Antimicrobial Resistance: Inappropriate Use of Antibiotics...
Transcript of Antimicrobial Resistance: Inappropriate Use of Antibiotics...
Special Winter School
Towards Excellence in Higher Education
University of Kashmir
Prof. Anita Kotwani, Department of Pharmacology
V. P. Chest Institute, University of Delhi, Delhi, India
Antimicrobial Resistance: Inappropriate Use
of Antibiotics in the Community
Feb 28, 2017
Presentation outline
Setting the scene
Antimicrobial resistance
Inappropriate antibiotic use
Surveillance system in developed and developing
countries to tackle AMR
Indian Experience: Studies conducted for
methodology development & validation for
antibiotic use; access to antibiotics in the community
Way forward
Definitions
ANTIBIOTIC is produced by a microorganism, at a low conc.
inhibits or kills other microorganisms. E.g., penicillin
ANTIMICROBIAL is any substance of natural, semisynthetic
(amoxycyllin) or synthetic origin (quinolone)that kills or inhibits
the growth of microorganisms
Antimicrobials include all agents that act against all types of
microorganisms – bacteria (antibacterial), viruses (antiviral),
fungi (antifungal) and protozoa (antiprotozoal)
Antibacterials being the largest class of antimicrobials, is often
used interchangeably with the term “antimicrobials” and
usually referred as “antibiotics” in the community
Antimicrobials, Antimicrobial resistance,
Post antibiotic era
Discovery of antimicrobials/antibiotics
(wonder drugs) revolutionized
treatment of infectious diseases
Antibiotics, have been a mainstay of modern
medicine for the last eight decades
Soon realized bacteria could
develop antimicrobial resistance
What is antimicrobial resistance?
(AMR)
AMR happens when microorganisms (such as
bacteria, fungi, viruses, and parasites) change when
they are exposed to antimicrobial drugs (such as
antibiotics, antifungals, antivirals, antimalarials, and
anthelmintics)
As a result, the medicines become ineffective and
infections persist in the body, increasing the risk of
spread to others
Microorganisms that develop AMR resistance are
sometimes referred to as “superbugs”
AMR
Among AMR, the biggest threat is antibacterial
resistance (ABR):
common infections (respiratory, skin, wound, diarrheal
infections) could become untreatable
Many common and safe surgical or medical interventions
(cancer therapy, caesarean section) would become at risk
AMR increases the cost of health care with lengthier
stays in hospitals and more intensive care required
Impact on mortality and economic losses
Downward trend in development of
new antibiotics
After 1970 very few new classes of antibiotics
launched
Topical antibiotic
- Mupirocin 1985
- Retapamulin 2007
Systemic antibiotic
- Linezolid 2000
- Daptomycin 2003
7
Butler & Cooper. Antibiotics in the ….J Antibiotics 211;64:413-425
Post-antibiotic era
Bacteria, not humans or animals, become antibiotic-
resistant. These bacteria may infect humans and
animals, and the infections they cause are harder to
treat than those caused by non-resistant bacteria
Infections could again become serious health
problem; AMR, a serious public health problem
worldwide
Current rise of AMR poses the threat of POST-
ANTIBIOTIC ERA?
What accelerates the emergence and
spread of antimicrobial resistance?
Resistance to antibiotic a natural phenomenon
Overuse and misuse in people, agriculture & in
animals; often given without professional oversight
Inappropriate use of antibiotics
result in rapid increase and spread of AMR
Antimicrobial resistance: a global issue
needs immediate action
Antimicrobial resistance (AMR) is a growing problem
Main contributor of AMR – Antibiotic (AB) use
Paradoxically this selective pressure comes from
Overuse
Poor use
Misuse
Underuse
Lack of access to affordable health care: Self medication
Widespread non-human use
Global trade and Travel
Rising antibiotic use
Between 2005 and 2009, the units of antibiotic sold
increased by about 40% in India (IMS data)
Increased sales of cephalosporins were particularly
striking, the sales increased by 60%
Survey conducted in part of Delhi in 2004* and
2008# showed increase in use of cephalosporins
11
*Kotwani A, Holloway K, Roy Chaudhury R. Methodology for surveillance of antimicrobials use
among out-patients in Delhi. Indian Journal of Medical Research 2009; 129: 555-560
#Kotwani A, Holloway K. Trends in antibiotic use among outpatients in New Delhi, India. BMC
Infectious Diseases 2011;11.
