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Microbio Exam 1 > Antibiotics > Flashcards

Antibiotics Flashcards

1
Q

Antibiotics are based on naturally occurring compound but are modified chemically to do what?

A
  • extend their range of action
  • improve potency and pharmacokinetics
  • avoid resistance mechanisms
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2
Q

Narrow vs. broad spectrum antibiotics

A

N: specific against a few bacteria
B: active against many different bacterial types

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3
Q

Define therapeutic index

A
  • lowest dose that is toxic to the patient divided by the dose used to typically treat a patient
  • LARGER THE INDEX THE BETTER
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4
Q

3 general types of adverse events from ABx

A
  • allergic reactions: hypersensitivity to a specific drug
  • toxic effects: can be drug specific
  • Suppression of normal flora: one reason to use narrow-spectrum ABx
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5
Q

How do disinfectants differ from antibiotics?

A
  • disinfectants (detergents, peroxide) have a NONSPECIFIC mechanism of action and so are BROADLY active and not tolerated by the host
  • usually need higher concentration relative to antibiotics due to lack of specificity
  • remember: ABx have specific spectrum of activity that is related a specific mechanism of action
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6
Q

5 major mechanisms by which antibiotics work:

A
  1. inhibit cell wall synthesismost common
  2. Inhibit protein synthesis second most common
  3. Inhibit nucleic acid function or production
  4. Disrupt metabolic pathways, like folate metabolism
  5. Disrupt cell membrane (Not cell wall, cell membrane)
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7
Q

ABx that target the bacterial cell wall work best against _________ bacteria while ABx that target cell membrane typically work best against ________ bacteria.

A
  • gram positive where cell wall is far more prominent

- gram negative where cell membrane is on outer surface

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8
Q

3 mechanisms that confer selectivity to antibiotics

A
  1. absence of target from the host: high therapeutic indexes
  2. permeability differences: bacteria take it up, our cells dont
  3. structural differences in the target: different ribosome size
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9
Q

Drugs that gain selectivity by permeability differences need to be given by IV, not the mouth…why?

A

-our cells will not pick up the drug, so it cannot reach infections internally

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10
Q

Bacteriostatic vs. bactericidal antibiotics

A
  • Static: reversibly inhibit bacterial growth; growth resumes when drug is removed
  • cidal: kill bacteria; usually requires bacteria to be growing actively
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11
Q

Drugs that target metabolic processes typically fall into (bacteriostatic/bactericidal) categories. Drugs that target the cell wall or membrane tend to be _______.

A
  • bacteriostatic

- bactericidal

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12
Q

Define Minimum Inhibitory Concentration

A

-lowest concentration of an antibiotic that effectively inhibits growth of a microorganism

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13
Q

2 ways to test susceptibility of bacteria to various antibiotics

A
  1. Tube dilution assay for antibiotic sensitivities

2. Disc diffusion method

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14
Q

Tube dilution assay for antibiotic sensitivies

A
  • bacteria are gown in small cultures in the presence of different concentrations of antibiotics
  • tells you sensitivies of a given bacterial isolate to a range of drug concentrations
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15
Q

Disc diffusion method for antibiotic sensitivies

A
  • bacterial isolate is spread over plate and grown into “bacterial lawn”
  • small antibiotic impregnanted discs are placed on the agar, and drug diffuses in
  • if isolate is not sensitive, it will continue to grow, but if it is sensitive, you will see clear area around disk
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16
Q

In a disk diffusion method, the width of the clear area is related to the _______. Does this procedure inform us if the drug is bacteriostatic or bactericidal?

A
  • MIC: minimum inhibitory concentration

- no

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17
Q

Generally, we prescribe one drug whenever possible and it is usually the simplest to minimize evolution of drug resistance. What are some cases when 2 or more ABx will be prescribed?

A
  • chronic infections
  • emergencies: cannot wait for cultures to come back
  • mixed infections
  • drug synergies
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18
Q

What are the 4 possible outcomes that can arise if more than 1 drug is being used?

