This document discusses antibiotic resistance and the role of the environment in the transmission of resistant bacteria. It begins with an overview of antibiotic resistance and how easy it is to make bacteria resistant to penicillin in the laboratory. It then discusses how improper use of antibiotics can educate bacteria to become resistant and infect others. The document notes that any antibiotic use can lead to resistance and discusses some evolutionary advantages bacteria have over humans in developing drug resistance. It also presents a hypothetical case study of a MRSA outbreak in high school students and how one would investigate such an outbreak. Finally, it discusses major drivers of antibiotic resistance in the environment, including biocides, metals, and antibiotics themselves, as well as pathways by which resistance can spread environmentally through

1. Pranab Chatterjee MD
Senior Research Associate
Public Health Foundation of India
Environmental Health Module, MPH batch 2016-2018, IIPH, Delhi
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2.  Review the basics of antibiotic/antimicrobial resistance
 Understand the role of environment in transmission of antibiotic/antimicrobial
resistance
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6.  It is not difficult to make microbes resistant to
penicillin in the laboratory by exposing them
to concentrations not sufficient to kill them, and
the same thing has occasionally happened in
the body.
 The time may come when penicillin can be
bought by anyone in the shops.Then there is
the danger that the ignorant man may easily
underdose himself and by exposing his
microbes to non-lethal quantities of the drug
make them resistant. Here is a hypothetical
illustration. Mr. X. has a sore throat. He buys
some penicillin and gives himself, not enough
to kill the streptococci but enough to educate
them to resist penicillin. He then infects his
wife. Mrs. X gets pneumonia and is treated with
penicillin. As the streptococci are now resistant
to penicillin the treatment fails. Mrs. X dies.
Who is primarily responsible for Mrs. X’s
death? Why Mr. X whose negligent use of
penicillin changed the nature of the microbe.
Moral: If you use penicillin, use enough.
Alexander Fleming, Nobel Lecture,
December 11, 1945
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11.  Balance of the humours…
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14.  In World War I, ratio of battle
and wound deaths to “war
pestilence” deaths was 1:0.4
 War pestilence = Diseases
which spread in war time:
cholera, dysentery, plague,
small pox, typhoid, typhus,
etc.
 A lot of the wounded ended
up with infections which they
succumbed to.
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15.  The ability of bacteria (or other
microbes) to resist the effects of
antibiotics (or antimicrobials).
 This occurs when microbes
change in some way that reduces
or eliminates the effectiveness of
the agent.
 The resistant microbe continues
to survive and continues
multiplying, causing
progressively more harm.
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16.  ANY antibiotic use can precipitate resistance!
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17.  ANY antibiotic use can precipitate resistance!
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20.  Can you identify some of the evolutionary advantages
that microbes have over us – thus making them generate
drug resistant generations so quickly?
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21.  17 students from a local high school report with skin infections which refused to be
managed by topical ointments, followed by oral co-amoxiclav.Their wounds
rapidly worsen, develop cellulitis and skin breakage, suppuration, and systemic
signs. Cultures revealed the presence of MRSA.
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Group 1:What is/are the potential
source of this outbreak?
Group 2: How would you go about
investigating the outbreak to find its
cause?
If you need additional
information to investigate
this outbreak, please ask
me!

22.  17 students from a local high school report with skin infections which refused to be managed
by topical ointments, followed by oral co-amoxiclav.Their wounds rapidly worsen, develop
cellulitis and skin breakage, suppuration, and systemic signs. Cultures revealed the presence
of MRSA.The demographic analyses show:
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Factors Frequencies
Gender Male 14, Female 3
Age range 15-18 years
Infection
locations
(multiple)
Upper Extremities: 13
Lower Extremities: 8
Face: 5
Torso: 2 (both males)
Co-curricular
profile
Football players: 12 males
Cheerleaders: 3 females
Track athletes: 2 males
Healthcare
contacts
No hospital visits
Group 1:What is/are the potential source
of this outbreak?
Group 2: How would you go about
investigating the outbreak to find its
cause?

