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Antimicrobials Flashcards

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1
Q

What do coordinate or global regulatory circuits do?

A

control the expression of genes encoding multiple virulence factors in some bacteria

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2
Q

What is quorum sensing?

A

a signaling system between bacterial cells that regulates the transcription of multiple genes

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3
Q

What is quorum sensing dependent on?

A

the production of one or more diffusable signal molecules called autoinducers or pheromones which enable a bacterium to monitor its own population density

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4
Q

Quorum sensing is an example of _____ _____ _____ in single-celled prokaryotic organisms.

A

coordinated multicellular behavior

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5
Q

What is quorum sensing used to regulate?

A

diverse physiological processes such as production of virulence determinants, swarming, bioluminescence and antibiotic synthesis

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6
Q

What are defensins?

A

antibacterial polypeptides that are the major effector mechanism of the natural immune system

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7
Q

What are some cell types tat produce defensins?

A

epithelial cells of the intestine, respiratory tract, mammary gland, skin, kidney, eye, and tongue, and granulocytes

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8
Q

What is the function of defensins?

A

they behave as amphiphiles that bind to the target cell membrane and form a pore or channel, attack fungi and eukaryotic cells, and stimulate wound healing by inducing synthesis of other compounds

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9
Q

What does the activation of toll-like receptors result in?

A

the production of inflammatory mediators and other products

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10
Q

What is the role of toll-like receptors on immune cells?

A

they signal that bacteria are attacking the cell

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11
Q

What defense mechanisms does the skin have?

A

mechanical barrier of dry, nonliving tissue, fatty acids, lysozyme, and normal flora

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12
Q

What are the defense mechanisms of mucous membranes?

A

mucus, cilia, phagocytic cells, saliva, stomach acid, proteolytic enzymes, flushing action of urine, tears, etc., and normal flora

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13
Q

What is iL1s role as a defense mechanism?

A

it induces fever and attracts and activates phagocytes

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14
Q

Normal tissues with a ___ ___ ____ are a very _____ environment for bacteria.

A

good blood supply, hostile

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15
Q

What are killed bacterins made from?

A

bacteria grown in culture that are then killed

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16
Q

How is an autogenous bacterin made?

A

a bacterial isolate is obtained from a diseased herd, then the isolate was used to make a bacterin for immunization of new animals coming into the same herd

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17
Q

What organisms are difficult to make a bacterin from?

A

organisms that have capsules composed of polysaccharides or organisms with polysaccharide outer layers

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18
Q

What is used to make a modified live vaccine?

A

living organisms

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19
Q

What is the advantage of modified live vaccines?

A

living pathogens are more likely to express antigens that are important in a good immune response

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20
Q

What are the types of genetically engineered vaccines?

A

Gal E, Aro A, carrier

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21
Q

What are Gal E vaccines?

A

galactose epimerase-less mutants - cell wall deficient organisms that do not survive host immune responses well

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22
Q

What are Aro A vaccines?

A

aromatic pathway mutants - these organisms are unable to synthesize PABA and thus folic acid, and subsequently DNA

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23
Q

What is a carrier vaccine?

A

an avirulent organism into which genes for antigens of other bacteria or viruses have been cloned

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24
Q

What is a toxoid?

A

an immunizing product derived from a toxin whereby the toxic portion has been inactivated but the immunogenicity has been preserved

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25
Q

How are toxoids made?

A

you use a toxin and inactivate it with formaldehyde

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26
Q

When are toxoids useful?

A

when toxins play a major role in the production of disease and where antibody against the toxin is protective

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27
Q

What are adjuvants used for?

A

they are added to bacterial vaccines to enhance the efficacy of a product

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28
Q

How do adjuvants work?

A

by slowing down the absorption of the immunogen or by enhancing or modifying the interaction of the antigen with the immune system

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29
Q

What immunoglobulin production is stimulated by intradermal injection or introduction of protein antigens on mucosal surfaces?

A

IgA

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30
Q

What immunoglobulin production is stimulated by an intramuscular injection?

A

IgG

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31
Q

What are biological response modifiers?

A

agents that alter normal host defense mechanisms or immune response

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32
Q

What are the two modes of action for biological response modifiers?

A
  1. enhance the ability of the host to overcome bacterial virulence factors
  2. overcome immunosupression
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33
Q

What are endogenous biological response modifiers?

A

those that are produced normally by the host - may be produced as recombinant proteins and administered

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34
Q

What are some examples of endogenous biological response modifiers?

A

interleukin I, interleukin II, interferon, and granulocyte-macrophage-colony-stimulating factor (GM-CSF)

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35
Q

What is interleukin I?

A

a cytokine produced mainly by mononuclear phagocytes

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36
Q

What is interleukin II?

