Formative 2 Flashcards

1
Q

Salmonella strain isolated from pt was resistant to tetracycline, ampicillin, sulfisoxazole, gentamicin, tobramycin, streptomycin and ceftriaxone. Therefore:

A

Strain is likely to carry a plasmid.

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2
Q

Large number of resistance in one strain is usually due to

A

Presence of a plasmid

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3
Q

Do phages have antibiotic resistant genes?

A

None found so far

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4
Q

Target of Fluoroquinolones

A

Gram (-) infections

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5
Q

Penicillins target

A

Gram (+) infections

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6
Q

Ampicillin targets

A

Gram (+) and some Gram (-)

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7
Q

Salmonella is

A

Gram (-)

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8
Q

Ceftriaxone

A
3rd Generation Cephalosporin
Broad Gram (-) coverage
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9
Q

Sulfisoxazole

A

Mimics PABA

Competitively inhibits dihydropteroate synthase

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10
Q

Bacterial Protein Synthesis

A
  1. Initiate Process (Aminoglycosides/Linezolid
  2. Add tRNA (tetracycline)
  3. Add peptides: translocate (Chloramphenicol, Macrolides, Clindamycin)
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11
Q

Gentimicin

A

Aminoglycoside so blocks initiation of protein synthesis
Binds to 30s
Misread proteins will increase permeability of cell membrane
Bactericidal

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12
Q

Tobramycin

A

Aminoglycoside

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13
Q

Streptomycin

A

Aminoglycoside

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14
Q

Aminoglycosides treat

A

Gram (-) infections

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15
Q

Streptomycin can be used for

A

Tuberculosis

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16
Q

Aminoglycosides have synergestic effects with

A

Beta-lactams

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17
Q

Vancomycin/Gentamicin

A

Endocarditis

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18
Q

Ampicillin/Gentamicin

A

Newborn Meningitis

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19
Q

Tetracycline

A

Transported into bacterial cells
Binds 30s ribosome
Prevents attachment of tRNA

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20
Q

Which drug should not be taken with antacids or milk?

A

Tetracyclines

Chelation with cations

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21
Q

Hfr strains are generated by which of the following mechanisms?

A

Chromosomal integration of F

  • F integrates into the bacterial chromosome using IS elements for homology
  • IS element serves as a source of homology for homologous recombination leading to integration
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22
Q

HFr Conjugation

A

recombination of chromosomal DNA fragments are transferred to recipient after F plasmid transfer

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23
Q

IS element

A

IS element – insertion sequence, simplest transposon, provide regions of homology with chromosome to allow recombination

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24
Q

Phage Conversion

A

Involves phage gene affecting the phenotype of a bacterium

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25
Q

Transformation

A

Direct uptake of DNA from surrounding environment

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26
Q

Conjugation

A

Transfer from one cell to another via pilus

DNA transferred via plasmids

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27
Q

Plasmids

A

Small DNA molecule within a cell
Physically separated from chromosomal DNA
Can replicate independently
Can contain genes for antibiotic resistance, toxins
Can be transferred from one bacteria to another

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28
Q

Transduction

A

Transfer of DNA via a bacteriophage
-Virus that infects bacteria
Virus picks up DNA, transfers to another bacteria

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29
Q

Generalized Transduction

A

Virus infects bacteria
Multiplies, randomly picks up host DNA
Host DNA transferred to other bacteria

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30
Q

Specialized Transduction

A

Transfer of specific genes
Virus DNA inserts into host DNA (lysogeny)
When bacteriophage DNA excised, packaged into virus with specific host DNA

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31
Q

Transduction occurs via

A

Lytic or Lysogenic Cycles

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32
Q

Generalized Transduction via

A

Lytic Cycle
Nuclear material enters bacteria
Multiplies, lyses cell
Releases progeny viruses

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33
Q

Specialized Transduction via

A

Lysogenic Cycle
Nuclear material enters cell
Incorporates into host DNA
May later become excised (enter lytic phase)