A
  1. indifference: 2 drugs have no effect on eachother
  2. Additive response: response is the same as the sum of the 2 drugs individually
  3. Synergistic response: response is greater than the sum of the two drugs used individually
  4. antagonistic response: response is less than sum of the two drugs used individually
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19
Q

2 drug examples of synergism

A
  1. Bactrim: Sulfamethoxazole (inhibits production of THF-acid, but not utilization of current pool)+ Trimethoprim (prevents use of THF-acid pool, but not its synthesis)
  2. Augmentin: amoxicillin (extended spectrum penicillin)+ beta-lactamase inhibitor clavulanic acid
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20
Q

Drug example of antagonistic response

A
  • penicillin and erythromycin
  • erythomycin is bacteriostatic and slows bacterial growth that is necessary for penicillin (bacterocidal) to function properly
  • if E is used first, it will make subsequent application of the cell wall inhibitors less effective
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21
Q

Name 4 issues that can limit successful antimicrobial therapy

A
  1. location: some drugs cannot cross BBB and some bacteria are intracellular
  2. abscess formation and necrosis: decreased circulations in the area of an abscess will limit drug concentrations; low nutrients may slow bacterial growth that makes some ABx less effective
  3. presence of foreign bodies and obstructions: adhere to objects and make biofilms
  4. drug resistance
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22
Q

5 general mechanisms of drug resistance

A
  1. enzymatic inactivation of the antibiotic
  2. Inadequate or decreased uptake of the drug into the microbe (mutate porins)
  3. Increased efflux of the antibiotic out of the microbe (active transport)
  4. Alteration of drug target (mutations in PBPs)
  5. Altered metabolic pathways (new enzyme expression)
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23
Q

Many bacteria, as a form of resistance, produce an enzyme called a beta lactamase that does what?

A

-cleaves the beta-lactam ring present in penicillins, cephalosporins, and carbapenems

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24
Q

Are community acquired or hospital acquired bacterial infections more likely to be resistant to drugs?

A

-hospital

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25
Q

If you know what bacterium is causing the infection, you should prescribe drugs that are as ____________. When would you want to do the opposite?

A
  • narrow spectrum as possible

- if life threatening, you need to treat more broadly since you can’t run the risk of guessing wrong

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26
Q

Gram positive vs. gram negative structure

A

+: thick, exposed peptidoglycan layer

-: thinner peptidoglycan layer that is beneath an outer membrane

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27
Q

Peptidoglycan has repeating units of disaccharides that are crosslinked to each other via ________. What catalyzes formation of these cross-linked?

A
  • peptide bonds

- transpeptidase

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28
Q

Penicillins bind to __________, so these enzymes are also referred to as __________.

A
  • transpeptidase

- penicillin binding proteins (PBPs)

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29
Q

Beta lactams are competitive inhibitors of __________ and inhibit its function. What is the result of this?

A
  • transpeptidase
  • do not destroy existing cross-links but prevent formation of new ones; causes weak points at growth sites and become fragile
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30
Q

In general, Beta-lactam ABx are more effective against what type of bacterial cells?

A
  • gram-positives because the cell wall is exposed

- those that are effective against G(-) cells must cross the cell membrane

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31
Q

Beta-lactams are __________ and work more effectively against rapidly/slowly growing bacteria?

A
  • bactericidal

- rapidly growing bacteria

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32
Q

What do the 3 classes of penicllins have in common? Describe this feature

A
  • common structure of the beta-lactam ring

- 4 sided ring with a nitrogen in it

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33
Q

Are penicillins the only ABx to have a beta-lactam ring?

A
  • no; cephalosporins, carbapenems, and monobactams

- different side groups can alter the properties of the drug

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34
Q

Penicillins, cephalosporins, and carbepenems are drug classes that ALL contain a beta-lactam ring and target ________.

A
  • bacterial cell wall

- called beta-lactam antibiotics

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35
Q

Name the 3 classes of penicillins

A
  1. Natural penicillins
  2. Penicillinase-resistant penicillins
  3. Extended spectrum penicillins
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36
Q

List the 2 natural penicillins and how they are taken

A
  • Penicillin G: inactivated by low pH so given by IV

- Penicillin V: acid stable, so can be taken PO

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37
Q

List the 5 penicillinase-resistant penicillins

A
  1. Methicillin
  2. Oxacillin
  3. Naficillin
  4. Cloxacillin
  5. Docloxicillin
    * *VERY NARROW SPECTRUM**
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38
Q

What is unique about penicillinase-resistant penicillins?

