L02: Vaccine Guidelines (Brown) Flashcards
Non-core vaccine
- licensed
- use based on geographical and lifestyle exposure with assessment of risk-benefit ratios
Core canine vaccines (2006 AAHA)
1) Canine adenovirus-2 (CAV-2); (MLV parenteral)
2) Canine distemper virus (CDV) (MLV or rCDV)
3) Canine parvovirus (CPV-2) (MLV)
4) Rabies 1 year (killed) or 3 year (killed)
Non-core canine vaccines (2006 AAHA guidelines)
1) Parainfluenza virus (CPIV)
2) Bordetella bronchiseptica (killed bacterin - parenteral; cell wall Ag extract - parenteral)
3) Bordetella bronchiseptica (live avirulent bacteria) + Parainfluenza virus (MLV) - intranasal application
Recommended for at-risk:
4) Borrelia burgdorferi (lyme borreliosis; killed bacterin or recombinant)
5) Crotalus atrox toxoid (rattlesnake vax)
Non-core canine vaccine that has adverse rxns or has better alternative
Distemper-measles virus (MLV)
Canine vaccines that are NOT recommended (insufficient validation)
1) Porphyromonas sp. (periodontal disease vaccine)
2) Babesia vaccines
3) Canine herpesvirus vaccine
4) Canine parvo (KILLED)
5) Canine adenovirus-1 (MLV and killed)
6) CAV-2 (killed or MLV-oral)
7) Canine coronavirus (CCV) (killed and MLV)
8) Leptospira interrogans + canicola and icterohaemorrhagiae serovars (killed bacterin)
#2 and 3 licensed in EU #1 has conditional USDA license
Overall feline vaccination guidelines
Only vax if:
- realistic risk of exposure
- agent causes significant dz
- potential benefits outweigh risks
- no more frequently than necessary
- greatest # possible in at risk populations
- appropriately to protect human/PH
Core feline vax
1) Feline Calicivirus (FCV)
2) Feline herpesvirus -1 (FHV-1)
3) Feline leukemia virus (FeLV) for all kittens
4) Panleukopenia (FPV)
5) Rabies
Non-core, highly recommended feline vax
1) FeLV for adult cats
* Need to test prior to vaccine administration!*
Non-core, recommended for at risk cats only, feline vaccines
1) Bordetella bronchiseptica - intranasal only
2) feline immunodeficiency virus (FIV)
3) Chlamydophila felis (use in multi-cat environments with confirmed clinical disease) - conjunctival inoculation of vaccine may cause CS of infection
Feline vaccines generally NOT recommended unless at risk
Feline infectious peritonitis (FIP)
Reasons vaccines fail
1) Maternal-derived Ab neutralizes vaccine virus
2) vaccine poorly immunogenic
3) animal is poor responder and fails to recognize vaccinal Ag (underlying immune deficiency)
Active immunization succeeds in >98% of puppies if last vaccine dose given at which age?
14-16 wks
Does maternal Ab affect oral immunization?
NO
Only practical way to ensure a puppy’s immune system has recognized the vaccinal Ag
Testing for Ab
- should test at least 2 weeks after final puppy vaccine
- if positive, booster @ 1 yr, then q3yrs
- if negative, repeat vax + serology. If negative again, pup may be serological non responder and may be unprotected or have cell-mediated immunity or innate immunity affording some protection
Antimicrobial groups that are critically important in both humans and vet med
1) aminoglycosides
2) cephalosporins (3rd + 4th gens)
3) macrolides
4) penicillins
5) quinolones
6) tetracyclines
AVMA recommendations for judicious therapeutic use of abx
1) adhere to guidelines
2) parasite control
3) nutritional counseling
4) dental health care
5) client ed. And preventative health care programs
6) appropriate hygiene + husbandry
7) use of abx only justified if bacterial infection LIKELY to occur
8) confine use to appropriate clinical indications
9) therapeutic alternatives should be considered first
10) C/S results aid in appropriate selection of abx
11) use narrow spectrum abx when possible
12) treat for shortest effective period possible
13) caution with use of abx used to tx refractory infections in humans AND animals
1 prescribed abx
Ampicillin-clavulanate (Clavamox) - also has the worst % of confirmed cases before use
2-5:
2) Cephalexin or cefazolin
3) Enrofloxacin
4) Amoxicillin or ampicillin
5) Doxycycline
Which abx has the highest % of confirmed AND not confirmed infections before use?
