contract hospital-acquired infections. The hospital is an important source of medicine-resistant infections. Important hospital pathogens include— MRSA, Enterococcus faecium, E. faecalis, E. coli, Klebsiella pneumoniae, Enterobacter spp., Citrobacter spp., Pseudomonas aeruginosa, and Acinetobacter calcoaceticus AMR in Hospitals

11. Nosocomial transmission of commonly encountered, community-acquired, multidrug resistant organisms includes pneumococcus, Mycobacterium tuberculosis,Salmonella, Shigella. Hospital-acquired infections are among the most prevalent cause of death in the developing world. Horizontal transfer of resistant genes from one strain to another can also exacerbate the possibility of resistant nosocomial infections. Nosocomial Infections and AMR Source: Okeke I. N.. et al. 2005. Antimicrobial Resistance in Developing Countries. Part I: Recent Trends and Current Status. Lancet Infectious Diseases 5(8):481–93.

12. Individual and public health consequences are enormous in terms of— Increased morbidity and mortality Prolonged periods of infectiousness with increased risk of transmission of the resistant pathogen to others Increased direct cost (longer hospital stay, use of more expensive second- or third-line medicines) Indirect costs (e.g., prolonged absence from work) Impact of AMR

13. Increased morbidity and mortality Treatment 300 times more expensive Standard treatment = 20 U.S. dollars (USD) MDR-TB treatment = USD 6,000 Treatment duration much longer Cure rate much less, even in the best centers Prolonged infectiousness with transmission of resistant pathogen to others in the community (public health impact) Impact of AMR: Example of Multidrug-Resistant TB

14. XDR-TB cases—cases that are resistant to three of the six classes of second-line medicines—carry a high mortality rate and are increasing. An XDR-TB strain in South Africa killed 52 of 53 identified cases in 2006 causing widespread concern in the public health community. Impact of AMR: Example of XDR-TB Source: Singh, J.A., R. Upshur, and N. Padayatchi. 2007. XDR-TB in South Africa: No Time for Denial or Complacency. Public Library of Science Medicine 4(1):e50.

15. Primary blood stream infections due to nosocomial methicillin-resistant Staphylococcus aureus caused an approximate three-fold increase in cost and extended hospital stay when compared with infections due to methicillin-sensitive Staphylococcus aureus. Impact of AMR: Cost Implications of Nosocomial MRSA Source: Abramson, M.A., and D.J. Sexton. 1999. Nosocomial Methicillin-Resistant and Methicillin-Susceptible Staphylococcus aureus Primary Bacteremia: At What Costs? Infection Control and Hospital Epidemiology 1999; 20(6): 408–11.

16. Because of failing treatment with chloroquine or sulfadoxine-pyrimethamine (SP), most malaria-affected African countries have changed to an artemisinin-based combination therapy (ACT) regimen, which has significant cost implications. Impact of AMR: Cost Implications of Changing to ACT Regimen for Malaria Treatment Source: Omari, A.A., C. Gamble, and P. Garner. 2004. Artemether-Lumefantrine for Uncomplicated Malaria: A Systematic Review. Tropical Medicine and International Health 9(2):192–99.

17. Overuse and abuse of antimicrobials Poor prescribing Lack of adherence to prescribed medicine Patient demand Economic incentives Unregulated availability of antimicrobials Poor-quality medicines Causes of AMR (1)

18. Inadequate infection control in hospitals Inadequate health care systems to manage antimicrobials Lack of knowledge by prescribers and users Pharmaceutical company advertising and influence Causes of AMR (2)

19. Antimicrobials represent one of the most widely used and misused agents 20–50% of human use isUNNECESSARY 40–80% of animal use isHIGHLY QUESTIONABLE Inappropriate Use Is a Major Contributor to AMR Source: Wise, R. et al. 1998. Antimicrobial Resistance Is a Major Threat to Public Health. British Medical Journal 317:609–10.