A

a glycoprotein secreted by T-lymphocytes after antigen and IL1 stimulation

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37
Q

What is interleukin II required for?

A

the production for the proliferation of activated T-cells, natural killer cells, and other cytotoxic effector cells

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38
Q

What are the types of interferon?

A

alpha, beta, and gamma

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39
Q

What is GM-CSF?

A

a major cytokine for hemopoiesis

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40
Q

What does GM-CSF enhance?

A

eosinophil chemotaxis, maturation of macrophages and dendritic cells, granulocyte activation, adjuvant effect, and inhibition of apoptosis

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41
Q

What does GM-CSF regulate?

A

immune responses based on development and maturation of antigen-presenting cells

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42
Q

GM-CSF skews the immune system toward a ____ _________.

A

Th1 response

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43
Q

What are exogenous biological response modifiers?

A

those that are not produced by the host but whose mechanisms of action include the induction of endogenous biological response modifiers and alteration of the biological response of the host

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44
Q

What are some examples of exogenous biological response modifiers?

A 
components of mycobacteria
C. parvum, C. granulosum, and Lactobacillus casei
Coley treatment
Listeria monocytogenes + GM-CSF
gut flora
Toxoplasma gondii
LPS
monophosphoryl lipid a
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45
Q

What is a bacteriostatic antimicrobial agent?

A

an agent if it merely inhibits the growth of bacteria

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46
Q

What are some examples of bacteriostatic antimicrobial agents?

A

tetracycline, sulfonamides, and chloramphenicol

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47
Q

What is a bactericidal antimicrobial agent?

A

agents that usually rapidly kill the target organism

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48
Q

What are some examples of bactericidal antimicrobial agents?

A

penicillin, streptomysin, cephlasporins, polymyxin, and neomycin

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49
Q

When a bacterial pathogen is isolated from a diseased animal or human what two questions need to be answered?

A
  1. What is the identity of the pathogen?

2. What antimicrobial drugs could be used to treat the infection?

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50
Q

What is the minimum inhibitory concentration (MIC)?

A

the minimum concentration of the drug necessary to inhibit the growth of the organism

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51
Q

What are breakpoints?

A

known MIC values that have been empirically determined for a given antimicrobial with a given pathogen in a given animal species

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52
Q

What is minimum bactericidal concentration (MBC)

A

a test use to give a better indication of the usefulness of antimicrobials that are bactericidal rather than bacteriostatic

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53
Q

What is the spectrum of an antimicrobial agent determined by?

A

how wide a variety of bacteria are affected by it

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54
Q

How do bacteria develop resistance to antimicrobials?

A
  • transfer of this genetic material to other bacteria
  • high replication rate
  • alteration of a ribosomal binding site
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55
Q

What can the transfer of genetic material into bacteria be mediated by?

A

any of the mechanisms of genetic exchange such as the transfer of R-plasmids, transposons, and integrons, infection with a bacteriophage etc.

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56
Q

What are the groups of antimicrobial agents?

A

inhibition of growth by analogues, inhibition of cell wall synthesis, cell membrane inhibitors, inhibitors of DNA synthesis, inhibitors of the 30S ribosomal subunit, inhibitors of the 50S ribosomal subunit, and inhibitors of protein assembly

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57
Q

What antimicrobials are in the ‘inhibition of growth by analogues’ group?

A

sulfonamides, sulfones, and para aminosalicyclic acid

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58
Q

How do sulfa drugs work?

A

they are analogues of PABA and compete with it in the pathway for folic acid synthesis - in sufficient concentration, the sulfa drug will competitively inhibit this pathway and prevent the growth of bacteria

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59
Q

What species are sulfonamides banned in and why?

A

food animals because they are known to precipitate in the kidney

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60
Q

What are sulfonamides given in combination with?

A

trimethoprim

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61
Q

What does trimethoprim do?

A

inhibits the same folic acid synthetic pathway but does so by acting on dihydrofolate reductase

62
Q

What is a commonly used trimethoprim-sulfa combination product?

A

tribrissen

63
Q

What antimicrobials are in the ‘inhibition of cell wall synthesis’?

A

beta lactams (penicillins), semisynthetic penicillins, cephalosporins, bacitracin, vancomycin, and bambermycin

64
Q

What do beta lactams do?

A

they bind to the transpeptidase enzyme and become irreversibly bound and thus incativated - cross-bridging cannot occur

65
Q

What is beta lactams mechanism of action?

A

to kill actively growing cells by weakening the peptidoglycan to the point that the bacterium cant undergo normal cell division and bursts

66
Q

Is penicillin more active against gram positive or gram negative bacteria?

A

gram positive

67
Q

What is an example of a semisynthetic penicillin?

