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Microbiology > Antibiotics > Flashcards

Antibiotics Flashcards

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1
Q

When to use combined antibiotic therapy?

A

1) chronic infections: chance of double mutant arising is decreased
2) emergency situations
3) mixed infections (abdominal perforations)
4) synergistic effects (sum greater than alone)

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2
Q

Drug-drug interactions can be:

A

1) indifferent
2) additive: SUM
3) synergistic: combined action is GREATER than sum

EXAMPLE: bactrim and augmentim

4) antagonistic: combined action LESS than the sum

EXAMPLE: bacterial meningitis treated by penicillin and erythromycin. Penicillin disrupts cell wall formation so only effective when the cell is replicating, combined with erythromycin which inhibits protein synthesis (stops cell from replicating)

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3
Q

Minimum Inhibitory Concentration:

A

lowest amount of antibiotic that inhibits growth of microorganism

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4
Q

Selecting antibiotic/why treatments may or may not work:

A
  • know if it is active
  • know its MIC
  • avoid drug-drug interactions
  • location: intracellular bacteria may be difficult for drug to access, blood-brain barriers limit access, biofilms have poor drug penetration
  • abscess formation and necrosis: decreased circulation limits the acess of the drug
  • presence of foreign bodies: decreased circulation/biofilms
  • DRUG RESISTANCE
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5
Q

Mechanisms of antibiotic resistance:

A

1) enzymatic inactivation/alteration of antibiotic: beta lactamases produced by bacteria to hydrolyze beta lactam antibiotics (penicillin)
2) inadequete uptake: no transporter
3) increased efflux out: can share efflux systems via pathogenicity islands
4) alteration of target
5) pathways that bypass the reaction inhibited by the antibiotic:

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6
Q

Three ways antibiotics are used (types of therapies)

A

1) Empiric: know there is infection, do NOT know the organism
2) definitive: know infection and organism
3) prophylaxis: to prevent an infection (ie) before surgery

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7
Q

Cell wall antibiotics:

A
  • target gram + bacteria
    1) penicillins
    2) cephalosporins
    3) carbapenems
  • CELL WALL = PCC
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8
Q

Cell membrane antibiotics:

A

-target gram negative

Glycopeptides/polypeptides

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9
Q

Protein synthesis antibiotics:

A
  • macrolides
  • aminoglycosides
  • tetracyclines
  • chloramphenicol
  • Terminate making AA copies
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10
Q

nucleic acid synthesis:

A
  • quinolones
  • rifampin (RNA)
  • metronidazole
  • Quit replicating me
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11
Q

antimetabolites:

A

-sulfonamides

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12
Q

Two types of bacteria:

A
  • positive: Peptidoglycan layer is thicker and on the surface
  • negative: thinner and beneath the outer membrane
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13
Q

PBP

A
  • penicillin binding protein (transpeptidase is makor one)

- catalyze the building of pentaglycine bridges (make up the peptidoglycan layer)

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14
Q

Beta Lactam antibiotic mechanism:

A
  • competitively inhibit PBP
  • they bind to transpeptidase and inhibit bridge formation between glycan molecules
  • causes the cell wall to develop weak points and become fragile
  • penicillin/cephalosporins bactericidal
  • more effective against gram +
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15
Q

Penicillin:

A
  • from mould
  • beta lactam inhibits peptidoglycan synthesis
  • all penicillins have same core structure
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16
Q

3 classes of penicillin:

A

1) natural penicillins: gram +, especially strep (G and V)
2) penicillinase-resistant penicillins: narrow spectrum (staph - methicillin)
3) extended-spectrum: can be used with gram - (ampicillin, amoxicillin)

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17
Q

Penicllin side effects:

A

1) hypersensitivity: 1-10%, reaction IgE mediated, can get whole body rash
2) anaphylaxis: rare, falling BP and difficulty breathing

others:

  • hepatic dysfunction, interstitial nephritis, diarrhea, salt overload, platelet dysfunction, macupapular rash
  • overall safe
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18
Q

beta lactam resistance:

A

1) beta lactamases are produced that destroy the beta lactam drug
2) transpeptidase acquires a new mutation that prevents the drug from binding
3) gram negatives can have a pump that removes the drug from the periplasmic space

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19
Q

beta lactamase inhibitors:

A
  • alone have weak antibacterial activity
  • combined with some penicillins
  • irreversibly bind and inactivate certain beta lactamases
20
Q

Natural penicllin uses:

A
  • staph that is resistant to penicillin
  • good against strep, poor against staph
  • drug of choice for strep and meningococcus (anaerobes)
  • syphilis
  • pneumococci
  • poor against gram -
21
Q

beta-lactamase (pencillinase) resistant penicillins:

A
  • oxacillin, naficillin, methicillin (not used at Penn), dicloxacillin
  • very narrow spectrum (no gram - coverage)
22
Q

Extended spectrum penicillins:

A
  • ampicillin, amoxicillin, piperacillin
  • sensitive to beta lactamases so should add inhibitor
  • typically used fro UTI, otitis media, pneuomonia (community acquired), H. influenza, Lyme, meningitis
  • amoxicillin used more often
23
Q

addition of beta lactamase inhibitor:

A
  • improved activity against staph and gram -
  • piperacillin/tazobactam is most active
  • have activity against pseudomonas
24
Q

Cephalosporin:

