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Microbiology > 1.4 > Flashcards

1.4 Flashcards

1
Q

Antibiotics:

A 
a class of chemotherapeutic
agents
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2
Q

Chemotherapeutic agents are

A

chemical

compounds used to treat disease

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3
Q

Antimicrobials destroy

A

pathogenic microbes or

inhibit their growth within host

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4
Q

Antibiotics destroy or inhibit

A

bacteria

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5
Q

Most antibiotics are — products or their

derivatives

A

microbial

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6
Q

selective toxicity

A

– ability of drug to kill or inhibit pathogen while

damaging host as little as possible

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7
Q

therapeutic dose

A

– drug level required for clinical treatment

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8
Q

toxic dose

A

– drug level at which drug becomes too toxic for patient

i.e., produces side effects

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9
Q

therapeutic index

A

– ratio of toxic dose to therapeutic dose

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10
Q

Bacteriocidal antibiotics

A

– kill bacteria

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11
Q

Bacteriostatic antibiotics

A

– inhibit growth of bacteria

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12
Q

Broad-spectrum antibiotics

A

– attack many different bacteria (Gram + and Gram -)

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13
Q

Narrow-spectrum antibiotics

A

– attack only a few different bacteria

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14
Q

Determining the Level of
Antimicrobial Activity
• effectiveness expressed in two ways

A

– minimal inhibitory concentration (MIC)

– minimal bacteriocidal concentration (MBC)

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15
Q

– minimal inhibitory concentration (MIC)

A

• lowest concentration of drug that inhibits growth of pathogen

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16
Q

– minimal bacteriocidal concentration (MBC)

A

• lowest concentration of drug that kills pathogen

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17
Q

Dilution Susceptibility Tests

A

• involves inoculating media containing different
concentrations of drug
– broth or agar with lowest concentration showing no
growth is MIC
– if broth used, tubes showing no growth can be
subcultured into drug-free medium
• broth from which microbe cannot be recovered is MBC

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18
Q

Disk Diffusion Tests

A

• disks impregnated with specific drugs are
placed on agar plates inoculated with test
microbe
• drug diffuses from disk into agar,
establishing concentration gradient
• observe clear zones (no growth) around
disks

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19
Q

Kirby-Bauer method

A

• standardized method for carrying out disk
diffusion test
• sensitivity and resistance determined using tables
that relate zone diameter to degree of microbial
resistance
• table values plotted and used to determine if
concentration of drug reached in body will be
effective

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20
Q

Kirby-Bauer method (steps)

A 
Inoculate plate
evenly with
bacteria whose
susceptibility is
being studied
Place discs containing
antibiotics or control
solutions onto the plates
Incubate a defined
amount of time at a
defined temperature
Measure zone of inhibition
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21
Q

Measurement of Drug
Concentrations in the Blood
• concentration of drug at infection site must
be > — to be effective

A

MIC

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22
Q

microbiological, chemical, immunological,
enzymatic, or chromatographic assays can
be used to determine

A

concentration of

drug in blood

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23
Q

Factors Influencing the
Effectiveness of Antimicrobial
Drugs (3)

A

• ability of drug to reach site of infection
• ability of drug to reach concentrations in body
that exceed MIC of pathogen
• susceptibility of pathogen to drug

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24
Q

Ability of drug to reach site of
infection
• depends in part on mode of administration (3)