20. Training deficiencies Diagnostic uncertainties Formularies or STGs not available or not used Fear of poor patient outcome and need for self reassurance Fear of litigation Dispensing prescribers Microbiological information not available or not used Patient demand Economic incentives Pharmaceutical manufacturers’ influence Reasons for Irrational Prescribing

21. Global Strategies to Address AMR

22. Develop new antimicrobials—No longer a dependable option because few new agents are in the pipeline Preserve effectiveness of existing antimicrobials—Key strategy Rational use of medicines Infection control strategies Key Approaches to Contain AMR

23. To help preserve the effectiveness of existing antimicrobials DTC is a Key Body in the Hospital Setting—

24. Updating and managing antimicrobial formulary Developing policies on antimicrobial procurement and quality Developing and updating antibiotic guidelines Developing policies to improve compliance with guidelines (e.g., reserve antibiotics, levels of prescribing, automatic stop orders, antimicrobial order forms) Evaluating antimicrobial use based on pre-established criteria of appropriateness (i.e., drug use evaluations) and applying remedial measures DTCs Can Help Preserve Effectiveness of Existing Antimicrobials by— (1)

25. Providing preservice and in-service education on rational use and AMR Liaising with the Infection Control Committee and/or microbiology department with regard to the assessment and use of data obtained from the monitoring of antimicrobials Providing education to patients on the use and abuse of antimicrobials and encouraging adherence Supporting pharmacovigilance activities for antimicrobials DTCs Can Help Preserve Effectiveness of Existing Antimicrobials by— (2)

26. First-choice antimicrobials (nonrestricted use) Used by all prescribers without approval by senior prescribers Safe, effective, reasonably priced antimicrobials Restricted use For more serious clinical conditions under certain conditions Less safe, more expensive, newer antimicrobials Conditions could include the following: Specific infections known to be sensitive to the antimicrobial medicine after culture and sensitivity testing Empirical treatment for suspected life-threatening infections pending the result of culture and sensitivity Counter-signature by a senior physician approved by DTC Reserve antimicrobials (very restricted use) For life-threatening infections known to be resistant to other antimicrobials Approval needed by the DTC or microbiologist Antimicrobial Policies: Classification

27. Surveillance is an essential component of containing AMR because staff will take AMR seriously only when seeing actual data Use the data For individual patient care To inform formulary process only if appropriate data collection methods have been followed Data collection methods to inform the formulary Analyze isolates from community-acquired infection separately from isolates from nosocomial infection Exclude duplicate isolates from the same patient Laboratory quality assurance Inaccurate, poor data are worse than no data. Internal and external quality assurance are needed for laboratory. Monitoring Antimicrobial Sensitivity Patterns (Surveillance)

28. Develop policies concerning use of antimicrobials for approval by the DTC and medical staff Assist in evaluating and selecting antimicrobials for the formulary and guidelines Organize educational programs for providers and patients Monitor antimicrobial use and resistance patterns Address other issues relating to antimicrobials DTC Can Create an Antimicrobial Subcommittee to Help

29. Terms of reference and scope of work developed for the subcommittee Multidisciplinary in nature Clinical pharmacist Microbiologist Nurse Physician Chief pharmacist Establishment of an AMR Subcommittee within DTC: Experience from Kenya 2006 Courtesy: Sital Shah, Chief Pharmacist, Aga Khan University Hospital, Nairobi, Kenya. Former participant of International DTC Training of Trainers course, Malaysia, 2005.

30. Antibiotic order form (AOF) was piloted in intensive care unit (see the Participants’ Guide for an example) Order form was initially met with much resistance and compliance was poor Advocacy and consensus meeting was organized for hospital staff and private doctors AMR Subcommittee Functionality: Experience from Kenya (1)

31. DTC presented antibiotic usage report using simple indicators with microbiological data. Description and purpose of AOF were discussed in the consensus meeting. This meeting became a forum for discussion about which antibiotics to be restricted and how to audit practice. AOF is currently being implemented. Preliminary results show a decrease in the use of expensive broad-spectrum antimicrobials AMR Subcommittee Functionality: Experience from Kenya (2)

32. Three costly broad-spectrum antimicrobial agents were restricted: imipenem, vancomycin, and injectable ciprofloxacin. A completely filled-out AOF was required by pharmacists before dispensing the medicines. The AOF guided physicians to give explicit information about anatomic and etiologic diagnosis and suspected antimicrobial patterns of the organisms. Success of Antibiotic Order Form: Example from Thailand(1) Source: Sirinavin, S. P., et al. 1998. Effect of Antibiotic Order Form Guiding Rational Use of Expensive Drugs on Cost Containment. Southeast Asian Journal of Tropical Medicine and Public Health 29:636–42.

