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Superbugs the bacteria that resists

The document discusses the emergence of superbugs, bacteria resistant to antibiotics, and highlights the global health threat they pose, including rising mortality rates and impacts on medical procedures. It attributes the growth of antimicrobial resistance (AMR) to factors such as over-prescription in humans, agricultural antibiotic use, and lack of hygiene, with particular emphasis on the situation in India. The document also mentions the responsibility of various stakeholders from healthcare to the pharmaceutical industry in addressing this crisis.

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SUPERBUGS EMERGING THREAT AND WHO IS RESPONSIBLE ? By: Dr. KUSHAL GRAKH VET INSIDER
What is Superbug ? ā–ŗ When bacteria resist the effects of an antimicrobial agent, it is referred to as resistant. ā–ŗ If a bacterial strain is exceedingly resistant to almost every known/antibiotics available, it is informally called ā€œa superbugā€ or ā€œa super bacteriumā€ implying a super fighter against antimicrobial agents (Reinhardt, 2010). VET INSIDER
Mechanism of resistance
Rise of Superbugs ā–ŗ AMR - existed ten thousand years before modern man discovery of medicines. ā–ŗ A 1000 year-old mummies- Inca Empire ā€“resistant bacteria from gut. ā–ŗ DNA found in 30, 000-year-old permafrost sediments from Bering - contain genes that encode resistance to a wide range of antibiotics (Balamurugan et al 2018).
Superbugs ā€“ Emerging Threat ā–ŗ The effective treatment of infections and diseases- under threat. ā–ŗ Infections by superbugs claims 700,000 lives annually around the world. ā–ŗ Every year- 23,000 deaths in America (CDC 2018), 25,000 in Europe and 80,000 deaths in China -antibiotic-resistant infections. ā–ŗ 300 million premature deaths are expected over the next 35 years due to AMR worldwide (WHO 2018). (Review on Antimicrobial Resistance, December 2014, Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations)
ā–ŗ Superbugs would make medical procedures such as organ transplants, surgery and chemotherapy impossible. ā–ŗ The rise in super bugs causing Ventilator-Associated Pneumonia (VAP) - major cause of mortality despite recent advances in management (Quereshi et al 2015). ā–ŗ Post-antibiotic era-minor injuries - lethal ā–ŗ Once curable diseases - untreatable. ā–ŗ If not addressed -expected loss - US$100 trillion (globally), lowering projected GDP by 2 to 3.5 percent. ā–ŗ Due to global spread - serious and highly contagious illnesses such as gonorrhoea and pneumonia, may soon become incurable. (Review on Antimicrobial Resistance, December 2014, Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations) Emerging Threatā€¦ā€¦
Nightmare superbugs ā–ŗ In Nevada (USA) woman in her 70s was hospitalized (August 2016) after returning from an extended trip to India. ā–ŗ Infected with multidrug-resistant Klebsiella pneumoniae resistant to 26 antibiotics. ā–ŗ Died in September from multiple organ failure and sepsis. ā–ŗ Klebsiella pneumoniae was found in patients at Christian Medical College (CMC), Vellore after they were admitted for sepsis. ā–ŗ At CMC, Vellore- 31 per cent patients treated for sepsis in the hospital become infected by a strain of Klebsiella pneumoniae - both resistant to antibiotics and hypervirulent.
India Every section of the population is at risk. ā–ŗ More than 23,000 adults die annually due to AMR. ā–ŗ Newborns are particularly vulnerable to AMR because- immune systems are fragile, leaving little time for doctors to find a drug that works. ā–ŗ More than 58,000 Indian babies died in 2013 as a result of AMR - a serious setback to progress in reducing Indian infant mortality rates.
Resistance trends- India During the period from 2008-2014 in India ā–ŗ MRSA ā€“ from 29% to 47% ā–ŗ Cabapenam resistant E. coli- from 10 to 13%. ā–ŗ Flouroquinolones resistant Salmonella isolates from 8% to 28%. ā–ŗ Kebsiella pneumoniae- pneumonia, meningitis, bloodstream infections and urinary tract infections - 29% to 57%. ā–ŗ V. cholerae O1 resistant to ampicillin, furazolidone, ciprofloxacin, and tetracycline. Source: The State of Worlds Antibiotics, 2015 Center for Disease Dynamics, Economics and Policy (CDDEP) National action Plan ā€“AMR 2017
Who is responsible?