A

– oral
– topical
– parenteral routes

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25
– oral
• some drugs destroyed by stomach acid
26
– parenteral routes
• nonoral routes of administration
27
drug can be excluded by (2)
blood clots or necrotic | tissue
28
Factors influencing ability of drug to reach concentrations exceeding MIC (4)
* amount administered * route of administration * speed of uptake * rate of clearance (elimination) from body
29
Mechanism of Action of Antimicrobial Agents • can impact pathogen by targeting some function necessary for its (2)
reproduction or | survival
30
Ideally, targeted function is very specific to | pathogen =
high therapeutic index. | – Not always possible
31
b-lactams (4)
penicillins cephalosporins carbapenems & monobactams (+ b-lactamase inhibitors)
32
Glycopeptides (2)
vancomycin & teichoplanin
33
Polypeptides (2)
bacitracin & polymixins
34
Others (3)
cycloserine isoniazid & ethionamide ethambutol
35
1. Disruption of bacterial cell wall (2)
– Peptidoglycan is unique to bacteria | – Most pathogens contain peptidoglycan
36
peptidoglycan repeat unit forms in cytoplasm • involves use of
uridine | diphosphate (UDP) as a carrier
37
repeat unit then transported across | membrane by
bactoprenol (“lipid”)
38
repeat unit attached to growing
peptidoglycan chain
39
cross-links formed by
transpeptidation
40
Transpeptidation creates crosslinks in
peptidoglycan
41
Transpeptidation is the exchange of one
peptide bond for another
42
b-lactam antibiotics inhibit ---
transpeptidation
43
penicillin G
higher activity against most gram-positive bacteria, low agaist gram negative; destroyed by acid and penicillinase
44
penicillin V
more acid restraint than penicillin G
45
ampicillin
active against gram-positive and gram-negative bacteria; acid stable
46
carbenicillin
active against gram negative bacteria like pseudomonas and proteus; acid stable, not well absorbed by small inteastine
47
methicillin
penicillinase-resistant, but less active than penicillin G, acid liable
48
ticarcillin
similar to carbenicillin but more active against pseudomonas
49
first generation cephalosporin
cephalothin
50
second generation cephalosporin
cefoxitin
51
third generation cephalosporin
cefoperazone | ceftriaxone
52
Carbapenems and monobactams
Two newer classes of b-lactam antibiotics
53
b-lactamase inhibitors
Not antibiotics, but help b-lactam antibiotics by | preventing their degradation by b-lactamases
54
b-lactamases are enzymes produced by some bacteria that are | resistant to
b-lactam antibiotics
55
Examples of b-lactamase inhibitors: (3)
clavulanic acid, sulbactam, and tazobactam
56
Use in combination with b-lactam antibiotic --- was 1st combination = amoxicillin + clavulanic acid
Augmentin | = amoxicillin + clavulanic acid
57
Vancomycin binds terminal D-Ala-D-Ala and sterically inhibits
addition of peptidoglycan subunits to the cell wall.
58
Vancomycin binding to existing peptidoglycan chains inhibits | the
transpeptidation reaction that crosslinks the chains.
59
``` vancomycin has been important for treatment of antibiotic resistant (2) ```
staphylococcal and | enterococcal infections
60
Vancomycin and teichoplanin are ---
glycopeptides
61
bacitracins
Prevent recycling of lipid carrier
62
polymixins
Binds phospholipids and disrupts outer and inner membranes of gram negative bacteria (topical because of more general mode of action = toxic)
63
Cycloserine
Second line treatment for | Mycobacterium tuberculosis
64
Cycloserine is a cyclic | analog of
``` alanine - Also crosses blood brain barrier and is an NMDA receptor agonist (with uses and side effects) ```
65
Isoniazid & Ethionamide Inhibits Mycobacteria by affecting synthesis of
mycolic acid (abundant wax in the cell wall)
66
Ethambutol Inhibits Mycobacteria by affecting attachment of
mycolic acid in the cell | wall
67
Oxazolidinones | linezolid
Binds 23S rRNA and prevents formation of 70S initiation complex
68
Inhibition of protein synthesis | Tetracyclines
Bind 16S rRNA of 30S subunit and prevent binding of aa-tRNA to A site
69
Inhibition of protein synthesis | Aminoglycosides
streptomycin amikacin gentamycin tobramycin Bind to 30S subunit and distort A site, causing translation misreading, which inhibits protein synthesis
70
Inhibition of protein synthesis Chloramphenicol Lincosamides
Bind to 50S subunit and inhibit | peptidyltransferase activity
71
. Inhibition of protein synthesis | Macrolides
Erythromycin, azithromycin, clarithromycin • Bind 23S rRNA in the 50S subunit and block the translocation reaction • also prevent formation of the 50S subunit
72
Inhibition of nucleic acid synthesis | Quinolones
ciprofloxacin and other -floxacins Interfere with type II topoisomerases (DNA gyrase or topoisomerase IV) and stabilize DNA double strand breaks
73
Inhibition of nucleic acid synthesis Rifampin & Rifabutin Rifampin
Bind to RNA polymerase and prevent | the initiation of transcription
74
Inhibition of nucleic acid synthesis | Metronidazole
• a prodrug with no inherent antimicrobial activity • produces DNA-damaging radicals under anaerobic conditions via enzymes functioning in anaerobes and microaerophiles
75
Antimetabolites (4)
Sulfonamides, trimethoprim, dapsone, and p-aminosalicylic | acid
76
Drug Resistance Big problem for clinical treatment of --- Resistance can often be transmitted to other ---
infections | bacteria
77
New mutations of bacterial genes that | encode the targets of ---
antibiotics
78
Pre-existing resistance genes that are | transmitted from
one bacterium to another
79
Plasmids - some can promote their own transfer by
conjugation
80
Transducing bacteriophage
- can package non-phage DNA | = transfer by transduction
81
Bacterial chromosomal genes (2)
- mutations | - transfer by transformation
82
Transposons
- hop into other genetic elements
83
Integrons (2)
- segments of DNA containing complete sets of genes - found on plasmids, transposons, and bacterial chromosomes
84
Superinfection
development and spread of drug-resistant pathogens | caused by drug treatment, which destroys drug sensitive strains
85
Killing of normal flora removes | the
``` inhibitory effect of the normal flora (which produce antibacterial substances & compete for essential nutrients). This allows for uninhibited growth of potentially pathogenic bacteria & fungi ```
86
Common organisms in Superinfections include: (4)
Clostridium difficile (spore-forming agent of pseudomembranous colitis) MDR (multi-drug-resistant) gram-negative rods MRSA (methicillin-resistant Staphylococcus aureus) Candida or other fungi
87
Preventing emergence of drug | resistance (3)
* give drug in high concentrations * give two or more drugs at same time * use drugs only when necessary
88
possible future solutions (2)
– continued development of new drugs – use of bacteriophages to treat bacterial disease

Microbiology (42 decks)

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