Lecture 4 - Prevention and treatment of infections

What are the members of Beta Lactam antimicrobials

penicillin, ampicillin, cephalosporin, sublactams, carbapenems, monobactams

what is the mechanism of beta lactams?

inhibit cell wall synthesis (peptidoglycan synthesis)

what is the spectrum of activity of beta lactams?

differ in spectrum of activities (depends on bacteria)

what is the type of antibacterial acitvity?

bactericidal

what are the adverse effects of beta lactams

penicillin allergy and anaphylaxis reactions, time dependent killing (needs frequent dosing)

what are the members of Tetracyclines

oxytetracycline, doxycycline, micocyclineha

what is the mechanism of action for tetracyclines?

inhibit protein synthesis (bind to 30s ribosomes)

what spectrum of activity does tetracyclines have?

broad spectrum (gram pos, gram neg, protozoan)

what type of antibacterial activity do tetracyclines?

bacteriostatic

what are the adverse effects of tetracyclines?

irritant, cardiovascular effects (IV administration in horses = cardiovascular collapse), tooth discoloration, alteration of intestinal flora and enterocolitis, nephrotoxicity

what are other important characteristics of tetracyclines?

chelating agents (binds to metals), cross placental barrier, secreted in milk (withdrawal time), widely used in ruminants and swine

what are the members of the aminoglycosides?

gentamicin, amikacin, tobramycin

what is the mechanism of action of aminoglycosides?

inhibit protein synthesis

what is the spectrum of aminoglycosides?

broad spectrumwh

what is the type of antibacterial activity for aminoglycosides?

bactericidal

what is the adverse effects of aminoglycosides?

nephrotoxicity, otoxicity/cranial nerve toxicity

what are other characterisitcs of aminoglycosides?

• concentration dependent antimicrocial

• oxygen dependent uptake by microbe (not a good choice for anaerobic infections)

• need parenteral administration

• syngerism with beta lactams but physically incompatible

what are the members of fluoroquinolones?

enrofloxacin, ciprofloxacin

what is the mechanism of action of fluoroquinolones?

inhibit DNA gyrase (DNA replication)w

what is the spectrum of activity of fluoroquinolones?

broad spectrum

what is the type of antibacterial activity of fluoroquinolones?

bactericidal

what are the adverse effects of fluoroquinolones

arthropathy, ocular toxicity in cats

what are the other characteristics of fluoroquinolones

• synthetic antimicrobial agents

• concentration dependant

• high intracellular concetration in phagocytes

• prolonged antibiotic effect

• rapid resistance development

what are the macrolides?

erythromycin, azithromycin, clarithromycin

what is teh mechanism of action of macrolides?

inhibits protein synthesis (50s ribosome subunit)

what is the spectrum of activity of macrolides

broad spectrumw

what is the type of antibacterial activity of macrolides?

bacteriostatic

what are the adverse effects of macrolides?

GI effects

what is other critical info of macrolides?

intracellular accumulation in phagocytes and hence effective against intracellular baceteria

what are the members of sulfa drugs?

sulphonamide, sulfadiazine

what is the mechanism of action for sulfa

inhibit folic acid synthesis and prevents nucleic acid synthesis pathway

what is the spectrum of activity for sulfa drugs

broad

what is the type of antimicrobial activity of sulfa drugs

bacteriostatic

what is the adverse effects of sulfa drugs

allergic reaction in dogs, kcs in dogs

what are the reason bacterial culture and antimicrobial susceptibility drugs performed?

• to confirm the presence of bacterial infection

• to identify the responsible pathogen

• to direct antimicrobial therapy by choosing the most effective antibioitc

how will bacterial culture improve patient care?

• the chance and speed of patient recovery

• lower patient complications

• reduce the emergence of antimicrobial resistance

• reduce the expense and client frustration from inappropriate therapy

what are important points to consider with bacterial cultures?

• bacteria may be intrinsically resistant to treatment with antimicrobials

• knowledge of the intrinsic resistance of a pathogen of concern is important to avoid inappropriate and ineffective therapies

what is the antimicrobial susceptibility testing?

a lab test to determine whether bacteria are susceptible to a particular antimicrobial agent

performed for selecting an antimicrobial agent for tx or tracking resistance

what are the methods of AST

• broth/agar dilution test

• disk diffusion test (kibry bauer test)

how are AST results interpreted?

S - susceptible = high likelihood of therapeutic success

I - intermediate (dose dependent) = uncertain therapeutic outcome

R - resistant = high likelihood of therapeutic resistance

how is the disk diffusion/kirby bauer test performed?

standardized bacterical inoculum spread on agar plate —> single concentration antimicrobial disks placed on plate and incubated —> growth of inhibition zone diameter is measured

how are the kirby bauer results interpreted?

• zone of inhibition is measured

• based on published reference breakpoints

what is a susceptibility break point?

zone diamter or MIC value used to categorize a bacteria as susceptible intermediate or resistant

specific for

• animal species/location

• drug

• bacteria

how is the broth dilution test performed?

add multiple dilutions of antimicrobial agents in the wells of a microtiter plate or in tubes —> add a standardized inoculum of bacteria —> measure the growth inhibition endpoint

*must use bacterial isolate in pure culture

how are broth dilution test results interpreted?

based on published reference breakpoints

what is MIC?

minimum inhibitory concentration = minimum amount of drug required to inhibit bacterial growth

how does MIC influence antimicrobial treatments?

what is the E-test-gradient diffusion test?

uses diffusion and dilution; MIC can be measured - very expensive

what are some factors that help in the selection of antimicrobial drugs for treatment?

pharmacodynamics (effect on body, mechanism), pharmacokinetics (movement of drug in body)

what is the post-antibioitc effect?

describes the residual effect and the suppression of bacterial growth that persists after treament; impacts dosing regimens

• time dependent vs concentration dependent

what is the difference between time dependent and concentration dependent?

why should susceptibility testing be performed?

• helps patients today - guides vet to select correct therapy with expectation of optimizing of outcome

• help patients tomorrow - build antibiogram to guide other vets in selecting empiric therapy for future patients with the expectation of optimizing outcome

• help patients in the next decade - drive new drug research, monitor evolution of resistance

why would you use antimicrobial combinations?

• obtain antimicrobial synergism

• treat polymicrobial infections

• decrease the emergence of antimicrobial resistance

• to reduce drug toxicity

what is done if the pathogen is unknown?

four-quadrant therapy

what is the four-quadrant therapy?

• use antimicrobial or combo that has excellent activity against gram positive aerobes and anaerobes, along with gram negative aerobes and anaerobes

• used with consequense of tx failure is detrimental

• is effective against all likely bacteria

• maximizes effect of antimicrobial therapy when pathogen is unknown

  • not just using a broad spectrum antimicrobial therapy

what are important points to consider when performing susceptibility tests?

• tests conducted in vitro - cannot completely predict the behavior of the pathogen or antibiotic in vivo

• improper collection or storage of samples or previous antibiotic therapy can confound interpretation

• body sites may be colonized with bacteria, the removal of bacteria from those sites is not necessary, may by impossible

what is the most important concept to know when using antimicrobials that influence resistance?

using antimicrobials to “cover” or “just in case” is irrational and promote resistance selection pressure on existing commensal bacteria