Inappropriate use in humans Over-prescription/Overuse ā–ŗ In the 76 countries studied consumption increased from 21.2 billion in 2000 to 34.8 billion in 2015. ā–ŗ Global consumption - set to rise by 67% between 2010-2030. ā–ŗ In the BRICS countries(Brazil, Russia, India, China, and South Africa)- the estimated increase ā€“ 99% - up to seven times projected population growth. ā–ŗ India-largest consumer of antibiotics for human health. (Laxminarayan et al 2016) ā®š Patient with preconceived ideas and demand quick relief ā®š Fear of losing customers - Doctors compelled to give antibiotics (Chandy et al 2013)
In Humansā€¦ Prescription for non-bacterial illnesses ā®š Common cold, sore throat etc. Self medication ā®š To avoid financial burden of expensive allopathic medical visits ā®š Access to antibiotics without prescription (GARP India 2011; Barker et al 2017) ā®š Source: previous doctors prescription, leftover medicines from previous illness
High consumption of broad spectrum antibiotics ā®š Diagnostic uncertainties ā®š Lack of microbiology diagnostic laboratory services ā®š Incentives to prescribe new broad spectrum antibiotic ā®š Less time to counsel against use of antibiotic and instead prescribe them ā®š To dispose near to expire antibiotics (Kotwani et al., 2010; GARP India 2011) Failure to complete a course of treatment Prescription/treatment from informal healthcare providers/quacks/pharmacists ā®š Consider themselves not less than doctor ā®š Lack knowledge of when to use antibiotics
Non -therapeutic use of antibiotics Overuse In intensive livestock farming ā–ŗ More antibiotics are given to healthy animals than are used to treat diseases among human patients (WHO, 2012). ā–ŗ India accounts for 3% of the global consumption and is the fourth highest in the world, behind China (23%), the United States (13%) and Brazil (9%) in 2010. ā–ŗ The consumption of antibiotics in food animals in India will be double by 2030. (Inter-ministerial Review Meeting on Antimicrobial Resistance, 2016). Substitute for healthier living conditions (Laxminarayan 2016) ā–ŗ Routine feeding -to help them endure crowded, dirty, and stressful conditions. Use of enrofloxacin in FMD vaccines as preservative (Singh 2016)
ā–ŗ As a growth promoter ā–ŗ Poultry farmers ā€“ prevention is better than cure ā–ŗ Common practice ā–ŗ Cheap antibiotics ā–ŗ Antibiotics critical to human health such as tetracycline , doxycycline, ciprofloxacin and even colistin are commonly used for growth promotion in poultry. (Brower et al 2017; CSE 2014). ā–ŗ Residues of antimicrobials -detected in chicken meat (Sahu and Saxena 2014). ā–ŗ Use of polymixins in food animals-Emergence of plasmid mediated mcr-1 gene with (Liu et al 2016) ā–ŗ 149 unique resistance genes detected- manure from pigs ā€“China Non -therapeutic use of antibiotics
ā–ŗ "Some veterinarians' profit margins are bigger than those of cocaine dealers. When a veterinarian finds a sick chick among 20,000 other chicks, he treats the discovery as justification to preventively treat the entire flock with antibiotics. ( Der Spiegel 2012) Report on factory use of antibiotics in Germany, 2012 Spiegel, Addicted to Antibiotics: How Factory Farm Drug Abuse Makes Vets Rich.
Pharmaceutical industry ā–ŗ The Indian pharmaceutical industry supplied 20 percent of generic drugs ā€“ US $15 billion in 2014 ( Nordea Asset Management, 2014) ā–ŗ Almost 80 percent of the antibiotics sold by multinational companies on global market are manufactured in India and China (Sum of Us 2015). Release of antibiotics into the environment ā–ŗ Waste water effluents (Lubbert et al 2017) ā–ŗ Resistance to three major classes of antibiotics- cephalosporins, carbapenems and the fluoroquinolones detected in water samples from river, sewage treatment plant etc. in and around pharmaceutical companies in Hyderabad and Chennai (Sum of Us 2015). ā–ŗ Improper disposal of expired or leftover antibiotics- ideal breeding ground for drug resistant bacteria.
