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

Drug and Therapeutics Committee

Threat of Antimicrobial

Resistance

HIV/AIDS ARI (pneumococci)

Diarrhea (shigella)

Multidrug- resistant-TB

MRSA, VRSA, VRE, and other nosocomial infections

Avian influenza

Extensively drug- resistant TB

Multidrug-resistant malaria

Community acquired-MRSA

Multidrug-resistant gonorrhea

The Threat of AMR

Objectives

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

Outline

Introduction and Background

Global Situation and Impact of AMR

Causes of AMR

Role of DTC in Containing AMR

Activity

Summary

Introduction

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.

Global Situation of AMR (1) 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 (2) 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.

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.

Global Situation of AMR (3)

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%.

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.

Global Situation of AMR (4): Running out of Options—Example of N. Gonorrhea

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.

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.

AMR in Hospitals

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

Nosocomial Infections and AMR 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.

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.

Impact of AMR

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: Example of Multidrug-Resistant TB

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 XDR-TB

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.

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.

Impact of AMR: Cost Implications of Nosocomial MRSAPrimary 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.

Pathogen Median Hospital Stay (Days)

Median Total Cost (USD)

Methicillin-sensitive Staphylococcus aureus

4 9,661

Methicillin-resistant Staphylococcus aureus

12 27,083

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.

Impact of AMR: Cost Implications of Changing to ACT Regimen for Malaria Treatment

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.

Medicine Cost for an Adult Treatment Course (USD)

Artemether-lumefantrine (Coartem®)

2.4

Chloroquine 0.13

Sulfadoxine-pyrimethamine 0.14

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.

Causes of AMR (1)

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 (2)

Inadequate infection control in hospitals

Inadequate health care systems to manage antimicrobials

Lack of knowledge by prescribers and users

Pharmaceutical company advertising and influence

Inappropriate Use Is a Major Contributor to AMR

Antimicrobials represent one of the most widely used and misused agents

20–50% of human use is UNNECESSARY

40–80% of animal use is HIGHLY QUESTIONABLE

Source: Wise, R. et al. 1998. Antimicrobial Resistance Is a Major Threat to Public Health. British Medical Journal 317:609–10.

Reasons for Irrational Prescribing

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

Global Strategies to Address AMR

PTC andDTCs

Prevention

Improving health

systems

Research

Infection control

Medicine quality

Surveillance

Regulation

Advocacy

Educationprofessionals

public

Rational use of

medicines

AMR

Key Approaches to Contain AMR

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

DTC is a Key Body in the Hospital Setting—

To help preserve the effectiveness of existing antimicrobials

DTCs Can Help Preserve Effectiveness of Existing Antimicrobials by— (1)

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— (2)

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

Antimicrobial Policies: Classification 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

Monitoring Antimicrobial Sensitivity Patterns (Surveillance) 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.

DTC Can Create an Antimicrobial Subcommittee to Help 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

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.

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)

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)

Success of Antibiotic Order Form: Example from Thailand (1) 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.

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.

Success of Antibiotic Order Form: Example from Thailand (2)

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.

Example of Policy for Switching from IV to Oral Antibiotics: U.K. Experience (1)

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

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.

U.K. Experience (2)Developed in-house IV-to-oral switching guidelines

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

ConsensusMeeting

U.K. Experience (3) 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.”

DTC Can Collaborate with Other Units to Create Synergy in Action

With Infection ControlCommittee to reduce spread

of resistant pathogens

DTC

With pharmacy toimprove

antimicrobialprocurementand quality

With microbiology department for collection and management

of information on pathogens andresistance patterns

With different departments foreducation of students, physicians,pharmacists, nurses, and patients

With hospitalmanagement

to developand implement

policies onantibiotic use

Activity

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?

Summary (1)

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 (2) 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 (3)

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 (4)

DTCs must collaborate with different departments and units to produce synergy in action.