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VETM 443 Clin Pharm Tox > Antimicrobials > Flashcards

Antimicrobials Flashcards

1
Q

define antimicrobials

A

Chemicals that kill or inhibit the growth of microorganisms (can include bacteria, fungi, viruses, protozoa).

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2
Q

define antibacterials

A

chemical that kills or inhibits growth of bactera

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3
Q

define antiseptic

A

biocide that reduces microbial population on living tissue

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4
Q

define disinfectant

A

biocide that reduced microbial population on inanimate objects

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5
Q

define minimum inhibitory concentration MIC

A

lowest concentration of antimicrobial that completely inhibits growth in vitro

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6
Q

define minimum bactericidal concentration

A

lowest concentration of antimicrobial that kills 99.9% isolates in vitro

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7
Q

_______ drugs have activity against a single pathogen or limited group of pathogens and are less likely to have adverse affects

A

narrow-spectrum

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8
Q

_____ drugs have activity against a wide range of pathogens, useful when causative agent and have serious disease

A

broad-spectrum

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9
Q

drugs with intermediate range of pathogens are sometimes called

A

extended spectrum

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10
Q

fluoroquinolone, aminoglycosides, and metronidazole have ______-dependent and bacteri_______ effects

A

concentration-dependent, bactericidal (there are no concentration-dependent bacteriostatic drugs)

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11
Q

efficacy of _______-dependent antibacterials depend on amount of time at concentration at SITE OF INFECTION is higher than MIC

A

time-dependent

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12
Q

time-dependent effects: name 5 drugs with dosage regimen goal to maximize time above MIC

A

penicillins, phenicols, cephalosporins, macrolides, tetracyclines

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13
Q

time-dependent effects: name 3 drugs that 24 hour AUC/MIC ratio (daily total exposure to drug) is a better predictor of efficacy than just time above MIC

A

azithromycin, clarithromycin, clindamycin (they are time-dependent technically bu have concentration-depdendent-like effects)

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14
Q

name 4 time-dependent bactericidal drug classes

A

penicillins, cephalosporins, TMS, florfenicol (only bactericidal against BRD pathogens)

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15
Q

name the 6 time-dependent bacteriostatic drug classes

A

chloramphenicol, florfenicol (except bactericidal against BRD pathogens), tetracyclines, sulfonamides, lincosamides, macrolides

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16
Q

give 3 tests that can be sued to determine MIC for a drug and bacterial isolate

A

broth dilation, Kirby-Bauer (disk diffusion), and E-test (the strip)

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17
Q

bacterial are classified as ________ or _____ to antibacterials based on MIC breakpoints

A

susceptible or resistant

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18
Q

Bacteria are classified as susceptible or resistant to antibacterials based on ______

A

MIC breakpoints (breakpoint specific to drug, MIC values specific to bacteria)

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19
Q

what treatment is based on knowledge of what bacteria are likely causing disease, and what antibacterial drugs re likely effective against them, is called

A

empirical treatment

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20
Q

3 questions to consider for deciding if antimicrobials are necessary

A

do we have a suitable antimicrobials to treat disease? will the animal recover without antimicrobials? will the use of antimicrobials greatly improve disease outcome of reduce risk to other animals?

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21
Q

what is prophylactic vs metaphylactic treatment

A

preventative treatment of an animal (prophylactic) or group of animals (metaphylactic)

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22
Q

what is therapeutic treatment

A

treatment of a diagnosed bacterial infection

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23
Q

what are the 4 quadrants of bacteria types and antimicrobial selection

A

Gram + aerobes, Gram - aerobes, Gram + anaerobes, Gram - anaerobes

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24
Q

there are __ categories of drugs based on importance in human medicine

A

4

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25
Q

sulfonamides: give MOA and bacteri_____

A

folic acid inhibitors (prevent bacteria from synthesizing folic acid from PABA); therefore bacteriostatic

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26
Q

why did prontosil, a sulfonamide, protect mice and rabbits from streptococcal infections but not kill/harm bacteria in a test tube?

A

prontosil was a prodrug [has to get metabolized to sulfanilamide]

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27
Q

what do all the sulfonamide class drugs have in their name

A

:) sulfa

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28
Q

sulfonamide drugs: tell me their activity against aerobic vs anaerobic and gram + vs - bacteria

A

limited activity against Aerobic gram +: staph, strep, Nocardia
limited activity against Aerobic gram - : Klebsiella, Pasterurella, Proteus, some E. coli (there is fair amount of resistance)
not effective for ANaerobes in vivo
not effective for abscesses because PABA and thymidine inhibits sulfonamide activity

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29
Q

sulfonamide drugs: are they effective against any parasites?