Antibiotic Fixed dose Combination (FDCs) ā–ŗ Lack of diagnostic precision ā–ŗ Unavailability of diagnostic laboratory services ā€“ increased use of antibiotics FDCs in India (Gautam and Saha 2008). ā–ŗ Approximately 118 FDCs are available in India (Shankar et al 2016). ā–ŗ Of these 118 formulations, 64 per cent are not approved by the national drugs regulator, the Central Drugs Standard Control Organisation (Business world 2018). ā–ŗ The lack of investment in new drug discovery. ā–ŗ In 2004, in the 15 largest pharma companies, only 1.6% of the drugs in the development stages were antibiotics- none from novel classes, nor were they targeted to treat multidrug resistant agents. Pharmaceutical industry
Double Standards ā–ŗ According to pharmaceutical company Zoetis (a former subsidiary of Pfizer )- They are leader in providing ongoing education to veterinarians and livestock producers on the proper use of antimicrobial drugs. ā–ŗ In 2013, Zoetis said it ā€œsupports the FDAā€™s efforts to voluntarily phase out growth promotion indications for medically important antibiotics. ā–ŗ But company still sells its antibiotics to Indian farmers - regulation and enforcement is more lax (Bureau of Investigative Journalism). Ban - European countries and USA- removed growth promoter labels but continued supply in India. ā–ŗ In India Zoetis (Neftin-T), Venkys (Colis-V), Vetline (PROGRO-VET), Kaizen Bio Sciences, Vet-Needs Labs, NeoSpark (DoxiStin-FS, RimoDox-2%-FS CTC-150- FS etc.) ā–ŗ Zoetis recommends feeding Neftin-T to chickens to ā€œimprove weight gain and FCR.
Double Standards
Justification provided by companies ā–ŗ Officially there is no ban in India for the specified usage of colistin in farm animalsā€¦ As law abiding company, we will never deviates the law of the landā€¦ā€¦..Neospark. ā–ŗ Each country enacts regulations appropriate for their market needs and standards, and we work with the national regulatory authorities in various countries, including India, to understand, respect and comply with local regulatory interpretation and oversightā€¦ā€¦ā€¦.Pfizer and Venkys. ā–ŗ ā€œIf an American company follows one policy in America, they should follow the same policy in India- Chennai Declaration. Source: The Bureau of Investigative Journalism, The Hindu, The Daily Telegraph
Lack of overall hygiene and sanitation ā–ŗ Poor sanitation plays major role in the spread of resistant bacteria and ARGs (antibiotic resistant genes). ā–ŗ More than 50 percent Indian population lack access to sanitation facilities for safe disposal of human waste (World Bank 2017). ā–ŗ Untreated sewage into water bodies - contamination of rivers with antibiotic residues, antibiotic resistant organisms and ARGs (Marathe et al 2017). ā–ŗ Risk of asymptomatic colonization with ESBL producing E. coli among Swiss travelers visiting India was 87 percent (Kuenzli et al 2014).
Cultural activities ā–ŗ Mass bathing in rivers ā–ŗ blaNDM-1 was found to be 20 times greater in the river during pilgrimage season than at other times of year in Upper Ganges (Ahammad et al 2014). ā–ŗ Pilgrimage sites thus can act as hot spots for transmission of resistant bacteria and genes.
Hospital acquired ā–ŗ Medical equipment, such as ventilators and catheters, might be transmission sites for these new strains. ā–ŗ Human-to- human transmission may also be possible, but clinical settings are most vulnerable. ā–ŗ For eg; HA-MRSA, infections aquired with use of catheters and other surgical and diagnostic procedures.
WHO list of superbugs Priority 1: Critical Priority 2: High Priority 3: Medium 1. Acinetobacter baumannii, carbapenem-resistant 4.Enterococcus faecium, vancomycin- resistant 10. Streptococcus pneumoniae, penicillin-non-susceptible 2. Pseudomonas aeruginosa, carbapenem-resistant 5. Staphylococcus aureus, methicillin- resistant, vancomycin-intermediate and resistant 11. Haemophilus influenzae, ampicillin-resistant 3. Enterobacteriaceae, carbapenem- resistant, ESBL-producing 6. Helicobacter pylori, clarithromycin- resistant 12. Shigella spp., fluoroquinolone- resistant 7. Campylobacter spp., fluoroquinolone-resistant 8. Salmonellae, fluoroquinolone- resistant 9. Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant WHO, 2017
MRSA ā–ŗ Most recognized superbugs - common in many hospitals throughout the world. ā–ŗ Methicillin- introduced in 1959 -treatment of penicillin-resistant S. aureus. ā–ŗ MRSA was first detected in 1961 (Ippolito et al., 2010). ā–ŗ At first- limited to hospitals and healthcare settings -hospital acquired MRSA infection. ā–ŗ Since the late 1990s- emergence of community-acquired MRSA strains with rapid spread and causing fatal diseases (Ippolito et al., 2010). ā–ŗ Most MRSA strains exhibit resistance to multiple drugs including penicillin, methicillin, tetracycline, erythromycin and vancomycin (de Lencastre et al., 1996; Smith et al., 2014).