A

-they are resistant to beta-lactamases and were developed to combat Staph

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39
Q

Give the 4 examples of extending spectrum penicillins

A
  1. Ampicillin
  2. Amoxicillin
  3. Carbenicillin
  4. Pipericillin
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40
Q

What is unique about extending spectrum penicillins?

A

-must improved activity against gram-negatives, but less effective against gram positives

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41
Q

Extended spectrum penicillins are often used in conjunction with ____________.

A

-beta lactamase inhibitors

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42
Q

Penicillins are safe drugs, but have one significant side effect. Name it and describe a little bit about its risk.

A
  • hypersensitivity reactions
  • can be severe, causing anaphylaxis and can become more severe if a person is exposed to these drugs multiple times
  • can include hives, maculopapular-measles-like, include itchy skin, wheezing swollen lips, etc
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43
Q

Anaphylactic reactions to penicillins occur _________ and include what symptoms? What symptoms do they not include?

A
  • immediately
  • difficulty breathing, decreased blood pressure leading to dizziness and weak pulse, swelling of throat and tongue
  • Nausea and vomiting are NOT allergic reactions to the drug
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44
Q

Before administering a penicillin, what do physicians have to do?

A

-ask if there is a history of having taken these drugs before/allergies to medications

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45
Q

Any allergic reaction to penicillin can occur quickly, but more commonly _____________________.

A

-it takes a while, sometimes a day or two

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46
Q

3 mechanisms of Beta-lactam resistance

A
  1. Beta-lactamases are produced that destroy the drug
  2. Transpeptidases (major PBP) acquires a mutation the prevents drug binding
  3. Gram negatives can have membrane pumps that remove drug from pepiplasmic space
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47
Q

Describe the function of Beta-lactamase inhibitors

A

-little or no antimicrobial activity on their own, but can make beta lactam antibiotics more effective by binding to and inactivating beta lactamases

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48
Q

List 3 beta lactamase inhibitors

A
  1. clavulanate
  2. sulbactam
  3. tazolbactram
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49
Q

List 4 common combinations of penicillins and beta-lactamase inhibitors

A
  1. Amoxicillin-clavulanate = Augmentin
  2. Ampicillin-sulbactam
  3. Piperacillin-tazolbactam= Zosyn
  4. Ticarcillin-clavulanate= Timentin
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50
Q

When are natural penicillins the drug of choice and when are they not used?

A
  • drug of choice for community-acquired Strep, pneumococci, meningococci
  • treatment of choice for syphilis (a spirochete)
  • NOT effective against STAPH due to drug resistance
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51
Q

What genra of bacteria are natural penicillins not effective against and why?

A

-Staph!!! due to drug resistance

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52
Q

What is Staph’s method of resistance against natural penicillins? What is then used to treat them and are issues arising in this?

A
  • beta lactamases
  • use beta-lactamase resistant penicillins (oxacillin, methicillin, naficillin) but many strains are now resistant to these drugs–MRSA
  • now try to use oxacillin to treat Staph but this resistance is now rising
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53
Q

Characteristics of Ampicillin and Amoxicillin.

A
  • extended spectrum penicillins
  • similar to natural penicillins but can cross the membranes of some gram negatives and inactivate their transpeptidase enzymes
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54
Q

What are Ampicillin and Amoxicillin commonly prescribed for?

A

-uncomplicated urinary tract infections, otitis media, and uncomplicated community acquired penumonia, H. influenza, Lyme disease, and listeria meningitis

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55
Q

Characteristics and issue with Ticarcillin, Mexlocillin, and Piperacillin

A
  • extended spectrum penicillins
  • nice coverage of gram negatives, but at expense of not hitting gram positives as effectively
  • still sensitive to beta lactamases, which is a huge issue
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56
Q

What class of penicillins are often coadministered with beta lactamase inhibitors?

A

-extend spectrum penicillin

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57
Q

Summary of categories of bacterium natural penicillins are good at fighting against.

A
  • Strep
  • Meningococci
  • Spirochetes
  • Most other gram positive anaerobes
  • NOT STAPH
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58
Q

Why is selective toxicity crucial to antibiotics?

