Antimicrobial Stewardship and Antimicrobial Resistance Mechanisms Flashcards
describe the role of veterinarians in public health
- goal: reduce the need for antimicrobial use (AMU)
- keep animals healthy:
-preventative medicine
-biosecurity practices
-properly disinfect equipment - keep ourselves, workers, and animals owners healthy
-hand hygiene
-PPE - safely dispose of unused antimicrobials
when is antimicrobial use indicated?
- when inhibiting growth or killing of bacteria will allow treatment or prevention of infection
- clinical scenarios:
-prevention: at risk animals (severe immune compromise, peri-operative, high-risk cattle); targeted metaphylaxis
-treatment: sick animal (confirmed or suspected bacterial disease associated with a specific pathogen)
- minimum additional requirements:
-rest
-nursing care
-adequate nutrition
-immune function
what are the 5 rights of antimicrobial stewardship?
- right drug
- right dose
- right time
- right duration
- right route of administration
de-escalation/refine: target the pathogen based on culture and susceptibility results AND patient response
what are some considerations for AMU?
- VCPR
- species
- site of infection
- pathogen
- route of admin
- comorbidities
- side effects
- owner compliance
describe the tiers of antimicrobial stewardship programs
tier 1: prevention, peri-op, first line
tier 2: use if C&S of MIC indicates tier 1 won’t be effective; not responding to tier 1, or disease pathogen or process (sepsis) dictates used of a higher tier drug (rhodococcus equi in foals)
US FDA/USDA:
restricted: no extralabel drug use (ELDU) with cephalosporins for food producing species
prohibited: no use (illegal)
rule of thumb: prescribe like there is an ASP (antimicrobial stewardship program) even if there isn’t an established program in your practice
describe absorption, metabolism, and excretion
absorption/bioavailability:
-IV = 100% bioavailable
-other routes have reduced and variable bioavailability (especially oral and per rectum)
metabolism: drug is either metabolized or excreted unchanged
-some drugs have active metabolites
excretion:
-glomerular filtration
-renal tubular secretion
-hepatic metabolism and/or biliary excretion
-mixed renal and hepatic
describe distribution
- polar: hydrophilic and remain in the water compartments of tissue (plasma, extracellular fluid)
- lipophilic: penetrate into the tissues and are able to pass through lipid bilayer
-high volume of distribution - protein-binding: carried around on protein, which makes the half-life longer and can act as a reservoir/depot
-free drug is active drug; protein binding, pH of local environment, and purulent material in local environment can influence amount of free drug
describe opportunistic commensal bacteria by body location
- respiratory:
-streptococcus
-staphyloccocus
-pasteurellacea
-actinobacillus - skin:
-gram positive cocci: staph and strep - genitourinary tract:
-ascending infections: combo of skin and GI tract flora (gram positive and negative aerobes) - GI tract:
-gram negative enteric bacteria
-gram positive cellulolytic bacteria
-anaerobes - oral cavity:
-anaerobes (prevotella)
-facultative anaerobes
-pasteurellacea
-actinobacillus
describe privileged sites
- CNS (BBB)
- prostate (BPB)
- eye (BOB)
difficult to reach: bone, abscesses
in these sites: lipophilic drugs rule and polar drugs drool
how do the antimicrobials we give impact human health?
- direct contact
- the environment
- the food chain
describe risk factors for recovering a resistant isolate from veterinary patients
- current or prior antimicrobial exposure
-alteration in the microbiome (GI, skin, etc.) - environment
- contact with humans
-horses with MRSA - healthcare associated infections
- food exposure (raw diets)
describe campylobacteriosis
- campylobacter jejuni
-asymptomatic: self limiting in most
-puppies with disease: not a problem when with mom but can see when moving to different facilities and co-mingling - emergence of drug resistance campylobacter from just blasting these pups with antimicrobials (#fuckpetland)
-puppy to human transmission now also possible
contrast antimicrobial resistance to inherent/intrinsic resistance
antimicrobial resistance: a characteristic a microorganism has develop in response to antimicrobial pressure
inherent/intrinsic resistance: an inherent feature of a microorganism that makes it susceptible to an antimicrobial drug
-the drug never worked on that organism because of some structural or functional difference
-ex.) enterococcus can absorb folate from environment, so are resistant to TMS
how are mechanisms of resistance transferred
- horizontal gene transfer: multiple mechanisms
-conjugation: cell to cell transfer
-transduction: transfer from a bacteriophage (virus)
-transformation: absorption from environment - mobile genetic elements: plasmids, transposons, integrative and conjugative elements (ICEs)
-can carry resistance to multiple drug classes
describe the mutant selection window
- exposing bacteria to antimicrobial pressure that favors gene mutations achieving a concentration above MIC and below MPC (mutant prevention concentration)
-sometimes parameters for how above MIC you need to be are based on the MPC - kills the weak and favors the strong
- DOES NOT UNIVERSALLY KNOCK OUT ALL ISOLATES; leaves the really strong ones behind
- in a bacterial infection, growth and rapid replication of genetic material allows plenty of opportunities for “fortunate mistakes”/mutations that favor resistance and survival
once we have antimicrobial resistant bugs in the patient will they be there forever?
- once antimicrobial selection pressure is removed, wild type phenotypes re-emerge rapidly for some bacterial isolates within days
- bacteria will retain the antimicrobial resistance phenotype if there is a fitness advantage
are antimicrobial resistant organisms more pathogenic?
- generally no
- patient: infection is not more severe and organisms are not more virulent than wild-type strains
- environment: expected to respond to rigorous cleaning and disinfection similar to wild-type strain
describe antimicrobial susceptibility testing
- ID a source of infection and obtain proper sample
- submit for both cytology and culture
- from isolates, run disk diffusion via Kirby bauer method: MIC based on zone of inhibition; the smaller the zone the greater the MIC
- microdilution broth: MIC based on OD/visible growth
describe antimicrobial susceptibility results
- based on clinical and laboratory standards institute (CLSI) which helped make veterinary breakpoints
- veterinary breakpoints: for limited pathogens and veterinary species
-PK/PD dynamic data derived from studies of healthy animals/humans
-MIC of pathogen from in vitro data
-prospective clinical studies (rare in vet med) - reported as:
-susceptible
-intermediate
-resistant
-and give numeric MIC
