NATIONAL POLICY FOR

CONTAINMENT
OF
ANTIMICROBIAL RESISTANCE

INDIA

2011

Directorate General of Health Services

Ministry of Health & Family Welfare
Nirman Bhawan, New Delhi
Developed under the Chairpersonship
of
Dr. R. K. Srivastava,
Directorate General of Health Services,
Ministry of Health & Family Welfare
Nirman Bhawan, New Delhi

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2
 CONTENTS
S. No. Topic Page No.
I. Executive Summary ------------------------------------------------------------- 5
II. Members of Task Force--------------------------------------------------------- 9
III. Terms of reference of the task force committee ---------------------------- 10
IV. Background
i. Aims of the National Antimicrobial Policy ------------------------------ 11
ii. Promotion of rational usage of Antimicrobials -------------------------- 12
iii. Infection prevention and Control Program -------------------------------- 13
iv. Research in Antimicrobials ------------------------------------------------ 13
v. Monitoring and evaluation ------------------------------------------------- 14
1. ToR - 1 (Review the current situation regarding manufacture, use and
misuse of antibiotics in the country)
1.1 Functions of CDSCO--------------------------------------------------------- 15
1.2 Functions of State Drug Control Authorities------------------------------ 16
1.3 Mechanism for Enforcement of the Act In Respect of Sale
and Manufacture of Drugs -------------------------------------------------- 16
1.4 Proposed Action to monitor Sale of Antibiotics-------------------------- 19
1.5 Proposed action for development of newer antimicrobial---------------- 20

2. ToR - 2 (Design for creation of a National Surveillance System for

antibiotic resistance)
2.1 Background ----------------------------------------------------------------- 21
2.2 Types of AMR Surveillance----------------------------------------------- 22
2.3 Designs for AMR Surveillance ------------------------------------------- 23
2.4 Operationalization of the Action Plan for AMR Surveillance--------- 28
2.5 Research in AMR Surveillance ------------------------------------------- 28

3. ToR - 3 (Studies documenting prescription patterns and establish a

monitoring system for the same)
3.1 Introductions----------------------------------------------------------------- 29

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 3.2 Objectives------------------------------------------------------------------- 31
3.3 Methodologies---------------------------------------------------------------- 31

4. ToR - 4 (Enforce and enhance regulatory provisions for use of antibiotics in

human veterinary and industrial use)

4.1 Regulatory provisions for use of antibiotics in veterinary and

industrial use----------------------------------------------------------------- 35
4.2 Proposed Action Plan: ------------------------------------------------------- 38
4.3 Regulatory provisions for use of antibiotics in Human use------------- 39

5. ToR - 5 (Specific intervention measures such as rational use of antibiotics

and antibiotic policies in hospitals which can be implemented, as early
as possible)

5.1 Rational Use of Drugs------------------------------------------------------ 40

5.2 Interventions----------------------------------------------------------------- 41
5.3 Protocol ---------------------------------------------------------------------- 42
5.4 Implementation------------------------------------------------------------- 44
5.5 Constructive feedback of policy prior to implementation------------- 47
5.6 Monitor implementation: we may form Drug and Therapeutics
Committee which may carry out the following ------------------------ 47
5.7 Assess outcome of Intervention: as below------------------------------ 48
5.8 Education-------------------------------------------------------------------- 49
5.9 Implementation of Infection Control Guidelines---------------------- 49

6. ToR - 6 (Diagnostic Methods pertaining to antimicrobial Resistance

Monitoring------------------------------------------------------------------------ 51

7. Conclusions -------------------------------------------------------------------- 52

8. Important Abbreviations-------------------------------------------------- 53

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 EXECUTIVE SUMMARY

Antimicrobial Resistance Monitoring

Antimicrobial resistance in pathogens causing important communicable diseases has

become a matter of great public health concern globally including our country.
Resistance has emerged even to newer, more potent antimicrobial agents like
carbapenems. The factors responsible for this are widespread use and availability of
practically all the antimicrobials across the counter meant for human, animal and
industrial consumption. There are definite policies / guidelines for appropriate use of
antimicrobials at national level in specific national health programmes being run in the
country e.g. RNTCP, National AIDS control programme, etc. For other diseases of public
health importance like enteric fever, diarrhoeal disease, respiratory infections, etc the
individual hospitals are following their own antimicrobial policies and hospital infection
control guidelines. To monitor antimicrobial resistance it is necessary to have regulations
for use and misuse of antibiotics in the country, creation of national surveillance system
for antibiotic resistance, mechanism of monitoring prescription audits, regulatory
provision for monitoring use of antibiotics in human, veterinary & industrial sectors and
identification of specific intervention measures for rational use of antibiotics.

In this regard a task force has been constituted with following terms of reference:

1. To review the current situation regarding manufacture, use and misuse of

antibiotics in the country.

2. To recommend the design for creation of a national Surveillance System

for Antibiotic Resistance

3. To initiate studies documenting prescriptions patterns & establish a

Monitoring system for the same.

4. To enforce and enhance regulatory provisions for use of antibiotics in

human & veterinary and industrial use.

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 5. To recommend specific intervention measures such as rational use of
antibiotics and antibiotic policies in hospitals

6. Diagnostic Methods pertaining to antimicrobial Resistance Monitoring

The official from Animal husbandry Department was co-opted for providing inputs on
use of antimicrobials in veterinary sector. The members of the task force worked on
various ToRs and made a work plan for monitoring of antimicrobial resistance in the
country. Briefly the action plan of various ToRs is as follows:

 For monitoring use and misuse of antibiotics: Schedule H of the drug

and cosmetics act contains a list of 536 drugs which are required to be
dispensed on the prescriptions of a registered medical practitioner. In order
to have separate regulation to check unauthorized sale of antibiotics, a
separate schedule as Schedule H1 may be introduced under the Drugs and
Cosmetics Rules to regulate sale of antibiotics exclusively. Corresponding
provisions under the Rules could be framed for their implementation. A
system of colour coding of third generation antibiotics and all newer
molecules like Carbapenems (Ertapenem, Imipenem, Meropenem),
Tigecycline, Daptomycin may be put in place restricting their access to
only tertiary hospitals. Appropriate steps should be taken to curtail the
availability of fixed dose combination of antibiotics in the market
 Hospital based sentinel Surveillance System for monitoring antibiotic
resistance will be set up with the identification of one of more Central
Institutions under the ministry of health as coordinating centres at the
National Level. The design for AMR surveillance consists of

o Identification of pathogens/diseases of public health importance

o Creation of network of Antibiotic Susceptibility Testing (AST)
o Standardizing methodology for microbial identification and AST

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 o The laboratories will perform AST using standardized methods and
carbapenem resistant isolates will be stocked and sent to
designated central laboratory for further analysis, like
identification of NDM-1 isolates.
o Strengthen Quality Systems in the network laboratories
 We may also identify a central reference centre for Characterization and
epidemiological study of resistance factors in microbial pathogens.
 For documenting prescription patterns and establishing a monitoring
system for the same following would be done
o To study the consumption of various antibiotics in tertiary care
public hospitals in Delhi under central government
o To study the trends in antibiotic use in these hospitals of Delhi
o Data generated will be used for intervention studies for rational use
of antibiotics.

 For enforcement and enhancement of regulatory provisions for use of

antibiotics in human, veterinary and industrial use.
o In India, the antibiotics are used widely in food animals as growth
promoters and to prevent and treat infection. Non-therapeutic
usage of antibiotics has been especially common in poultry
production. However, there is no regulatory provision regarding
the use of antibiotics in livestock.

o Establish intersectoral coordination committee with experts from

various sectors.
o Develop regulations on usage of antimicrobials in poultry and
other animals as well as the requisite labelling requirements in
food.

