Antibiotic Resistance in India

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Antibiotic Resistance in India Sumanth Gandra MD, MPH Center for Disease Dynamics, Economics & Policy July 5, 2017 AMR Cross Council Initiative Challenges and Opportunities Workshop, Heathrow

Disclaimer/Disclosures Research funded by Bill and Melinda Gates Foundation No other Conflicts of Interest

Percentage of third generation cephalosporin resistant Escherichia coli, by country (2011 2014) State of the World s Antibiotics Report, CDDEP 2015

Percentage of carbapenem-resistant Klebsiella pneumoniae, by country (2011 2014) State of the World s Antibiotics Report, CDDEP 2015

Why India has high antibiotic resistance prevalence?

Global Trends in Antibiotic Consumption Global Antibiotic Consumption 2000-2010: an analysis of national pharmaceutical data In 2010- India is the largest consumer of antibiotics, followed by China and the United States

Percentage change in antibiotic consumption per capita 2000 2010 Van Boeckel T, Gandra S et al. Lancet ID 2014

Antibiotic consumption: 2014 Source: Laxminarayan R et al. Science, 2016.

Trends in antibiotic consumption in India: 2000-2010 Source: Laxminarayan R et al. PLOS Medicine, 2016.

Trends in antibiotic consumption in India Source: IMS Health

Peak month of antibiotic consumption Van Boeckel T, Gandra S et al. Lancet ID 2014

Fixed Dose Combination (FDC) Antibiotics - India 118 (at least) FDC antibiotics are available in India Cefixime + Azithromycin Cefixime + Linezolid Azithromycin + Levofloxacin Cefixime + Levofloxacin Ahmad A et al. Lancet GH 2016 Shankar PR et al. Lancet GH 2016

Faropenem consumption in India and China: 2010 2014 Standard units (10 5 ) 30 25 20 15 10 5 0 IMS Health 2010 2011 2012 2013 2014 India China In India, faropenem has been approved for respiratory, urinary tract, skin and soft-tissue, and gynecological infections Gandra S et al. CID, 2016 Tiberi S et al. CID, 2016

Attitude and Behavioral Aspects Reasons for prescribing antibiotics: Private Sector Patient Pressure Fear of losing patients Lack of follow up For profit Public Sector Huge workload Lack of diagnostic facilities Pressure to use short-dated medicines Kotwani A et al. IJMR in press

Global Antimicrobial Consumption in Food Animals Some Hot spots: Southeast coast China South coast of India, Mumbai, Delhi Van Boeckel et al PNAS- 2015

Countries with Highest Antimicrobial consumption in Food Animals 2010 2030 Van Boeckel et al PNAS. 2015.

Countries with Highest Antimicrobial consumption in Food Animals 2010 2030 Van Boeckel et al PNAS. 2015.

Colistin sulphate for growth promotion in Food Animals- India Source: Center for Science and Environment

Effluent Pollution From Antibiotic Manufacturing Units- India Nordea Report, Feb 2016

Effluent Pollution From Antibiotics Manufacturing Units China supplies up to 90 percent active pharmaceutical ingredients (API)for antibiotics APIs mostly exported to India, processed and sold on to markets around the world

Effluent Pollution From Antibiotics Manufacturing Units Good Manufacturing Practices (GMP), do not include environmental safeguards Unfortunately, environmental regulation are currently left up to national regulators

Ciprofloxacin concentration in Effluent from drug manufacturers, Hyderabad, India- 2006 Up to 31,000µg/L Discharge load of 45 kg per day = amount consumed in Sweden (population nine million) over 5-days Larson JDG et al. J Hazardous Material, 2007

Antimicrobials from environmental samples- Hyderabad, India- 2016 Corresponding microbiological analyses revealed carbapenemaseproducing Enterobacteriaceae (carrying mainly blaoxa-48, blandm, and blakpc) in more than 95% of the samples. Lubbert C et al. Infection, April 2017

Poor Environmental Sanitation World Bank 2016

Conditions suitable for rapid spread of resistance genes in India

Risk of Extended Spectrum Beta-lactamase(ESBL) Enterobacteriaceae colonization for a traveler South Asia: 55% Asia (except South Asia): 39% 100% 80% 87% 79% 78% 60% 40% 35% 20% 0% India Nepal Bhutan Sri Lanka Hassing RJ et al. Eurosurveillance 2015 Kuenzli E et al. BMC ID 2014

Most Common Organisms Isolated from Early Onset Neonatal Sepsis Cases in India Enterobacter spp Pseudomonas spp Enterococcus spp S. aureus E.coli Klebsiella spp CONS Acinetobacter spp 4.3% 5.9% 6% 10.5% 14% 15.7% 16.6% 27.1% 0% 5% 10% 15% 20% 25% 30% Delhi Neonatal Infection Study- Lancet GH, October 2016

Perfect conditions for emergence of Superbugs HUMAN SECTOR ANIMAL SECTOR BREEDING GROUND PHARMA SECTOR

Initiatives by Indian Government National Policy for Containment of AMR- 2011 (Ministry of Health & Family Welfare) AMR Surveillance Network establishment by ICMR and NCDC in 2011 Schedule H1 in March 2014- Selected group of antibiotics cannot be sold without prescription

Initiatives by Indian Government Medicines with Red Line : Public awareness campaign in February 2016 Banned 63 antibiotic FDCs in March 2016, but

Initiatives by Indian Government National Action Plan on Antimicrobial Resistance 2017-2021: April 2017

India-UK Bilateral Agreement on AMR UK India AMR Research Programme agreement- November 2016 RCUK and Dept. of Biotechnology, India will oversee AMR research Call for Scoping report on Mapping AMR Research in India June 2017 CDDEP selected to do the Scoping report which will be submitted by August 31 st, 2017.

AMR Research Landscape in India Task 1- A concise overview of AMR situation in India Literature search in Pubmed, Google Scholar and web search for grey literature for last five years Include AMR situation in humans, agriculture, environment Factors driving AMR Policy initiatives Task 2- Mapping current AMR research From Literature search in Task1, current AMR research will be collated in all areas (humans, agriculture, environment) Identify major manufacturers of antibiotics (CDSCO, OPPI, FICCI) and their research programs into antimicrobial compounds Task 3- Information on AMR relevant data sources From Literature search from Task1 AMR data sources will be identified

http://resistancemap.cddep.org/ Thank you