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.
2
Q
Large number of resistance in one strain is usually due to
A
Presence of a plasmid
3
Q
Do phages have antibiotic resistant genes?
A
None found so far
4
Q
Target of Fluoroquinolones
A
Gram (-) infections
5
Q
Penicillins target
A
Gram (+) infections
6
Q
Ampicillin targets
A
Gram (+) and some Gram (-)
7
Q
Salmonella is
A
Gram (-)
8
Q
Ceftriaxone
A
3rd Generation Cephalosporin Broad Gram (-) coverage
9
Q
Sulfisoxazole
A
Mimics PABA
Competitively inhibits dihydropteroate synthase
10
Q
Bacterial Protein Synthesis
A
- Initiate Process (Aminoglycosides/Linezolid
- Add tRNA (tetracycline)
- Add peptides: translocate (Chloramphenicol, Macrolides, Clindamycin)
11
Q
Gentimicin
A
Aminoglycoside so blocks initiation of protein synthesis
Binds to 30s
Misread proteins will increase permeability of cell membrane
Bactericidal
12
Q
Tobramycin
A
Aminoglycoside
13
Q
Streptomycin
A
Aminoglycoside
14
Q
Aminoglycosides treat
A
Gram (-) infections
15
Q
Streptomycin can be used for
A
Tuberculosis
16
Q
Aminoglycosides have synergestic effects with
A
Beta-lactams
17
Q
Vancomycin/Gentamicin
A
Endocarditis
18
Q
Ampicillin/Gentamicin
A
Newborn Meningitis
19
Q
Tetracycline
A
Transported into bacterial cells
Binds 30s ribosome
Prevents attachment of tRNA
20
Q
Which drug should not be taken with antacids or milk?
A
Tetracyclines
Chelation with cations
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
22
Q
HFr Conjugation
A
recombination of chromosomal DNA fragments are transferred to recipient after F plasmid transfer
23
Q
IS element
A
IS element – insertion sequence, simplest transposon, provide regions of homology with chromosome to allow recombination
24
Q
Phage Conversion
A
Involves phage gene affecting the phenotype of a bacterium
25
Transformation
Direct uptake of DNA from surrounding environment
26
Conjugation
Transfer from one cell to another via pilus
| DNA transferred via plasmids
27
Plasmids
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
28
Transduction
Transfer of DNA via a bacteriophage
-Virus that infects bacteria
Virus picks up DNA, transfers to another bacteria
29
Generalized Transduction
Virus infects bacteria
Multiplies, randomly picks up host DNA
Host DNA transferred to other bacteria
30
Specialized Transduction
Transfer of specific genes
Virus DNA inserts into host DNA (lysogeny)
When bacteriophage DNA excised, packaged into virus with specific host DNA
31
Transduction occurs via
Lytic or Lysogenic Cycles
32
Generalized Transduction via
Lytic Cycle
Nuclear material enters bacteria
Multiplies, lyses cell
Releases progeny viruses
33
Specialized Transduction via
Lysogenic Cycle
Nuclear material enters cell
Incorporates into host DNA
May later become excised (enter lytic phase)
34
Why lysogeny matters
Genes for some bacterial toxins are transferred to non-toxic strains via lysogeny
35
Transposons are
DNA segments within bacterial DNA
36
Transposons can be
Excised and reintegrated in new locations in DNA
37
Once transposon is excised, it can also be moved to
plasmid, which transfers to other bacteria
38
Mycobacteria
Mycolic acids in cell wall
| Lipid-rich cell wall that is "acid-fast"
39
M. Leprae (Leprosy)
Obligate IC organism
Cannot be cultured
Cool temps: skin, extremities, face
Granulomatous inflammation
40
M. Leprae infects
Skin and superficial nerves
41
Tuberculoid Leprosy
Mild (infection contained)
42
Lepromatous Leprosy
Severe (weak cell-mediated response)
43
Tuberculoid Leprosy
Patches of hypopigmented skin
Loss of sensation over affected area
Strong cell-mediated Th1 response contains infection
Lesions show granulomas, few bacteria
44
M. Leprae
| Leprosy Dx
Acid-fast organisms on skin biopsy
45
Tuberculoid Leprosy Tx
Dapsone and Rifampin (6 months)
46
Lepromatous Leprosy Tx
Dapsone, rifamipin, clofazimine (years)
47
Dapsone
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
Sulfonamides
Disrupt folic acid pathways
Pneumocystis jirovecii
Hemolysis in G6PD
49
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?
Dapsone
50
Dapsone is first-line therapy for
leprosy
51
Isoniazid
Do not use with antacids or dairy
52
Ethambutol
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
Isoniazid (INH)
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
Pyrazinamide
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
Streptomycin
Was only for severe (life-threatening) cases, now used more frequently
PK, adverse effects typical of aminoglycoside
56
Interferon γ assay
Interferon γ assay – M.tb antigens + whole blood → activated T cells produce INF-γ → ELISA
57
Pt diagnosed with miliary tuberculosis. Which test would best confirm latent infection of immediate family members?
Positive interferon-gamma blood test
58
Il-12 triggers
Differentiation of T cells into Th1 cells
59
Activated Th1 cells produce
Interferon gamma
60
Interferon gamma is important for
response to IC infections
61
BCG vaccine
live attenuated M. bovis, best for children, not in US
62
Interferon-gamma blood test is specific for
M. tuberculosis
63
Detection of acid-fast bacilli in sputum indicates
active infection
64
Tuberculin test resulting in an erythema 15 mm in diameter or more is
Positive
65
M. Tuberculosis Transmission
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
M. Tuberculosis lipoarabinomannan binds to
macrophage mannose receptor
67
Opsonization occurs via
C3B (component of complement system)
68
Capsules
Capsules – protection/phagocytosis evasion
69
Cord factor
Cord factor – cytotoxic to neutros by disrupting mitochondrial membranes
70
Virulence factor
Bacterial features that allow evasion of host defenses
71
Listeria is found in
Unpasteurized milk products
72
Listeria can
Cross the placenta and infect the fetus
73
Concentration-Dependent Cell Killing
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
Gentimicin
Aminoglycoside
75
Efficacy of aminoglycosides is related to their
Peak concentration
76
Aminoglycosides elicit a
post-antibiotic effect
77
Post-antibiotic effect
continued killing or suppression of bacteria after the drug concentrations have fallen below MBC
78
Aminoglycosides are rapidly cleared into the urine, and thus
have short half-lives
79
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
Nephrotoxicity
Ototoxicity
were more common and severe
80
```
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
```
Exhibits concentration-dependent killing
81
Piperacillin
Antipseudomonal Penicillin
- Greater porin channel penetration
- More gram (-) coverage vs. aminopenicillins
82
Pseudomonas
Gram (-)
83
Ampicillin administered
orally
84
Piperacillin administered
IV
85
Most penicillins have similar half-lives
Short: (1/2-1 hour)
86
Piperacillin
is one of the most expensive penicillins
87
Piperacillin
Anti-Pseudomonal Penicillin
Susceptible to beta-lactamases
Given with beta-lactamase inhibitor (tazobactam)