A

amoxicillin and cloxacillin

68
Q

What is the difference between beta lactams and semisynthetic penicillins?

A

they have been engineered to have different properties such as the ability to withstand stomach acid and are more active against gram-negatives

69
Q

What is the most important property of some of the semisynthetic penicillins?

A

their ability to resist breakdown by the penicillinase enzyme produced by many bacteria

70
Q

What are suicide molecules?

A

molecules that bind to penicillinase enzymes thus preventing them from destroying the active beta lactam ring structure of penicillins such as amoxicillin

71
Q

What are some examples of suicide molecules?

A

clavulanic acid and tazobactam

72
Q

What is clavamox?

A

a combined product of amoxicillin and clavulanic acid

73
Q

What is the structure of cephalosporins?

A

they have a nucleus that resembles the penicillin nucleus and have a similar mechanism of action

74
Q

What are some examples of cephalosporins used in food animals?

A

ceftiofur (naxel, excenel, and excede)

75
Q

What are some examples of cephalosporins used in small animal medicine?

A

cefodoxime (simplicef) and cefovecin (convenia)

76
Q

What are the advantages of cephalosporins?

A

resistance to penicillinase to varying degrees
they are not as allergenic as penicillin
as a group, they have a broad spectrum of activity

77
Q

What are older cephalosporins active against and what is an example?

A

cephalothin - active against most gram-positive bacteria but have limited activity against gram-negatives

78
Q

What are older cephalosporins referred to as?

A

first generation cephalosporins

79
Q

What are second generation cephalosporins active against?

A

most gram-positive bacteria but are also active against some gram-negatives

80
Q

What are some examples of third generation cephalosporins?

A

ceftiofur (naxcel, excenel), cefovecin, and cefpodoxime

81
Q

What are third generation cephalosporins active against?

A

gram-positives but are effective against most gram-negatives

82
Q

What is the structure of third generation cephalosporins?

A

they are highly protein bound which protect the drug from elimination and covey a long plasma elimination half life

83
Q

What is bacitracin?

A

a polypeptide isolated from B. subtilis that interacts with the bacterial cell membrane to prevent transfer of structural components

84
Q

What type of antimicrobial agent is bacitracin and what type of bacteria does it affect?

A

bactericidal - gram positives

85
Q

How is bacitracin given?

A

topically but it is highly toxic when given systematically

86
Q

What drug is vancomycin similar to?

A

bacitracin

87
Q

What is vancomycin used to treat?

A

serious staphylococcal infections in humans that are not responsive to other antimicrobials

88
Q

What is bambermycin?

A

a complex of antimicrobial substances produced by Streptomyces bamberiensis with a trade name of flavomycin

89
Q

What is bambermycin active against?

A

gram positive cell wall synthesis but has little activity against some of the normal flora such as lactobacillus

90
Q

What antimicrobials are ‘cell membrane inhibitors’?

A

polymyxin and polyenes

91
Q

Which polymyxins are in use?

A

B and E because the others are toxic

92
Q

How do polymyxins work?

A

they bind to the outer surface of cell membranes and disrupt the structure and function of the phospholipid and lipopolysaccharide components

93
Q

What are polymyxins active against?

A

gram-negatives

94
Q

What infections are polymyxins used for?

A

severe Pseudomonas aeruginosa infections

95
Q

How do polyenes work?

A

they selectively inhibit organisms whose cell membranes contain sterols and because of this are used to treat fungal infections

96
Q

What are some common polyenes?

A

amphoteracin B, nystatin, and azoles

97
Q

What is amphoteracin B used to treat?

A

systemic fungal infections but has a number of serious side effects such as nephrotoxicity

98
Q

How is nystatin used?

A

it is too toxic to use systemically, but is commonly found in topical preparations

99
Q

What are some examples of azoles?

A

ketoxonazole, miconazole, and clotrimizole

100
Q

How do azoles work?

A

they interfere with the synthesis of ergosterol in the fungal cell membrane

101
Q

How is Ketoconozole used?

A

systemically

102
Q

How are triazoles (fluconazole) given?

A

orally

103
Q

What drugs are ‘inhibitors of DNA synthesis’?

A

quinolones, metronidazole, novobiocin, carbadox

104
Q

What do quinolones do?

A

selectively block DNA synthesis in susceptible bacteria by inhibiting DNA gyrase A - knwon as DNA gyrase inhibitors

105
Q

Which quinolones are in widest use?

A

fluoroquinolones

106
Q

Provide some examples of quinolones used in veterinary medicine.

A

enrofloxacin (baytril) and danofloxacin

107
Q

What are some quinolones used in human medicine?

A

norfloxicin and ciprofloxicin

108
Q

What species are fluroquinolones banned in?

