This presentation talks about ÄMR: A public health threat, a “silent pandemic”. Infections caused by Antimicrobial-drug-resistant (AMR) pathogens caused >1.27 million deaths worldwide in 2019 (low level or no surveillance) and increasing year after year which may be > million in coming decades. Covid-19 caused ~6.8 million deaths in >3 years but now the pandemic is ending but the AMR pandemic has no timeline for its ending. Many deaths are also attributed to AMR pathogens. More antibiotic use (irrespective of the sector) = More AMR. This presentation also talks about ways and means to mitigate the AMR pandemic. 1. Stopping the blame game. All are equally responsible for the emergence of AMR, the share of developed and educated communities is much more than poor and un-educated communities. 2. Working together: On-Line Real-Time AST Data Sharing Platform for different diagnostic and research laboratories doing AST routinely. 3. Implementing not only antibiotic veterinary and medical stewardship but antimicrobial production and distribution stewardship too. 4. Educating for Environmental health not only human, plant, and animal health. 5. AMR's solution is not in searching for alternatives to antibiotics but in establishing environmental harmony. 6. More emphasis on AMR epidemiology than on AMR microbiology and pharmacology. 7. Development of understanding that bacteria and other microbes are more essential for life on earth than the human race. Microbes can live without humans, but humans can’t without microbes. Global-Health is of prime importance than economic growth/ greediness.

1. AMR challenges in humans from animal foods
Facts and Myths
Sans synchronized and multi-sectoral ‘One Health’ approach, control of
AMR is impossible and the world is destined to revert to the pre-antibiotic
era.
Bhoj R Singh
Head, Division of Epidemiology
ICAR-Indian Veterinary Research Institute, Izatnagar-243 122, India
Email: br.singh@icar.gov.in/ brs18762@gmail.com
Lecture at 9th One Health Conference on 28th March 2023 at HBT Medical
College and Rustom Narsi Cooper Municipal General Hospital

2. AMR
• A public health threat, a “silent pandemic”
• Infections caused by Antimicrobial-drug-
resistant (AMR) pathogens caused >1.27
million deaths worldwide in 2019 (low level or
no surveillance) and increasing year after year.
• Covid-19 caused ~6.8 million deaths in >3
years. Many deaths are also attributed to AMR
pathogens.
• More antibiotic use (irrespective of sector)=
More AMR

3. Antimicrobial Drug-resistance (AMR)
• Of the 4·95 million deaths associated with bacteria 1·27 million deaths
were directly attributable to resistance in 2019.
• About 28 deaths per 100 000 associated with AMR in 2019.
• Australasia had the lowest AMR burden, with 6·5 deaths per 100 000
attributable to AMR.
• Western sub-Saharan Africa had the highest AMR attributable deaths
114·8 per 100 000.
• Lower respiratory and thorax infections, bloodstream infections, and
intra-abdominal infections accounted for 78·8% of the deaths
attributable to AMR; lower respiratory infections alone accounted for
more than 400 000 AMR attributable deaths and 1·5 million associated
deaths.
(https://doi.org/10.1016/S0140-6736 Mohsen Naghavi et al. 2020.

4. Potential routes of AMR in the food chain
Samtiya et al., 2022
AMR is spreading rapidly through the
1. Indiscriminate use of antibiotics in humans, animals food production system
including agriculture and aquaculture.
2. Pollution of soil and water through untreated sewage, hospital wastes, industrial
wastes.
3. Integrated farming system for meeting the food demand
4. Globalization of the food supply,
5. Increased population in urban areas,
6. Lack of proper epidemiological understanding of AMR, and
7. International travel

5. Half Truths
The spread of AMR Salmonella is generally linked to contaminated
poultry meat, eggs, pork, and beef. AMR Salmonella has also been
linked to turkey (EFSA J. 2012; Joint ECDC–EFSA, 2014).
AMR genes in food products are derived from poultry, swine, goats,
cattle, and sheep (Price et al., 2014, Liu et al., 2016)
Poultry is one of the most prominent vehicles for the transmission
of AMR Campylobacter (EFSA, 2015).
Quinolone-resistant E. coli are common in cattle and the
surrounding farm environment (Duse et al, 2016).
(Fluoroquinolones and Quinolones are not used in dairy animals)
More incidences of antimicrobial-resistant E. coli infections are
associated with veal, beef, and dairy products (Catry et al. 2016).
Almost all AMR Salmonella infections are foodborne and linked to
the consumption of contaminated pork, turkey, and beef (Nair et al,
2018).