A

-due to specific mechanism of action, are typically well-tolerated by the host but lethal to harmful micrones

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59
Q

Define disinfectant and give 4 characteristics

A
  • an agent, such as heat, radiation, or a detergent, that destroys, neutralizes, or inhibits the growth of disease-carrying microorganisms
  • Nonspecific spectrum of action
  • Nonspecific mechanism of action
  • Not tolerated by host
  • Usually need high concentrations due to lack of specificity
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60
Q

Are bactericidal or bacteriostatic drugs better?

A
  • often believed that bactericidal is more beneficial, though massive bacterial death can enhance inflammatory response
  • bactericidal drugs are clearly better for meningitis and endocarditis
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61
Q

Efflux systems can be shared between bacteria via exchange of _________.

A

-Pathogenicity islands

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62
Q

3 ways antibiotics are used

A
  1. empiric therapy: given for proven or suspected infection, but organism not identified
  2. Definitive therapy: given for proven identification and based on a causative organism
  3. Prophylaxis: given to prevent infection
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63
Q

Hypersensitivity to penicillins are ______ mediated.

A

-IgE

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64
Q

MRSA’s method of resistance to penicillins

A

-transpeptidase acquires a mutation that prevents drug bindings

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65
Q

Staph’s method of resistance to penicillins

A

-beta lactamases

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66
Q

Mechanism of action of beta lactamase inhibitors

A

-irreversibly bind and inactivate certain beta-lactamases

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67
Q

Is amoxicillin or ampicillin used more?

A

-amoxicillin because it can be used 3 times a day instead of 4, and it is absorbed better

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68
Q

Extended spectrum penicillins with the addition of a beta-lactamase inhibitor have activity against _______.

A
  • improved activity against staph and gram negatives

- pseudomonas

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69
Q

Compare cephalorsporins mechanism of action to the penicillins. What are some differences?

A
  • same mechanism: inhibit peptidoglycan synthesis via PBPs–bactericidal
  • wider antibacterial spectrum
  • resistance to many beta-lactamases
  • improved pharmacokinetics
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70
Q

Are cephalosporins bactericidal or bacteriostatis?

A

-bactericidal

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71
Q

How do cephalosporins ring structures compare to penicillins?

A

-both have beta lactam rings, but cephalosporins are connected to a 6-member ring while penicillins are connected to a 5 member ring

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72
Q

In general, cephalosporins are resistant to _______ produced by __________ and common gram-negatives.

A

-beta-lactamases produced by staph

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73
Q

Cephalosporins do NOT cover ________.

A

-enterococci

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74
Q

Cephalosporin drugs have been described as “generations” from first generation (oldest) to fourth. Newer generations have better _______________.

A

-gram-negative coverage and poorer gram + coverage

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75
Q

Like penicillins, cephalosporins can induce ____________.

A
  • hypersensitivity reactions

- 5% of patients with penicillin reactions have reactions to cephalosporins as well

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76
Q

1st generation cephalosporins start with “ceph” except for ________ and _________.

A
  • Cefazolin

- Cefadroxil

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77
Q

What types of bacteria are cephalosporin (1st gen) active against and what are they commonly prescribed for?

A
  • very active against gram positives including Staph (except MRSA)
  • moderate use against some gram negatives, esp. E. coli and Klebsiella
  • used for community acquired UTIs and respiratory infections
  • Cefazolin is used for surgical prophylaxis
78
Q

For what instances are 1st generation cephalosporins commonly prescribed?

A
  • community acquired UTIs and respiratory infections

- Cefazolin for surgical prophylaxis

79
Q

When are 2nd generation cephalosporins prescribed?

A
  • otitis media in children
  • increased activity, esp. against gram negatives including H. influenzae
  • respiratory infections, UTIs
80
Q

3rd generation cephalosporin activity

A

-less activity against G+, more effective G- coverage

81
Q

What are 3rd generation cephalosporins prescribed for?