7
 For promoting rational use of drugs various strategies suggested are:

 Educational strategy: Training, printing materials, media-based

approach
 Managerial strategy: Monitoring & supervision, generic
substitution, patient cost sharing (economic incentives) etc
 Regulatory strategy: Enforcement, sanction, drug withdrawal,
market control etc
 Formulation & implementation of an antibiotic policy
 With quality assured laboratory data in real time develop antibiotic
policies that are standard national / local treatment guidelines
advocating evidence based immunotherapy or combination
therapy. This must include consideration of spectrum of antibiotics,
pharmacokinetics / pharmacodynamics, adverse effects monitoring,
cost and special needs of individual patient groups

 For strengthening diagnostics for antimicrobial resistance monitoring

the strategies are
 Appropriate diagnostic tools already known should be selected as well as
new ones developed for rapid identification of pathogens for AMR
surveillance.

 Robust quality assurance system should be implemented that could be

carried out by a “neutral” central institute.

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 MEMBERS OF TASK FORCE

1. Dr. R.K. Srivastava, DGHS - Chairperson

2. Prof. Ranjit Roy Chaudhury, Member, Board of Governors, M.C.I.

3. Dr. N.K. Ganguly, President, JIPMER, New Delhi

4. Dr. S.K. Bramhachari, Director General, CSIR, New Delhi

5. Dr. Surender Singh, Drugs Controller General of India, New Delhi

6. Dr. Randeep Guleria, Prof. of Medicine, AIIMS, New Delhi

7. Dr. Ajit Sinha, HoD, Deptt of Surgery, Safdarjung Hospital, New Delhi

8. Dr. Usha Gupta, Sr. Consultant, Clinical Pharmacology, Fortis Hospital, NOIDA

9. Dr. Manish Kakkar, Public Health Foundation of India, New Delhi

10. Dr. Camilla Rodrigues, Consultant, Lab Medicine, PD Hinduja Hospital, Mumbai

11. Dr. Chand Wattal, Chairperson, Clinical Microbiology, Sir Ganga Ram Hospital, New Delhi

12. Dr. Anita Kotwani, Associate Prof., Pharmacology, VP Chest Institute, Delhi

13. Director NCDC, Delhi - Member Secretary

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 TERMS OF REFERENCE
OF THE TASK FORCE COMMITTEE

1. Review the current situation regarding manufacture, use and misuse of

antibiotics in the country.

2. Design for creation of a National Surveillance System for antibiotic resistance.

3. Studies documenting prescription patterns and establish a monitoring system

for the same.

4. Enforce and enhance regulatory provisions for use of antibiotics in

human veterinary and industrial use.

5. Specific intervention measures such as rational use of antibiotics and

antibiotic policies in hospitals which can be implemented, as early as possible.

6. Diagnostic Methods pertaining to antimicrobial Resistance Monitoring

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 BACKGROUND

1. Aims of the National Antimicrobial Policy

a) Understanding emergence and spread of antimicrobial resistance and the factors

influencing it

b) Establish a nationwide well coordinated antimicrobial program with well defined

and interlinked responsibilities and functions of different arms of the program

c) Rationalizing the usage of available antimicrobials

d) Reducing antibiotic selection pressures by appropriate control measures

e) Promotion of discovery of newer and effective antimicrobials based on current

knowledge of resistance mechanisms

f) Rapid and accurate diagnosis of infections and infectious diseases

1.1 Action points

General

1. Establish government commitment and support for nation-wide antimicrobial

program and within it the policy & set up national focal point for collaborations
& compilation.

2. Establish a National Alliance for prevention and control of antimicrobial

resistance

3. Institute a surveillance system that captures the emerging resistance, seeks and
envisions trends in it’s spread and correlates with utilization of antimicrobial
agents in community as health care set ups

4. Promote rational usage of antimicrobial agents

5. Strengthen infection prevention and control measures- healthcare associated and

community based

6. Support research in developing newer antimicrobial agents and improving usage

of available ones, based on pharmacological properties

7. Educate, train and motivate all stake holders in rational and appropriate usage of
antimicrobials and its regulation

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 8. Establish a Quality System and a National registry for Antimicrobial resistance
for bacteria, fungi and viruses at national focal point.

9. Co-development of antimicrobial agents with pharmaceuticals and leaving the

distribution, sales and promotion with the government

1.2 Implementation

1. Establishing a Surveillance Program

- Establish that all Hospital/ health care set up should have an Infection control
officer with well defined role and responsibilities

- Formation of a Local Infection control team

- Protocols on antimicrobial testing to be formulated and distributed in a

categorized manner- primary/secondary tertiary health care set ups/standalone
labs with/without automation

- Interpretive criteria- e.g. CLSI/BSAC etc. to be standardized as per our needs and
adopted nationwide

- Software generation for data feeding and analysis

- Collection of Data from Microbiology laboratory for both health care setups and
community

- Collection of Data from Pharmacy for both health care setups and community

- Collection of Data from pharmaceuticals-sale by distributors and sale by retailers

to be compared

- Quality Control programs to be promoted and adopted EQAS to be set up at well

established institutes

2. Promotion of Rational Usage of Antimicrobials

A. Personnel involved:

- Local hospital/health care setup Infection prevention and Control Officer and
Infection Control professionals

B. Action points

- Local health care set up Antimicrobial policy to be drawn by each health care
setup

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- Training modules on rational prescription to be created

- Training of Undergraduate and postgraduate medical, dental, nursing, veterinary

and pharmacy

- Training and awareness of General Practitioners and Specialists

- CMEs and workshops for all concerned

- Banning non therapeutic usage in animals and farms

- Pharmacists involvement

- Ban over-the-counter (OTC) sale of antimicrobials - Schedule H1

- Adherence on all levels to be sent in annually to the State director who shall put
this data to the central director

3. Infection Prevention and Control Program

Establish and Strengthen Infection Control Programs

- In both Health care set ups

- Infection Control Plan and policy for tertiary care hospital

- Infection control Committee to be set up in all health care institutions

- Infection Control Team

- Standard Operating Procedures (SOPs)

- Immunization and vaccination of vaccine preventable diseases

4. Research in Antimicrobials

- Government sponsored, public-private partnership (PPP) model or pharmaceutical

industry collaboration with govt. and private health care setups

- Budget allotment, grants to be set aside

- Community based research

- Health care setup based research

- Veterinary research

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- Agriculture, fisheries, farms to be included

- Rapid diagnostics researched and promoted

- Regulatory mechanisms to be in place for prioritizing research

- National Commitment in the form of Antimicrobial Policy and later on legislation

Formation of Advisory Body

- Formation of Steering Committee under the advisory body

- Targets for all involved to be set up for tertiary care hospitals Deadlines to be
formulated and implemented

- Software to be generated & evaluated

5. Monitoring and evaluation

QC checks
Audits
Feedbacks to Advisory body
Review of Action Plan annually
New actionable for implementation to be developed regularly & give feed back

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ToR-1: Review the current situation regarding manufacture,
use and misuse of antibiotics in the country
The quality of the drugs imported, manufactured and sold in the country is regulated
under the provisions of Drugs and Cosmetics Act, 1940 and Rules made there under. The
Act visualize the regulatory control over the drugs imported in to the country by the
Central Government while the manufacture, sale and distribution of drugs is primarily
regulated by the State Drug Control Authorities appointed by the State Governments.
The manufacture and sale of the drugs is regulated through a system of licensing and
inspection by the Licensing Authorities.

The Central Drugs Standard Control Organization (CDSCO), headed by the Drugs
Controller General (India) in the Directorate General of Health Services, is concerned
with the regulatory control over the quality of drugs, cosmetics and certain notified
medical devices under the Drugs and Cosmetics Act, 1940 and rules made there under.
The organization has its head quarters at Food and Drug Bhawan, Kotla Road, Near ITO,
New Delhi-110002 and has six zonal offices, two sub zonal offices, seven sea
ports/Airports offices and six laboratories under its control.

1.1 Functions of CDSCO

a) Approval of new drugs including vaccines to be introduced in the country.

b) Permission to conduct clinical trials.

c) Registration and control on the quality of imported drugs and notified

medical devices.
d) Institutionalise regulatory measures and recommend amendments to the
Drugs and Cosmetics Act and Rules made there under.

e) Prescribing regulatory procedures and standards for drugs, cosmetics,

diagnostic reagents and medical devices.