6. Antimicrobial use in human and livestock
• Globally about 35 billion doses of antibiotics (3500-5000 tons) are used for
therapy and disease prevention in human medicine, and about 50000 tons
for treatment and growth promotion in livestock and agriculture sector.
• Globally, about 20% of antimicrobials are used in humans and 80% in
livestock, but in India?
Use in Humans
Use in livestock
In India antibiotic used decreased by 8.5% between 2016-19. Koya et al., 2022.
However, CDEEP says 30% increase in per capita antibiotic and 48% in total use in India in
2011-20.

7. Human versus animal: Antimicrobial use in India
Antimicrobials are used as per unit of body mass for therapy
Source: Togetherabx.com/8.php (2018)
Humans Animals
Individual treatment Usually mass treatment
Human units (2012) 1.22 billion
By mass Human: Livestock::1:1.89*
Livestock units (2012) 1.24 billion by
number & 2.3 billion by mass index
Antibiotics used
6.5 billion defined daily doses
= 2 billion grams= 2000 tons
~2160 tons
Ratio of antibiotic uses
Penicillin and cephalosporin use 2000
1
Quinolones and Fluoroquinolones 99000
1
Tetracyclines 0.4 0.6
Carbapenems and 4th Generation cephalosporin 1 0
31% of total antimicrobials used in livestock are ionophores that is non-antibiotics
*In US Human: Livestock::1:3.5; most commonly used antibiotics in livestock tetracycline & fluoroquinolones.

8. Common Microbes with AMR
• Carbapenem-Resistant Acinetobacter (CRA)
• Carbapenem-Resistant Enterobacteriaceae
(CRE) Carbapenems are not used in animals
• ESBL producing Enterobacteriaceae
• Vancomycin-Resistant Enterococcus (VRE)
(Vancomycin is not used in animals.
• Methicillin Resistant S. aureus (Methicillin has
rarely been used in animals)

9. 57.4
25.4
38.0
54.4
29.4
62.4
8.7
31.5
39.7
29.7
21.3
33.7
41.4
38.9
21.7
16.4
45.6
18.6
29.6
61.6
41.0
67.4
39.3
43.6
11.7
0.0 10.0 20.0 30.0 40.0 50.0 60.0 70.0 80.0
ESBL positive
Amikacin
Amoxi+clavulanic acid
Amoxicillin
Amoxicillin+sulbactam
Ampicillin
Ampicillin+sulbactam
Cefotaxime
Ceftazidime
Ceftazidime+Clavulanic acid
Chloramphenicol
Ciprofloxacin
Cotrimoxazole
Doxicycline
Gentamicin
Imipenem
Kanamycin
Meropenem
Minocycline
Nalidixic acid
Nitrofurantoin
Penicillin
Streptomycin
Tetracycline
Tigecycline
Percent Antibiotic resistant strains (tested on ~8000 bacterial strains, Singh et al., 2023)

10. RAC-March 2023, Division of Epidemiology
5.6
11.8
9.2 9.3 10.0 9.4 9.5 8.8
18.3
13.0
10.3
51.7
8.9 9.0
11.7
10.1
14.9
19.9
23.6
21.0
25.0
27.9
31.3
10.6
16.3
19.4
27.4 27.3
36.7 37.5
35.3
39.0 39.7 40.7
34.6
16.7
12.1
14.6
34.4 33.9
32.3
34.8
36.4
37.8
41.3
66.4
43.7
45.8
0
10
20
30
40
50
60
70
2011
(386)
2012
(416)
2013
(387)
2014
(199)
2015
(407)
2016
(534)
2017
(878)
2018
(1164)
2019
(1463)
2020
(1240)
2021
(1226)
2022
(766)
ESBL Producers Carbapenem Resistant
Tigecycline Resistant Gentamicin Resistant
Tetracycline Resistant Cotrimoxazole Resistant
Enrofrofloxacin resistant Colistin Resistant
Important antibiotic resistance trends in
pathogens of animals and birds (2011-2022)

