Micro- Antimicrobial Drugs and Drug Resistance

what are antimicrobials?

drugs that kill or stop the growth of microorganisms

can be natural or chemical compounds

what are antibiotics?

drugs that specifically target bacteria

produced naturally from molds or bacteria

what are the four uses of antibiotics in animals

therapy

prophylaxis

metaphylaxis

growth promotion

therapy

treats infection

administration of antibiotics to treat animals with clinical evidence of infectious diseases only

prophylaxis

to prevent disease

administration of antibiotics to animals at high risk of infectious disease

commonly used when environmental conditions or changes portend increased risk of infection (ex. transportation of animals, confining animals to a small, crowded space)

Metaphylaxis

mass medication in advance of an expected outbreak

treatment of a group of animals without evidence of disease, which are in close contact with other animals that do not have evidence of infectious disease

growth promotion

to increase feed efficiency

administration of sub-therapeutic doses of antibiotics to stimulate growth in animals or to increase feed efficiency

what are the four selection options for the ideal antibiotic agent

selective toxicity

spectrum of activity

antimicrobial action

mechanism of action

what is selective toxicity

causes more harm to the pathogen than to the host (ex., penicillin- inhibit bacterial growth but not the host cells)

the larger the therapeutic index, the safer the drug

what is therapeutic index

a ratio that compares the blood concentration at which a drug becomes toxic and the concentration at which the drug is effective

what do you do when the TI is small

dose the drug carefully and the patient should be monitored closely for any signs of toxicity

what is the spectrum of activity

the range of microorganisms (M.O)

what are the two types of spectrums

broad (target wide range)

narrow (target limited range)

broad-spectrum antibiotics

target many types of bacteria

useful when there is no time to wait for the identification of bacteria

using these when not needed can create resistant bacteria that are hard to treat

work well to treat infections

narrow-spectrum antibiotics

target few types of bacteria

usually require bacterial identification

less disruptive to normal flora

work well to treat infections

what is antimicrobial action

killing versus inhibiting growth of M.O

what are the two types of antimicrobial action

bacteriostatic

bactericidal

(NEVER PRESCRIBE THESE DRUGS TOGETHER)

what does bacteriostatic mean

‘static’ means stable

bacteria do not die, but they can’t grow or replicate

antibiotics→ stop bacterial growth and replication→allows host to get rid of bacteria

what does bactericidal mean

‘cidal’ means to kill

bacteria are killed

can antibiotics be both bacteriostatic and bactericidal

yes, depending on the dose, duration of exposure, and the state of invading bacteria.

what is mechanism of action

how they kill M.O

what are the five mechanisms of action

inhibition of wall synthesis

disruption of cell membrane (plasma membrane)

inhibition of protein synthesis

inhibition of nucleic acid synthesis

inhibition of metabolic pathways

inhibition of cell wall synthesis

this class of antibiotics inhibits the synthesis of cell walls in susceptible microbes by inhibiting peptidoglycan synthesis

to maximize the effectiveness, bactericidal drugs require actively growing cells

disruption of cell membrane (plasma membrane)

bind to the phospholipids of the membrane

cytoplasm and cell contents are lost

bactericidal

inhibition of protein synthesis

bacteria synthesize proteins for their structural and functional needs

prevents proteins from being made by acting as inhibitors of translation or transcription

impairing the growth of bacteria prevents them from making proteins

bacteriostatic

what is protein synthesis

process where DNA is first transcribed into a molecule of single-stranded messenger RNA (mRNA) then ribosomes translate with the help of transfer RNA (tRNA) into long strands of amino acids, which become proteins

inhibition of nucleic acid synthesis

act by interfering with DNA replication or RNA transcription

bactericidal

DNA replication

antibiotics interfere with DNA synthesis by inhibiting DNA gyrase (essential enzyme in bacterial DNA replication)

RNA transcription

antibiotics block initiation of RNA synthesis by specifically inhibiting bacterial RNA polymerase

inhibition of metabolic pathways

inhibits the folic acid synthesis pathway (all bacterial cells require folic acid for growth)

what two antibiotics work together to be bactericidal

sulfamethoxazole and trimethoprim

each inhibits a different enzyme and are bacteriostatic when used individually

what are the two types of combination therapy

synergism and antagonism

what is antibiotic synergism

the antibiotics work together to produce an effect more potent than if each were used singly (ex., streptomycin and penicillin combo)

how do streptomycin and penicillin work together

the penicillin damages the cell wall which allows the streptomycin to penetrate better

what is antibiotic antagonism

interaction between the antibiotics will have opposite effects on the body

can reduce the effectiveness of the antibiotics (ex., combination of bactericidal and bacteriostatic drugs)

how does antimicrobial resistance develop

accelerated when the presence of antibiotics puts pressure on the bacteria to adapt

the antibiotics kill some bacteria that cause infections, but also kill the helpful bacteria that protect from infection

the antimicrobial-resistant bacteria survive and multiply

how does resistance spread in human medicine

a patient had a cold→ prescribed antibiotics→ resistant bacteria develop in their gut

patients can spread bacteria in the community

hospitalized patients can spread resistant bugs to other patients in healthcare settings directly or indirectly

how does resistance spread in veterinary medicine

farm animals receive antibiotics which cause antibiotic-resistant bacteria to develop in the gut

fertilizer or water-contaminated with feces and resistant bacteria when used on food crops

meat products that are not handled or appropriately cooked can transfer resistant bacteria

what are the consequences of misuse of antibiotics

emergence of AMR pathogen → common infections are no longer treatable →longer hospital stay; higher medical costs; more debts