A
  • management of hospital-acquired (G-) bacteremia, inpatient pneumonia and UTIs
  • some can penetrate CNS!!! unlike 1st and 2nd generation)
  • gonococcal infections
82
Q

Single dose of __________ is used for gonococcal infections. It is also used to treat meningitis

A

-Ceftriaxone, a 3rd generation cephalosporin

83
Q

________ is the only licensed 4th generation cephalosporin in the US. What activities does it have?

A
  • Cefipime
  • enhanced activity to enterobacter, citrobacter, and pseudomonas
  • can be used when resistance is seen to a 3rd generation drug
84
Q

Side effects of Cephalosporins

A
  • overall relatively safe since drugs that target cell wall have a very high therapeutic index
  • hypersensitivity reactions just like penicillin
  • patients with significant PCN allergies should NOT be given cephalosporins, but you can risk it if PCN allergies are mild
  • greater incidence of GI problems due to better gram negative coverage- can lead to C. difficile colonization and colitis
85
Q

3 mechanisms of resistance to cephalosporins

A
  • Same to penicillin!
    1. beta lactamases
    2. increased efflux from periplasmic space of gram negatives
    3. change the target; mutate PBPs so they dont bind ABx well
86
Q

As you increase the generation of cephalosporins, you increase the ________ coverage.

A

-gram negative

87
Q

3 common first generation cephalosporins used at Penn

A
  1. Cafadroxil
  2. Cefazolin
  3. Cephalexin
88
Q

2nd generation cephalosporin commonly used at Penn

A
  1. Cefuroxime
89
Q

Name the 4 3rd generation cephalosporins used at penn

A
  1. Cefixime
  2. Cefotaxime
  3. Ceftazidime
  4. Ceftriaxone
90
Q

What 3rd generation cephalosporin is used to treat pseudomonas?

A

-Ceftazidime

91
Q

Carbapenems mechanism of action; how is it similar to penicillins? how is it different?

A
  • same as penicillins: inhibit PBPs

- wider antibacterial spectrum than other beta lactamases, resistance to beta-lactamases, improved pharmackkinetics

92
Q

4 carbapenems commonly used

A
  1. Imipenem
  2. Meropenem** commonly used at Penn and restricted**
  3. Ertapenem
  4. Doripenem
93
Q

Are Carbapenems bacteriostatic or bacterocidial? How are they administered?

A
  • bactericidal

- usually given IV

94
Q

What types of bacterial are carbapenems effective against?

A
  • gram positive, gram negative, aerobic, and anaerobic bacteria
  • typically cover everything except enterococci
95
Q

When are carbapenems administered?

A
  • often used as empiric therapy for critically ill patients

- last resort for E. Coli and Klebsiella infections

96
Q

Where are carbapenems metabolized? By what enzyme and can this be blocked?

A
  • Kidney by dehydropeptidase

- blocked by cilastatin, which is sometimes coadministered

97
Q

Why is the use of carbapenems so controlled?

A

-we dont want overuse as resistance to them so far is rare

98
Q

Resistance to carbapenems

A

-Carbapenemases (beta lactamases) have been found in enteric bacteria

99
Q

How do carbapenems penetrate gram negative rods?

A
  • bia OprD porins

- carbapenem resistant pseudomonas aeruginosa mutants lack OprD

100
Q

In summary, beta lactam drugs are generally more active against __________ bacteria, with variable coverage of ___________ bacteria.

A
  • gram positive

- gram negative

101
Q

Beta lactam side effects summary

A

-hypersensitivity is major side effect, along with GI disturbances with more potent cephaloporins

102
Q

What type of molecule is vancomycin?

A

-glycopeptide

103
Q

Function of vancomycin

A
  • interactions with D-alanine-D-alanine termini of the pentapeptide side chains interfering with formation of bridges between peptidoglycan chains
  • *Thus it works a step BEFORE beta-lactams in preventing transpeptidation**
104
Q

Is there cross resistance to vancomycin and beta-lactams?

A

-no; though V inhibits cell wall synthesis, it does so differently than beta-lactams

105
Q

How is vancomycin usually administered?

A

-IV due to poor absorption from intestinal tract, unless you are trying to treat a GI infection

106
Q

What coverage is vancomycin best at providing?

A
  • excellent gram positive coverage against Staph and Strep

- NO gram negative coverage

107
Q

Why does vancomycin not providing gram negative coverage make sense?