11. Foodborne Pathogens
 In 2007, WHO formed the Foodborne Disease Burden Epidemiology
Reference Group (FERG)
 In 2015, FERG estimates.
 31 major foodborne hazards resulted in over 600 million illnesses
and 420,000 deaths worldwide in 2010.
 33 million DALYs (The disability-adjusted life year is a measure of overall
disease burden)
 World Bank: Burden of ASF in Sub Saharan African countries with
adequate levels of operational funding for veterinary services =208
DALYs per 100,000 population, while it is 569 DALYs per 100,000
population in countries where such funding is inadequate.
 7 of these pathogens are transmitted exclusively by foods of Animal origin.
 Mycobacterium bovis : dairy products
 T. solium and Trichinella spp. : pork
 Paragonimus spp. : shell-fish (including crustaceans)
 Foodborne trematodes : finfish.
 Campylobacter spp., STEC, NTS, Cryptosporidium spp., Brucella spp.,
and T. gondii were transmitted by more than one food group
 Main pathogens contributing to this burden included non-typhoidal
Salmonella enterica, Taenia solium, and Campylobacter spp.

12. Burden of Foodborne Disease
Rank
(India)
Pathogen/Disease Global
(Mean no. of deaths)
India
(Mean no. of deaths)
1 Rotavirus 146480 21357
2 Shigella spp. 54905 11597
3 Campylobacter spp. 30931 10211
4 Adenovirus 46041 9999
5 Crytosporidiosis 60444 7319
6 ETEC 23649 6322
7 Salmonella spp. 38526 1748
8 EPEC 11284 1186
9 Cholera 38835 1038
10 Norovirus 14805 305
11 Clostridium difficile 808 17
12 Aeromonas spp. 7293 16
WHO (2007-2015) GBD; Lancet Infect Dis 2017; 17: 909–48

13. Campylobacter in animals in India
Area/Region Type of sample C. Jejuni
(%)
C. coli (%) Reference
Bareilly, Nainital,
Uttam Nagar,
Pantnagar
Chicken caeca
Quail caeca
3.76- 24.0 2.0-30.0 Kumar et al., 2015
Dog/Pig/
Cattle feces
0.88-6.25 2.0
Chicken 8.42-38.7 1.05-36.0 Monika et al., 2016
Chevon, Pork, Beef 3.33-5.46 0.78-2.14
Pune/Mumbai Chicken 95.0 Bandekar et al., 2005
Chennai Milk 1.3 ND Elango et al., 2012
Vellore Chicken feces 64.0 ND Rajendran et al., 2012
Kolkata Dog/Pig 4.29-8.33 32.85 Chattopadhyay et al., 2001,
Elango et al., 2012
Chicken 35.0 ND
Animal Handlers 17.50 2.0

14. Campylobacter in Humans in India
Area Type of sample C. jejuni C. coli Antimicrobial
susceptibility
Reference
Pantnagar Human stool 2.43 1.21 Rajagunalan et al.,
2014
Kumoan Human stools 3.40 ND Rawat et al., 2018
Human 8.00 ND CIP (100), E (97.8), TET
(97.8), NA (100), NX
(100), GEN (21.7)
Parkar et al.,
2014
Chennai Human stool 8.00 5.00 Dhanalakshmi et
al., 2018
Children Diarrhoea 4.50 Rajendran et al.,
2012
Human stool – HIV 8.00 ND CEP (93.75), NA (6.25),
TMP (100)
Kownhar et al.,
2007
Human stool- normal 0.50 ND
New Delhi Human stool 7.69/7.52/7.5
2
ND Ghosh et al., 2014
Kolkata Human Diarrhoeic 7.00 Sulpha-trimethoprim
(100)
Mukhopadhyay et
al., 2013
Chandigarh Human Diarrhoeic 2.35 ND NA (40%), CIP (23.3%),
TET (50.0%), S (20.0%)
Vaishnavi et al.,
2015
Lucknow Human Diarrhoeic 11.20 2.01 Jain et al., 2005
Human Healthy 0.56 ND
Puducherry Diarrhoeic patients 25.0 ND Salim et al., 2014
Dysentery 4.76 ND

15. Listeria
27.6% of the deaths by Listeria are foodborne deaths (www.cdc.gov.listeria)
GBDS (2010): 23,150 illnesses, 5463 deaths and 172,823 DALY by Listeria.
(De Noordhout et al. 2014)
 Reservoirs of Listeria: wide range. almost all species, 40 mammals, 20 birds,
crustaceans, ticks and fishes (Humphrey et al., 2007)
 GI tract of humans : major reservoir (Kampelmacher et al. 1972)
 S/G & poultry play a significant role (Dhama et al., 2015)
 Transmitted : Food and water (Brugere-Picoux 2008)
 Milk, , butter, chocolate milk, dairy products, meat, poultry, poultry
products, vegetables, salad and seafoods
(WHO, 1988; Maklon et al., 2010; Saha et al., 2015)
 Ready-to-eat and refrigerated : pose a higher risk
(Sakate et al., 2003; Ganguly, 2014a,b)
 Numerous outbreaks : milk and milk products
(CDC, 2007; Koch et al., 2010)
 Role of food in outbreak : 1977 in Boston (USA) (Ho et al., 1986)