A
  • beta lactam
  • wider spectrum, resistant to many lactamases
  • different R group, different from penicillin
  • newer generations = better gram negative but worse gram positive coverage
  • 5% of people with penicillin reactions will react to this
  • look for “cef”
25
Q

1st generation cephalosporin:

A
  • effective against gram +
  • moderate against -
  • UTI/respiratory infection
  • surgical prophylaxis
26
Q

2nd generation cephalosporin:

A

ottis media

increased gram - (respiratory infection, UTI)

27
Q

3rd generation cephalosporin:

A

hospital acquired gram negative

-can penetrate the CNS

ceftazidime = pseudomonaz

28
Q

4th generation cephalosporin:

A

-cefipime only 4th generation used at penn

29
Q

Side effects of cephalosporins:

A

1) hypersensitivity: people that are very sensitive to penicillin shouldnt use
2) more GI problems than penicillin because of greater gram - coverage

30
Q

therapeutic index:

A
  • lowest dose toxic to patient divided by the dose used to treat the patient
  • want it to be high
  • usually drugs that target cell wall have high index
31
Q

Carbapenems:

A
  • beta lactam (inihibit PBP)
  • wider spectrum
  • bactericidal (usually via IV)
  • highly active against +, -, anaerobic and aerobic
  • empiric therapy for critically ill patients
  • meropenem used at penn but RESTRICTED
  • cover almost everything (except enterococci)
  • don’t want to overuse
  • some carbapenemases have already been found in India
  • Well tolerated
32
Q

Vancomycin:

A
  • glycopeptide
  • also inhibits cell wall synthesis by interacting with alanine termini of the side chains (prevents bridge formation)
  • since it is a different mechanism of action there is no cross-resistance with beta lactam drugs
  • usually given via IV
  • large peptide so doesnt go through cell membrane, mostly gram + coverage
33
Q

Vancomycin uses:

A
  • great gram +
  • no gram -
  • MRSA
  • must be infused slowly, red man syndrom can occur or thrombophlebitis
34
Q

Glycopeptides:

A
  • bacitran: interfers with paptidoglycan transport, can’t be taken orally (toxic), topical use against gram _
  • daptomycin: given by IV, active against MRSA
  • Vancomyin
35
Q

Mechanism of action against protein synthesis:

A

-prokaryotic ribosome allows selective toxicity

36
Q

Macrolides:

A

“mycins”

  • reversibly bind 50 S
  • bacteriostatic
  • broad activity against gram +, some gram -
  • drug of choice for patients allergic to penicillin (good against strep)
  • first line against pneumonia
  • no side effects
  • resistance usually due to altered binding site
37
Q

Aminoglycosides:

A
  • irreversibly bind 30s
  • blocks initiation of translation
  • bactericidal
  • not effective against anaerobes
  • not effective against enterococci or streptococci unless beta lactam drug is coadministered (so they can enter the cell)
38
Q

Aminoglycoside uses:

A
  • gram negatives: aerobic gram negative rods (pseudomonas)

- usually reserved for serious gram negative infections because they have issues with toxicity

39
Q

Aminoglycoside resistance:

A

-pseudomonas and enterococci resistance increasing

mechanism includes enzymatic modification, reduced uptake, altered ribosome binding site

40
Q

Aminoglycoside side effects:

A

1) nephrotoxicity: usually reversible

2) ototoxicity

41
Q

tetracyclins:

A
  • reversibly bind 30S
  • bacteriostatic, prevents protein synthesis
  • atypical organisms: acne, Lyme, chlamydia, mycoplasma

SIDE EFFECTS:

-discolored teeth in children, GI, phototoxic dematitis (sensitive to sun)

42
Q

Chloramphenicol:

A
  • binds 50S
  • wide array of organisms
  • rare but deadly side effects
  • used in underdeveloped countries because broad spectrum and cheap

SIDE EFFECTS:

  • aplastic anemia: bone marrow is wiped out and fatal
  • neonates also cannot metabolize drug
43
Q

Quinolones:

A
  • target DNA gyrase therefore inhibits replication because DNA unwinding cannot occur
  • AKA fluoroguinolones
  • levofloxacin, norfloxacin, cirpofloxacin
  • not good for gram + or anaerobes
  • good for gram negatives: complicated UTIs, anthrax, pseudomonas, enterococci
  • safe, oral, good absorption

Resistance: due to drug binding site on gyrase

Side effects: GI

44
Q

metronidazole:

A
  • AKA flagyl
  • bactericidal
  • administered as inactive “prodrug” and activated in vivo by bacterial reductases

ONLY active against anaerobes

  • good for c. difficile
  • antiprotozoal

RESISTANCE: decreased uptake, reduced activation

45
Q

Sulfonamides:

A
  • inhibit growth of gram + and - through competitive inihibition of enzyme that aids in production of folic acid
  • human cells do not have this enzyme so allows for selevtive toxicity
46
Q

trimethoprim:

A
  • inhibits folic acid production
  • used with sulfa drugs (then called bactrim)

Resistance: due to plasma encoded alternative enzyme, the genes for sulfa and trimethoprim often on same plasmid

47
Q

Bactrim:

A
  • no anaerobic
  • strep and h. flu
  • gram - that cause diarrhea

SIDE EFFECTS:

hypersensitivity, dont give to patients with warfarin (blood thinner)

Microbiology (16 decks)

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