Antimicrobials Flashcards

(51 cards)

1
Q

Empiric antimicrobial therapy

A

Use of antimicrobial agents before the pathogen responsible for an illness has been identified, used in cases where there is a significant risk of morbidity if a therapy is withheld until specific pathogen is detected

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2
Q

Steps in empiric therapy

A

Formulate clinical diagnosis of microbial infection, obtain specimens for lab, formulate microbiologic diagnosis, determine necessity for empiric therapy, institute treatment

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3
Q

Selective toxicity

A

The ability of a drug to injure a target cell or organism without injuring other cells or organisms that should not be injured

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4
Q

Methods of selective toxicity

A

Unique target must be present in pathogen but absent in the host OR target must be structurally different in the pathogen than in the host OR target must be more important in the pathogen than in the host

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5
Q

Things to consider in the selection of antibiotics

A

Identity and sensitivity of the organism, site of infection, safety of the agent, patient factors, the cost of therapy

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6
Q

Narrow spectrum antibiotics

A

Gram positive cocci and gram negative bacilli, gram negative aerobes, Mycobacterium tuberculosis

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7
Q

Gram positive cocci and gram negative bacilli

A

Narrow spectrum- penicillin G and V, penicillinase-resistant penicillins (nafcillin methicillin), vancomycin, erythromycin, clindamycin

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8
Q

Gram negative aerobes

A

Narrow spectrum- aminoglycosides (gentamicin), cephalosporins (2nd generation)

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9
Q

Mycobacterium tuberculosis

A

Isoniazid, rifampin, ethambutol, pyrazinamide

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10
Q

Broad spectrum antibiotics

A

Gram positive and negative organisms

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11
Q

Gram positive and negative organisms

A

Broad spectrum- broad spectrum penicillins (ampicillin), extended-spectrum penicillins (carbenicillin), cephalosporins (3rd generation), tetracyclines, imipenem, trimethoprim, sulfonamides (sulfamethoxazole), fluoroquinolones (ciprofloxacin, norfloacin)

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12
Q

Disruption of bacterial cell wall

A

Without cell walls, bacteria absorb water, swell, and burst, several families of drugs act to weaken cell wall and promote lysis of the bacteria, mammalian cells have no cell wall

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13
Q

Disruption of bacterial protein synthesis

A

Synthesis of proteins employs ribosomes, target bacterial ribosomes

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14
Q

Inhibition of enzymes unique to bacteria

A

Sulfonamides inhibit bacterial enzyme required for folic acid synthesis, bacteria cannot take up folic acid from environment, mammals do not synthesize folic acid, making it selective

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15
Q

Inhibition of nucleic acid

A

DNA gyrase

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16
Q

Inhibition of membrane function

A

Fungal membranes

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17
Q

Minimal inhibitory concentration (MIC)

A

Minimal concentration where the antimicrobial can inhibit bacterial growth

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18
Q

Minimal bactericidal concentration (MBC)

A

Minimal concentration where the antimicrobial kills bacteria

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19
Q

Things that determine an anti-microbial’s effectiveness against an organism

A

Antibiotic must bind to its target site in the bacterium, drug most occupy an adequate number of binding sites related to its concentration within the microorganism, antibiotic should remain at the binding site for a sufficient period of time to cause sufficient inhibition

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20
Q

Factors that may cause resistance to antibiotics

A

Failure of drug to reach its target, drug inactivation, target alteration

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21
Q

Failure of drug to reach its target

A

Outer membrane of a gram negative bacteria is a barrier that excludes large polar molecules from entering the cell, small polar molecules enter through porins

22
Q

Mutations of porin

A

Can cause loss or blockage of a porin that the antibiotic used to gain access to the cell

23
Q

Mutations inhibiting transport mechanisms

A

Can confer resistance to a drug with an intracellular target that requires active transport across the cell membrane (gentamicin)

24
Q

Drug inactivation

A

Bacterial resistance may result from the production of enzymes that modify or destroy the antibiotic

25
Antibiotics affected by drug inactivation
Bacteria may develop resistance to aminoglycosides and beta-lactam antibiotics, isoniazid requires bacteria to convert prodrug to active form
26
Target alteration
Change in the conformation or binding sequence of the target, antibiotic can no longer bind to the target
27
Efflux pumps
Can transport drugs out of cells- tetracyclines, chloramphenicol, fluoroquinolones, macrolides, beta-lactam antibiotics
28
Which antibiotics are most likely to promote resistance
Broad-spectrum antibiotics kill off more competing organisms, are more likely to produce resistance
29
Superinfection
New infection that appears during the course of treatment of a primary infection, can develop due to elimination of normal flora, most common with broad-spectrum antibiotics
30
Factors of therapeutic objectives
Identity of the infecting organism, drug sensitivity of the infecting organism, host factors, drug of choice has greater efficacy, lower toxicity, and is narrow spectrum
31
Alternative agents
Should only be used when the first choice drug is inappropriate due to: allergy, inability of drug to penetrate to the site of infection, or unusual susceptibility of the patient to the toxicity of the first choice drug
32
Reasons for therapy with antibiotic combinations
Initial therapy of a severe infection, mixed infections, prevention of resistance, decreased toxicity, enhanced antibacterial action
33
Mixed infections
Caused by more than one microbe, common in brain abscesses, pelvic infections, infections from perforation of abdominal organs
34
Prevention of resistance
Often multiple antibiotic use is associated with promotion of resistance, combinations of drugs are used in tuberculosis
35
Decreased toxicity
Combination of flucytosine with amphotericin B in the treatment of fungal meningitis, can reduce dose of amphotericin B and decrease the risk of damage to the kidney
36
Enhanced antibacterial action
Penicillins and aminoglycosides in the treatment of enterococcal endocarditis, penicillin weakens cell wall, aminoglycoside suppresses protein synthesis
37
Two antibiotics used together may have different effects
Additive, potentiative (synergistic), or antagonistic
38
Additive response
Antimicrobial effect of the combination is equal to the sum of the effects of each drug alone
39
Synergistic (potentiative) interaction
Effect of the combination is greater than the sum of the effects of the individual agents, one of the two drugs must show a 4-fold increase in activity
40
Synergistic blockade of sequential steps in a metabolic sequence
Trimethoprim-sulfamethoxazole for folic acid production
41
Synergistic inhibition of enzymatic inactivation
Beta-lactams and beta-lactamase inhibitor (sulbactam)
42
Synergistic enhancement of antibiotic uptake
Penicillins increase uptake of aminoglycosides in staph and enterococci
43
Antagonism
Combination of two antibiotics may be less effective than one of the agents by itself, usually static agents are antagonistic to cidal agents
44
Examples of antagonism
Chloramphenicol and penicillin in treatment of pneumococcal meningitis, tetracycline and penicillin
45
Initial therapy of severe infection
Most common indication for use of combination is initial therapy for sever infections of unknown etiology, drug selection can be adjusted once the identity of the microbe is known
46
Penicillins
Amoxicillin, bind to PBP, end in "cillin"
47
Tetracyclines
Tetracycline, act at 30S ribosome, end in "cycline"
48
Aminoglycosides
Streptomycin, affects protein synthesis, "mycin" or "micin"
49
Quinolones
Levofloxacin, DNA gyrase inhibitors, end in "oxacin"
50
Cephalosporins
Cefaclor, affects protein synthesis, start with "cef" or "ceph"
51
Macrolides
Erythromycin, acts at 50S ribosome, end in "mycin"