A

yes! some protozoa and coccidians: Toxoplasma, sarcocystis

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30
Q

sulfonamides ALONE are mainly used in what animal species

A

production animals. eg. in pork, may promote better growth.
but not listed on the “reasonable empirical choices for cattle” cart - we really just use potentiated sulfonamides now

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31
Q

sulfonamides + diaminopyrimidine, which have better antimicrobial activity than sulfonamides alone, are known as what

A

potentiated sulfonamides

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32
Q

give mechanism of action for diaminopyrimidines

A

folic acid synthesis inhibitors (remember, they have sulphonamides) because they inhibit dihydrofolate reductase

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33
Q

name the two diaminopyrimidines to know

A

trimethoprim and ormetoprim

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34
Q

PK of diaminopyrimidines: unlike sulphonamides, what do these drugs penetrate via diffusion

A

cell membranes (can enter prostate, CNS, milk; like sulphonamides, still not great in abscesses)
they are lipid-soluble organic bases

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35
Q
  • this drug is delivered as a combination product in appropriate ratio
  • labelled q24h but more effective given q12h
  • used in companion animals for enteric bacteria, and used in cattle for streptococcus, and in horses used against a variety of aerobes because it is one of few safe oral antibacterials in horses
  • category III
A

trimethoprim/sulfadiazine, ie. TMS (1:5 trimethoprim:sulfa formulation)

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36
Q

TMS is labelled for acute strangles in horses, but what should you be cautious about

A

not effective in abscesses bc it is a potentiated sulfonamide (reduced activity due to PABA and thymidine in the abscesses)

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37
Q

bacterial resistance to sulphonamides and potentiated sulphonamides is common. name 3 mechanisms of cross-resistance

A

efflux pumps, failure to penetrate organism, changes in target membrane
note complete cross-resistance means that resistance to one = resistance to all

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38
Q

the beta lactam class of drugs, which are drugs that have a beta-lactam ring, includes these three groupings

A

penicillins, cephalosporins, carbapenems, and “related drugs”

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39
Q

what is beta-lactam MOA

A

β‐lactams bind to penicillin binding proteins (transpeptidases) that cross‐link peptidoglycans within the cell wall, causing cell wall to be nonfunctional and cells undergo osmotic rupture (“pop”) (as such, they are bactericidal)

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40
Q

why do bata-lactamh generally have few adverse effects

A

mammals don’t have cell walls

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41
Q

PK of beta-lactams: excreted largely unchanged by the kidneys, so what does that tell you?

A

metabolism not a big part of PK for these drugs

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42
Q

what is the post-antibiotic effect?

A

period of time after the drug concentration falls below the MIC during which bacterial growth is still inhibited; bactericidal drugs of ten have a post-antibiotic effect

43
Q

what are 3 mechanisms of resistance against beta-lactam drugs

A

beta-lactamase production, reduced penetration thorugh outer cell membrane (efflux pumps), or altered targets (PBPs that resist binding be beta-lactams)

44
Q

should penicillins be given in combination with bacteriostatic drugs? why or why not?

A

no! penicillins are bactericidal and they kill the growing bacteria. if the bacteria aren’t growing due to bacteriostatic drug use, the penicillin can’t do as much, so not as effective

45
Q

do beta-lactams penetrate eye, joints, CSF, or milk well?

A

no. but penetrate better when there is inflammation

46
Q

this narrow-spectrum penicillin is active against some Gram + & - aerobes, many anaerobes, many spirochetes, and susceptible to beta-lactamase degradation
- given at a label dose may result in underusing
- not given orally; certain formulations can’t be given IV

A

penicillin G
[the procaine penicillin G formulation can result in CNS toxicity if given IV, and the benzathine penicillin G formulation can result in cardiac arrest if given IV]

47
Q

compared to penicillin G, this category of penicillins is active against the same bacteria, but is better at penetrating Gram- cell membranes which increases its spectrum. what is this category of penicillins? what are the two drugs to know from this category?
- many Gram - are still resistant

A

aminopenicillins - amoxicillin (can be given PO) and ampicillin (can be given IV, IM, SQ)