Appropriate use of medicine
Patients receive the appropriate medicines, in doses
that meet their own individual requirements, for an
adequate period of time and at the lowest cost,
both to them and to the community (WHO))
Definition true for antibiotic
Inappropriate use of antibiotic when one or more of
or more of these conditions are not met
Appropriate antibiotic prescribing &
inappropriateness in antibiotic use
I. Prescriber Appropriate indication
Appropriate antibiotic
Appropriate patient
Appropriate information
2. Pharmacists
Prescribe and dispense antibiotics in developing countries
3. Patients Incomplete doses
Self-medication
4. Non-human Use
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How to evaluate & tackle use
(inappropriate) of antibiotics?
Need to provide evidence to stakeholders
Surveillance/measure antibiotic use
Investigating the reasons and factors underlying
Identify the barriers to behaviour change
Education and awareness of all stakeholders
Implementing suitable and sustainable interventions
Continuous monitoring and evaluation
Each country needs to measure AB use and AMR and
have a policy for their state or country
Developed country settings
Extensive surveillance programs to track pattern of
antibiotic use and AMR over time
Provides information, insights, & tools needed to
guide policy & evaluate measures taken to promote
appropriate ABs use at all levels: local to global
Successful Programs
Swedish program – STRAMA
European program – ESAC and EARSS
ASPs in U.S.A
Developing country settings
Complexity – dynamics of resistance and use
AMR not a priority area
Lack of knowledge for inappropriate AB use & AMR
Unregulated access in many settings
Lack of reliable diagnostic tools & lab facilities
Overcrowding in hospitals & communities
Lack of record keeping on AB use & quality data on AMR
Lack of resources for extensive surveillance
The current statusDeveloping country settings
Countries have recognized the need for containment
of AMR but the surveillance system still not in place
Fragmented data available (high use of AB)
Obtaining data are often problematic, more so for
community where about 80% ABs are used
A reproducible and sustainable surveillance
methodology needed for quantifying antibiotic use
and resistance in the community
Steps in right direction…
Indian Experience
WHO collaborated 5 pilot projects to develop
validated reproducible and sustainable
surveillance methodology for AB use (2002-05)
Pilot project at New Delhi: Data on AB use collected
monthly over one year from 30 retail pharmacies
Antibiotic use data was collected by two methods –
1. Bulk purchase data for each pharmacy (Defined Daily Dose,
DDD/1000 population)
2. Patient exit interviews at pharmacies (DDD/1000 patients
and % of patient receiving antibiotic)
Conclusions from Pilot study
Bulk purchase and exit interview methodologies
showed a similar pattern of antibiotic use
Patient exit interviews methodology allows collection
of additional information from patients
Standardized units of measure was used
ATC/DDD classification
1. Kotwani A, Holloway K, Roy Chaudhury R. Methodology for surveillance of antimicrobials use among out-patients in Delhi. Indian Journal of Medical Research 2009; 129: 555-560
2. World Health Organization. 2009. Community-based surveillance of antimicrobial use and resistance in resource-constrained settings. Report on five pilot projects.
