Embed Size (px)
Citation preview
Pranab Chatterjee MD
Senior Research Associate
Public Health Foundation of India
Environmental Health Module, MPH batch 2016-2018, IIPH, Delhi
1
Review the basics of antibiotic/antimicrobial resistance
Understand the role of environment in transmission of antibiotic/antimicrobial resistance
2
3
4
5
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
6
7
8
9
10
Balance of the humours…
11
12
13
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.
14
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.
15
ANY antibiotic use can precipitate resistance!
16
ANY antibiotic use can precipitate resistance!
17
18
19
Can you identify some of the evolutionary advantages that microbes have over us – thus making them generate
drug resistant generations so quickly?20
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.
21
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!
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:
22
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?
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 surveillance23
24
25
26
27
3 drivers:
Biocides
Metals
Antibiotic resistance genes
3 pathways:
Municipal and industrial wastewater;
Land spreading of animal manure and sewage sludge; and
Aquaculture.
28
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
29
Generally two sources:
Household or domestic use
Use in food production or for biosecurity
30
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
31
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
Conceptual model describing the environmental pathways that result in an increased risk of human and animal infection with antibiotic-resistant bacteria.
32
33
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
34
High levels of ciprofloxacin were found in river sediments downstream from the Indian treatment plant.
35
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. PLoSOne. 2011 Feb 16;6(2):e17038.
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.
36
37
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
38
39
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?
40
41
