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Microbiology Lecture Slides > Antibiotics: Agents Interfering with Bacterial Protein, and DNA Synthesis > Flashcards

Antibiotics: Agents Interfering with Bacterial Protein, and DNA Synthesis Flashcards

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1
Q

Which type of antibacterial agents inhibit DNA replication?

A

DNA Gyrase & Topo IV Inhibitors

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2
Q

What is an example of a DNA gyrase and topo IV inhibitor?

A

Fluoroquinolones

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3
Q

Which type of antibacterial agents inhibit protein synthesis?

A

50S Inhibitors and 30S inhibitors

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4
Q

What are 4 examples of 50S Inhibitors

A

Macrolides, Clindamycin, Streptogramins, and Linezolid

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5
Q

Which type of antibacterial agents inhibit cell wall synthesis?

A

Penicillins, Cephalosporins, Carbapenems, Monobactams, and Vancomycin

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6
Q

Which type of antibacterial agents inhibit folate metabolism?

A

Sulfonamides and Trimethoprim

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7
Q

What are two types of 30S inhibitors?

A

Aminoglycosides and Tetracyclines

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8
Q

Exploit differences between bacterial 70S and mammalian 80S ribosomes

A

Protein synthesis inhibitors

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9
Q

Inhibits the 30S ribosonal subunit in Streptomycin, Gentamicin, Tobramycin, Amikacin, Neomycin, and Kanamycin

A

Aminoglycosides

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10
Q

Inhibits the 30S ribosomal subunit in Tetracycline, Demeclocycline, Minocycline, Doxycycline, Oxytetracycline, and Tigecycline

A

Tetracyclines

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11
Q

Inhibits the 50S subunit in Erythromycin, Clarithromycin, Azithromycin, and Telithromycin

A

Macrolides

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12
Q

Inhibit the 50S ribosomal subunit of Clindamycin

A

Lincosamide

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13
Q

Inhibits the 50S ribosomal subunit of Quinupristin/Dalfopristin

A

Streptogramins

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14
Q

Inhibits the 50S ribosomal subunit of Linezolid

A

Oxazolidinone

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15
Q

Bind to the 30S subunit and irreversibly interfere with protein synthesis in 3 ways

A

Aminoglycosides

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16
Q

They are rapidly bactericidal vs. many aerobic Gram-negative bacteria

A

Aminoglycosides

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17
Q

Aminoglycosides also exhibit a significant

-antibacterial activity persists beyond the time that measurable drug is present

A

Postantibiotic effect

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18
Q

Mainly used as a second-line agent for the treatment of tuberculosis

A

Streptomycin

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19
Q

For this application, it should be used in combination with other agents (e.g., INH and rifampin) to prevent emergence of resistance

A

Streptomycin

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20
Q

Mainly used in cases of severe infection (e.g., sepsis and pneumonia) caused by Gram-negative bacteria that are likely to be resistant to other drugs

A

Tobramycin and Gentamicin

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21
Q

Tobramycin and gentamicin are often used in combination with a

A

B-lactam

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22
Q

Tobramycin and gentamicin are often used in combination with a B-lactam antibiotic to take advantage of synergistic effects and to prevent the emergence of

A

Resistance

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23
Q

Often preferred over tobramycin due to its reduced cost

A

Gentamicin

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24
Q

A semisynthetic derivative of kanamycin that is less toxic than the parent molecule

A

Amikacin

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25
Q

It is resistant to many enzymes that inactivate gentamicin and tobramycin, and can thus be employed against microorganisms resistant to the latter drugs

A

Amikacin

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26
Q

They are used on infected surfaces (skin or eyes) or injected into joints, the pleural cavity, tissue spaces, and abscess cavities where infection is present

-Both are primarily limited to topical use

A

Neomycin and Kanamycin

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27
Q

The primary adverse reaction of aminoglycosides is that all aminoglycosides are

A

Nephrotoxic

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28
Q

More likely to occur when therapy is continued for >5 days, at higher doses, in the elderly, and in cases of renal insufficiency

A

Nephrotoxicity

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29
Q

What are the three most nephrotoxic aminoglycosides

A

Neomycin, tobramycin, and gentamicin

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30
Q

Another adverse effect of aminoglycosides, is that all aminoglycosides are

A

Ototoxic

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31
Q

Like the nephrotoxic effects, is more likely to occur when therapy is continued for >5 days, at higher doses, and in the elderly

A

Ototoxicity

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32
Q

Can be manifested either as auditory damage (e.g., tinnitus, highfrequency hearing loss) or as vestibular damage (e.g., vertigo, ataxia)

A

Ototoxicity

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33
Q

Which 3 aminoglycosides cause the most auditory damage?