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34
Q

Why lysogeny matters

A

Genes for some bacterial toxins are transferred to non-toxic strains via lysogeny

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35
Q

Transposons are

A

DNA segments within bacterial DNA

36
Q

Transposons can be

A

Excised and reintegrated in new locations in DNA

37
Q

Once transposon is excised, it can also be moved to

A

plasmid, which transfers to other bacteria

38
Q

Mycobacteria

A

Mycolic acids in cell wall

Lipid-rich cell wall that is “acid-fast”

39
Q

M. Leprae (Leprosy)

A

Obligate IC organism
Cannot be cultured
Cool temps: skin, extremities, face
Granulomatous inflammation

40
Q

M. Leprae infects

A

Skin and superficial nerves

41
Q

Tuberculoid Leprosy

A

Mild (infection contained)

42
Q

Lepromatous Leprosy

A

Severe (weak cell-mediated response)

43
Q

Tuberculoid Leprosy

A

Patches of hypopigmented skin
Loss of sensation over affected area
Strong cell-mediated Th1 response contains infection
Lesions show granulomas, few bacteria

44
Q

M. Leprae

Leprosy Dx

A

Acid-fast organisms on skin biopsy

45
Q

Tuberculoid Leprosy Tx

A

Dapsone and Rifampin (6 months)

46
Q

Lepromatous Leprosy Tx

A

Dapsone, rifamipin, clofazimine (years)

47
Q

Dapsone

A

Competes with bacterial para-aminobenzoic acid (PABA)
Inhibits dihydropteroate synthase
Disrupts folic acid pathways (like sulfonamides)
Also used for pneumocystis jirovecii (like sulfonamides)
Hemolysis in G6PD (like sulfonamides)
Rarely can cause agranulocytosis (ANC=0)

48
Q

Sulfonamides

A

Disrupt folic acid pathways
Pneumocystis jirovecii
Hemolysis in G6PD

49
Q

Hypopigmented anesthetic skin patch over R side face. C/o occasional ‘electric current’-like sensation radiating from her R elbow to hand. Stain shows acid-fast bacilli. Which drug for first-line treatment?

A

Dapsone

50
Q

Dapsone is first-line therapy for

A

leprosy

51
Q

Isoniazid

A

Do not use with antacids or dairy

52
Q

Ethambutol

A

Inhibits synthesis of mycobacterial cell wall glycan
Well absorbed and distributed
CNS level variable, but usually reaches therapeutic level
Most excreted in urine– accumulates in renal failure
Dose-dependent optic neuritis, decreased acuity, loss of red-green differentiation
Resistance– Rapid, use in combination

53
Q

Isoniazid (INH)

A

Mechanism
Blocks synthesis of Mycolic Acids for mycobacterial cell wall
Bactericidal in growing cells only
Pharmacokinetics
Well absorbed and distributed after oral administration
CNS levels 20-100% of serum level; Intracellular = extracellular
Metabolism key factor in pharmacokinetics– acetylated in the liver
Genetic differences (polymorphism) in acetylation
Fast acetylators may require higher doses
“Fast” acetylators–50% of US Blacks and Whites, most Asians, Native Americans
t1/2 for “Fast acetylators < 1 hrs, “slow” acetylators– t1/2 > 3 hrs
Excretion– Urine (INH and acetylated product)
Alter dosing in hepatic, not renal disease
Clinical use
Prophylaxis– Used alone for TB exposure, tuberculin convertors
Combination chemotherapy for TB– With ethambutol, rifampin, or pyrazinamide
Adverse effects
Dose- and duration-dependent
Hepatotoxicity– Increases with age of patient,
more common in alcoholics, maybe during pregnancy
Peripheral and central neuropathy– Treat with pyridoxine (Vitamin B6)
Resistance– Can develop rapidly, or is already present
10% of isolates in US resistant
Higher in Caribbean, Asia (approaching 20%)
Deletion of katG gene in mycobacterium