A

-it is a glycopeptide and is too big to pass through porins in the gram negative membranes

108
Q

Compare vancomycin and oxacillin effectiveness against MRSA

A

-vancomycin is inferior to oxacillin, but V is still used

109
Q

What is vancomycin prescribed for?

A
  • Staph and Strep infections
  • MRSA and othwr beta-lactam resistant gram positive organisms
  • oral form used for C. difficile colitis
110
Q

Vancomycin can cause a hypersensitivity reaction; rarely this can be more severe, leading to what is called ____________. In general, it is well tolerated but must be infused slowly. What else can it cause?

A
  • Red Man Syndrome with a red rash on the face, neck, and trunk
  • occurs monutes after administration due to secondary mast cell degranulation and histamine release
  • can also cause thrombophlebitis
111
Q

Bacitracin, like vancomycin, is a ________.

A

-peptide; although, B is technically a mixture of cyclic peptides

112
Q

How does bacitracin function?

A

-inhibits cell wall synthesis by preventing the transport of peptidoglycan precursors across the bacterial cytoplasmic membrane

113
Q

How is bacitracin used and what is it most effective against?

A
  • only used topically; toxicity issues if taken orally

- most effective against gram-positives

114
Q

Where is bacitracin a common ingredient?

A

-in non-prescription first-aid ointments

115
Q

Daptomycin

A
  • lipophilic peptide that disrupts the membranes of gram positives
  • can be given IV
116
Q

Daptomycin is approved for _____________ infections and is active against _________.

A
  • gram positive skin infections and S. aureus bacteremia

- MRSA

117
Q

What is the target of many antimicrobials that function by inhibiting protein synthesis?

A
  • prokaryotic ribosome

- it is different enough from the eukaryotic ribosomes responsible for selective toxicity

118
Q

4 drugs comprising class of antimicrobials that act via inhibiting protein synthesis

A
  1. Macrolides**
  2. Aminoglycosides**
  3. Tetracyclins
  4. Chloramphenicol
119
Q

What are the 4 macrolides commonly used at penn?

A
  1. Azithromycin
  2. Clarithromycin
  3. Clindamycin
  4. Erythromycin
120
Q

Mechanism of macrolides

A

-reversibly bind to 50S ribosome and prevent protein elongation

121
Q

Are macrolides bactericidal or bacteriostatic?

A

-Bacteriostatic

122
Q

Macrolides have broad activity against __________ and some _______.

A
  • gram positive

- some gram negatives

123
Q

When are macrolides prescribed?

A
  • first line agents for community acquired pneumonia and often drugs of choice for those allergic to penicillin
  • good activity against strep pneumonia
  • atypical pathogens like legionella, chlamydia, and mycoplasma
  • skin infections not due to MRSA
  • URTI
124
Q

Usual form of resistance to macrolides

A
  • usually due to altered binding sites

- can also be due to hydrolysis of drug and enhanced efflux

125
Q

Macrolide side effects

A

-no unusual side effects

126
Q

Eukaryotic ribosome have _____ and _____ subunits, while prokaryotes have ____ and ______ subunits.

A
  • 60S,40S

- 50S,30S

127
Q

6 commonly used aminoglycosides

A
  • streptomycin
  • gentamicin
  • tobramycin
  • amikacin
  • neomycin
  • spectinomycin
128
Q

Mechanism of action of aminoglycosides

A
  • IRREVERSIBLY binds to 30S ribosomal subunit
  • causes distortion and malfunction of ribosome
  • blocks initiation of translation
  • causes misreading of mRNA
129
Q

Are aminoglycosides bactericidal or bacteriostatic?

A

-bactericidal because they bind irreversibly

130
Q

Are aminoglycosides effective against anaerobes? explain.

A

-no; penetration through membrane is an aerobic, energy-dependent process

131
Q

Aminoglycosides are not effective against _____ and _______ unless…

A
  • enterococci and streptococci
  • UNLESS a Beta lactam drug is coadministered
  • this allows aminoglycosides to enter cells that are often resistant
132
Q

Typical uses of aminoglycosides

A
  • good coverage against aerobic, gram negative rods (E. coli, Klebsiella, enterobacter, pseudomonas, shigella)
  • usually reserves for serious gram negative infections (complicated UTIs with pylonephritis, penumonia and used with beta-lactam to cover G+ and G-, pseudomonas)
133
Q

Are aminoglycosides used in everyday practice?