A

food producing animals

109
Q

What is metronidazole used against?

A

infections with anaerobic bacteria and some protozoa

110
Q

What is metronidazole ineffective against?

A

aerobes and facultative anaerobes

111
Q

What is novobiocin used for?

A

it is a bactericidal for a number of bacteria, especially gram positives

112
Q

How does novobiocin work?

A

it inhibits DNA gyrase B which accounts for the differences in spectrum compared to quinolones

113
Q

What is Novobiocin used for in bovine?

A

mastitis

114
Q

What is carbadox used for?

A

swine feed at weaning to control bacterial enteritis and as a growth promoter

115
Q

What does carbadox do?

A

it intercalates into bacterial DNA and causes mutations

116
Q

How does rifampin work?

A

it selectively inhibits DNA-dependent RNA polymerase of bacteria

117
Q

What is rifampin useful against?

A

gram-positives, mycobacteria, and rhodococcus equi

118
Q

What drugs are in the ‘inhibitors of the 30S ribosomal unit’?

A

aminoglycosidic aminocyclitols, tetracyclines, and nitrofurans

119
Q

What are some aminoglycosidic aminocyclitols?

A

streptomycin, neomycin, kanamucin, gentamicin, spectinomycin, amikacin, and tobramycin

120
Q

How must aminoglycosidic aminocyclitols given?

A

parenterally or topically applied

121
Q

Why must you be cautious when giving aminoglycosidic aminocyclitols to renal compomised animals parenterally?

A

because they can be nephrotoxic and ototoxic

122
Q

What is a negative of aminoglycosidic aminocyclitols?

A

they can produce residues in tissues in food producing animals

123
Q

What do tertracyclines do?

A

inhibit protein synthesis at the 30S ribosomal subunit

124
Q

What are some examples of tetracyclines?

A

chlortetracycline, aureomycin, oxytetracycline, and doxycycline

125
Q

What do nitrofurans do?

A

they inhibit protein synthesis by preferentially inhibiting the synthesis of inducible enzymes necessary for translation

126
Q

What is nitrofurantion used for?

A

urinary tract infections

127
Q

What is a common nitrofuran?

A

furacin

128
Q

What drugs belong in the ‘inhibitors of the 50S ribosomal subunit’ group?

A

chloramphenicol, florfenicol, macrolides, erythromycin, lincomycin, tilmicosin, and tiamulin

129
Q

How does chloramphenicol work?

A

it acts by binding to the 50S subunit, preventing fRNA from binding and thus inhibiting peptide bond formation

130
Q

What are the side effects of chloramphenicol?

A

severe, fatal, aplastic anemia in humans

131
Q

What species is chloramphenicol prohibited in?

A

food-producing animals

132
Q

How is resistance to chloramphenical gotten?

A

through the high level production of chloramphenicol acetyltransferase or through changes in the permeability or the bacterial membrane that prevent the drug from reaching its target

133
Q

What are some examples of florfenicol?

A

nuflor, nuflor gold and aquaflor

134
Q

What is florfenicol used for?

A

bovine CNS and respiratory disease

135
Q

What is erythromycin?

A

a macrolide antibiotic that attaches to the same site on the 50S ribosomal subunit as cloramphenicol

136
Q

What shouldn’t erythromycin be combined with?

A

lincomycin because they compete with the same sites

137
Q

How does resistance to erythromycin occur?

A

by genetic mutation resulting in structural alteration of the 50S ribosomal subunit

138
Q

What is lincomycin?

A

a macrolide that is commonly used in feed in the US

139
Q

What is an example of lincomycin?

A

clindamycin

140
Q

What does lincomycin cause in horses?

A

severe, potentially fatal diarrhea

141
Q

What species is tilmicosin used in?

A

cattle, sheep, and swine

142
Q

What is tilmicosin used to treat?

A

respiratory disease

143
Q

How is tilmicosin administered?

A

subcutaneously

144
Q

What is tilmicosin toxic to?

A

humans, goats, and swine

145
Q

What are some examples of tilmicosin?

A

Drazzin, zactran, and zuprevo

146
Q

What is tiamulin used for?

A

fattening swine

147
Q

How does tiamulin work?

A

it binds to the 50S ribosomal subunit and inhibits protein synthesis primarily in staphylococci, streptococci, and spirochetes

148
Q

What is tiamulin not active against?

A

gram negative bacteria

149
Q

What drugs belong in the ‘inhibitors of protein assembly’ group?

A

griseofulvin

150
Q

What is griseofulvin used for?

A

the treatment of dermatophyte infections

151
Q

How does griseofulvin work?

A

it acts by inhibiting mitosis and thereby preventing replication of actively growing fungi

Microbiology (50 decks)

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