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 f) Approval of License as Central License Approving Authority for
manufacture of large volume potentials, sera and vaccines, biotechnology
products, medical devices and operation of blood banks and manufacture
of blood products.

g) Coordinating the activities of the States and advising them on matters

relating to uniform administration of the Act and Rules in the country.

State Drugs Control Organization is appointed by the State/Union Territory Governments

to regulate the manufacture and sale of Drugs and Cosmetics.

1.2 Functions of State Drug Control Authorities

a) Licensing of Manufacturing Site for Drugs including API and Finished
Formulation

b) Licensing of Establishment for sale or distribution of Drugs

c) Approval of Drug Testing Laboratories

d) Monitoring of Quality of Drugs and Cosmetics marketed in the country

e) Investigation and prosecution in respect of contravention of legal

provision

f) Recall of sub-standard drugs

1.3 Mechanism for Enforcement of the Act in Respect of Sale and

Manufacture of Drugs

The manufacture and sale of drugs is a licensed activity under the Drugs and Cosmetics
Act, 1940 and the licensees are required to comply with the provision of the Act and the
conditions of the licence. The Act specifies offences and penalties for violations of the
provisions of the Act.

The licences for sale of drug (wholesale or retail) are granted by the State Licensing

16
Authorities. The licences are required to comply with the condition of licence as provided
under Rule 65 of the Drugs and Cosmetics Rules. Some of the salient conditions are as
under:
I. The supply, otherwise than by way of wholesale dealing of any drug
supplied on the prescription of a Registered Medical Practitioner should be
effected only by or under the personal supervision of a registered
pharmacists.

II. The supply of any drug on a prescription of a registered medical

practitioner should be recorded at the time of supply in a prescription
register specially maintained for the purpose and the serial number of
entry in this regard shall be entered on the prescription. The following
particulars should be entered in the register-

a) The date of supply.

b) The name and address of the prescriber.
c) Name and address of the patient.
d) The name of the drug or preparation and the quantity.
e) Batch number and date of expiry.
f) Signature of the registered pharmacists.

The licences should maintain an Inspection Book to enable an Inspector to record his
impression and defects noticed.

Schedule H of the drug provide a list of the drug which are required to be sold on the
prescription of a registered medical practitioner and the manufacturer is required to label
the drug with the symbol Rx and with the following words:

‘Schedule H drug - warning: To be sold by retail on the prescription of a Registered

Medical Practitioner only’.

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The Drugs and Cosmetics Act provide penalty for manufacture, sale etc. of drugs in
contravention in Act or the Rule made there under. Drug Inspector appointed under the
Act is empowered to institute prosecutions in respect of breaches of the Act and Rules
there under.
Schedule M to the Drugs and Cosmetics Rules provides requirements for Good
Manufacturing Practices and requirements of plant and equipment for manufacture of
drugs. It specify in detail the requirements of premises, surroundings, personnel,
sanitation, storage of raw materials, documentation and records, self inspections and
quality control systems and site master files etc. The manufacturer should comply with
the requirements of Schedule M under the conditions of the license.

The manufacturer should provide and maintain adequate staff, premises, plant and
machinery for manufacture of drugs under the conditions of license for manufacture of
drugs. He should maintain records of manufacture including the testing of raw material
and finished products. Each batch of the product should to be tested by the manufacturer
either in their quality control laboratory or any laboratory approved by the Licensing
Authority before releasing the product into market.

A Drug Inspector appointed by the respective Governments should to inspect not less
than once a year all establishment licensed for manufacture or sale within the area
assigned to him and to satisfy himself that the conditions of license are being observed.
He may draw samples of a drugs or cosmetics from the manufacturing or sale premises,
where he has reason to doubt the quality of drug, in a prescribed manner and send them
for test and analysis to the Government analyst to check the quality.

The manufacturer should allow an inspector to inspect all registers and records
maintained by him and to take samples of manufactured products, if required, and
provides such information as required for the purpose of ascertaining whether the
provisions of the Act and Rules there under have been observed. The inspection may be
conducted by one or more inspectors to examine the premises, plant, appliances and
process of manufacture, professional qualifications of technical staff and capability of the
manufacturer to comply with the requirements of Good Manufacturing Practices and

18
requirements of plant and equipment before a license is granted.

1.4 Proposed Actions to monitor Sale of Antibiotics

 Schedule H of the drug and cosmetics act contains a list of 536 drugs
which are required to be dispensed on the prescriptions of a registered
medical practitioner. In order to have separate regulation to check
unauthorized sale of antibiotics, a separate schedule as Schedule H1 may
be introduced under the Drugs and Cosmetics Rules to regulate sale of
antibiotics exclusively. Corresponding provisions under the Rules could be
framed for their implementation. A provision could be incorporated for
spot suspensions /cancellation of the sale licence for contravention of the
provision of Schedule H1. Drug Inspectors in the Zonal and sub-zonal
offices of CDSCO along with the State Drug Inspectors may conduct
surprise raids at the chemist shops to ensure that the provision of the
Drugs and Cosmetics Rules especially in respect of Schedule H1 are
strictly complied by the licensees.
 A system of colour coding of third generation antibiotics and all newer
molecules like Carbapenems (Ertapenem, Imipenem, Meropenem),
Tigecycline, Daptomycin may be put in place restricting their access to
only tertiary hospitals.
 Appropriate steps should also be taken to curtail the availability of fixed
dose combination of antibiotics in the market, by and large combinations
should be discouraged except for naturally interactive ones like Co-
trimoxazole, Amoxyclav, etc.
 A similar review needs to be carried out on the composition of topical
antibiotics
 The drug testing laboratories in the country should be strengthened in
terms of infrastructure, number and also training of drug inspectors.

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  Incentives should be given to pharmacies for not selling antibiotics
without prescription and appropriate regulation for the same should be
formulated.

1.5 Proposed action for development of newer antimicrobials

 The universities and prominent research institutes in the country should be

encouraged by appropriate incentives to develop newer antimicrobials. In
this regard, a National Technical Advisory Group on development of
Newer Antimicrobials may be established.

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ToR-2: Design for creation of a National Surveillance System
for Antimicrobial Resistance

2.1 Background:
Antimicrobial resistance in pathogens causing important infectious diseases is a matter of
great public health concern globally, as well as in India. A major factor responsible for
this is the widespread use and availability of practically all antimicrobials over the
counter for human as well as animal consumption.

Though, there are definite policies / standard treatment guidelines for appropriate use of
antimicrobials in specific national health programmes e. g. RNTCP (Revised National
Tuberculosis Control Programme), NACP (National AIDS Control Programme),
NVBDCP (National Vector Borne Disease Control Programme), the same are not
available for other diseases of public health importance like enteric fever, diarrhoea /
dysentery, pneumonia, etc.

Reliable Indian data on antimicrobial resistance (AMR) for important pathogens of

public health importance is an essential pre-requisite for developing appropriate
guidelines for use of antimicrobials. Currently, there is no accepted national database of
antimicrobial resistance in different pathogens except for those where there is a specific
national health programme.

Despite many microbiology laboratories (in both public as well as private sector)
performing routine antibiotic susceptibility testing (AST) of at least bacterial pathogens,
the data is neither analysed regularly nor disseminated for use by clinicians / public
health experts / programme managers. Quality control and data sharing by these
laboratories are other important issues that need attention.

Analysis of the AST results from laboratories in India reveals an increasing trend of
development of resistance to commonly used antimicrobials in pathogens of public health
importance like Salmonella spps, Shigella spps, V. cholerae, Staph aureus, Gonococcus,
Meningococcus, Klebsiella spps, Mycobacterium tuberculosis, HIV, and others.