Doxycycline
Top 3 worst abx in terms of vets not performing culture before use
1) clavamox
2) cefazolin or cephalexin
3) amoxicillin or ampicillin
Why is resistance not a new event
Most abx have natural origin
Ex: resistance to penicillin occurred the same year it was discovered
Methods of sensitivity testing
- Kirby Bauer Disk Diffusion
- Broth dilution
- estrip test (combo of first 2)
- PCR arrays for specific genetic mutations (in development)
Minimum Inhibitory Concentration (MIC)
Lowest concentration of an antimicrobial agent that prevents visible growth in agar or broth dilution susceptibility test
Minimum Bactericidal Concentration (MBC)
Lowest dilution where NO bacteria survive
-not routinely determined
Breakpoint
MIC or zone diameter value used to indicate susceptible S, intermediate I, and resistant R
NI = not interpreted (means no established breakpoint)
Efficacy Ratio
MIC obtained by broth dilution
-tool to evaluate relative efficacy of different antimicrobial drugs
Core vaccine
Recommended for all animals; may include non-core if legal or endemic reasons
Main targets or antibacterial drugs
1) cell wall biosynthesis
2) protein biosynthesis
3) DNA replication and repair
Which classes of abx target cell wall biosynthesis?
Beta-lactams
Glycopeptides
Cephalosporins
Which classes of abx target protein biosynthesis?
Macrolides
Tetracyclines
Aminoglycosides
Oxazolidinones
Which class of abx targets DNA replication and repair?
Fluoroquinolones
Intrinsic resistance
Innate ability to resist activity of antimicrobial
Natural insensitivity
Causes of intrinsic resistance:
- lack of affinity of drug for bacterial target
- inaccessibility of drug into bacterial cell
- extrusion of drug by chromosomally-encoded active exporters
- innate production of enzymes that inactivate drug
Anaerobic bacteria are naturally resistant against which abx? Why?
Aminoglycosides; lack of oxidative metabolism to drive uptake of aminoglycosides
Aerobic bacteria are naturally resistant to which abx and why?
Metronidazole; inability to anaerobically reduce drug to its active form
Gram + bacteria are naturally resitant to which abx and why?
Aztreonam (a beta-lactam); lack of penicillin binding proteins that bind and are inhibited by this beta lactam abx
Gram - bacteria are naturally resistant to which abx? WHy?
Vancomycin; vancomycin can’t penetrate the outer membrane
Klebsiella spp. Are naturally resistant to which abx? Why?
Ampicillin; Klebsiella produces beta-lactamases that destroy ampicillin before the drug can reach the PBP targets
Lactobacilli is naturally resistant to which abx and why?
Vancomycin; lack of appropriate cell wall precursor target to allow vancomycin to bind and inhibit cell wall synthesis
Pseudomonas aeruginosa is naturally resistant to which abx and why?
Sulfonamides, trimethoprim, tetracycline, chloramphenicol; lack of uptake resulting from inability of abx to achieve effective intracellular concentrations
Enterococci are naturally resistant to which abx and why?
Aminoglycosides due to lack of sufficient oxidative metabolism to drive uptake of aminoglycosides
All cephalosporins due to lack of PBPs that effectively bind and are inhibited by these beta-lactam abx
Acquired Resistance
Previously susceptible microbe obtains ability to resist activity of drug
Mechanisms:
- mutation of chromosomal genes involved w/ bacterial physiology/cell structures
- acquisition of foreign resistance genes (horizontal gene transfer)
- combo of both
Genetic transfer occurs by 3 methods:
1) Conjugation
2) Transformation
3) Transduction
Conjugation
Transposon or copy of plasmid transferred from one bacteria to another
*relies on a competent cell w/ ability to take it up and integrate it into its own DNA
Ex: Enterobacteriaciae encode fertility factor that allows them to better integrate and move from one organism to another
Transformation
Genes transferred from one bacterium to another as naked free-floating DNA released from a dead bacteria
Transduction
Bacterial DNA transferred via a virus that infects another bacteria
MOA of beta-lactams
Target bacterial wall synthesis; blocks cross-linking of enzymes of peptidoglycan layer of cell wall
MOA of beta-lactam resistance
Beta-lactamase or penicillin binding proteins (PBPs)
How does clavulanate amoxicillin (Clavamox) work better than just penicillin?