23. 1. Identify investigation team
and resources
2. Establish the existence of an
outbreak
3. Verify the diagnosis
4. Construct case definitions
5. Find cases systematically and
develop line listing of cases
6. Perform descriptive
epidemiology and/or
develop hypotheses
7. Evaluate hypotheses and/or
perform additional studies as
needed
8. Implement control measures
9. Communicate findings
10. Maintain surveillance
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28.  3 drivers:
 Biocides
 Metals
 Antibiotic resistance genes
 3 pathways:
 Municipal and industrial
wastewater;
 Land spreading of animal
manure and sewage
sludge; and
 Aquaculture.
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29.  Disinfectants:
 Triclosan, Ethanol, Formaldehyde, Chlorhexidine, etc.
 Some resistance mechanisms are common to antibiotics and biocides
 So use of biocides predisposes to select resistant organisms
 Co-resistance: Resistance to biocide is caused by similar genetic element that also
encodes for antibiotics
 Cross-resistance: Resistance is coded for by different genetic elements, but
selected bacteria are resistant to both biocides and antibiotics
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30.  Generally two sources:
 Household or domestic use
 Use in food production or for
biosecurity
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31.  Copper: Often used in sprays with pesticides and fertilizers
 Other heavy metals may be sprayed or arise as contaminants
 Heavy metals and antibiotics share resistance mechanisms
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Mechanism of Resistance Metals Antibiotics
Reduced membrane
permeability
As, Cu, Zn, Mn, Co,
Ag
Ciprofloxacin,Tetracycline, Chloramphenicol, Beta
lactams
Metabolic alteration As, Hg Beta lactams, Chloramphenicol
Efflux Cu, Co, Zn, Cd, Ni, As Tetracycline, Beta lactams
Alteration of cellular targets Hg, Zn, Cu Ciprofloxacin, Beta lactams,Trimethoprim, Rifampicin
Sequestration Zn, Cd, Cu Couermycin A

32.  Conceptual model
describing the
environmental pathways
that result in an increased
risk of human and animal
infection with antibiotic-
resistant bacteria.
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34. PHARMACEUTICAL EFFLUENTS AND AMR
 Pharmaceutical effluents may contain antibiotics
 These are released into the waste water, which are typically discharged in rivers in
India
 Studies have shown alarming levels of antimicrobial agents downstream from
pharmaceutical industries
 Not only that, it has been seen to encourage the development of antibiotic
resistance genes in the bacterial flora
 The Pitfall: There has been no conclusive link between such resistance genes in
the environment and resistant infections in man
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35.  High levels of ciprofloxacin were
found in river sediments downstream
from the Indian treatment plant.
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 Exposure to
antibiotic-
contaminated
effluent promotes
resistance genes in
bacterial
communities in
river sediment.
Kristiansson E, Fick J, Janzon A, et al
Pyrosequencing of antibiotic-contaminated
river sediments reveals high levels of
resistance and gene transfer elements. PLoS
One. 2011 Feb 16;6(2):e17038.

36.  There is a farmer who rears cattle and pigs. He rears them in a very unhealth
environment and often gives them sub-therapeutic doses of antibiotics to prevent
the occurrence of illnesses. He does this so that the animals stay healthy and
productive and he does not suffer economic losses.
 He also has a little plot of land on which he grows fodder for the cattle. He uses the
manure from the cattle as fertiliser for the fodder crops to cut down on input costs.
 Develop a conceptual model which shows how using such manure may lead to the
emergence of antibiotic resistant organisms in the context of his farm.
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38.  A high frequency of isolates
(58.73%) were multidrug
resistant (resistance to three or
more class of antimicrobials)
and the most frequent resistance
was detected against
streptomycin (88.36%),
sulfisoxazole (67.2%), and
tetracycline (57.67%).
Genotypic characterization by
pulse field gel electrophoresis
revealed clonally related
Salmonella in both manure and
soil at multiple time points in the
positive farms. Our study
highlights the potential role of
swine manure application in the
dissemination and persistence
of antimicrobial resistant
Salmonella in the environment
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40.  Are there direct or indirect implications to the health, reproduction or ecosystem
services of organisms or populations resulting from chronic exposure to elevated
AMR drivers, as in Figure 1, in the environment?
 What are the relative contributions of the different AMR pathways, as in Figure 1,
for establishing, maintaining and disseminating ARGs in the environment?
 What are the relative contributions of the different AMR drivers, as in Figure 1, for
establishing, maintaining and disseminating ARGs in the environment?
 What concentrations of AMR drivers are relevant for assessing the risk of AMR
selection and co-selection?
 Are there direct or indirect implications from the trophic transfer of antibiotics,
biocides, metals, or ARGs found within microorganisms, animals (aquaculture), or
plants?
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42. Pranab Chatterjee, MD
Email: mail@pranab.in OR infectionscape@gmail.com
Twitter: @Scepticemia
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