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There are a few examples of successful networking of laboratories carrying out
antimicrobial sensitivity testing of gonococcus in the country under the GASP
(Gonococcal antimicrobial susceptibility programme) with regional STD laboratory at
Safdarjung Hospital, New Delhi being the referral laboratory.

Evidence from the experience of countries like UK, Sweden and other European
countries shows that a national plan on antimicrobial resistance monitoring has shown to
impose restrictions on the injudicious use of antibiotics. It shall help to contain the
problem of AMR in the country to a large extent.

2.2 Types of AMR surveillance:

Three types of surveillance can be done for AMR - Comprehensive surveillance,

sentinel surveillance and point prevalence studies. Comprehensive AMR surveillance
though giving actual estimate of AMR burden, includes the study of the whole population
at risk / under study and needs the involvement of a large number of laboratories which is
not practical specially in our country. Point prevalence studies are useful for validation of
the representativeness of the surveillance data. Sentinel surveillance studies have been
found to be quite useful in such situations.

Sentinel surveillance for AMR

Though it provides only indicative data, the same can be extrapolated to the rest of the
population. It is also a suitable mode of surveillance when prolonged and detailed data is
needed. This seems to be the best approach for our country. One or more central
institutions under the Ministry of Health may be the coordinating centre(s) at the national
level depending on the size of the laboratory network.

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2.3 Design for AMR surveillance

2.3.1 Identification of the pathogens / diseases of public health

importance for surveillance

Following bacterial pathogens isolated from different human infections / anatomical sites
e.g. Blood stream infections, Skin and Soft tissue and surgical site infections, Respiratory
infections, Gastro intestinal tract infections and Urinary Tract Infections (UTI) may be
included in a phased manner for the purpose of AMR surveillance.

First phase (Non fastidious bacterial pathogens)

1. Following Gram Negative Bacilli (should address Extended Spectrum -

lactamases [ESBLs] and Metallo -lactamases [MBLs], including NDM-1)
may be included.
 Pseudomonas aeruginosa
 Acinetobacter spps
 Klebsiella pneumoniae
 Esch. coli

2. Staphylococcus aureus (should address Methicillin Resistant Staph aureus

- MRSA) Second phase in addition to the above the following organism surveillance
will be added:
 Enterococci specially VRE (Vancomycin Resistant Enterococci)
 Salmonella , Shigella sp and Vibrio cholerae
 Streptococcus pneumoniae, and H. influenzae

2.3.2 Creating a network of AST laboratories

Surveillance networks at different levels of healthcare system should be set up
with unified protocols and SOPs, at least up to district level. Later on it may
be expanded up to Peripheral Health Facility level also to obtain community
based data on AMR. It was felt that since at the moment the basic
infrastructure for AMR surveillance does not exist at the district level in the

23
 country, it may not be feasible to carry out AMR surveillance at the district
level to begin with. However, efforts should be made to develop the
infrastructure at the district level in a phased manner.
 The laboratory should preferably be a part of a large hospital having different
types of facilities Outdoor and Indoor, ICU, Operation theatres, etc.
 Identification of microbiology laboratories based in medical institutions or
medical colleges across the country with an existing infrastructure for AST
testing to generate data on the identified bacterial pathogens. The laboratory
must have qualified microbiologists well versed with antimicrobial
susceptibility testing techniques and should be carrying out AST for at least
last 5 years. The laboratory must also be conversant with and following the
quality control procedures for AST. Since at the moment very few laboratories
in the country are NABL accredited specially in the public sector, this need
not be the criterion for selecting the laboratories for the network at the
moment and however, the network laboratories should be encouraged for
NABL accreditation later on in a phased manner.

 We may also identify a central reference centre for Characterization and

epidemiological study of resistance factors in microbial pathogens
 In the first phase, the following three central Govt. Hospital in Delhi will be
included for AMR surveillance.

 Sucheta Kriplani Hospital (SKH) & Lady Hardinge Medical College

(LHMC), New Delhi
 Dr Ram Manohar Lohia (RML) Hospital, New Delhi
 Vardhman Mahavir Medical College (VMMC) and Safdarjung
Hospital, New Delhi
 Subsequently, in a phased manner, the surveillance network should be linked
with existing special networks such as one for resistance monitoring in
malaria, pneumonia or low-respiratory tract infection, tuberculosis and HIV
etc.

24
2.3.3 Standardize methodology for microbial identification and AST

 Develop standardized AST (Antimicrobial Susceptibility Testing) methodology

including identification of antimicrobials to be tested and reported for each
identified pathogen for AMR surveillance

 Develop detailed Standard Operating Procedure (SOPs) for microbial

identification and AST based on current CLSI (Clinical Laboratory Standards
Institute) guidelines; the same may be made available to all the testing
laboratories.

 Though the network laboratories would be recommended to do the AST by Disc

diffusion test using Modified Kirby Bauer method ,those following other
standard methods e.g. Stokes method or doing MIC testing by methods like ‘E’
test, automated systems may also be included provided they are following
appropriate Quality control measures. Laboratories should also be having
expertise to do MRSA, ESBL and Carbapenemase (Modified Hodge test /
Imipenem + EDTA E test) testing. Carbapenem resistant isolates may be stocked
and sent to a designated central laboratory for further molecular analysis (For
NDM-1 etc). The identified central laboratory should be equipped with facilities
to analyze mutations and Single Nucleotide Polymorphisms (SNPs) along with
deep sequencing and DNA fingerprinting to identify strains with differential
activities.

 DNA-based technologies should be included wherever possible at it will not only

identify the organism, but will also give a glimpse of resistance.

 Reporting of results: AST results should be reported on a predestined

format/template in terms of percentage sensitivity/resistance/ intermediate
sensitivity with a clear denominator. Only isolates numbering more than 10
should be used for the purpose of reporting, the data should also indicate the
location and the site/source of the pathogen. Attempts should also be made to
incorporate the history of use of antimicrobials in the given subject. The data can

25
 be entered using excel sheet on a predesigned template taking into account the
following parameters to generate surveillance data of OPD,WARD &ICU with
validity period:
 1. Identify organism

 2. Segregate as per Grams Reaction: Gram positive/ Gram Negative organism

 3.Source : Blood, Urine, Respiratory, Pus / body fluids

 4. Percent sensitivity to the CLSI designated antibiotics

 The above data is used in formulating the surveillance results as per the following
template:

Hospital surveillance data Validity of these data: Dec x + 1 yr

(Jan-Dec of x year)
S. No Most % prevalence S. No. Most sensitive 
common antibiotics in
pathogens descending order

1   1  

2   2  

3   3  

4   4  

5   5  

2.3.4 Strengthen Quality Systems in the network laboratories

 Standardization of lab variables like qualities of antibiotic discs, different

methodologies, different interpretation criteria, etc will help to generate reliable
data on AMR.

26
  Institution of uniform testing methodology supported by availability of quality
reagents and a robust quality assurance system (internal quality control and
external quality assurance).

 EQA (External Quality Assurance) for the network laboratories in the country
should be established & this work can be assigned to one or more reputed
institutions in the country who are already having infrastructure for quality
assurance for AST testing

2.3.5 AST Data analysis

 Many laboratories are carrying out the analysis of AMR data manually or using
Excel software. Few laboratories use WHONET 5 for AST data reporting and
analysis.
 The network laboratories should compile & analyzed data on regular basis & send
the data quarterly to designated central coordinating institution.
 There is a need of developing a user friendly tool / software for AST data
compilation and analysis.

2.3.6 Dissemination of AMR data

 Development of a system of regular and timely dissemination of AST data to the

participating labs, clinicians and policy makers is important.
 The AMR data generated by the respective network laboratories should be sent to
the coordinating centre, regularly on a quarterly (once in 3 months) basis.
 The data to be sent electronically in a predefined template.

 The data shall be collated and analyzed by the coordinating institution and
subsequently made available to the policy makers and other stake holders.