Clavulanate Inactivates the beta-lactamase by forming a slowly hydrolysing acyl enzyme intermediate
Amoxicillin blocks cell wall crosslinking transpeptidase, also by forming a slowly hydrolysing covalent acyl enzyme intermediate
Primary mechanisms of resistance *
1) Impermeable barrier
2) Efflux pumps
3) Resistance mutation
4) Drug inactivation
Bacterial resistance mechanism to erythromycins and tetracyclines
Efflux pumps (pump it out before can reach lethal concentrations), target modification
MOA of macrolides, lincsamides, streptogramins (MLS)? How has resistance developed to these abx?
MOA: target protein synthesis (binds 50s ribosomal subunit)
Resistance due to reduced intracellular uptake and target modification
MOA of aminoglycosides? How has resistance developed to this abx?
MOA: targets protein synthesis (binds to 30s ribosomal subunit)
Resistance due to structural modification to the antibiotic, target modification, decreased uptake/efflux pumps
MOA of tetracyclines and MOA of resistance to it?
MOA: targets protein synthesis
Resistance due to drug efflux, target modification
MOA of fluoroquinolones and MOA of resistance?
MOA: targets DNA replication/repair by targeting DNA gyrase and topoisomerase IV of the bacteria; inhibits supercoiling
Resistance due to mutation of DNA gyrase genes and DNA topoisomerase IV genes (target modification), efflux pumps
MRSP
Methicillin-resistant staphylococcus pseudointermedius
Spectrums of abx activity
Broad
Intermediate
Narrow
(May change w/ acquisition of resistance genes)
Broad spectrum includes action against:
Both Gram + and Gram - organisms
Common broad spectrum abx
Tetracyclines
Phenicols
Fluoroquinolones
3rd and 4th gen. Cephalosporins
Narrow spectrum
Limited activity and are primarily only useful against particular species of microorganisms
Narrow spectrum abx again Gram + bacteria
Glycopeptides
Bacitracin
Narrow spectrum abx against gram - bacteria
Polymixins
Narrow spectrum abx against aerobes
Aminoglycosides
Sulfonamides
Narrow spectrum abx against anaerobes
Nitroimidazoles
MOA of glycopepties and MOR (mech. Of resistance)?
MOA: inhibit the last stages of cell wall assembly by preventing cross-linking reactions
MOR: target modification, production of false targets
MOA of beta-lactams and MOR
MOA: target and bind to penicillin-binding proteins, inhibit bacterial bell wall synthesis
MOR: enzymatic destruction of beta-lactam rings, target (PBP) modification, efflux pumps
MOA of Rifampicins and MOR
MOA: interacts with the beta-subunit of the bacterial RNA polymerase to block RNA synthesis
MOR: target modification
MOA of sulfonamides and MOR
MOA: targets dihydropteroate synthase (DHPS) and prevents addition of para-aminobenzoic acid, inhibiting folic acid synthesis
MOR: target modification
Aminoglycosides MOA
Target peptidyl transferase in protein synthesis
Aminoglycoside abx
Streptomycin Dihydrostreptomycin Neomycin Kanamycin Gentamycin Amikacin
Streptomycin & dihydrostreptomycin spectrum
Narrow-spectrum aminoglycosides active against aerobic gram negatives
Neomycin & kanamycin spectrum
Expanded-spectrum aminoglycosides active against several gram positives and many gram negative aerobes
Gentamicin and amikacin spectrum
Expanded-spectrum aminoglycosides active against an expanded spectrum including Pseudomonas aeruginosa
Common uses of aminoglycosides
- control of local and systemic infections caused by aerobic (usually gram - ) bacteria
- septicemia, tracheobronchitis, pneumonia, osteoarthritis, UTI, GI tract infection, skin wounds, topical ear and eye meds
Contraindication of aminoglycosides
Potential for nephrotoxicity; don’t use if plasma creatinine >5 mg/dL
Penicillin G spectrum
Narrow spectrum penicillin active against most aerobic and anaerobic gram positives, including Clostridium spp.