16. Year Listeria in Foods in India Reference
Raw
milk
1996 Buffalo milk Barbuddhe
1997 Cow milk Bhilegaonkar et al.
2000 Goat milk Barbuddhe et al.
2000 Sheep Milk Barbuddhe et al
2003 Raw & pasteurized milk Dhanashree et al 2003
2011 Cow milk Soni et al 2012
Raw
meat
1993 Buffalo, sheep, goat Brahmbatt et al
1996 Buffalo Barbuddhe
1996 Goat Patnaik et al
1997 Buffalo Chaudhari
1997 Goat Banu Rekha
2000 Sheep, Goat Barbuddhe et al
2018 Chevon, Beef, Chiken Shakuntala et al 2019
Raw
fish
&
sea
foods
1989 Fresh fish, dried fish and
other seafood’s
Fuchs and Surendran
1991 Fish and shrimp Manoj et al
1992 Seafood Karunasagar et al
1996 Finfish and shellfish Jaysekaran et al
Ready-to-
eat
foods
1997 Ice cream Pednekar et al
1998 Milk products Bandekar et al
2000 Ice cream Warke et al
2007 Milk products Aurora et al

17. Aeromonads
 Aeromonas ranking : 3rd (Figueras & Beaz-Hidalgo, 2015)
 Diarrhea mortality in child in 2013: 5.5/1000 (Kotloff et al., 2013)
 In Asia, 76 cases per million population (Batra et al., 2016)
 GBDS (2013): Death : 7293
 India: 11% incidence & 5-33% prevalence in humans (Joseph, 1996)
 Complications: hemolytic-uremic syndrome (HUS), septicaemia,
meningitis, cellulitis, peritonitis, and pneumonia in immunocompromised
 50% of patients who develop HUS require renal dialysis, and the
mortality rate is particularly high for children (Figueras et al., 2007)

18. Aeromonads in animals in India
Area Type of sample A. hydrophila
(%)
A. sobria (%) Reference
Meghalaya
and Assam
Fish 13.13 NA Sharma et al., 2009
Coimbatore Fish 50.0 NA Vivekanandhan et al.,
2002, Das et al., 2012
Fresh water fish 2.0 NA
Prawns 18.34 NA
Fish pickle 25.0 NA
Mumbai Frozen fish 46.67 NA Yogananth et al., 2009
Bareilly Fish 28.57 & 22.2 NA Kumar et al., 2000;
Agarwal et al., 2000
Meghalaya
and Assam
Chicken, pork, chevon 10.0 - 22.5 NA Sharma et al., 2009
Coimbatore Fresh, frozan chicken,
raw milk, vegetables
5.0 – 28.0 79.0 Das et al., 2012
Bareilly Chicken, egg, chevon,
buffalo meat, cow milk,
tortoise, snail
5.56 – 16.67 33.39
A. caviae - 9.09
Kumar et al., 2000;
Agarwal et al., 2000
Various foods 2.36 – 14.17 Heena, 2016
Anand Chicken 16.67 72.21,
A. caviae - 12.12
Smita and
Brahmabhatt, 2011
Hyderabad Bottled, tapped, well
water
16.52 NA Didugu et al., 2015
Goa Human Diarroic Stool A. caviae (83.8%) Kaur et al., 1999

19. Aeromonads in our lab (2011-2012)
Cases Source Species of aeromonads
isolated
% Cases with
ESBL
producers
Carbapenem
resistance
Tigecycline
resistance
Fosfomyc
in
resistance
227 Clinical/
postmortem
heart blood
samples
A. bestiarum (63), A. caviae
(13), A. eucranophila (8), A.
hydrophila (14), A. jandei (7),
A. media (30), A. popoffii
(14), A. salmonicida (28), A.
schubertii (17), A. sobria (7),
A. trota (20), A. veronii (6)
63.7 24.4 83.9 76.8
72 Environmen
t (water,
sewage,
fodder)
A. bestiarum (12), A. caviae
(1), A. eucranophila (1), A.
hydrophila (10), A. jandei (9),
A. media (9), A. popoffii (3),
A. salmonicida (11), A.
schubertii (6), A. sobria (5),
A. trota (5)
39.7 33.3 15.9 87.5

