Antimicrobials: Resistance, Susceptibility Testing & Use

Question 1

Explain why antimicrobial resistance (AMR) is a clinical and societal problem.

Answer 1

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.

Question 2

Explain the difference between intrinsic and acquired resistance

Answer 2

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.

Question 3

What is MRSA and what are its implications to public and animal health

Answer 3

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.

Question 4

What is MRSP and what are its implications to public and animal health.

Answer 4

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.

Question 5

What is ESBL and what are its implications to public and animal health?

Answer 5

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.

Question 6

How can bacteria acquire resistance?

Answer 6

Mutation

Horizontal gene transfer (transformation, transduction, conjugation)

Question 7

What is transformation?

Answer 7

uptake of freely circulating DNA by a bacteria.

Question 8

What is transduction?

Answer 8

gene transfer mediated from phage delivery.

Question 9

What mechanism does ESBL use to confer drug resistance?

Answer 9

enzymatic drug inactivation

Question 10

What mechanism does MRSA/MRSP use to confer drug resistance?

Answer 10

Target modification

Question 11

What are the (6) mechanisms bacteria can confer drug resistance?

Answer 11

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

Question 12

Salmonella is a clinically-relevant (how is it transmitted) bacteria that is resistant to ___.

Answer 12

Foodborne bacteria

Resistant to cephalosporins and fluoroquinolones.

Question 13

Campylobacter is a clinically relevant ___ bacteria that is resistant to ____.

Answer 13

Foodborne bacteria

Resistant to macrolides and fluoroquinolones.

Question 14

For salmonella and campylobacter that is resistant to fluoroquinolones, what situations should fluoroquinolone be used as therapy?

Answer 14

Invasive infections

Question 15

What is the term used to describe a pathogen that is acquired mainly in hospitals?

Answer 15

Nosocomial pathogen

Question 16

What are the most common infections associated with ESBL-producing E. coli in dogs and cats?

Answer 16

UTI

Question 17

What are the most common infections associated with ESBL-producing E. coli in horses?

Answer 17

post-surgical (abdominal) infections.

Question 18

In what resistant bacterial species should topical treatments be utilized?

Answer 18

MRSP

Question 19

Chloramphenicol: used to treat __. Drawbacks to use __.

Answer 19

MRSP & ESBL in small companion animals

has to be administered every 8 hours and is difficult to find

Question 20

Rifampicin: used to treat ___. Drawbacks to use: ___.

Answer 20

MRSP and ESBL in small companion animals.

Hepatotoxic; resistance may emerge during therapy

Question 21

Nitrofurantoin: used to treat ___. drawbacks to use: ___.

Answer 21

MRSP and ESBL in small companion animals.

Has a very short half-life. Only suitable to treat UTI

Question 22

What is MIC?

Answer 22

Minimum Inhibitory Concentration - the lowest concentration that inhibits completely growth of the test strain

Question 23

What is MBC?

Answer 23

the lowest concentration that kills the test strain.

Question 24

What are the different methods for antimicrobial susceptibility testing (AST)?

Answer 24

Dilution and diffusion

Question 25

What are the advantages of using dilution over diffusion? Disadvantages?

Answer 25

High reproducibility, high potential for automation. Very expensive. (diffusion method is cheap, but not as reproducible)

Question 26

What is a breakpoint?

Answer 26

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

Question 27

How is quality control performed?

Answer 27

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.

Question 28

Define epidemiological cut-off

Answer 28

MIC distribution to determine the MIC value that separates the wild type (WT) population.

Question 29

What does it mean if a drug is listed as intermediate (I) susceptibility?

Answer 29

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.

Question 30

What does it mean if a strain is listed as resistant (R) susceptibility?

Answer 30

The strain is NOT inhibited at blood concentrations achieved by standard dosage of the drug.

Question 31

What are the limitations of interpretation of AST results?

Answer 31

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)

Question 32

What are the most frequent bacterial contaminants?

Answer 32

Coagulase-negatie staphylococci (skin contamination) Bacillus spp (soil contamination) Enterococci (fecal contamination)

Question 33

Define surrogate antmicrobials

Answer 33

Surrogate antimicrobials are used in the lack of approved clinical breakpoints to predict susceptibility to other drugs belonging to the same class.

Question 34

Ampicillin is a surrogate for ___.

Answer 34

Amoxicillin (aminopenicillins)

Question 35

Sulfamethoxazole is a surrogate for ___.

Answer 35

sulfadiazine (sulfonamides)

Question 36

Lincomycin is a surrogate for ___.

Answer 36

Clindamycin (lincosamides)

Question 37

Cephalotin is a surrogate for ___.

Answer 37

Cefalexin and cefazolin (1st generation cephalosporins)

Question 38

What two drugs are used in the detection of MRSA/MRSP?

Answer 38

Oxacillin & Cefoxitin

Question 39

What is the significance of a strain testing resistant to oxacillin/cefoxitin?

Answer 39

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

Question 40

When is empirical treatment recommended?

Answer 40

* 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

Question 41

Who provides international guidelines for empiric treatment of infections?

Answer 41

International Society for Companion Animal Infectious Disease (ISCAID)

Question 42

What class(es) of drug(s) should be reserved for difficult infections?

Answer 42

3rd & 4th generation cephalosporins (Cefavecin, cefpodoxime, ceftiofur, cefquinome) & fluoroquinolones (enrofloxacin, marbofloxacin, pradofloxacin)

Question 43

What is the meaning behind "shoot high" and "shoot regular"?

Answer 43

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