Drug and Therapeutics
Committee
Session 13. The Role of the DTC in
Containing Antimicrobial Resistance
The Threat of AMR
Avian
influenza
HIV/AIDS
ARI
(pneumococci)
Diarrhea
(shigella)
MRSA, VRSA,
VRE, and other
nosocomial
infections
Threat of
Antimicrobial
Resistance
Multidrugresistant-TB
Extensively drugresistant TB
Community
acquiredMRSA
Multidrugresistant malaria
Multidrugresistant
gonorrhea
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 drugresistant (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 hospitalacquired infections.
 The hospital is an important source of medicineresistant 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 MRSA
Primary blood stream infections due to nosocomial methicillinresistant 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 sulfadoxinepyrimethamine (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
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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
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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 and
DTCs
Rational
use of
medicines
Education
professionals
public
Prevention
Advocacy
AMR
Improving
health
systems
Regulation
Surveillance
Research
Infection
control
Medicine
quality
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
Establishment of an AMR Subcommittee
within DTC: Experience from Kenya 2006
 Terms of reference and scope of work developed
for the subcommittee
 Multidisciplinary in nature
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Clinical pharmacist
Microbiologist
Nurse
Physician
Chief pharmacist
Courtesy: Sital Shah, Chief Pharmacist, Aga Khan University Hospital, Nairobi, Kenya. Former
participant of International DTC Training of Trainers course, Malaysia, 2005.
AMR Subcommittee Functionality:
Experience from Kenya (1)
 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 (2)
 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 broadspectrum antimicrobials
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
Consensus
Meeting
Background, rationale, objectives
 Recognition of sepsis parameters
 Indications for IV therapy
 Blood culture when needed
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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
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 Control
Committee to reduce spread
of resistant pathogens
With pharmacy to
improve
antimicrobial
procurement
and quality
With microbiology department
for collection and management
of information on pathogens and
resistance patterns
DTC
With different departments for
education of students, physicians,
pharmacists, nurses, and patients
With hospital
management
to develop
and implement
policies on
antibiotic 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.