48
Q

which species should you NOT give oral penicillins to

A

hindgut fermenters: horses and rabbits
[disrupts essential GI microbes and can cause potentially fatal clostridial overgrowth’

49
Q

most penicillinase-resistance penicillins are rarely used clinically, except for one, which given intramammary (eg. for dairy cows) and is active against many penicillinase-producing staphylococcus organisms

A

cloxacillin
[explanation of why given IMM: remember that the beta-lactams aren’t good at distributing into eye, milk, CSF, or joints, so if you want to treat mastitis this is a good route of delivery]

50
Q

you suspect a staphylococcus infection, so perform C&S with oxacillin (which is a penicillinase-resistance penicillin commonly used for sensitivity testing) and find that your bacterial isolate is resistant. what kind of staph do you have? what are you NOT going to use to treat?

A

methicillin-resistant staphylococcus [aureus or pseudointermedius, MRSA or MRSP]
do NOT use beta-lactams

51
Q

what are the potentiated penicillins made of?
what is one commonly used in vet med

A

a beta-lactamase inhibitor plus a penicillin
in vet med, clavulanic acid + amoxicillin is commonly used (also sublactam/ampicillin, and tazobactam/piperacillin)

52
Q

the potentiated aminopenicillin, clavulanic acid + amoxicillin, is effective against most bacteria commonly targeted except for what genus

A

Pseudomonas

53
Q

cephalosporins are effective against many pathogens and are often a good first-line treatment. they are similar to aminopenicillins in their spectrum of activity, but with more activity against some gram negative bet-lactamase producing strains.
what do they have good efficacy against (of particular importance)?
what are they not effective against?

A

beta-lactamase producing staphylococci
not effective against methicillin-resistance staphylococci [except fifth generation, but not used in vet med]
also not generally effective against anaerobes

54
Q

the 2 first-generation cephalosporins used are

A

cephalexin, cefazolin
[these are good against gram positive aerobes other than Enterococcus, certain Gram - aerobic respiratory bacteria (Pasteruella, Mannheimia, Histophilus), but use with caution against anaerobes]

55
Q

cephalosporins are ____ bactericidal than penicillins. why does this matter?

A

less. need more time above MIC and often need more frequent administration [not a red card]

56
Q

cephalosporins are excreted really and high concentrations are obtained in urine. what does this imply [not a red card]

A

good for UTI treatment

57
Q

most common cephalosporin used in companion animal practice, given PO, a first generation cephalosporin, and most commonly used to treat staphylococcal pyoderma in dogs

A

cephalexin

58
Q

injectable cephalosporin in companion animals, given IV IM or SQ, a first generation cephalosporin, commonly used as a preoperative prophylactic antibacterial

A

cefazolin

59
Q

what is the main difference between second and first generation cephalosporins [not a red card]

A

similar spectrum, but second generation has some activity against anaerobes, especially Bacteroides

60
Q

how are third generation cephalosporins different from earlier generations?

A

greater activity against gram negative pathogens
[good for gram + aerobes except Enterococcus, gram - aerobes except Pseudomonas, and ceftiofur specifically good for the footrest Gram - anaerobes]

61
Q

this category I third-generation cephalosporin is commonly used in horses an production animals, is approved for UTIs, only in dogs, and can be delivered as a short acting of long acting formulation

A

ceftiofur

62
Q

this category I third-generation cephalosporin is long-acting, used in companion animals, highly protein bound (and therefore long half-life), maintains therapeutic concentrations against some bacteria for up to 14 days after 1 SQ injection, and despite its convenience (wide spectrum compared to first generation cephalosporins) should not be used as first choice due to AMR CONCERNS

A

cefovecin [think, also known as Convenia, but also concerns for AMR if it gets used a lot]

63
Q

what class of beta-lactams is the most bactericidal, has the broadest spectrum, and is a LAST RESORT for very severe, resistant infections due to very high importance in human medicine? [not red]

A

carbapenems

64
Q

MOA of tetracyclines

A

bind to 30S and interfere with binding oof tRNA to ribosomal complex, inhibiting protein synthesis reversibly
(thus for PD: inhibit protein synthesis = bacteriostatic; reversible = need to maintain concentrations for long time = time-dependent)

65
Q

tell me about PK of tetracyclines: administration? lipophilic? protein binding? excretion?