20. Bacteria Source Number
of cases
Species of bacteria % positive samples for
ESBL+ CR+ TIGR Fosfo
R
Brucella Clinical/ postmotem
heart blood samples
20 B. Abortus (19), B.
melitensis (1)
25 5 10 NT
Edwardsiella Clinical/ postmotem
heart blood samples
43 E. hoshiniae (5), E.
ictaluri (2), E. tarda
(36)
39.5 11.6 6.9 NT
Escherichia Clinical/ postmotem
heart blood samples
2029 E. voli (1953), E.
fergusonii (50), E.
hermanii (3), E.
vulneris (23)
51.3 16.8 25.9 69.5
Escherichia Environment (water,
sewage, fodder)
154 E. coli (143), E.
fergusonii (3), E.
vulneris (8)
33.96 17.6 16.7 16.7
Salmonella Clinical/ postmotem
heart blood samples
55 20 Serovars
11 S. Typhimurium
0 S. Enteritidis
28 4 10 80
Salmonella Environment (water,
sewage, fodder)
61 22 Serovars
7 S. Typhimurium
1 S. Enteritidis
12.5 1.5 9.1 NT
Potentially Foodborne pathogens in our lab

21. Bacteria Source Bacteri
a tested
Spp. % of isolates showing resistance to
ESB
Ls
Carbap
enems
Tigecy
cline
Linez
olid
Vanco
mycin
MRS
A
Staphylococcus Clinical/
postmotem heart
blood samples
1173 36 38.3 13.8 6.5 9.4 49.5 63.6
Staphylococcus Environment
(water, sewage,
foods)
140 21 34.1 28.0 5.6 7.8 52.8 63.9
Streptococcus Clinical/
postmotem heart
blood samples
470 34 25.2 27.0 7.9 9.5 24.2
Streptococcus Environment
(water, sewage,
foods)
12 4 20.0 45.5 0.0 12.5 50.0
Source % of Staphylococcus species associated with infections and environment
S. aureus S. capitis S. delphini S. epidermidis S. haemolyticus S. hominis S. intermedius
Clinical
>70%
13.9 6.3 4.0 17.6 13.6 2.5 12.1
Environ 14.5 4.6 1.3 7.2 12.5 0.0 3.3
S. agalactiae S. bovis S. dysgalactiae S. equi S. milleri S. pneumoniae S. porcinus S. pyogenes
3.4 2.1 8.7 4.3 25.7 6.2 6.4 16.6
% of Streptococcus species associated with infections in animals environment (70%)

22. Some AMR challenges to ponder
Source of
Microbes
Potential
pathoges
isolates
tested
Genera % Producing % Resistant to
ESBL Carbape
nemase
Tigecy
cline
Fosfom
ycin
Linez
olid*
Vanco
mycin*
Environment 1654 70 34.0 18.2 16.9 57.6 11.0 45.5
Zoo animals 705 42 41.7 32.3 12.8 42.5 11.1 46.6
Wild animals 591 39 48.6 18.6 4.2 74.1 5.9 26.8
Pet animals 1820 64 42.0 17.3 12.8 45.4 8.5 43.8
Cattle, buffalo,
sheep & goats
2259 68 46.3 17.6 10.2 58.0 9.3 35.4
Humans 818 47 43.4 18.0 11.8 51.1 10.4 41.7
Meat and Milk 676 37 42.9 13.2 12.9 49.2 10.6 48.5
Vegetable foods 473 38 66.0 13.2 15.9 63.1 17.8 78.2
*for G+ve bacteria only

23. What to do for AMR problem?
• Stopping blame game. All are equally responsible for emergence of AMR,
share of developed and educated communities is much more than poor
and un-educated communities.
• Working together: On-Line Real-Time AST Data Sharing Platform for
different diagnostic and research laboratories doing AST routinely.
• Implementing not only antibiotic veterinary and medical stewardship but
antimicrobial production and distribution stewardship too.
• Educating for Environmental health not only human, plant and animal
health.
• AMR solution is not in searching alternatives to antibiotics but in
establishing environmental harmony.
• More emphasis on AMR epidemiology than on AMR microbiology and
pharmacology.
• Development of understanding that bacteria and other microbes are
more essential for life on earth than human race. Microbes can live
without human but humans can’t without microbes.
• Global-Health is of prime importance than economic growth/
greediness.

24. Thanking you