Expanded AB use survey
New Delhi (Dec 2007-Nov 2008)
Surveillance of AB use in the community using the
established methodology of Exit Interviews
Antibiotic use data was collected from
- Public facilities (10)
- Private retail pharmacies (20)
- Private practitioners (20)
ATC/DDD measurement units were assigned; AB use
was measured as DDD/1000 patients visiting the
facility & also the % of patients receiving an AB
Salient findings of the survey
New Delhi (Dec 2007-Nov 2008)
High use of antibiotics: 39% patients visiting public
facilities and private retail pharmacies received AB;
43% patients at private clinics got an AB
The surveillance system successfully captured
the pattern of antibiotic use (newer AB used)
Repeat survey could catch change in trend of AB
use over a period of time-cephalosporins use
increased & macrolides use decreased since 2004
Methodology for surveillance of AB use in the out-
patient setting is working well
Annual use of antibiotics by facility type measured
as percentage of prescriptions containing a
specific antibiotic
0
5
10
15
20
25
30
35
40
PS PrS PrC
Facility type
Pe
rce
nta
ge
Ce
F
P
M
T
Co
AG
PS- Public Sector, PrS- Private Sector retail pharmacies, PrC- Private Clinics
M - Macrolides, P - Penicillins, Ce - Cephalosporins, F - Fluoroquinolones, Co - Cotrimoxazole,
T - Tetracyclines, AG - Aminoglycosides
Trends in antibiotic use (DDD/ 1000 patients) in the
areas surveyed in New Delhi (Dec 2007- Nov 2008)
Antibiotic name Public
sector
Private
retail
Private
clinic
Cephalosporins
Cefuroxime (2nd Gen)
Cephalexin (1st Gen)
Cefixime (3rd Gen)
Cefixime + clavulanic acid
3132
971
-
-
13511
-
8065
4127
8987
-
5919
2896
Fluoroquinolones
Ofloxacin
Ciprofloxacin
Levofloxacin
Norfloxacin
5516
4367
-
2590
15652
7557
5559
3332
13222
5434
4586
-
Penicillins
Amoxicillin
Amoxicillin+Clavulanic acid
Amoxicillin+Cloxacillin
Ampicillin
6403
2873
-
2234
8240
16299
4082
-
2263
14370
3065
-
Trends in antibiotic use (DDD/ 1000 patients) in the
areas surveyed in New Delhi (Dec 2007- Nov 2008)
Antibiotic name Public sector Private retail Private clinic
Macrolides
Roxithromycin
Azithromycine
Erythromycin
3995
-
2286
6836
5404
2535
3353
3648
-
Tetracycline
Doxicycline
Tetracycline
4210
1759
6147
949
4440
-
Kotwani A, Holloway K. Trends in antibiotic use among outpatients in New Delhi, India. BMC Infectious Diseases 2011;11:99
Methodology (absence of - community-based databases on AB
use, disease-code classification and doctors often not writing the name of
disease on the prescription)
After consultation with a prescriber, patients of
common cold/sore throat/cough for not more than
five days (symptoms of acute uncomplicated RTIs) or
acute diarrhoea (1-2 days) without any blood &
mucus were enrolled for exit interview
Antibiotic use data was collected per month over one
year (December 2007–November 2008)
Use of antibiotics for acute
uncomplicated RTIs
At public facilities 45% and at private facilities 57% of patients with acute uncomplicated RTIs were prescribed at least one antibiotic
Public sector-penicillins followed by macrolide, fluoroquinolone, and cephalosporins while at
Private facilities - cephalosporins, followed by fluoroquinolone, penicillins, and macrolide were prescribed
Pattern of AB use for acute uncomplicated RTIs
Antibiotic name Public sector (% 0f total
DDDs of AB
prescribed)
Private clinic (% of
total AB
prescribed)
Cephalosporins (J01DA)
Cefuroxime (2nd gen.)
Cefpodoxime Proxetil(3rd gen.)
Cefixime (3rd gen.)
Cefixime + clavulanic acid
Cephalexin (1st gen.)