A

Neomycin, kanamycin, and amikacin

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34
Q

Which two aminoglycosides cause the most vestibular damage?

A

Streptomycin and gentamicin

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35
Q

Tend to be irreversible, even upon discontinuation of therapy

A

Ototoxicity

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36
Q

Bind to the 30S ribosomal subunit and prevent aminoacyl-tRNA binding to the A-site, thereby blocking peptide elongation

A

Tetracyclines

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37
Q

Bacteriostatic for many aerobic and anaerobic Gram-positive and Gram-negative bacteria, including rickettsiae, chlamydiae, and mycoplasmas

A

Tetracyclines

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38
Q

Tetracyclines are also active against some

A

Protozoa

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39
Q

Antibacterial activities of most tetracyclines are similar, with differences in clinical efficacy being due primarily to differences in

A

PK properties

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40
Q

Absorption of orally administered tetracyclines is impaired by food except for

A

Doxycycline and Minocycline

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41
Q

Chelate multivalent cations (Ca2+, Mg2+, Fe2+, and Al3+)

A

Tetracyclines

42
Q

Tetracycline absorption is therefore also impaired by these

A

Cations

43
Q

Poorly absorbed orally and must be administered IV

A

Tigecycline (a glycylcycline)

44
Q

Has a longer half-life than the other tetracyclines

A

Tigecycline (a glycylcycline)

45
Q

What 4 things are tetracyclines used for?

A

Rickettsial Infections, Sexually Transmitted Infections, Respiratory Tract Infections, and Skin and Soft-Tissue Infections

46
Q

Used in the treatment and prevention of anthrax and malaria, as well as for the treatment of Lyme disease

A

Doxycycline

47
Q

Used for treatment of community-acquired pneumonia, intra-abdominal, skin, and soft tissue infections caused by MDR bacteria, including

A

Tigecycline

48
Q

Which tetracycline is used to treat infections caused by multidrug-resistant (MDR) bacteria

A

Tigecycline

49
Q

Nausea, vomiting, and diarrhea are the most common reasons for discontinuing

A

Tetracycline use

50
Q

Bind calcium that is deposited in newly formed teeth and bone in young children

A

Tetracyclines

51
Q

The drug can be deposited in teeth (including fetal teeth during pregnancy), causing fluorescence, discoloration, and enamel dysplasia

A

Tetracyclines

52
Q

Tetracyclines can also be deposited in bone, where it may cause deformity or

A

Growth inhibition

53
Q

Another major adverse reaction of tetracyclines is

A

Photosensitization

54
Q

Tetracyclines are contraindicated during pregnancy because of susceptibility to

A

Liver disturbances

55
Q

Bind the 50S ribosomal subunit and inhibit the translocation step of protein synthesis

A

Macrolides

56
Q

Generally bacteriostatic vs. aerobic Gram-positive and some Gramnegative bacteria

A

Macrolides

57
Q

Clarithromycin, azithromycin, and telithromycin (a ketolide) are semi-synthetic derivatives of

A

Erythromycin

58
Q

Active against many macrolide-resistant bacterial strains

A

Telithromycin

59
Q

Antibacterial activities of the macrolides are similar, with differences in clinical properties being due primarily to differences in

A

PK properties

60
Q

The longer t½ values of clarithromycin, telithromycin, and azithromycin allow

A

Less frequent dosing

61
Q

Used for community-acquired pneumonia, acute exacerbations of chronic bronchitis

A

Macrolides

62
Q

Useful as a penicillin-substitute in penicillinallergic individuals with susceptible Staph infections

A

Macrolides

63
Q

What are the two primary adverse effects of Macrolides?

A

GI effects and Liver toxicity

64
Q

Anorexia, nausea, vomiting, and diarrhea occasionally accompany oral administration of

A

Macrolides

65
Q

GI intolerance caused by direct stimulation of gut motility is less so for

A

Clarithromycin and azithromycin

66
Q

Can produce acute cholestatic hepatitis, probably as a hypersensitive reaction

A

Macrolides

67
Q

The liver toxicity effect has caused the approved use of telithromycin to be limited only to

A

Community-acquired pneumonia

68
Q

50S inhibitor that is used for the treatment of skin and soft-tissue infections caused by aerobic and anaerobic Gram-positive bacteria

A

Clindamycin (Lincosamide)

69
Q

Combination (IV only) approved for treatment of infections caused by vancomycin-resistant Enterococcus faecium and complicated skin infections caused by methicillin-sensitive S. aureus (MSSA)

A

Quinupristin/dalfopristin (Streptogramins)

70
Q

The newest synthetic antibiotic approved for treatment of infections caused by MDR Gram-positive bacteria, including MRSA, VRE, and penicillinresistant streptococci

A

Linezolid (Oxazolidinone)

71
Q

What are the two functional classes of DNA synthesis inhibitors?