LA-MRSA ā–ŗ LA-MRSA- increasingly identified in humans and could be associated with very severe diseases and even death(Chen et al 2018). ā–ŗ MRSA - reported in diverse species - dogs, cats, sheep, chickens, horses, rabbits, seals, birds, one turtle, bat, guinea pig and chinchilla (Morgan et al 2008). ā–ŗ In one report, four dogs suffered postoperative infections with MRSA after a surgery at veterinary hospital. ā–ŗ Around 5-7% of veterinary personnel and students found to be nasal carriers in Netherland and USA. ā–ŗ LA-MRSA was identified in 78% of 373 MRSA-colonized patients upon admission to two hospitals during 2008 and 2009 (Bruinsma et al 2015). ā–ŗ These studies are enough to introduce the challenge to veterinarians in form of newer and stronger zoonoses.
NDM-1 ā‘ Escherichia coli and Klebsiella pneumoniae harboring New Delhi metallo Ī²- lactamase (NDM-1) ā‘ The NDM-1 gene encodes Ī²-lactamase enzymes carbapenemases -resistance to a broad range of Ī²-lactams. ā‘ Produced by Gram-negative bacteria, in particular E. coli and K. pneumoniae (Paterson, 2006). ā‘ Gene - first detected in a K. peumoniae isolate- Swedish patient who travelled to New Delhi in 2008 (Yong et al., 2009) and emerged as a newest superbug - most feared pathogens.
ā–ŗ Apart from the Enterobacteriaceae family NDM-1 has also recently been found in Acinetobacter species in India, China, and Egypt. ā–ŗ After NDM- 1 a variant in Egypt is designated as NDM-2. ā–ŗ Infections caused by bacteria carrying NDM-1 have been reported in many other countries, including the USA, Canada, Australia, France, Germany, Belgium, Sweden, Denmark, the Netherlands, Norway, Oman, Kenya, China, South Korea, Japan(Luo et al., 2013; Yoo et al., 2013). ā–ŗ Mcr-1 gene conferring resistance against colistin and other polymixins has been found in multiple countries around the world (Liu et al, 2015; Roschanski et al., 2016) NDM-1ā€¦..
NDM 1 controversy Donā€™t blame superbug on India, itā€™s everywhere Thursday, Dec 06, 2018 New Delhi Ā°C VET INSIDER
ā–ŗ ā€œridiculous to call it NDM-1 when none of the samples that tested positive were picked in New Delhi,ā€ - Chairman, Medanta-The Medicity. ā–ŗ Commercially motivated campaign to hurt Indiaā€™s Rs 1,200-crore medical tourism industry. ā–ŗ Lead researcher from Chennai KK Kumarasamy got funding from Wyeth, a pharma company, while another author has shares in companies such as AstraZeneca, Merck, pfizer and GlaxoSmithKline. ā–ŗ A frightening picture not supported by any scientific data. ā–ŗ Many British NDM-1 positive patients had no travel or connection to India : Union Health Ministry official. Shrivastva et al 2011
Alternatives ā–ŗ Antimicrobial peptides- host defense peptides-short and generally positively charged pptides found in variety of life forms from microorganisms to humans. ā–ŗ Potential therapeutic source of future antibiotics-broad spectrum activities and different mechanisms of actions (Seo et al 2012). ā–ŗ Phage therapy ā–ŗ Intraperitoneal administration of a single phage strain was sufficient to rescue 100% mice in bacteremia model using ESBL producing E. coli and imipenem resistant P. aeruginosa (Wang et al 2006).
Alternatives ā–ŗ Antimicrobial polymers/polymeric biocides- engineered polymers to mimic antimicrobial peptides ā€“used by immune system to kill bacteria. ā–ŗ Positive charge- attach to bacteria ā€“polymer crosses cell membrane- solidification of proteins and DNA in cell. ā–ŗ Endophytes ā–ŗ Microbes colonizing living internal tissues of plant without causing any immediate overt negative effects. ā–ŗ Wide range of antimicrobial producing strains-important potential source of antimicrobial substance (Ryan et al 2008).
Containment of AMR ā–ŗ AMR related policies were initiated in 2011 by publishing the National Policy on Containment of AMR. ā–ŗ NGO initiative such as Chennai Declaration-published to create a roadmap to tackle AMR problem. ā–ŗ ICMR launched the program on Antimicrobial Stewardship, Prevention of Infection and Control (ASPIC) in 2012. ā–ŗ The Antimicrobial Resistance Surveillance Research Network (AMRSN) established by the ICMR. ā–ŗ The Red Line Campaign developed along with Organization of Pharmaceutical Producers of India (OPPI) was launched in New Delhi in February 2016. ā–ŗ In 2017, a comprehensive National Action Plan for Containment of AMR - launched. Visit vetinsider.veteaselab.com for more
Focus areas of NAP-AMR strategic priorities
Visit vetinsider.veteaselab.com for more
VET INSIDER Visit vetinsider.veteaselab.com for more

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Superbugs the bacteria that resists

  • 1.