A

-no, issues with toxicity limit their use

134
Q

How are aminoglycosides administered?

A
  • not absorbed in the gut

- thus given IV or IM

135
Q

What are the 2 most commonly used aminoglycosides

A
  • Gentamicin

- Tobramycin

136
Q

Why are aminoglycosides coadministered with beta lactams?

A

-beta lactams will damage cell wall and allow aminoglycosides to penetrate

137
Q

Aminoglycoside resistance is increasing with _______ and _______.

A
  • pseudomonas and enterococci

- incidence of resistance is low for other organisms

138
Q

3 resistance mechanisms to aminoglycosides

A
  1. enzyme modification of the drug: typically on plasmids and results in high-level resistance
  2. reduced uptake or decreased cell permeability: intermediate resistance since block is not complete
  3. Altered ribosome binding site: not common
139
Q

Why are there such strict concerns over aminoglycosides?

A

-these drugs have a low therapeutic index, so you need to follow drug levels

140
Q

2 common side effects of aminoglycosides

A
  1. nephrotoxicity: relatively common (10-20%), generally reversible toxicity, appears assoc. with high trough levels (lowest levels of drug seen in plasma)
  2. Ototoxicity: appears assoc with high peak levels, can cause tinnitus and permanent deafness due to loss of hair cells; may not be reversible
141
Q

Aminoglycosides being used with beta-lactams is a good example of _______.

A

-synergy

142
Q

Why can administering aminoglycosides be of help to CF patients?

A

-important drug against pseudomonas which cause serious problems for patients with CF

143
Q

3 common drugs used from tetracyclins

A
  • tetracyclin
  • doxycycline
  • minocycline
144
Q

Mechanism of action for tetracyclins

A
  • REVERSIBLY bind to 30S ribosomal subunit

- blocks attachment of tRNA to ribosome and prevents continuations of protein synthesis

145
Q

Are tetracyclins bacteriostatic or bactericidal?

A

-bacteriostatic: reversibly! bind 30s

146
Q

Common uses of tetracyclins

A
  • good coverage of mycoplasma and chlamydia
  • Drug of choice for lyme disease
  • acne treatment
147
Q

What class of drugs is the drug of choice for lyme disease?

A

-tetracyclins

148
Q

3 common side effects of tetracyclins

A
  • discolored teeth in children
  • GI upset
  • Phototoxic dermatitis
149
Q

Who should NOT receive tetracyclins?

A

-children or pregnant women

150
Q

Most common resistance mechanism to tetracyclins

A

-increased efflux from cells

151
Q

Mechanism of action of chloramphenicol

A
  • binds to 50S subunits

- prevents peptide bonds from forming and blocking protein synthesis

152
Q

Chloramphenicol is effective against a VERY wide variety of organisms, but used as drug of last resort for life-threatening infections. Why?

A
  • has rare, but deadly side effects

- aplastic anemia

153
Q

Aplastic anemia

A
  • rare, often fatal side effect of chloramphenicol

- bone marrow is wiped out

154
Q

Give 2 examples when Chloramphenicol is used

A
  • young children and pregnant women with Rocky Mountain Spotted Fever, which is usually treated with tetracyclins but can’t use these with these people
  • meningitis if organism not known and patient has penicillin allergy
155
Q

Who should not be given chloramphenicol under any condition?

A

-neonates: they cannot metabolize the drug, resulting in high levels and vasomotor collapse

156
Q

3 types of drugs that inhibit nucleid acid synthesis. Name them and if they work on DNA or RNA

A

DNA replication: quinolones/fluoroquinolones and metronidazole
RNA replication: Rifamycins

157
Q

Quinolones target ________.

A
  • DNA gyrase

- DNA gyrase nicks and reannels DNA to relieve supercoiling, and relieves tension as DNA is unwound during replication

158
Q

Drugs that target DNA gyrase inhibit ________.

A

-DNA replication

159
Q

Commonly used fluoroquinolones

A
  • levofloxacin
  • norfloxacin
  • Cirpofloxacin
160
Q

What bacterium are fluoroquinolones not good against?