A
  1. ) Antifolate Drugs

2. ) DNA Gyrase/Topo IV Inhibitors

72
Q

Inhibit bacterial biosynthesis of purine bases and thus DNA.

A

Antifolate drugs (Sulfonamides and Trimethoprim)

73
Q

Block bacterial DNA replication by inhibiting bacterial topoisomerase II (DNAgyrase) and topoisomerase IV

A

DNA Gyrase/Topo IV Inhibitors

-Fluoroquinones

74
Q

Unlike mammals, sulfonamide-susceptible microorganisms cannot use exogenous folate, but must synthesize it from

A

p-aminobenzoic acid (PABA)

75
Q

PABA analogs that act as competitive inhibitors of dihydropteroate synthase, which converts PABA to dihydrofolic acid

A

Sulfonamides

76
Q

Bacteriostatic when administered as single agents

A

Sulfonamides

77
Q

Combination with a dihydrofolate reductase inhibitor produces synergistic activity, due to inhibition of sequential steps in

A

Folate synthesis

78
Q

The combination is typically

A

Bactericidal

79
Q

Used almost exclusively to treat urinary tract infections (UTIs), but rarely as monotherapy due to resistance

A

The Sulfonamides sulfisoxazole and sulfamethoxazole

80
Q

Widely used in ulcerative colitis, enteritis, and other inflammatory bowel disease

A

Sulfasalazine

81
Q

All sulfonamides are considered to be partially

A

Cross-allergic

82
Q

Most common unwanted effects are fever, skin rashes, exfoliative dermatitis, photosensitivity, urticaria, nausea, vomiting, and diarrhea

A

Sulfonamides

83
Q

May precipitate in the urine, producing crystalluria, hematuria, or even obstruction

A

Sulfonamides

84
Q

Selectively inhibits bacterial dihydrofolate reductase, which converts dihydrofolate to tetrahydrofolate

A

Trimethoprim

85
Q

~50,000 times less efficient at inhibiting mammalian dihydrofolate reductase

A

Trimethoprim

86
Q

Trimethoprim is typically combined with sulfamethoxazole to make

A

TMP-SMX (Bactrim®, Septra®).

87
Q

Used for uncomplicated UTIs, pneumocystis jiroveci pneumonia, and acute exacerbations of chronic bronchitis

A

TMP-SMX

88
Q

The most common adverse effect with short courses (<5 days) of TMP-SMX treatment is allergy to the

-occurs in up to 10% of patients

A

Sulfonamide component

89
Q

Longer courses of treatment (>5 days) can result in more serious adverse effects typical of antifolates, including

A

Magaloblastic anemia and leukopenia

90
Q

Block DNA synthesis by inhibiting bacterial topoisomerase II (DNA gyrase) and topoisomerase IV

A

Fluoroquinolones

91
Q

Inhibition of DNA gyrase prevents the relaxation of positively supercoiled DNA that is required for

A

DNA replication

92
Q

Interferes with separation of replicated chromosomal DNA into the respective daughter cells during cell division

A

Inhibition of topoisomerase IV

93
Q

Bactericidal against both Gram-negative (gyrase is the primary target) and Gram-positive (topo IV is the primary target) bacteria

A

Fluoroquinolones (FQ’s)

94
Q

Ciprofloxacin, lomefloxacin, levofloxacin, and ofloxacin make up a group of similar agents with excellent

A

Gram Negative activity (moderate Gram-positive)

95
Q

Gemifloxacin and moxifloxacin make up a 2nd group with improved activity against

A

Gram-positive organisms

96
Q

Effective in UTIs, even when caused by MDR bacteria

A

FQ’s

97
Q

The drug of choice for prophylaxis and treatment of anthrax (caused by B. anthracis)

A

Ciprofloxacin

98
Q

Dubbed the “respiratory FQs,” and are effective and used increasingly for treatment of upper and lower respiratory tract infections

A

Levofloxacin, gemifloxacin, and moxifloxacin

99
Q

May damage growing cartilage and cause arthropathy, and, thus, are not routinely recommended for patients under 18 years of age

A

FQ’s

100
Q

However, the arthropathy is reversible and there is a growing consensus that in some cases, FQs may be used in

A

Children

Microbiology Lecture Slides (24 decks)

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