Cefaclor
10.4
6.7
-
-
-
3.7
-
39.1
11.9
8.6
8.5
8.2
0.6
0.4
Fluoroquinolones (J01MA)
Levofloxacin
Ofloxacin
Ciprofloxacin
Norfloxacin
19.7
-
15.6
3.7
0.4
23.6
12.7
8.7
2.2
-
Penicillins J01C
Amoxicillin+Clavulanic acid
Amoxicillin
31.0
7.5
15.9
19.1
14.0
3.0
Pattern of AB use for acute uncomplicated RTIs
Antibiotic name Public sector (% 0f
total DDDs of AB
prescribed)
Private clinic (% of
total AB
prescribed)
Macrolides J01FA
Roxithromycin
Azithromycine
Erythromycin
24.6
14.7
-
9.9
15.5
11.4
4.0
0.1
Tetracycline (J01AA)
Doxicycline
Tetracycline
9.5
7.1
2.3
2.7
2.7
-
Cotriamoxazole (J01EE)4.8 0.03
Kotwani A, Holloway K. Antibiotic prescribing practice for acute, uncomplicated respiratory tract infections in primary care settings in New Delhi, India. Tropical medicine & International Health 2014; doi: 10.1111/tmi.12327. Online published 22 April, 2014.
Use of antibiotics for
acute diarrhoea
Patient exit interview methodology showed at public facilities
43% and at private facilities 69%, of patients with acute
diarrhoea were prescribed at least one antibiotic in New Delhi
The main antibiotic class that was prescribed in both public and
private sector facilities was fluoroquinolones, J01MA (91.5%
and 96%)*
Another study showed low adherence to standard treatment
guidelines for management of acute diarrhoea in children by
all healthcare providers in Ujjain city (India)#
*Kotwani A, Roy Chaudhury R, Holloway K. Antibiotic prescribing practices of primary care prescribers for acute
diarrhoea in New Delhi, India. Value in Health, 2012; 15: S116-S119.
#Pathak D,…Lundborg C .Adherence to treatment guidelines for acute diarrhoea in children up to age of 12 in
Ujjain, India. BMC Infectious Diseases 2011; 11: 32
Moving ahead…
qualitative studies
FGDs were conducted with doctors*, pharmacists#,
community, high school children. Salient findings:
1. Lack of microbiology testing; peer & commercial pressure
2. Doctors’ perceived demand and expectation
3. Retail pharmacists copying the prescription of neighbourhood
doctors and dispensing antibiotics for common conditions like
cold, sore throat, and diarrhoea
4. Incentives for pharmacists to make a profit
#Kotwani A, et al. Irrational use of antibiotics and role of pharmacists:…..qualitative study New
Delhi, India. Journal of Clinical Pharmacy Therapeutics 2011 Online published 23 AUG 2011
*Kotwani A, et al. Antibiotic use in the community: what factors influence primary care physicians
to prescribe antibiotics in Delhi, India? Family Practice 2010; 27: 684-690
Qualitative studies with high school
teachers & students
Salient findings*-
Students had poor knowledge regarding antibiotics
and antibiotic resistance, while only some teachers
had a basic understanding.
Broad themes needing attention emerged: antibiotic
use behavior, doctor–patient relationship, suggested
a multipronged approach - robust public awareness
campaigns also involving schools, better doctor–
patient relationships, and stronger regulations
*Kotwani A, et al. Knowledge and perceptions on……..a qualitative study. Indian Journal of Pharmacology 2016; 48: 365-371.
Access to antibiotics in
New Delhi (2011)
Data on price and availability of a basket of 24
essential ABs and 8 high-end ABs from public and
private sector was collected using a standardized
WHO/HAI methodology
Public sector: total of 83 public facilities, 68
primary care, 10 secondary care and 5 tertiary
care facilities under 3 public health care providers
Private sector: 40 private retail and 40 retail chain
pharmacies were enrolled
Kotwani A, Holloway K. Access to antibiotics in New Delhi, India: implications for antibiotic policy. Journal of Pharmaceutical Policy and Practice.2013, 6:6.