what are the two types of bacterial resistance

intrinsic and acquired

what are the three possible outcomes when a bacteria is exposed to an antibiotic

they will die

they will stagnate (not multiply)

they will multiply

what three factors will predict what is more likely to happen

antibiotic concentration

bacterial mutation

bacterial genetic exchange

what is intrinsic resistance

a bacterial species is naturally resistant to a certain antibiotic or family of antibiotics without the need for mutation or gain of further genes

can never be used to treat infections caused by that species of bacteria

what kind of bacteria is resistant to vancomycin

gram negative because the extra outer membrane prevents a large molecule like vancomycin from entering the cell

what is acquired resistance

happens when a type of bacteria changes in a way that protects it from the antibiotic

what two ways can bacteria acquire resistance

mutation and gene transfer

how can mutation make bacteria acquire resistance

through a new genetic change that helps the bacterium survive

how can gene transfer make a bacterium acquire resistance

getting DNA from a bacterium that is already resistant

(vertical gene transfer: resistance passed to daughter cells)

(horizontal gene transfer: transferred by DNA packets between bacteria of the same or different species of environment)

what are the four mechanisms of resistance

altered target

enzyme degradation

efflux pump

DNA mutation and gene transfer

altered target

ex. MRSA

common mechanism that bacteria use to become resistant to antibiotics by modifying the target of the antibiotic

modify the antibiotic binding receptor and antibiotics no more attach

enzyme degradation

ex. penicillinase

destroy or inactivate the drug before it enters the bacterial cell

efflux pumps

function primarily to rid the bacterial cell of toxic substances and many of these pumps will transport a large variety of compounds

pump antibiotics out of the cell thereby preventing them reaching lethal concentrations

work along with reduced permeability of the cell membrane to mediate resistance

reduced permeability, lower the intracellular antibiotic concentration in the bacterial cell by not allowing its importation

DNA mutation

when bacteria multiple, some will mutate

some mutations can make the bacteria resistant to drug treatment

in the presence of antibiotics, only the resistant survive, multiply, and thrive

(REMEMBER: the presence of antibiotics does not increase the frequency of mutation)

(the presence of antibiotics does apply selection pressure favoring resistant bacteria)

Gene transfer

facilitates the spread of drug resistance

bacteria that have drug resistant DNA may transfer a copy of these genes to other bacteria

non-resistant bacteria receive the new DNA and become resistant to drugs

what are the three ways in which gene transfer occurs

tranduction

transformation

conjugation

transduction

bacteriophages (viruses infecting bacteria) mediate transfer of DNA between bacteria via transduction, whereby DNA from a donor bacterium is packages into a virus particle and transferred into a recipient bacterium during infection

transformation

some bacteria are able to take up free DNA from the environment and incorporate it into their chromosome

conjugation

a sex pilus (small tube) forms between two bacterial cells through which a plasmid is transferred from one to the other

what are the five main points to patient compliance for emergence of antimicrobial resistance

low dose of bactericidal antibiotics can function as active mutagens

forgetting to give medication

skipping the doses

not giving the right dose

stopping antibiotics before the prescription is finished

what is antimicrobial stewardship

the actions veterinarians take individually and as a profession to preserve the effectiveness and availability of antimicrobial drugs through judicious use

what are the three points to antimicrobial stewardship

determine whether an antimicrobial is needed

select an appropriate antimicrobial

use antimicrobial drugs in an effective way that does not increase resistance

determining whether an antimicrobial is needed

infection versus inflammation

bacterial versus viral

if it is bacterial, treat or not treat?

selecting an appropriate antimicrobial

empirical therapy- guessing which antibiotic is most likely to be effective given the location of the infection and the bacterium most likely inhabiting that area

used often in culture and susceptibility results or other data

does NOT account for the changing resistance patterns or lengths of any prior antibiotic treatment

using antimicrobial drugs in an effective way that does not increase resistance

check and determine if the drug will reach the infection site

complete the entire dose regimen

what are the four roles of veterinary nurses as antibiotic guardians

role in reducing the incidence of antibiotic resistance in animals

role in antibiotic stewardship

role in reducing the spread of antibiotic resistance in hospitals

role in reducing the spread of antibiotic resistance in the community

what are the three main points in reducing the incidence of antibiotic resistance in animals

education of clients

implementation of clinical protocols to avoid unnecessary use of antibiotics

excellent hygienic conditions

education of clients

managing client expectations- newsletters and information in the waiting room

conveying instructions about correct use of prescribed antibiotics

explain holistic approach to pet health to prevent hospitalization

implementation of clinical protocols to avoid unnecessary use of antibiotics

implementing infection control practices

following surgical asepsis

excellent hygienic conditions

clinic hygiene- to avoid nosocomial infections

personal hygiene- hand washing; street dress; scrubs

what are the four roles within antibiotic stewardship for a veterinary nurse

promoting culture and sensitivity

encouraging good biosecurity and husbandry practices

maintaining awareness of AMR

ensuring that there are effective and up to date cleaning and disinfection protocols in place

what are biosecurity measures to help reduce the spread of antibiotic resistance in hospitals

maintaining proper isolation and barrier nursing precautions

wearing personal protective equipment

following cleaning and hygiene practices

aseptic techniques for invasive and surgical procedures

what are ways to inform the clients about to help prevent the spread of antibiotic resistance in the community

continue to isolate animals

provide fact sheets and verbal consultations to minimize the spread of resistant bacteria into the wider community

holistic approach to pet health will prevent the need for antibiotics and hospital stays (ex. good nutrition; vaccine and parasite control, neutering)