    SUPERBUGS EMERGING THREAT ANDWHO IS RESPONSIBLE ? By: Dr. KUSHAL GRAKH VET INSIDER
  • 2.
    What is Superbug? ā–ŗ When bacteria resist the effects of an antimicrobial agent, it is referred to as resistant. ā–ŗ If a bacterial strain is exceedingly resistant to almost every known/antibiotics available, it is informally called ā€œa superbugā€ or ā€œa super bacteriumā€ implying a super fighter against antimicrobial agents (Reinhardt, 2010). VET INSIDER
  • 3.
  • 4.
    Rise of Superbugs ā–ŗAMR - existed ten thousand years before modern man discovery of medicines. ā–ŗ A 1000 year-old mummies- Inca Empire ā€“resistant bacteria from gut. ā–ŗ DNA found in 30, 000-year-old permafrost sediments from Bering - contain genes that encode resistance to a wide range of antibiotics (Balamurugan et al 2018).
  • 5.
    Superbugs ā€“ EmergingThreat ā–ŗ The effective treatment of infections and diseases- under threat. ā–ŗ Infections by superbugs claims 700,000 lives annually around the world. ā–ŗ Every year- 23,000 deaths in America (CDC 2018), 25,000 in Europe and 80,000 deaths in China -antibiotic-resistant infections. ā–ŗ 300 million premature deaths are expected over the next 35 years due to AMR worldwide (WHO 2018). (Review on Antimicrobial Resistance, December 2014, Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations)
  • 6.
    ā–ŗ Superbugs wouldmake medical procedures such as organ transplants, surgery and chemotherapy impossible. ā–ŗ The rise in super bugs causing Ventilator-Associated Pneumonia (VAP) - major cause of mortality despite recent advances in management (Quereshi et al 2015). ā–ŗ Post-antibiotic era-minor injuries - lethal ā–ŗ Once curable diseases - untreatable. ā–ŗ If not addressed -expected loss - US$100 trillion (globally), lowering projected GDP by 2 to 3.5 percent. ā–ŗ Due to global spread - serious and highly contagious illnesses such as gonorrhoea and pneumonia, may soon become incurable. (Review on Antimicrobial Resistance, December 2014, Antimicrobial Resistance: Tackling a Crisis for the Health and Wealth of Nations) Emerging Threatā€¦ā€¦
  • 7.
    Nightmare superbugs ā–ŗ InNevada (USA) woman in her 70s was hospitalized (August 2016) after returning from an extended trip to India. ā–ŗ Infected with multidrug-resistant Klebsiella pneumoniae resistant to 26 antibiotics. ā–ŗ Died in September from multiple organ failure and sepsis. ā–ŗ Klebsiella pneumoniae was found in patients at Christian Medical College (CMC), Vellore after they were admitted for sepsis. ā–ŗ At CMC, Vellore- 31 per cent patients treated for sepsis in the hospital become infected by a strain of Klebsiella pneumoniae - both resistant to antibiotics and hypervirulent.
  • 9.
    India Every section ofthe population is at risk. ā–ŗ More than 23,000 adults die annually due to AMR. ā–ŗ Newborns are particularly vulnerable to AMR because- immune systems are fragile, leaving little time for doctors to find a drug that works. ā–ŗ More than 58,000 Indian babies died in 2013 as a result of AMR - a serious setback to progress in reducing Indian infant mortality rates.
  • 14.
    Resistance trends- India Duringthe period from 2008-2014 in India ā–ŗ MRSA ā€“ from 29% to 47% ā–ŗ Cabapenam resistant E. coli- from 10 to 13%. ā–ŗ Flouroquinolones resistant Salmonella isolates from 8% to 28%. ā–ŗ Kebsiella pneumoniae- pneumonia, meningitis, bloodstream infections and urinary tract infections - 29% to 57%. ā–ŗ V. cholerae O1 resistant to ampicillin, furazolidone, ciprofloxacin, and tetracycline. Source: The State of Worlds Antibiotics, 2015 Center for Disease Dynamics, Economics and Policy (CDDEP) National action Plan ā€“AMR 2017
  • 16.
  • 17.
    Inappropriate use inhumans Over-prescription/Overuse ā–ŗ In the 76 countries studied consumption increased from 21.2 billion in 2000 to 34.8 billion in 2015. ā–ŗ Global consumption - set to rise by 67% between 2010-2030. ā–ŗ In the BRICS countries(Brazil, Russia, India, China, and South Africa)- the estimated increase ā€“ 99% - up to seven times projected population growth. ā–ŗ India-largest consumer of antibiotics for human health. (Laxminarayan et al 2016) ā®š Patient with preconceived ideas and demand quick relief ā®š Fear of losing customers - Doctors compelled to give antibiotics (Chandy et al 2013)
  • 18.