Salient findings from access survey for
policy implications
Public sector: Delhi state government has its essential medicine
list and was using Delhi state EML 2007 for procurement; the
other two agencies had their own procurement list not the EML
All ABs procured including second and third generation
antibiotics were available at primary care facilities. Antibiotic
available were on the basis of supply rather than rationality
or the Delhi state EML and none was 100% available
Availability of ABs at tertiary care facilities was sub-optimal
Private sector: Availability of ABs was good. For most of the
antibiotics the most expensive and popular trade names were
often available. High-end antibiotics, meropenam,
gemifloxacin, and moxifloxacin were commonly available.
For Community-acquired pneumonia
Antibiotic use in tertiary care
hospitals
Antibiotic drug use in hospitalised
patients
WHO recommends use of simple indicators to follow trends in
antibiotic use that provides guidance for local agencies in the
identification of deficiencies and priority areas for intervention
Community-acquired pneumonia (CAP) is an infectious disease
needs treatment with AB
Study was conducted: To determine patterns and frequency of
antimicrobial drug use for hospitalised patients with CAP
A retrospective five-year (April 2007-March 2012) medical
record review of patients discharged to home with a diagnosis
of CAP from non-ICU respiratory medicine wards of two public
tertiary care hospitals of Delhi was performed
Important findings from in-patient study
of CAP
For two antimicrobials, beta-lactam and macrolide;
For three antimicrobials, usually a beta-lactam,
macrolide and aminoglycoside were prescribed
Reasons for prescribing various ABs, previous history
of AB use, often discharge treatment were not
mentioned in the medical records
Hospitals did not have treatment guidelines or AB
policy to be followed and a variety of antimicrobial
regimens were prescribed at both the hospitals
Suggested interventions and Way forward
Main findings from the studies
Important conclusions from the various
studies
Community-based surveillance of AB use is possible in
resource-constrained settings, consumption & pattern of
use can be surveyed over years by Exit Interviews
High use of antibiotics in the community and for self-
limiting viral infections
AB choice inappropriate for acute uncomplicated RTIs
Stakeholders behavior for AB use a cause of concern
Inappropriate availability of AB esp. at primary care
Availability of ABs for children is poor at public sector
Cont..
Important conclusions from the various
studies (2)
Federal government run tertiary care and Municipal
corporation do not have EML
For Delhi state EML is not followed for distribution of
antibiotics for primary care
Availability of ABs in public sector is based on supply
Treatment guidelines are not available in any facility
Hospitals generally do not have treatment guidelines or
antibiotic policy for inpatients as well
Medical case sheet is not filled completely & properly
Interventions and policy options suggested
to improve rational use of antibiotics
National policies can influence rational use of ABs; infection
prevention and control measures can decrease use of ABs
Policy makers to urgently prepare and implement at national
and state level Antibiotic Policy and Antibiotic Stewardship
Program for both public and private sector
All public sector agencies to develop STGs & EML in an
evidence-based manner for various level of health care,
implement & adherance to guidelines
Proper quantification and order of antibiotics for public health
facilities and reliable delivery from suppliers
Interventions and policy options suggested
to improve rational use of antibiotics
Establish hospital antibiotic committee or infectious control
committee
Continuous surveillance of AB use in the community and
hospitals in public and private sector
Restricting use & regulations for AB use in agriculture, poultry,
and livestock; education of farmers and other stakeholders
Education and awareness programs for all stakeholders
Newer ABs should not be available without prescription; strict
implementation of law (schedule H1)
Efforts by researchers are only worthwhile if policy
makers invest in the interventions urgently
Next steps……. Globally
Inappropriate antibiotic use in the community? YES
Variation in health systems and stakeholders
Each country needs to
Measure, monitor antibiotic use
Factors responsible at all stakeholders
Committed program for intervention & monitor
Required political commitment and multidisciplinary
team
Conclusions
Antibiotics are indeed wonder drugs
Use antibiotics judiciously
Save the newer generations of antibiotics for next
generations and severely ill patients