33. Indications of restricted medicines were also recorded. The AOFs were audited daily by the Antimicrobial Subcommittee. Feedback was given to prescribers by infectious disease specialists at least twice a week. Significant cost savings to the hospital (30%) were recorded in three years. Support by senior hospital administrators is necessary. Success of Antibiotic Order Form: Example from Thailand (2)

34. Problem: Overuse of expensive broad-spectrum IV agents Intervention: Pharmacy led implementation of in-house guidelines. Criteria for IV therapy and switching to oral route was established. Setting: No infectious disease physician; no strategy for restricting selected antimicrobials Example of Policy for Switching from IV to Oral Antibiotics: U.K. Experience (1) Source: McLaughlin, C.M., et al. 2005. Pharmacy-Implemented Guidelines on Switching from Intravenous to Oral Antibiotics: An Intervention Study. Quarterly Journal of Medicine 98:745–52.

35. U.K. Experience (2) Developed in-house IV-to-oral switching guidelines Consensus Meeting • Background, rationale, objectives • Recognition of sepsis parameters • Indications for IV therapy • Blood culture when needed Dissemination of IV-to-oral switching guidelines • Guidelines posted at ward doctors’ room and nursing unit • Continuous education and training • Pharmacist–prescriber dialogue and feedback

36. IV-to-oral switching was appropriate 90% of the time in a group of patients, with guidelines and feedback provided by pharmacist (versus 17% in a group with no intervention). Day-to-day contact with prescribers and nursing staff reinforced adherence to guidelines. This initiative benefited nursing staff because their unnecessary workload was reduced. Prescribers did not feel that they were being “policed.” U.K. Experience (3)

37. DTC Can Collaborate with Other Units to Create Synergy in Action With microbiology department for collection and management of information on pathogens and resistance patterns With Infection Control Committee to reduce spread of resistant pathogens With pharmacy to improve antimicrobial procurement and quality DTC With hospital management to develop and implement policies on antibiotic use With different departments for education of students, physicians, pharmacists, nurses, and patients

38. Each group will identify known problems in antibiotic use in its hospital and prioritize one problem. What strategies will you use to solve the antibiotic use problem? How will you utilize the DTC (if it exists) to lead or support the process? How will you monitor your strategy? What may be the potential barriers in implementing your strategy? Activity

39. Antibiotics are the most widely used and misused agents, and they contribute to the huge and growing global problem of loss of efficacy due to resistance—inappropriate use is the key driver of AMR. DTCs play an important role in preserving the effectiveness of existing antimicrobials and to contain the development and spread of AMR. Summary (1)

40. Key Strategies Updating and managing an antimicrobial formulary Developing policies on antimicrobial procurement and quality Developing and updating antimicrobial guidelines Developing policies to improve compliance with guidelines (e.g., reserve antimicrobials, levels of prescribing, automatic stop orders, and antimicrobial order forms) Evaluating antimicrobial use based on pre-established criteria of appropriateness and applying remedial measures Summary (2)

41. Key Strategies (continued) Providing preservice and in-service education on rational use and AMR Liaising with the infection control committee, the microbiology department, or both with regard to the assessment and use of data obtained from the monitoring of antimicrobial resistance Providing education to patients on the use and abuse of antimicrobials and encouraging adherence Supporting pharmacovigilance activities for antimicrobials Summary (3)

42. DTCs must collaborate with different departments and units to produce synergy in action. Summary (4)