2.3.7 Development of National Repository of Bacterial strains / cultures

There is also a strong need to establish a national repository of standard bacterial strains
required for quality control of AST as well as repository of drug resistant strains
(including molecular components like DNA / plasmids) isolated from the different

27
network laboratories. Already, Institute of Microbial technology (IMTECH), Chandigarh
has the requisite infrastructure and expertise to do the same. The responsibility can be
assigned to this institute for maintaining the repository of cultures and also supplying the
same to the network laboratories as per the need/demand. In addition to IMTECH, other
institutes can be identified for the purpose.

2.4 Operationalization of the Action plan for AMR surveillance:

2.4.1 A one (1) day sensitization workshop for the senior microbiologists of
the network laboratories

2.4.2 A 2-3 days training workshop for junior microbiologist/ data reporting
personnel on various aspects of AST specially quality control and data
analysis/ transmission.

2.4.3 Followed by regular monitoring and review meetings once in 6/12 months

2.5 Research in AMR Surveillance

2.5.1: New and simple surveillance tools with the capability to detect AMR at the
lowest capable health centre should be developed and its ability to track the
infection should be established.

2.5.2: All surveillance activities should be linked with epidemiological studies

particularly surveillance around relevant vaccination programs.

2.5.3: A National Health Policy Unit should be entrusted with analysis of the
surveillance data and provide advisory for framing of policies for use of antibiotics
according to region, nation or hotspots.

28
ToR-3: Studies documenting prescription patterns and
establishing a monitoring system for the same

3.1 Introduction
The current worldwide increase in antimicrobial resistance and, simultaneously, the
downward trend in the development of new antibiotics have serious public health and
economic implications. The increased antimicrobial resistance (AMR) is a result of many
factors, but the foremost cause is the overall volume of antibiotic consumption,
particularly for indications that do not require such therapy.
About 80% of antibiotics are used in the community and the rest are used in hospitals. It
is estimated that 20-50% of all antibiotics use is inappropriate, resulting in an increased
risk of adverse side effects, higher costs of therapy and higher rate of antimicrobial
resistance of community pathogen.

3.1.1 Need for surveillance of antibiotic use in the community

Enhanced antibiotic surveillance is one of the strategies is one of the strategies to guide
control of antibiotic overuse or misuse. This is because the ability to study population-
based pattern of antimicrobial use provides a more comprehensive understanding of how
the physician and patient use these agents. Promoting appropriate use of antibiotics
through various interventions will help stop unnecessary prescribing and misuse of
antibiotics. For suitable interventions to be carried out in the community it is essential to
know the extent of antimicrobial use and pattern of antimicrobials in the population.
In a number of developed country settings, extensive programmes have been developed
to track patterns of AMR and antibiotic use over time. Most developing countries do not
have systems for routinely monitoring AMR. Measuring AMR rates on the basis of
hospital isolates and having in-patients antibiotic policy as is presently done in few
hospitals, is inadequate for understanding the burden of increasing AMR on the
community.

29
3.1.2 Situation in India
Data on the use of antimicrobial agent at the population level are lacking in India as we
do not have any database for the consumption of antimicrobials (antibiotics) in the
community. This is mainly because in India, unlike many developed countries,
prescriptions are kept by the patient and not with the pharmacist and antibiotics may be
obtained with or without a prescription. Therefore, determining consumption of antibiotic
use or trends in antibiotic use is problematic, more so in private sector, since there are no
prescription records. Hence, there was an utmost need to develop a methodology that can
measure consumption and trends in antibiotic use in the community.

3.1.3 Methodology for surveillance of antibiotic use in the community

Recently a methodology was established for surveillance of antibiotic use in the
community for out-patients. The methodology used was bulk purchased data and
conducting exit interviews of patients buying any antibiotic at private retail pharmacies in
New Delhi.1 The methodology was replicated and extended in public and private sector.
This study of surveillance of antibiotic use in the community (December 2007-
November 2008) utilized the established methodology of patient exit interviews at three
types of facilities: 20 private retail pharmacies, 10 public sector facilities, and 20 private
clinics to obtain a complete picture over a year in New Delhi. The Anatomical
Therapeutic Chemical (ATC) classification and the Defined Daily Dose (DDD)
measurement units were assigned to the data. 39% of the patients had encountered with at
least one antibiotic at private retail pharmacies and public facilities whereas 43% of
patients visiting private clinics were prescribed antibiotics. Consumption pattern of
antibiotics were similar at private retail pharmacies and private clinics where
fluoroquinolones, cephalosporins, and extended spectrum penicillins were the three
commonly prescribed groups of antibiotics. At public facilities, fluoroquinolones,
penicillins, macrolides, tetracyclines, cephalosporins and co-trimoxazole group of

1
Kotwani A, Holloway K, Chaudhury R R. Methodology for surveillance of antimicrobials use among out-patient in Delhi. Indian
Journal of Medical Research 2009; 129: 555-60.

30
antibiotic class were used in this descending order. Newer members from each class of
antibiotics were prescribed.

Based on this methodology and experience in conducting drug utilization and rational use
of medicines studies, surveillance of antimicrobials will be conducted in selected
hospitals of India in a phase manner. The first phase of the study will be conducted in
three tertiary care hospitals under central government in Delhi.

3.2 Objectives
 To study the consumption of various antibiotics in tertiary care public hospitals in
Delhi under central government
 To study the trends in antibiotic use in these hospitals of Delhi
 Data generated will be used for intervention studies for rational use of antibiotics.
 Later on, the network should also include peripheral heath facilities as well as
pharmacies to obtain community based data on antimicrobial usage.
 Auditing of the pharmacies in the hospital, prescription of the practitioner as well
as the pharmacies in the cities, districts and villages should be audited through a
random selection basis.

3.3. Methodology
The first phase of the study will be conducted in NCT, Delhi and at tertiary care level of
health care. Study will have a multi-disciplinary advisory committee of experts who will
meet at regular intervals and their inputs will be helpful for implementation of the study.

3.3.1 Facilities included:

1. Sucheta Kriplani Hospital, New Delhi

2. R. M. L. Hospital, New Delhi

3. Safdarjung Hospital. New Delhi

3.3.2 Study design and duration

31
Prospective study for approximate 3 months but will be continued as surveillance.
Fourth month data will be analysed for overall consumption and trends of antibiotic use.
3.3.3 Data collection methodology
In-patients
Consumption of antibiotics in various departments: Data on antibiotic consumption will
be collected from all the important departments like, medicine, surgery, gynaecology,
orthopaedics, ICU, etc.
a. Data collection from medical store: Total consumption of all antibiotics
used/consumed will be collected every month from in-patient indent/issued to
each department.

b. Prescription data: Prescription audit of approximate 10% of total in-patient in

each department for each month will be done. For this data collectors will
randomly pick 10% of prescriptions for the previous month and note down the
details including the condition for which antibiotic was prescribed.

Outcome measures: Consumption of each group of antibiotic will be defined in terms of

total number of DDDs using the WHO ATC/DDD system2. Consumption will be
expressed as DDD/100 bed/day.
Out-patients
a. Exit interview: Exit interviews will be carried out at the pharmacy of public
hospital and for each special clinic operating in the public hospitals.

For private hospital data collectors will do exit interview for each speciality in their OPD
days and time.
Exit Interviews – Exit interviews of the patient receiving any antibiotic at the
chosen hospital/department/special clinic would be done. Two trained data
collectors will carry out exit interviews outside the pharmacy of hospital. One
counts all the patients visiting the pharmacy during the period of data collection

2
World Health Organization. The anatomical therapeutic chemical classification system with defined daily doses
(ATC/DDD) Norway: WHO, 2004. Available at
http://www.who.int/classifications/actddd/en/

32
and checked whether they receive any antibiotic medicine. If the prescription has
any antibiotic she/he will refer to the other data collector standing/sitting nearby
and will interview the patient receiving an antibiotic as referred by his/her
colleague. A pre-designed Performa will be used to collect data. The data
collected would be
 Total number of drugs prescribed in the prescription
 Number of antibiotic(s) in the prescription
 Name of the antibiotic as prescribed
 Antibiotic prescribed as generic or trade name
 Strength, dose and duration of antibiotic prescribed
 Total amount prescribed
 Total amount purchased/dispensed
 Name, dose and duration of antibiotic dispensed
 Nutritional (body weight)/ HIV status (anonymous) etc.