More active against strep than staph
Disadvantages of penicillin G
- sensitive to beta-lactamase degradation
- inactive against most gram negative organisms
- widespread resistance
Spectrum of ampicillin
- Gram positives (including alpha and beta-hemolytic strep, sensitive staph)
- most Clostridia spp.
- SOME gram negs (E. Coli, Salmonella, Pasteurella multocida)
Spectrum of amoxicillin
Same as ampicillin with slightly better activity against gram negatives
Most anaerobic bacteria are sensitive
Spectrum of clavulanate-potentiated amoxicillin (Clavamox)
Gram positives AND gram negatives, including staph, strep, corynebacterium, clostridium, escherichia, Klebsiella, Shigella, Salmonella, Proteus, Pasteurella
More effective due to combo of beta-lactamase inhibitors and broad spectrum penicillins
First generation cephalosporins and spectrum
Cefazolin
Cephalexin
Cephalothin
Cefadroxil
Spectrum: mainly gram positive cocci
Second gen. Cephalosporins and spectrum
Cefamandole
Cefaclor
Cefoxitin
Spectrum: E. Coli, Klebsiella, Proteus, haemophilus influenzae
3rd gen. Cephalosporins and spectrum
Cefpodoxime (Simplicef) Cefovecin Ceftazidime Cefoperazone Ceftiofur (Excede, Naxcel in LA)
Spec: enterobacteriaceae, pseudomonas aeruginosa, gram positive cocci
4th gen. Cephalosporins and spectrum
Cefepime
Cefpirome
Cefclidine
Similar spectrum as 3rd gen but more resistant against beta-lactamases
Tetracycline MOA
BIND REVERSIBLY TO BACTERIAL 30S RIBOSOMES AND INHIBIT PROTEIN SYNTHESIS
Name 4 tetracyclines
1) tetracycline
2) DOXYCYCLINE
3) oxytetracycline
4) chlortetracycline
Spectrum of tetracyclines
Gram + and -
Some anaerobes
Chlamydia, mycoplasmas, some protozoa
Rickettsiae (ie. Anaplasma, Ehrlichia)
Fluoroquinolone MOA
Target DNA gyrase which helps DNA supercoiling
Name 5 fluoroquinolones
1) enrofloxacin (Baytril)
2) Ciprofloxacin
3) Difloxacin
4) Orbifloxacin
5) Marbofloxacin
Fluoroquinolones have synergistic effect with which abx?
Beta-lactams
Aminoglycosides
Clindamycin
Metronidazole
Fluoroquinolones should NOT be used prophylactically or for anaerobes
They are second line drugs!
Use for serious infections and short term therapy only!
Spectrum of activity of fluoroquinolones
Most aerobic gram negatives, and some gram positives
PARTIALLY effective against gram negative enterics and pseudomonas spp.
Variable against enterococcus and streptococcus
NOT effective against anaerobes*
Common uses of fluoroquinolones
- deep-seated infections and intracellular pathogens
- respiratory, intestinal, urinary, and skin infections
- bacterial prostatitis, meningoencephalitis, osteomyelitis, arthritis
Fluoroquinolones should be avoided in which animals?
Immature animals; high prolonged dosages in growing dogs produces cartilaginous erosions leading to permanent lameness
Target of macrolides
Interferes with protein synthesis by reversibly binding to the 50 S subunit of the ribosome, preventing translocation to keep peptide chain growing
Macrolides are active against which bacteria?
Most aerobic and anaerobic G+ bacteria
Mycobacterium, Mycoplasma, Chlamydia, and Rickettsia
Generally not active against G- bacteria
Target of lincosamides
Bind to ribosome subunit causing premature dissociation of peptidyl-tRNA from ribosome
Name 2 lincosamides
Clindamycin
Lincomycin
Which abx targeted by lincosamides?
Staph, strep Anaerobic organisms Bacteroides Fusobacterium Clostridium perfringens Actinomyces sp. Peptostreptococcus sp. Propionibacterium sp.