    In Humansā€¦ Prescription fornon-bacterial illnesses ā®š Common cold, sore throat etc. Self medication ā®š To avoid financial burden of expensive allopathic medical visits ā®š Access to antibiotics without prescription (GARP India 2011; Barker et al 2017) ā®š Source: previous doctors prescription, leftover medicines from previous illness
  • 19.
    High consumption ofbroad spectrum antibiotics ā®š Diagnostic uncertainties ā®š Lack of microbiology diagnostic laboratory services ā®š Incentives to prescribe new broad spectrum antibiotic ā®š Less time to counsel against use of antibiotic and instead prescribe them ā®š To dispose near to expire antibiotics (Kotwani et al., 2010; GARP India 2011) Failure to complete a course of treatment Prescription/treatment from informal healthcare providers/quacks/pharmacists ā®š Consider themselves not less than doctor ā®š Lack knowledge of when to use antibiotics
  • 20.
    Non -therapeutic useof antibiotics Overuse In intensive livestock farming ā–ŗ More antibiotics are given to healthy animals than are used to treat diseases among human patients (WHO, 2012). ā–ŗ India accounts for 3% of the global consumption and is the fourth highest in the world, behind China (23%), the United States (13%) and Brazil (9%) in 2010. ā–ŗ The consumption of antibiotics in food animals in India will be double by 2030. (Inter-ministerial Review Meeting on Antimicrobial Resistance, 2016). Substitute for healthier living conditions (Laxminarayan 2016) ā–ŗ Routine feeding -to help them endure crowded, dirty, and stressful conditions. Use of enrofloxacin in FMD vaccines as preservative (Singh 2016)
  • 21.
    ā–ŗ As agrowth promoter ā–ŗ Poultry farmers ā€“ prevention is better than cure ā–ŗ Common practice ā–ŗ Cheap antibiotics ā–ŗ Antibiotics critical to human health such as tetracycline , doxycycline, ciprofloxacin and even colistin are commonly used for growth promotion in poultry. (Brower et al 2017; CSE 2014). ā–ŗ Residues of antimicrobials -detected in chicken meat (Sahu and Saxena 2014). ā–ŗ Use of polymixins in food animals-Emergence of plasmid mediated mcr-1 gene with (Liu et al 2016) ā–ŗ 149 unique resistance genes detected- manure from pigs ā€“China Non -therapeutic use of antibiotics
  • 22.
    ā–ŗ "Some veterinarians'profit margins are bigger than those of cocaine dealers. When a veterinarian finds a sick chick among 20,000 other chicks, he treats the discovery as justification to preventively treat the entire flock with antibiotics. ( Der Spiegel 2012) Report on factory use of antibiotics in Germany, 2012 Spiegel, Addicted to Antibiotics: How Factory Farm Drug Abuse Makes Vets Rich.
  • 23.
    Pharmaceutical industry ā–ŗ TheIndian pharmaceutical industry supplied 20 percent of generic drugs ā€“ US $15 billion in 2014 ( Nordea Asset Management, 2014) ā–ŗ Almost 80 percent of the antibiotics sold by multinational companies on global market are manufactured in India and China (Sum of Us 2015). Release of antibiotics into the environment ā–ŗ Waste water effluents (Lubbert et al 2017) ā–ŗ Resistance to three major classes of antibiotics- cephalosporins, carbapenems and the fluoroquinolones detected in water samples from river, sewage treatment plant etc. in and around pharmaceutical companies in Hyderabad and Chennai (Sum of Us 2015). ā–ŗ Improper disposal of expired or leftover antibiotics- ideal breeding ground for drug resistant bacteria.
  • 25.
    Antibiotic Fixed doseCombination (FDCs) ā–ŗ Lack of diagnostic precision ā–ŗ Unavailability of diagnostic laboratory services ā€“ increased use of antibiotics FDCs in India (Gautam and Saha 2008). ā–ŗ Approximately 118 FDCs are available in India (Shankar et al 2016). ā–ŗ Of these 118 formulations, 64 per cent are not approved by the national drugs regulator, the Central Drugs Standard Control Organisation (Business world 2018). ā–ŗ The lack of investment in new drug discovery. ā–ŗ In 2004, in the 15 largest pharma companies, only 1.6% of the drugs in the development stages were antibiotics- none from novel classes, nor were they targeted to treat multidrug resistant agents. Pharmaceutical industry
  • 27.