A

administered IV, IM, or PO depending on drug
lipophilic so can cross membranes, doxycycline more so than oxytetracycline
variable protein binding
variable excretion; doxycycline by GIT and oxytetracycline by kidneys

66
Q

can you use metronidazole in production animals

A

NO

67
Q

give MOA of metronidazole, a nitroimidazole

A

produce short-lived intermediates/free radicals inside bacteria or protozoans that damage their DNA (therefore bactericidal, also they are concentration-dependent)

68
Q

what is spectrum of activity for metronidazole

A

anaerobes and protozoans

69
Q

tell me about metronidazole: how it is delivered, use in dogs and cats, use in horses

A

good oral availability and can be used IV for prophylactic colorectal or sepsis surgery; dog and cat giardiasis, horse anaerobic bacterial infections (horses don’t like taste so can also give rectally)

70
Q

tell me about tetracycline spectrum of activity and overall resistance

A

broad spectrum generally (not for enteric gram - aerobes or Pseudomonas)
but lots of resistance and cross-resistance, especially in the gram - aerobes

71
Q

this is the most commonly used tetracycline is production animals, used in cattle for pneumonia and metritis, horses for Potomac horse fever mainly, sometimes given high-dose to neonates to treat tendon contracture but significant adverse effects are possible and hydration is essential. As with other tetracyclines, there is a lot of resistance. Category III.

A

oxytetracycline

72
Q

most commonly used tetracycline in companion animals, used for vector-borne intracellular pathogens; resistance is common in its class; category III
- drug of choice for treatment of tick‐borne infections such as Ehrlichia canis, Borrelia burgdorferi and Rickettsia, as well as Mycoplasma haemofelis (flea transmitted)
- also recommended for firstline treatment of Mycoplasma and Chlamydia respiratory infections in small animals
- recommended as part of combination treatment for heart worm disease

A

doxycycline

73
Q

give at least 4 adverse effects of oxytetracycline in production animals (there are many).
with IV administration, what can you do to reduce risk?

A
  • young animals: tooth discoloration, inhibited bone growth (can be due to crossing placenta, gets into milk, or giving to young animals)
  • high doses: nephrotoxicity
  • especially if pregnant: hepatotoxicity (especially if pregnant, but a rare effect)
  • rapid IV administration: hypotension and collapse, so give slowly!
74
Q

give at least 4 adverse effects of doxycycline in companion animals (there are many).
with PO administration, what can you do to reduce risk?
with IV administration, what can you do to reduce risk?

A
  • young animals: teeth discoloration, inhibited boen growth (either given to young animals or crosses placenta/gets into milk)
  • cat: fever; oral form esophageal strictures so DON’T GIVE DRY
  • hepatotoxicity: rare, especially occurs in pregnant animals
  • rapid IV administration: hypotension and collapse, so give slowly
  • note that doxycycline isn’t commonly given to horses, but never give iV to them because they die
75
Q

how does treating dogs with doxycycline help (in combination treatment) to treat heartworm

A

doxycycline kills Wolbachia organisms which are symbionts within heart worms, so killing them facilitates heart worm elimination
[doxycycline both reduces Wolbachia released into dog bloodstream, reducing inflammation in dog host, and reduces worm mass]

76
Q

what is a non-antibacterial effect of doxycycline

A

anti-inflammatory / immunomodulatory effect [Doxycycline inhibits matrix metalloproteinase activity, neutrophil activation, and T‐cell proliferation]

77
Q

what is MOA of aminoglycosides

A

there are 2 MOAs!

irreversibly bind to receptor proteins of 30S ribosomal subunit and disrupting initiation complex, causing dysfunction and DEATH
(they are bactericidal! other protein synthesis inhibitors are not. also they have a significant post-antibiotic effect due to irreversible binding)

against Gr- primarily: disrupt bacterial biofilms because they are positively charged, and competitively displace Ca2+ and Mg2+ from cell outer membrane, destabilizing it and causing DEATH.

78
Q

why do aminoglycosides have a significant post-antibiotic effect (POE)

A

bind irreversibly to target (30S ribosomal subunit) and they are bactericidal. so they have significant POE and long dosing interval

79
Q

describe 2-phase process of aminoglycoside entry into gram negatives

A
  • enter Gr- cell through porins in outer membrane
  • transported through inner membrane via O2-dependent process (note: they need O2 to do so so are ineffective against anaerobes)
80
Q

aminoglycosides are not that effective against Gram positives unless they are administered with what?