Thirty exit interviews per month from each special clinic would be done and from
general pharmacy 600 exit interviews will be done. For this required number of
exit interviews to be conducted data collectors should visit 4-5 times the same
facility/clinic to get a comprehensive picture.
Outcome measures: Percentage of patients receiving antibiotics would be found
out. Results would be expressed as DDD/100 patients. The denominator for exit
interviews data is the number of patients attending the pharmacy/clinic during the
time taken to do the target number of exit interviews.

3.3.4 Data entry and data analysis

A sophisticated software programme will be developed for entering the data and
double entry will be done to check for errors.

Data obtained will be analyzed to show monthly patterns of use and consumption
of various group of antibiotic in all three public hospitals. Data will be compared

33
between hospitals, between various departments using different methodologies. A
detailed secondary analysis will be done to find trends of antibiotic use.
A meeting to disseminate the results of the study will be held at the end (4
months) for all the stakeholders and participants of the study.

3.3.5 Implementation
Govt. of India, Ministry of Health will be coordinating the study with advisory
committee/ task force .Project coordinator and the surveillance team set up for the
purpose in the selected tertiary care hospitals will implement the surveillance of
antimicrobials.
3.3.6 Personnel required for the project
 Project coordinator

 Research Officer

 Office assistant 1

 Data collectors - 6

 Office attendant 1

 Software computer programmer

 Bio Statistician

 Data entry personnel

3.3.7 Partners from each hospital

 M. S. of each hospital

 Officer who will coordinate the study from each hospital

 Sister-in Charge

 Pharmacy in-charge

34
ToR-4 : Enforce and Enhance regulatory provisions for
use of antibiotics in human, veterinary and industrial use

4.1 Regulatory provisions for use of antibiotics in veterinary and

industrial use
In livestock production, antibiotics are dispensed to animals for a number of different
reasons viz. therapeutic treatment, disease prophylaxis and growth promotion. The
administration of antibiotics against bacterial populations is a significant driving force for
selection of resistant forms of bacteria, which can spread from one organism to another.
There is therefore an important question of whether the use of antibiotics in animal food
production poses a threat to human health. In particular, the worry is that resistant forms
of bacteria may spread from animals and/or the environment (ground water / surface
water / soil) to humans.

4.1.1 The effects of use of antibiotics in food animals on human health

There is a broad scientific consensus that the use of antibiotics in livestock, on some
occasions, has detrimental effect on human health. The use of the antibiotic avoparcin as
a growth promoter in food animals in Europe resulted in the development and
amplification of Vancomycin-Resistant Enterococci (VRE) and subsequent colonization
in human intestine. Vancomycin-resistance is a cause of concern because vancomycin is
used as a last-line antibiotic for some hospital-acquired infections due to enterococci and
staphylococci that have become resistant to the more commonly used antibiotics.

The use of antibiotic enerofloxacin was approved for use in food production animals in
many countries. The use of this antibiotic in food animals has resulted in the
development of ciprofloxacin-resistant strains of Salmonella spp. and Campylobacter
spp. These resistant bacteria have subsequently caused human infections. The use of
animal feed supplements with the antibiotic tylosin has led to the development of

35
erythromycin-resistant streptococci and staphylococci not only in the animals but also in
their handlers.

WHO held a conference on use of antimicrobials issue and concluded that there is
sufficient evidence showing that “the major transmission pathway for resistant bacteria is
from food animals to humans” and has led to “increased frequency of treatment failure
(in some cases deaths) and increased severity of infections”. In their recommendations,
WHO specifically called for stricter legislation to minimize antimicrobial usage in
livestock because as it may pose a significant risk to the human health.

In 1997, the WHO’s report on `The medical impact of antimicrobial use in food animals’
highlighted several causes where transfer of resistance from animals to human had
occurred. It can happen through: direct contact with animals; the consumption of meat;
drinking contaminated water or the transfer of genes between animal and human bacteria.
The best known examples are the food borne pathogenic bacteria viz. Salmonella and
Campylobacter and the commensal bacteria like Enterococcus. Scientific data has shown
that resistance of these bacteria to routine antimicrobial treatment in humans is often a
consequence of the use of certain antimicrobials in agriculture.

4.1.2 International Regulations

Driven by a concern for human health, Denmark initiated in 1995 a process to end the use
of antibiotics as growth promoters in livestock production. This process involved both
voluntary and legislative elements, which led to a total ban on use of antimicrobial
growth promoters in Denmark since the end of 1999.

Recognizing that antibiotic-resistance poses such a serious health threat, the European
Union (EU) has banned the use of growth promoting antibiotics (specially those which
are also used in human medicine) in animal feed. In December 1997, the EU banned the
Animal Growth-Promoter (AGP) avoparcin in all its member states. In July 1997, the
EU banned another four AGPs (tylosin, spiramycin, bacitracin and virginiamycin)
because they belonged to classes of antimicrobial drugs used in human medicine.

36
Although the United States has yet to pass such a far-reaching policy decision about
antibiotics in livestock production, the Food & Drug Administration (FDA) did ban one
class of antibiotics used in poultry. Based on studies showing that high levels of
fluoroquinolones in poultry led to drug resistance in humans, the FDA finally decided in
2005 to prohibit the use of fluoroquinolones in animal husbandry

4.1.3 Indian Scenario

In India, the antibiotics are used widely in food animals as growth promoters and to
prevent and treat infections. Non-therapeutic usage of antibiotics has been especially
common in poultry production. However, cuurently there is no regulatory provision
regarding the use of antibiotics in livestock.

The Prevention of Food Adulteration Rules, 1995-part XVIII: Antibiotic and other
Pharmacologically Active Substances, regulates the use of antibiotics and other
pharmacologically active substances as given below:

The amount of antibiotics for sea foods including shrimps, prawns or any other variety of
fish and fishery products, shall not exceed the prescribed tolerance limit (mg/Kg[ppm])
as mentioned below:

a. Tetracycline (0.1)
b. Oxytetracycline (0.1)
c. Trimethoprim (0.05)
d. Oxolinic acid (0.3)

The use of any of the following antibiotics and other pharmacologically active substances
shall be prohibited in any unit processing sea foods including shrimps, prawns or any
other variety of fish and fishery products: All Nitrofurans, Chloramphenicol, Neomycin,
Nalidixic Acid, Sulphamethoxazole, Aristolochia spp. and preparations thereof,
Chloroform, Chlorpromazine, Colchicine, Dapsone, Dimetridazole, Metronidazole,

37
Ronidazole, Ipronidazole, other Nitroimidazoles, Clenbuterol, Diethylstilbistrol,
Sulphonamide drugs, Fluoroquinolones and Glycopeptides

4.2 Proposed Action Plan:

4.2.1 Establishment of inter-sectoral coordination committee comprising

experts from the following agencies:
 Central Council for Scientific and Industrial Research (CSIR) (Chairperson: DG,
CSIR)
 Ministry of Health and Family Welfare
 Ministry of Agriculture
i. Indian Council for Agricultural Research
ii. Department of Animal Husbandry
 Food Safety and Standards Authority of India (FSSAI)
 Agricultural and Processed Food Products Export Development Authority
(APEDA)
 Marine Products Export Development Authority (MPEDA)
 Drug Controller General of India (Member Secretary)

4.2.2 The inter-sectoral coordination committee may undertake the

following activities:
 Review of available data regarding the use of antimicrobials.
 Generation of data by undertaking studies on the use of antimicrobials as Animal
Growth-Promoters.
 Specify the antibiotics for use in Livestock
 Review of current laws on use of AGPs in other countries and feasibility of their
implementation in India.
 Development of regulations on usage of antimicrobials in poultry and other
animals as well as the requisite labelling requirements in food.