    Double Standards ā–ŗ Accordingto pharmaceutical company Zoetis (a former subsidiary of Pfizer )- They are leader in providing ongoing education to veterinarians and livestock producers on the proper use of antimicrobial drugs. ā–ŗ In 2013, Zoetis said it ā€œsupports the FDAā€™s efforts to voluntarily phase out growth promotion indications for medically important antibiotics. ā–ŗ But company still sells its antibiotics to Indian farmers - regulation and enforcement is more lax (Bureau of Investigative Journalism). Ban - European countries and USA- removed growth promoter labels but continued supply in India. ā–ŗ In India Zoetis (Neftin-T), Venkys (Colis-V), Vetline (PROGRO-VET), Kaizen Bio Sciences, Vet-Needs Labs, NeoSpark (DoxiStin-FS, RimoDox-2%-FS CTC-150- FS etc.) ā–ŗ Zoetis recommends feeding Neftin-T to chickens to ā€œimprove weight gain and FCR.
  • 29.
  • 30.
    Justification provided bycompanies ā–ŗ Officially there is no ban in India for the specified usage of colistin in farm animalsā€¦ As law abiding company, we will never deviates the law of the landā€¦ā€¦..Neospark. ā–ŗ Each country enacts regulations appropriate for their market needs and standards, and we work with the national regulatory authorities in various countries, including India, to understand, respect and comply with local regulatory interpretation and oversightā€¦ā€¦ā€¦.Pfizer and Venkys. ā–ŗ ā€œIf an American company follows one policy in America, they should follow the same policy in India- Chennai Declaration. Source: The Bureau of Investigative Journalism, The Hindu, The Daily Telegraph
  • 31.
    Lack of overallhygiene and sanitation ā–ŗ Poor sanitation plays major role in the spread of resistant bacteria and ARGs (antibiotic resistant genes). ā–ŗ More than 50 percent Indian population lack access to sanitation facilities for safe disposal of human waste (World Bank 2017). ā–ŗ Untreated sewage into water bodies - contamination of rivers with antibiotic residues, antibiotic resistant organisms and ARGs (Marathe et al 2017). ā–ŗ Risk of asymptomatic colonization with ESBL producing E. coli among Swiss travelers visiting India was 87 percent (Kuenzli et al 2014).
  • 32.
    Cultural activities ā–ŗ Massbathing in rivers ā–ŗ blaNDM-1 was found to be 20 times greater in the river during pilgrimage season than at other times of year in Upper Ganges (Ahammad et al 2014). ā–ŗ Pilgrimage sites thus can act as hot spots for transmission of resistant bacteria and genes.
  • 33.
    Hospital acquired ā–ŗ Medicalequipment, such as ventilators and catheters, might be transmission sites for these new strains. ā–ŗ Human-to- human transmission may also be possible, but clinical settings are most vulnerable. ā–ŗ For eg; HA-MRSA, infections aquired with use of catheters and other surgical and diagnostic procedures.
  • 34.
    WHO list ofsuperbugs Priority 1: Critical Priority 2: High Priority 3: Medium 1. Acinetobacter baumannii, carbapenem-resistant 4.Enterococcus faecium, vancomycin- resistant 10. Streptococcus pneumoniae, penicillin-non-susceptible 2. Pseudomonas aeruginosa, carbapenem-resistant 5. Staphylococcus aureus, methicillin- resistant, vancomycin-intermediate and resistant 11. Haemophilus influenzae, ampicillin-resistant 3. Enterobacteriaceae, carbapenem- resistant, ESBL-producing 6. Helicobacter pylori, clarithromycin- resistant 12. Shigella spp., fluoroquinolone- resistant 7. Campylobacter spp., fluoroquinolone-resistant 8. Salmonellae, fluoroquinolone- resistant 9. Neisseria gonorrhoeae, cephalosporin-resistant, fluoroquinolone-resistant WHO, 2017
  • 35.
    MRSA ā–ŗ Most recognizedsuperbugs - common in many hospitals throughout the world. ā–ŗ Methicillin- introduced in 1959 -treatment of penicillin-resistant S. aureus. ā–ŗ MRSA was first detected in 1961 (Ippolito et al., 2010). ā–ŗ At first- limited to hospitals and healthcare settings -hospital acquired MRSA infection. ā–ŗ Since the late 1990s- emergence of community-acquired MRSA strains with rapid spread and causing fatal diseases (Ippolito et al., 2010). ā–ŗ Most MRSA strains exhibit resistance to multiple drugs including penicillin, methicillin, tetracycline, erythromycin and vancomycin (de Lencastre et al., 1996; Smith et al., 2014).
  • 36.