A

-gram positives or anaerobes

161
Q

What are fluoroquinolones effective against?

A

-multi-drug resistant pseudomonas (Cipro is best)
-Enterics: E.coli, salmonella, shigella, campylobacter
-Complicated UTIs: usually caused by gram negs
-Anthrax
-GNR including pseudomonas
-

162
Q

Levofloxacin is active against many _________.

A

-penicillin-resistant pneumococci

163
Q

How are fluoroquinolines administered?

A
  • PO

- good tissue absorption

164
Q

Resistance mechanism against fluoroquinolones

A

-due to mutations in drug binding site in gyrase

165
Q

Side effects of fluoroquinolones

A

-generally safe, but can disrupt normal gut flora, increasing chance of getting C. difficile

166
Q

Tradename of metronidazole

A

-Flagyl

167
Q

Is metronidazole bacteriostatic or bactericidal?

A

-bactericidal

168
Q

Mechanism of action of metronidazole

A

-inhibits DNA replication, causes DNA breaks and secondary mutations

169
Q

Metronidazole is administered as a _________. What does this mean?

A
  • pro-drug
  • it is inactive (or significantly less active) until it is metabolized in vivo into an active form
  • in metronidazole, the nitrogroup is chemically reduced by bacterial oxidoreductases to become active
170
Q

What enzymes create the active form of metronidazole?

A
  • bacterial oxidoreductases

- it is activated INSIDE bacterial cells

171
Q

Metronidazole is only active against ________.

A
  • anaerobes

- one of the most reliable anti-anaerobic agents available

172
Q

Aside from anaerobes, metronidazole is also good against what other pathogens?

A
  • good for C.difficile, behind vancomycin

- Protozoa: trichomonas, giardia, amebic infections

173
Q

Resistance mechanisms against metronidazole

A
  • decreased uptake into the cell

- reduced activation of the ABx

174
Q

Mechanism of action of sulfonamides

A

-inhibit growth of gram + and gram - organisms through competitive inhibition of enzyme that aids in production of folic acid

175
Q

What is sulonamides structurally similar to?

A

-para-aminobenzoid acid which is substrate in folic acid pathway

176
Q

What is the basis of selective toxicity of sulfa-drugs?

A

-humans lack specific enzyme in folic acid pathway

177
Q

Resistance mechanism to sulfa-drugs

A
  • due to plasmid

- plasmid codes for enzyme that has lower affinity to drug

178
Q

Trimethoprim mechanism of action

A
  • inhibits folic acid production

- interferes with activity of enzyme following enzyme inhibited by sulfonamides

179
Q

Trimethoprim is often used synergistically with _______.

A

-sulfonamide

180
Q

Most common mechanism of resistance to trimethoprim

A

-plasmid-encoded alternative enzyme

181
Q

Genes encoding resistance to sulfonamide and tripmethoprim are often ________.

A

-carried on the same plasmid

182
Q

What is bactrim a combination of?

A

-trimethoprim and sulfamethaxazole

183
Q

Bactrim has no _______ coverage.

A

-anaerobic

184
Q

What is bactrim good for?

A
  • strep and H. flu (otitis media, sinusitis, bronchitis)
  • gram negatives causing diarrhea: shigella, salmonella, E. coli
  • pneumocystis (seen in AIDS patients)
185
Q

Bactrim side effects

A
  • hypersensitivity

- don’t give to patients taking warfarin (blood thinner) as it increases warfarin levels and can lead to bleeding

186
Q

List the 3 classes of drugs that target the cell wall

A
  • Penicillins
  • Cephalosporins
  • Carbapenems
187
Q

List the 1 class of drug that targets the cell membrane

A

-Glycopeptides/polypeptides

188
Q

List the 4 classes of drugs that target protein synthesis

A
  • Macrolides
  • Aminoglycosides
  • Tetracyclins
  • Chloramphenicol
189
Q

List the 3 classes of drugs that target nucleic acid synthesis

A
  • Quinolones
  • Rifampin
  • Metronidazole
190
Q

List the class of drugs that targets antimetabolites

A
  • Sulfonamides

- Trimethoprim

Microbio Exam 1 (13 decks)

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