38
  Review of Prevention of Food Adulteration Rules, 1995-part XVIII: Antibiotic
and other pharmacologically active substances, if required, to enhance the scope
(inclusion of other food products and antimicrobials).
 Any other related issue.

4.3 Regulatory provisions for use of antibiotics in Human use

The regulations regarding manufacture, use and prevention of misuse of antibiotics for
humans and animals in India are governed by the Drug Controller General of India with
the help of State Drug Controllers.

The current situation regarding “manufacture, use, misuse of antibiotics in the country”
has been covered under ToR-I. The same also applies for the use of antibiotics in
livestock.

The recommendations made by the subgroup constituted for ToR-I, which is headed by
DCG (I) would also be applicable for human and animal component of ToR-IV.

39
ToR-5 : Specific intervention measures such as rational use of
antibiotics and antibiotic policies in hospitals

5.1 Rational Use of Drugs

Over the last 60 years, bacteria &in particular those pathogenic to humans have evolved
towards antimicrobial drug resistance. Antimicrobial resistance is an issue of great
significance for public health at the global level. Antibiotics are considered as wondered
drug, but its irrational use & often inappropriate prescriptions makes it as abused drugs
sometimes. The pathogens causing acute illness are showing resistance to antibiotics &
pose a great threat to public health. Thus it is a fact that wide spread practices of
medically ineffective and economically inefficient use of medicines has become a serious
public health threat in many countries, jeopardizing quality of care, wastage of limited
resources ,access to essential medicines and development of antibiotic resistance .

Despite of existing policies, programs in different countries in various stages of

implementation, sustainable effective interventions are lacking with significant impact in
many of the countries including some part of India.

Overuse, under-use, and misuse of medicines & antimicrobials remains a world wide
hazard, as has been reported in the literature - over 15 billion injections per year, half un-
sterile, many unneeded, 25-75% of antibiotic prescriptions inappropriate, 50% of people
worldwide fail to take medicines correctly (Health quick 2003).
Misuse and overuse of antibiotics, overuse and unsafe use of injections has been reported
in Southeast Asian countries. All over the world 30-60% of PHC patients receive
antibiotics which may be twice a s high as it may be clinically required. Large number of
viral URTI and diarrhoea are treated with antibiotics in the world and inappropriate use is
also being used in teaching hospitals all over the world.

40
Examples of irrational drug use are as follows:

 No drug needed e.g. unnecessary & ineffective antimicrobials or antidiarrhoeals

given instead of Oral Rehydration Solution.
 Unsafe drugs e.g. Analgin (Dipyrone) banned in most developed countries, is
used in many developing countries.
 Under use of available effective drugs e.g. ORS not used effectively.
 Ineffective drugs & drugs with doubtful efficacy e.g. unnecessary excessive use
of tonics & multivitamin preparations
 Incorrect use of drugs e.g. overuse of Injections
 Wrong drugs used in unwarranted situations

Rational use of drug involves using the correct drug with appropriate indication i.e. the
reason to prescribe the drug should be based on sound clinical consideration appropriate
drug should be administered keeping in mind the safety, suitability, efficacy and cost.
Apart from this the duration and administration of drug should also be done
appropriately. Drug administration should also take into consideration the chances of
drug reaction. Correct prescription and patient adherence to the treatment should also be
considered.

5.2 Interventions

 A mandated multi-disciplinary national body should be established to coordinate

medicines use policy
 Developing evidence-based clinical guidelines in a participatory way that are easy
to implement and reinforced by prescription audit, etc
 An essential medicines list should be developed
 To form a national drug and therapeutics committees
 Problem-based pharmacotherapy training should be undertaken at regular
intervals
 Continuing in-service medical education (CME) is a requirement for licensure of
health professionals

41
  Continuous supervision, audit and feedback should be done
 Independent medicine information to be coordinated by the pharmacist
 Public education about medicines
 Appropriate and enforced regulation by drug controller of India
 While procuring antibiotics, efforts should be made to procure generics only with
appropriate quality checks before bulk purchases.

The following three strategies should be followed to improve drug use:

 Educational strategy: Training, printing materials, media-based approach

discourage self medication by the general public.
 Managerial strategy: Monitoring & supervision, generic substitution, patient cost
sharing (economic incentives) etc
 Regulatory strategy: enforcement, sanction, drug withdrawal, market control etc

5.3 Protocol
To recommend specific intervention measures such as rational use of antibiotics and
antibiotic policies in hospitals which can be implemented as early as possible.
Intervention Measures:
 Formulation of antibiotic policy
 Education and Training of all prescribers
 Implementation of infection Control guidelines

5.3.1 Formulation & implementation of an antibiotic policy

With quality assured laboratory data in real time develop antibiotic policies that are
standard national / local treatment guidelines advocating evidence based immunotherapy
or combination therapy. This must include consideration of spectrum of antibiotics,
pharmacokinetics / pharmacodynamics, adverse effects, cost and special needs of
individual patient groups.

42
5.3.2 Formulation:

Step I:

 Compile Local Hospital data based. on AMR

 Site of infection

 Geographic Variations (ICUs / Wards / Surgical Site Infections etc.)

 Percent Distribution of organisms

 Percent Susceptibility to identified antibiotics

Step II:

Put the data in given template:

 Site of Infection, Type of Infection.

 Causative pathogens.

 Recent 12 month antimicrobial data.

 Capture pathogens contributing to 80-90% of infections.

 Capture the susceptibility of antimicrobials from highest to lowest.

 Pneumonia

 IAI

 UTI

 BSI

 SSTI

 Surgical Prophylaxis.

Step III

 Put in database, based on site of infection?

 Data will be separate for Ward and ICU isolates

43
  5 most common pathogens be identified and most antibiotics in decreasing order
of sensitivity also be identified. Refer ToR-2 (Page no. 19 to 21) For details

 Generate the Validity period (X+1yr)

Hospital surveillance data (Jan-Dec of X year) Validity of these data: Dec X+1yr

S. No Most % prevalence S. No. Most sensitive 

common antibiotics in
pathogens descending order

1   1  

2   2  

3   3  

4   4  

5   5  

5.4 Implementation:

Defining patient type: Do Risk Stratification for each patient’s type

TYPE 1 TYPE2 TYPE 3

Health Care No Yes Prolonged

Contact No Minimum Major invasive procedures
Procedures
Antibiotic Rx No in last 90 days Yes in last 90 days Repeat multiple antibiotics
History Elderly
Patients Young – No co- Few co-morbid Immuno-compromised +/-
Characteristics morbid conditions conditions many co-morbid conditions

44
Possible No MDRs ESBLs / MRSA ESBLs + Pseudomonas +
Causative Pathogens MRSA
Pathogen susceptible to
common
antibiotics

For example, an antibiotic policy for blood stream infections (BSI)

Note: Patient Type 4 can also be added in special circumstances where suspicion of
fungal (Candida) infection is highly suspect

5.4.1 Set up an Antibiotic Management Team (AMT)

This is a Multi disciplinary team with experts in: Infectious diseases, Internal medicine,
Intensive care, Surgery, Paediatrics, Clinical microbiology, Pharmacology and Hospital
pharmacy.

45
The functions of the AMT are

• Develop the hospital antimicrobial policy both from existing policy (if any) and
evidence based guidelines and adapt to suit local circumstances.

5.4.2 The policy should be for presumptive / empiric therapy and

prophylactic therapy
(i) Presumptive/ Empiric antibiotic policy

The policy should be simple, clear, non-controversial, clinically relevant, flexible

and applicable to day-to-day practice and available in user friendly format. It
should also include optimal selection dosage, route of administration, duration,
alternatives for allergic to first-line agents; adjusted dosage for patients with
impaired renal functions.
The policy should risk stratify patients if this has not been done by the
antimicrobial surveillance
Previous history of antimicrobials or current antibiotics along with patient co
morbidities may play a role in final prescribing.
Note: Case index ratio has not been addressed at present (will be done
subsequently).