    LA-MRSA ā–ŗ LA-MRSA- increasinglyidentified in humans and could be associated with very severe diseases and even death(Chen et al 2018). ā–ŗ MRSA - reported in diverse species - dogs, cats, sheep, chickens, horses, rabbits, seals, birds, one turtle, bat, guinea pig and chinchilla (Morgan et al 2008). ā–ŗ In one report, four dogs suffered postoperative infections with MRSA after a surgery at veterinary hospital. ā–ŗ Around 5-7% of veterinary personnel and students found to be nasal carriers in Netherland and USA. ā–ŗ LA-MRSA was identified in 78% of 373 MRSA-colonized patients upon admission to two hospitals during 2008 and 2009 (Bruinsma et al 2015). ā–ŗ These studies are enough to introduce the challenge to veterinarians in form of newer and stronger zoonoses.
  • 38.
    NDM-1 ā‘ Escherichia coliand Klebsiella pneumoniae harboring New Delhi metallo Ī²- lactamase (NDM-1) ā‘ The NDM-1 gene encodes Ī²-lactamase enzymes carbapenemases -resistance to a broad range of Ī²-lactams. ā‘ Produced by Gram-negative bacteria, in particular E. coli and K. pneumoniae (Paterson, 2006). ā‘ Gene - first detected in a K. peumoniae isolate- Swedish patient who travelled to New Delhi in 2008 (Yong et al., 2009) and emerged as a newest superbug - most feared pathogens.
  • 39.
    ā–ŗ Apart fromthe Enterobacteriaceae family NDM-1 has also recently been found in Acinetobacter species in India, China, and Egypt. ā–ŗ After NDM- 1 a variant in Egypt is designated as NDM-2. ā–ŗ Infections caused by bacteria carrying NDM-1 have been reported in many other countries, including the USA, Canada, Australia, France, Germany, Belgium, Sweden, Denmark, the Netherlands, Norway, Oman, Kenya, China, South Korea, Japan(Luo et al., 2013; Yoo et al., 2013). ā–ŗ Mcr-1 gene conferring resistance against colistin and other polymixins has been found in multiple countries around the world (Liu et al, 2015; Roschanski et al., 2016) NDM-1ā€¦..
  • 41.
    NDM 1 controversy Donā€™tblame superbug on India, itā€™s everywhere Thursday, Dec 06, 2018 New Delhi Ā°C VET INSIDER
  • 42.
    ā–ŗ ā€œridiculous tocall it NDM-1 when none of the samples that tested positive were picked in New Delhi,ā€ - Chairman, Medanta-The Medicity. ā–ŗ Commercially motivated campaign to hurt Indiaā€™s Rs 1,200-crore medical tourism industry. ā–ŗ Lead researcher from Chennai KK Kumarasamy got funding from Wyeth, a pharma company, while another author has shares in companies such as AstraZeneca, Merck, pfizer and GlaxoSmithKline. ā–ŗ A frightening picture not supported by any scientific data. ā–ŗ Many British NDM-1 positive patients had no travel or connection to India : Union Health Ministry official. Shrivastva et al 2011
  • 43.
    Alternatives ā–ŗ Antimicrobial peptides-host defense peptides-short and generally positively charged pptides found in variety of life forms from microorganisms to humans. ā–ŗ Potential therapeutic source of future antibiotics-broad spectrum activities and different mechanisms of actions (Seo et al 2012). ā–ŗ Phage therapy ā–ŗ Intraperitoneal administration of a single phage strain was sufficient to rescue 100% mice in bacteremia model using ESBL producing E. coli and imipenem resistant P. aeruginosa (Wang et al 2006).
  • 44.
    Alternatives ā–ŗ Antimicrobial polymers/polymericbiocides- engineered polymers to mimic antimicrobial peptides ā€“used by immune system to kill bacteria. ā–ŗ Positive charge- attach to bacteria ā€“polymer crosses cell membrane- solidification of proteins and DNA in cell. ā–ŗ Endophytes ā–ŗ Microbes colonizing living internal tissues of plant without causing any immediate overt negative effects. ā–ŗ Wide range of antimicrobial producing strains-important potential source of antimicrobial substance (Ryan et al 2008).
  • 45.
    Containment of AMR ā–ŗAMR related policies were initiated in 2011 by publishing the National Policy on Containment of AMR. ā–ŗ NGO initiative such as Chennai Declaration-published to create a roadmap to tackle AMR problem. ā–ŗ ICMR launched the program on Antimicrobial Stewardship, Prevention of Infection and Control (ASPIC) in 2012. ā–ŗ The Antimicrobial Resistance Surveillance Research Network (AMRSN) established by the ICMR. ā–ŗ The Red Line Campaign developed along with Organization of Pharmaceutical Producers of India (OPPI) was launched in New Delhi in February 2016. ā–ŗ In 2017, a comprehensive National Action Plan for Containment of AMR - launched. Visit vetinsider.veteaselab.com for more
  • 46.
    Focus areas ofNAP-AMR strategic priorities
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