A

if given with a cell wall disrupting agent (eg. beta-lactam antimicrobial) synergistic if given together

81
Q

tell me more about aminoglycoside activity (PD). how it is affected by pH, oxygen, debris, and when combined with other drugs?

A

pH dependent: inactivated at low pH
oxygen dependent
inactivated by necrotic debris or purulent material
inactivated if combined in syringe with other drugs, especially penicillins, but this will not occur in vivo because concentrations are not high enough
and remember they are concentration dependent and bactericidal

82
Q

tell me about amino glycoside PK: what won’t they cross? where do they accumulate? what is the consequence of where they accumulate?

A

not absorbed from GIT, don’t cross BBB well, not bound to plasma proteins, and get Eli innate by kidney without prior metabolism. they accumulate in renal cortex so you can’t give systemically to food animals.

83
Q

can you give aminoglycosides to production animals systemically

A

NO

84
Q

give 2 key adverse effects of aminoglycosides

A

nephrotoxic, ototoxic

85
Q

this aminoglycoside is important for treating aerobic gram negative infections. compared to the other member of its class, it has less resistance and is broader spectrum because it is effective against more Staph spp.
features common to both aminoglycosides: can be given IV, IM, SQ, or regionally, often used for joint infections in horses, as well as eye and ear infections. not good at crossing cell membranes (not BBB, not ocular tissue, low volume of distribution). ototoxic, nehprotoxic, and not given systemically in food animals

A

amikacin

86
Q

this aminoglycoside is effective at treating Gram negative aerobic species, but not as effective at treating staph infections as the other member of its class
features common to both aminoglycosides: can be given IV, IM, SQ, or regionally, often used for joint infections in horses, as well as eye and ear infections. not good at crossing cell membranes (not BBB, not ocular tissue, low volume of distribution). ototoxic, nehprotoxic, and not given systemically in food animals

A

gentamicin

87
Q

give MOA of -phenicols

A

act at the 50S ribosomal subunit to interfere with the action of peptidyltransferase and inhibit peptide bond formation (also affects mammalian protein synthesis)

88
Q

give MOA of macrocodes and lincosamides

A

block the 50S polypeptide exit tunnel, preventing peptide chain elongation

89
Q

why shouldn’t you use macrocodes and lincosamides together

A

physically overlap each other’s binding sites, so prevent one another from binding to target at 50S ribosomal subunit

90
Q

do lincosamides and macrolides bind to mammalian ribosomes

A

no. this makes them safe

91
Q

macrolides and lincosamides are bacteria____ and _____-dependent

A

bacteriostatic and time-dependent

92
Q

what 3 macrolides are used in production animals

A

erythromycin, tularomycin, tilmicosin [typically used for gram negative respiratory pathogens]

93
Q

what 2 lincosamides are used in vet med

A

lincomycin [usually for swine and poultry], clindamycin [usually for small animal med]

94
Q

tell me about tilmicosin toxicity

A

cardiotoxic! cattle and sheep tolerate it fine, but goats, horses, swine, companion animals, and humans can die. consider using less toxic products. inadvertent injection can be fatal.

95
Q

in which species are lincomycin and clindamycin contraindicated in? why?

A

horses, ruminants rabbits ,hamsters, guinea pigs
due to adverse effects on GI flora

96
Q

tell me about -phenicols: bacteri_____, ______-spectrum, _____-depent, do they distribute well

A

bacteriostatic, broad-spectrum, time-dependent, cross membranes well and distribute to all tissues well

97
Q

why should we use caution handling chloramphenicol

A

may cause fatal aplastic anemia in humans, so caution when handling and wear gloves

98
Q

should you use chloramphenicols in food animals

A

no it is banned (human health risk)

99
Q

which is safer to use, florfenicol or chloramphenicol

A

florfenicol, does not have same bone marrow suppressive risk

100
Q

what is the only antibacterial class of drugs with good activity against Pseudomonas

A

fluoroquinolones. unfortunately also a category I drug

101
Q

fluoroquinolone are bacteri_____, ____-dependent, and accumulate _________

A

bactericidal, concentration-depdendent, accumulate intracellularly

102
Q

can you use fluoroquinolones eg. enrofloxacin in production animals

A

yes, but ONLY ON-LABEL

103
Q

true or false, resistance to fluoroquinolones

A

VETM 443 Clin Pharm Tox (18 decks)

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