L9 - antimocrobila resistance in the food chain

Antimicrobial

theraputic drug that kills bacteria or stops their growth

Empiric vs definitive antimicrobial therapy

Empiric is an initial therapy given for community anf hospital-aquired infections:

• due to unavailability of microbial results within 24hrs

• empiric and guided by clinical presentation

• commonly through broad-spectrum antimicrobials or sometimes through combination of antimicrobials

Definitive therapy:

• starts once microbiological results are available

• attempt should be made to switch broad-spectrum intimicrobial therapy to narrow-spectrum regime

• to reduce toxicity and cost of antimicrobials and prevent antimicrobial resistance

Bacteriostatic VS bactericidal

Bactericidal agents kill bacteria directly, whereas bacteriostatic agents inhibit bacterial growth and reproduction, relying on the host's immune system to clear the infection.

antimicrobial combinations

• When antimicrobials exhibit synergistic activity against a
  microorganism

• When critically ill patients require empiric therapy before
  microbiological etiology and/or antimicrobial susceptibility can be
  determined (Empiric vs Definitive Antimicrobial Therapy)

• To extend the antimicrobial spectrum beyond that achieved by
  the use of a single agent for treating polymicrobial infections

• To prevent the emergence of antimicrobial resistance

  
  

Antimicrobial resistance

ability of a microorganism to survive and multiply in the presence of an antimicrobial agent that would normally inhibit or kill that particular type of microorganism

timeline of microbial resistance

key targets of antimicrobials

• Cell walls/membrane synthesis

• Nucleic acid synthesis (DNA gyrase, folate synthesis)

• Protein synthesis (RNA and ribosomes)

Intrinsic resistance

innate ability of a bacterial species to resist activity of an antimicrobial through its inherent structural or functional characteristics

• Lack of affinity of the antimicrobial for bacterial target

• Inaccessibility of the antimicrobial into bacterial cell

• Extrusion of the antimicrobial by chromosomally encoded active exporters

• Innate production of enzymes that inactivate the antimicrobia

bacterial strategies for antimicrobial resistance (genetic)

• selection pressure leads to increasign population of mutated resistant bacteria

• horizontal gene transfer - bacterial transformation, transduction or conjugation

  • transformation - bacteria uptake naked DNA

  • transduction - bacteriophages transfer bacteria; DNA

  • bacterial cells transfer DNA (i.e. plasmids, transposons, integrons) through pili

bacterial strategies for antimicrobial resistance (mechanistic)

• Efflux and decreased antimicrobial penetration

  • efflux pumos and decreased uptake/permeability

• modification of antimicrobial

  • chemical alterations of the antibiotic

  • destruction of the antibiotic molecule

• modification of target

  • target protection and modification (mutational or enzymatic or complete replacement) of target site

Antimicrobial resistance (AMR) globally

• resistance can spread across borders - travel, tourism, global trade

• case study - 2008 swedish patient travelled to India, became sick with a newly identified multidrug resistant infection

AMR global burden

4.95 million deaths associated - 2019

key drivers of AMR emergence

• germs from food and animals

• intensive farming practices - increasing demand for food

• biological causes:

  • selection pressure

  • mutation

  • horizontal gene transfer

• Environmental resistome

• Over-or innapropriste prescription of antibiotics

source and transmission routes of AMR - food chain

antimicrobial consumption in food animals

rise by 67% by 2030 - double in Brazil, Russia, India, China, South Africe

rise is driven by increased consumer demand in middle income countries. also shift to large scale farms where antimicrobials are used routinely

initiatives to preserve antibiotic effectiveness while simultaneously ensuring food security in low(er)-income countries

antibiotic use in singapore aquaculture sectors

• Individual factor

  • Personal experience and knowledge about antibiotic use in farming systems

    • participants generally found better alternative strategies to increase fish survival including purchase of better quality fish fry, good hygiene practices, and other nonconventional forms of disease management

• marker related factor

  • high price of antibiotics in singapore coupled with stiss competition from neighbouring countries

• regulatory factor

  • regular oversight from food authority as well as the stringent antibiotic-free requirements by fish harvesters and exporters

    • Regular oversight from local food authority was helpful. Economic disincentive was particularly salient among farmers raising lower-value food fish such as tilapia and milk fish. In addition, fish farmers were sensitive to increasing consumer awareness about food safety

non-antimicrobials and AMR

farm-fork continuum

Roles of coastal aquaculture environment in dynamic of AMR

High concentrations of ARG and MDR E. coli in surface waters of
farms and transect; limiting antimicrobial use in feed, and improving microbial water quality monitoring are keys.

Roles of vectors in dissemination of AMR

Wild birds and rodents could play a role in AMR transmission across
sectors; close monitoring and environment management are keys

• Multi-drug resistant (MDR) E. coli found in wild birds (23%, 6/26) and rodents (10%, 2/20) droppings.
• These MDR strains were detected with various antimicrobial resistance genes and could be considered as part of the environmental resistome.
• Findings underscores: o close monitoring on AMR bacteria in potential reservoirs; and o necessity of environment management (including food and farm environment).