54
Q

Pyrazinamide

A

Oral, absorbed, distributed
Bacteriostatic
Activated by mycobacterium, blocks membrane functions
Rapid resistance if used as monotherapy
Causes hyperuricemia (gouty arthritis) in up to 40%
1-5% incidence of hepatotoxicity
Contraindicated in pregnancy

55
Q

Streptomycin

A

Was only for severe (life-threatening) cases, now used more frequently
PK, adverse effects typical of aminoglycoside

56
Q

Interferon γ assay

A

Interferon γ assay – M.tb antigens + whole blood → activated T cells produce INF-γ → ELISA

57
Q

Pt diagnosed with miliary tuberculosis. Which test would best confirm latent infection of immediate family members?

A

Positive interferon-gamma blood test

58
Q

Il-12 triggers

A

Differentiation of T cells into Th1 cells

59
Q

Activated Th1 cells produce

A

Interferon gamma

60
Q

Interferon gamma is important for

A

response to IC infections

61
Q

BCG vaccine

A

live attenuated M. bovis, best for children, not in US

62
Q

Interferon-gamma blood test is specific for

A

M. tuberculosis

63
Q

Detection of acid-fast bacilli in sputum indicates

A

active infection

64
Q

Tuberculin test resulting in an erythema 15 mm in diameter or more is

A

Positive

65
Q

M. Tuberculosis Transmission

A

Transmission – respiratory droplets → taken up by alveolar macros via LAM – mannose binding and opsonization → prevention of phagosome-lysosome fusion and oxidant breakdown → spread through lymph and blood to marrow, spleen, kidney, CNS

66
Q

M. Tuberculosis lipoarabinomannan binds to

A

macrophage mannose receptor

67
Q

Opsonization occurs via

A

C3B (component of complement system)

68
Q

Capsules

A

Capsules – protection/phagocytosis evasion

69
Q

Cord factor

A

Cord factor – cytotoxic to neutros by disrupting mitochondrial membranes

70
Q

Virulence factor

A

Bacterial features that allow evasion of host defenses

71
Q

Listeria is found in

A

Unpasteurized milk products

72
Q

Listeria can

A

Cross the placenta and infect the fetus

73
Q

Concentration-Dependent Cell Killing

A

Concentration-dependent (aminoglycosides, fluoroquinolones)
Peak serum concentration relates to extent of killing (continues to increase above MBC)
Higher peak values result in increased efficacy and decreased development of resistance

74
Q

Gentimicin

A

Aminoglycoside

75
Q

Efficacy of aminoglycosides is related to their

A

Peak concentration

76
Q

Aminoglycosides elicit a

A

post-antibiotic effect

77
Q

Post-antibiotic effect

A

continued killing or suppression of bacteria after the drug concentrations have fallen below MBC

78
Q

Aminoglycosides are rapidly cleared into the urine, and thus

A

have short half-lives

79
Q

Aminoglycosides used to be administered 3 or 4 times daily to maintain their plasma concentrations. That was effective for bacterial killing, but by maintaining high systemic concentrations for extended periods of time the adverse effects of aminoglycosides

A

Nephrotoxicity
Ototoxicity
were more common and severe

80
Q
Pseudomonas infection
Extended spectrum penicillin prescribed
Gentamicin ordered for combination chemo
Gentamicin administered as a single 30-min infusion daily
This is appropriate b/c gentamicin
A

Exhibits concentration-dependent killing

81
Q

Piperacillin

A

Antipseudomonal Penicillin

  • Greater porin channel penetration
  • More gram (-) coverage vs. aminopenicillins
82
Q

Pseudomonas

A

Gram (-)

83
Q

Ampicillin administered

A

orally

84
Q

Piperacillin administered

A

IV

85
Q

Most penicillins have similar half-lives

A

Short: (1/2-1 hour)

86
Q

Piperacillin

A

is one of the most expensive penicillins

87
Q

Piperacillin

A

Anti-Pseudomonal Penicillin
Susceptible to beta-lactamases
Given with beta-lactamase inhibitor (tazobactam)