5.4.3 The presumptive / empiric policy should set the levels for
prescribing antibiotics:
 First choice antibiotics: Can be prescribed by all doctors
 Restricted list of antibiotics: Only after permission from HoD or
AMT representative
 Reserve antibiotics: Only after permission from AMT member
Presumptive therapy only applicable for 48 hrs after that the therapy needs
to be converted into a definitive therapy (de-escalation step) based on
evidence whether clinical or microbiological. AMT should interact with
the unit that prescribes more than two antibiotics and satisfy them to the
correctness of the regimen.

46
5.4.4 Prophylactic antibiotic policy
Procedure for which antibiotic are needed should be posted in Operating Room with
Optimal agents, dosage, timing, route and duration of administration e.g. Inj Cefuroxime
1.5 gm I/V before induction of anaesthesia, repeat another dose if procedure extends
beyond 4 hrs.
Prophylactic antibiotics should be given for a short duration, free of side effects and
relatively inexpensive and should not be used as a therapy

5.4.5 De-escalation for targeted therapy should also be a vital aspect of

the policy after microbiology reports are available

5.5 Constructive feedback of policy prior to implementation

After formulation of the presumptive / empiric & prophylactic policies they should be
circulated to receive constructive feedback. Policy should be reviewed by respected peers
who are not the members of the AMT, but are also experts in the relevant field
.Ownership should be complete.

5.6 Monitor implementation: we may form Drug and Therapeutics

Committee which may carry out the following:

5.6.1 Basis for approval of new drugs: The DTC has to fix criteria for the approval of
new drugs. Those criteria include safety, efficacy, availability and cost of the medication.

5.6.2 Fixing of three brands per generic: The DTC may decide to keep a maximum of
three brands of an approved generic.

5.6.3 Banning of harmful drugs in the Hospital: The DTC can ban the use of few
harmful drugs like Phenylpropanolamine (PPA) and Nimesulide in the hospital.

5.6.4 Removal of irrational fixed dose combinations from the hospital drug list: The
committee can remove few irrational fixed dose combinations from the hospital drug list.

47
These combinations include the fixed dose combination of ampicillin with cloxacillin,
amoxicillin with cloxacillin etc.

5.6.5 Development of over the counter (OTC) drug list: Hospital DTC should develop
the OTC drug list for the Hospital. This OTC drug list should also contain the quantity to
be dispensed

5.7 Assess outcome of Intervention: as below

A monthly update of antibiotic consumption of a unit is sent with a comparison of

other units in the institute this highlights any excess, for e.g. a monthly update on
antibiotic prescribed can be shared with the doctors of their speciality:

Unit: Cardiology

 Your unit prescribed 117 DDD/100 bed-days

 Average for all specialties: 189 DDD/100 bed-days
 Average for your specialty: 133 DDD/100 bed-days
 3 % of units in this hospital prescribe fewer DDDs of antibiotics per 100 bed-days
than your unit
DDDs are a standardized measure of drug consumption used by WHO: They represent
the average daily maintenance dose of a drug used for its main indication in adults
Table 1. Breakdown of antibiotic use by class (in DDDs/100 bed-days). When your unit’s
prescribing rate for an antibiotic class is above the average for all units in this study, it is
shown in red

Your unit’s Average for all Average for

Antibiotic class
prescribing rate specialties Cardiology
Penicillins 7 1 1
Cephalosporins 29 89 26
BL BLIs 41 35 50
Quinolones 18 15 32
Aminoglycosides 4 20 4
Macrolides 9 7 12
Clindamycin 3 7 3
Carbapenems 4 6 2
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Glycopeptides 1 5 4
Figure 1 - The distribution of prescribing rates. The green is your unit and blue
rectangles represent other units in your specialty and the red rectangles represent all
units in other specialties of the hospital. Similarly this should be made for each unit at a
particular hospital
Note: Confidential: circulation to unit only

5.7.1 Update and revise

The policy should be updates every year based on local surveillance of antimicrobial
susceptibility data, clinical practice and local circumstances

5.7.2 Set prescription audit targets

5.8 Education

Train and educate doctors at all levels for usage of this antibiotic policy.
Ensure training on types of organisms in each type of infection and the ideal choice
should be in the form of weekly CMEs seminars etc., in the beginning of the launch of
the antibiotic policy.

5.9 Implementation of Infection Control Guidelines

Ensure Infection prevention guidelines to prevent cross transmission of resistant
pathogens (guidelines for good infection control practice and SOPs should be circulated
including waste disposal guidelines to prevent release of antimicrobials in the
environment through human excreta and other body fluids)

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After the IC guidelines are adopted regular point Surveillance Audit are essential aspects
to ensure implementation
 Preoperative prophylaxis: Surgeons should regularly follow up on feasibility of
not giving oral antibiotics on post-op day 2-5 after perioperative antibiotics on
day one.

 Audit: should be the collective responsibility of the members of the AMT. For
this the microbiologist of the hospital can take ward rounds at least once a week
and do spot or point surveillance.

 Cost related issues to be decided by the committee set up in each hospital for
antibiotic policy.

Reference to the other Terms of Reference can be given where ever necessary.

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ToR-6 : Diagnostic methods pertaining to Antimicrobial
Resistance Monitoring

Appropriate diagnostic tools already known should be selected as well as new ones
developed for rapid identification of pathogens for AMR surveillance.

Robust quality assurance system should be implemented that could be carried out by
a “neutral” central institute.

If needed, linkages should be established with some of the existing institutes for
strengthening quality assurance. This strengthening of quality assurance should span
animal health, industrial surveillance and environmental surveillance.

Environmental surveillance should be an interface between veterinary, industrial and

human health.

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 7. Conclusions

 It is imperative that all the clinicians understand the principles and standard
methods of antibiotic susceptibility tests. They should also insist on the laboratory
to follow these recommended procedures to generate antibiotic susceptibility test
reports that are quality assured. Antimicrobial susceptibility data generated based
on consistent reproducible and comparable data between different laboratories
will produce better outcomes and help in developing region-wise antibiograms.

 All the tertiary care hospitals (public or private) need to develop their SOP’s and
guidelines as per the national guidelines and implement in their setting.

 The guidelines in the hospital to be reviewed every 6 months; national guidelines

to be reviewed on yearly basis.

Public Private Partnership:

 All health care facilities need to implement the Antibiotic Policy which should be
one of the components of hospital infection control guidelines & share the data
with national agency.

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8. Important Abbreviations
AGP : Animal Growth-Promoter
AMR : Antimicrobial Resistance
APEDA : Agricultural and Processed Food Products Export Development Authority
AST : Antibiotic Susceptibility Testing
ATC : Anatomical Therapeutic Chemical
BSI : Blood Stream Infection
CDSCO : Central Drugs Standard Control Organization
CLSI : Clinical Laboratory Standard Institute
CME : Continuing Medical Examination
DCGI : Drug Controller General India
DDD : Defined Daily Dose
DTC : Drug Therapeutics Committee
EQA : External Quality Assurance
ESBL : Extended Spectrum Beta Lactamase
EU : European Union
FDA : Food & Drug Administration
FSSAI : Food Safety & Standards Authority of India
GASP : Gonococcal Antimicrobial Susceptibility Programme
IAI : Intra-abdominal Infection
ICU : Intensive Care Unit
MBL : Metallo--Lactamase
MDR : Multi Drug Resistance
MPEDA : Marine Products Export Development Authority
MRSA : Methicillin Resistant Staphylococcus Aureus
NACP : National AIDS Control Programme
NDM : New Delhi Metallo--Lactamase
NVBDCP : National Vector Borne Disease Control Programme
ORS : Oral Rehydration Therapy

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RNTCP : Revised National Tuberculosis Control Programme
SOP : Standard Operating Procedure
SSTI : Skin and Soft Tissue Infection
ToR : Terms of Reference
URTI : Upper Respiratory Tract Infection
UTI : Urinary Tract Infection
VRE : Vancomycin Resistant Enterococcus

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