Antimicrobials: Resistance, Susceptibility Testing & Use Flashcards
Explain why antimicrobial resistance (AMR) is a clinical and societal problem.
It’s a clinical problem because it’s difficult to treat and eradicate the infection.
It’s a societal problem because these bacteria can be spread to the rest of the population.
Explain the difference between intrinsic and acquired resistance
Intrinsic resistance is the resistance due to structural or functional traits present in all members of a given bacterial species or group. Whereas acquired resistance only occurs in select members.
What is MRSA and what are its implications to public and animal health
Methicillin Resistant Staphylococcus Aureus - has acquired the resistance gene (mecA) encoding a penicillin-binding protein (PBP2A) with low affinity to most beta-lactams (penicillins & cephalosporins). It is mainly found in pigs but can cause infection in other species (companion animals and dairy cows).
Pig farmers can introduce infection to the community.
What is MRSP and what are its implications to public and animal health.
Methicillin Resistant Staphylococcus Pseudointermedius - has acquired mecA gene (same as MRSA).
This is mainly found in dogs and can cause animal infection. It is resistant to all antimicrobials licensed for veterinary use. Human infections are rare and generally due to transmission from the household pet.
What is ESBL and what are its implications to public and animal health?
Extended Spectrum Beta Lactamase - enzyme hydrolyzing/inactivating most beta-lactams (except carbapenems) produced by gram-negative bacteria. This can affect all animal species and has a high risk of transmission via food/meat.
How can bacteria acquire resistance?
Mutation
Horizontal gene transfer (transformation, transduction, conjugation)
What is transformation?
uptake of freely circulating DNA by a bacteria.
What is transduction?
gene transfer mediated from phage delivery.
What mechanism does ESBL use to confer drug resistance?
enzymatic drug inactivation
What mechanism does MRSA/MRSP use to confer drug resistance?
Target modification
What are the (6) mechanisms bacteria can confer drug resistance?
Target modification - target is changed so the drug no longer can bind to it or has a change in affinity
Target protection
Drug trapping - drug affinity for the “trap” is higher than the target
Enzymatic drug inactivation
Reduced permability - the cell will no longer admit drug entry
Active efflux of the drug - drug is actively pumped out of the cell
Salmonella is a clinically-relevant (how is it transmitted) bacteria that is resistant to ___.
Foodborne bacteria
Resistant to cephalosporins and fluoroquinolones.
Campylobacter is a clinically relevant ___ bacteria that is resistant to ____.
Foodborne bacteria
Resistant to macrolides and fluoroquinolones.
For salmonella and campylobacter that is resistant to fluoroquinolones, what situations should fluoroquinolone be used as therapy?
Invasive infections
What is the term used to describe a pathogen that is acquired mainly in hospitals?
Nosocomial pathogen
What are the most common infections associated with ESBL-producing E. coli in dogs and cats?
UTI
What are the most common infections associated with ESBL-producing E. coli in horses?
post-surgical (abdominal) infections.
In what resistant bacterial species should topical treatments be utilized?
MRSP
Chloramphenicol: used to treat __. Drawbacks to use __.
MRSP & ESBL in small companion animals
has to be administered every 8 hours and is difficult to find
Rifampicin: used to treat ___. Drawbacks to use: ___.
MRSP and ESBL in small companion animals.
Hepatotoxic; resistance may emerge during therapy
Nitrofurantoin: used to treat ___. drawbacks to use: ___.
MRSP and ESBL in small companion animals.
Has a very short half-life. Only suitable to treat UTI
What is MIC?
Minimum Inhibitory Concentration - the lowest concentration that inhibits completely growth of the test strain
What is MBC?
the lowest concentration that kills the test strain.
What are the different methods for antimicrobial susceptibility testing (AST)?
Dilution and diffusion
What are the advantages of using dilution over diffusion? Disadvantages?
High reproducibility, high potential for automation.
Very expensive.
(diffusion method is cheap, but not as reproducible)
What is a breakpoint?
A breakpoint is a chosen concentration (mg/L) of an antibiotic which defines whether a species of bacteria is susceptible or resistant to the antibiotic
How is quality control performed?
Reference strains are incorporated in the testing. The MIC or inhibition zone diameter has to fall within as certain range as proof that standardization is successful.
Define epidemiological cut-off
MIC distribution to determine the MIC value that separates the wild type (WT) population.
What does it mean if a drug is listed as intermediate (I) susceptibility?
The drug may be clinically effective if the strain infects body sites where the drug concentrates or if the dosage can be increased compared to standard dosage.
What does it mean if a strain is listed as resistant (R) susceptibility?
The strain is NOT inhibited at blood concentrations achieved by standard dosage of the drug.
What are the limitations of interpretation of AST results?
Mixed cultures
Absence of antimicrobials used in clinical practice (drugs with no approved veterinary breakpoints, topical drugs)
Presence of antimicrobials not used in clinical practice (surrogate antimicrobials, antibiotics for ID of MRSA/MRSP)
What are the most frequent bacterial contaminants?
Coagulase-negatie staphylococci (skin contamination)
Bacillus spp (soil contamination)
Enterococci (fecal contamination)
Define surrogate antmicrobials
Surrogate antimicrobials are used in the lack of approved clinical breakpoints to predict susceptibility to other drugs belonging to the same class.
Ampicillin is a surrogate for ___.
Amoxicillin (aminopenicillins)
Sulfamethoxazole is a surrogate for ___.
sulfadiazine (sulfonamides)
Lincomycin is a surrogate for ___.
Clindamycin (lincosamides)
Cephalotin is a surrogate for ___.
Cefalexin and cefazolin (1st generation cephalosporins)
What two drugs are used in the detection of MRSA/MRSP?
Oxacillin & Cefoxitin
What is the significance of a strain testing resistant to oxacillin/cefoxitin?
These strains should be regarded as resistant to all beta-lactams irrespective of their susceptibility to penicillins and cephalosporins in the report. This is an indication of MRSA/MRSP
When is empirical treatment recommended?
- When the infection is suspected on the basis of well-grounded clinical and/or cytological data
- Life-threatening infections
- Infections where collection of relevant samples and interpretation of results are difficult
- Infection that is treated with topical therapy
Who provides international guidelines for empiric treatment of infections?
International Society for Companion Animal Infectious Disease (ISCAID)
What class(es) of drug(s) should be reserved for difficult infections?
3rd & 4th generation cephalosporins (Cefavecin, cefpodoxime, ceftiofur, cefquinome) & fluoroquinolones (enrofloxacin, marbofloxacin, pradofloxacin)
What is the meaning behind “shoot high” and “shoot regular”?
Shoot high refers to concentration dependent drugs - go for the higher dose to increase efficacy of the drug
Shoot regular refers to time dependent drugs. These must be given at regular intervals