Climate in changing epidemioligy of AMR

• An increase in 10°C across was associated with an increases in
antimicrobial resistance of 4.2%, 2.2% and 2.7% for the common pathogens (E. coli, K. pneumoniae and S. aureus)
• Increasing climatic temperature and population density are associated with increasing antimicrobial resistance

Tackling AMR

• Political factors – governance, health system & infrastructure, antimicrobial stewardship, surveillance systems, multi-stakeholder engagement, access to water and sanitation

• Economic factors - resources, access to appropriate antimicrobials

• Sociological factors - educational status and awareness, cultural practices and beliefs e.g. anti-vaccines, traditional practitioners and borrow medicines from their neighbours

• Technological factors - laboratory facilities and human resources, healthcare innovations through computerised real-time reporting of data

• Industry factors – investments and incentives in research and development of newer drugs

Global priority list of AMR

highest priority:

• cephalosporins

• glycopeptides

• macrolides and kelolides

• polymyxins

• quinoloncs

NSAP

National strategic plan of action

• developed in 2017 by one health government agencies

• progress report released in 2020

• NSAP identified 5 core strategies to combat AMR

  • communication and education

  • surveillance and risk assesement

  • research and evidence

  • prevention and control of infection and

  • optimisation and stewardship of antimicrobials

2 globalstrategies for tackling AMR

• Reduce the demand for antimicrobials so the current stock of drugs lasts longer

• increase the supply of new antimicrobials effective against drug-resistant bugs

reduce demand for antimicrobials

• A global public awareness campaign
• Improve sanitation and prevent the spread of infection
• Reduce unnecessary use of antimicrobials in agriculture and their
dissemination into the environment
• Improve global surveillance of drug resistance and antimicrobial consumption in humans and animals
• Promote new, rapid diagnostics to reduce unnecessary use of antimicrobials
• Promote development and use of vaccines and alternatives
• Improve the number, pay and recognition of people working in infectious disease

Increase supply of new antimicrobials

• A global innovation fund for early stage and non-commercial R&D for new
antimicrobials
• Better incentives to promote investment for new drugs and improving
existing ones

Build a global coalition for real action - via the G20 and the UN

SFA’s efforts in SG against AMR

Education surveillance and risk assessment

research

prevention and control of infection

optimisation of antimicrobial use

AMR surveillance in food chain

E.coli in raw meat

• higher in market than supermarkets

• retail and storage conditions can impact AMR bacterial contamination and proliferation

• 30% raw meat samples found with ESBL E. coli.

• Highest positive rate found in chicken, then raw pork then raw beef

• positive rates are significantly higher in wet markets

• positive rates vary with sample categories accros various countries

Active surveillance

AMU surveys local farms and veterenary industries

Antimicrobial Residues Surveillance

AST of foodborne and veterenary bacterial isolates obtained through surveillance programs

Passive surveillance

AST of bacterial isolates obtained through the existing monitoring programs across food chain and animal sectors

Genome monitoring

Genomi analysis of targeted bacteria from food animals and humans

AMR data generation

• phenotypic AMR profile by AST

  • methods: disk diffusion, E-test, VITEK AST, Broth microdilution using regional plates

  • breakpoint interpretation - CLSI or EUCAST

• Genotypic AMR profile by PCR and/or while genome sequencing

• drug residue detection and quantification

Data and exposure science

• horizon scan and data analytics

• quantitative risk modelling

AMR surveillance

• in companion and wildlife animals, local farms and food products

• measures level of AMR in bacteria from food

• monitor the use of veterinary drugs in imported foods and local farms

• Identify gentic traits of AMR bacteria

• who does this? - centre for animal and veterenary sciences, NParks, Nationa centre for food science, SFA

Innovative AMR methodology

• aquaculture environments - highly dynamic - creates contamination patterrns that point-in-time may miss

• patho-bio-gen monitoring with hydrodynamic modelling conducted at SG coastal sites, integrated with mathmatical modelling incorporating hydrodynamics

• identified hotspots at coastal sites near fish farms and seasonal variation during southwest monsoon

impact:

• developed and published for global knowledge sharing

• international interest in applying these models

• SG benefits strategically from enhanced AMR detection and capability being atopted by key exporters of aquaculture products

raising stakeholders awareness

• SFA AMR webpage

• world antimicrobial awareness week outreach

• collaboration with IHLs on education curricula and programme

• outreach to local farmers on AMR annd good AMU practices

continued food safety vigilance and joint responsibility

• good hygiene and manufacturing practices. including through cleaning, chilling, and avoiding cross-contamination, reducing exposure to bacteria

• thorough cooking

local farms

• control drug usage

  • list of banned drugs

  • prohibition of antimicrobials in growth promotion

  • proper recod keepig of drug usage

• educate local farmers

  • implement good animal husbandry practices for disease presention and management - reduce use of antibiotics

  • adopt prudent and responsible use fo antibiotics

International efforts

One health global leaders on AMR

• established by quadripartite organizations, consultation with UNSG, launched Nov 2022

ASEAN

• SG lead country for AMR initiatives for livestock and aquaculture

• strengthen regional capabilities through provision of training, such as drug residues testing of food products

FAO collaboration

• surveillance guidelines for livestock and aquaculture

• participating in missions to assess countries AMR surveillance capabilities in livestock and food

Enhance AMR communication - data driven

promote prudent use of antimicrobials and disease prevention

• Government - Sharing AMR surveillance data to overseas competent authorities in the form of report cards to raise awareness. professional educatioin in the form of training and briefing

• Industry - communication on AMR findings to local poultry farms. guides to farmers on fighting AMR through good animal husbandry practices and prudent use of antimicrobials

• Consumers - WAAW outreach, public campaigns raise awareness for condumers about preventing AMR