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FM2 > Cell wall antibiotics > Flashcards

Cell wall antibiotics Flashcards

1
Q

Describe the goal of antimicrobial chemotherapy

A

To provide an adequate amount of active drug at the site of infection to help eliminate invading pathogens in your patient

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2
Q

Describe time dependent killing

A

Time above MIC is the parameter that predicts efficacy (ex beta lactams)

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3
Q

Describe concentration dependent killing

A

Peak/MIC and AUC/MIC ratios are the parameters that predict efficacy (ex aminoglycosides- don’t need drug to be in system for long time, just need high peak concentration)

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4
Q

List three “cardinal truths” about antibiotics

A
  1. They are a lot easier to start than to stop
  2. Most problems have > 1 acceptable solutions
  3. Some problems have only 1 acceptable solution
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5
Q

List five general mechanisms of resistance

A
  1. enzyme inactivation (ex beta lactamase)
  2. alteration in target site (ex PBPs)
  3. altered bacterial membrane
  4. efflux pumps (more common in Gram -)
  5. environmental (ex oxygen tension- metrondiazole works in anaerobic env, aminoglycosides owrk in aerobic env)
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6
Q

List the two emerging carbapenem resistant Enterobacteriacae

A

Klebsiella producing carbapenemase (KPC) and New Delhi Metallo Beta Lactamase 1 (NDM-1)

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7
Q

List four classes of antibiotics that are considered beta lactams

A

penicillins
cephalosporins
carbapenems
monobactams

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8
Q

List one glycopeptide antibiotic

A

vancomycin

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9
Q

List one cyclic lipopeptide antibiotic

A

daptomycin

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10
Q

Beta lactams are ____ antibiotics- they cause bacterial cell death

A

cidal

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11
Q

List three steps in beta lactam mechanism of action

A
  1. Penetration and binding to Penicillin Binding Proteins (PBPs)
  2. Inhibition of transpeptidation so that peptidoglycan cross-linking cannot occur
  3. Loss of cell wall integrity ignites cell autolysis (inhibition of the inhibitor)
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12
Q

In Gram negative organisms, antibiotic must pass through a ____ before binding to PBPs. In gram positive organisms, the antibiotic diffuses directly across peptidoglycan and binds to PBP

A

porin

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13
Q

List some organisms that natural penicillin is effective against

A

Gram positives: strep, enterococci, pneumococci, peptostreptococci, listeria, clostridia
Gram negatives: pasturella, Neisseria
Spirochetes: T. pallidum, Borrelia

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14
Q

List clinical uses of natural penicillin

A

Strep infections, enterococcal infections, meningococcal infections, all stages of syphilis, gas gangrene, periodontal infection

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15
Q

List two aminopenicillins

A

Amoxicillin (oral) and ampicillin (IV)

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16
Q

Describe the spectrum of coverage of aminopenicillins

A

Same as penicillin (strep, enterococci, pneumococci, peptostreptococci, listeria, clostridia, pasturella, Neisseria, T. pallidum, Borrelia)
PLUS E coli, proteus mirabilis, hemophilus

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17
Q

Describe clinical uses of aminopenicillins

A

upper and lower respiratory tract infection, UTI, enterococcal infection, listeria, endocarditis prophylaxis

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18
Q

List four semi-synthetic penicillins

A

dicloxacillin (oral)

nafcillin, oxacillin, methicillin (IV)

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19
Q

Semi-synthetic penicillins have a niche role in treating ________

A

Staphylococci

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20
Q

Semi-synthetic penicillins have NO coverage for _____ or Gram ______ organisms

A

anaerobes, Gram -

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21
Q

List two extended spectrum penicillins

A

ticarcillin and piperacillin

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22
Q

Describe the spectrum of coverage of the extended spectrum penicillins

A

Gram negative aerobes
Pseudomonas
Some enterococci, strep, staph

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23
Q

Explain why extended spectrum penicillins are not commonly used in practice

A

Rarely used in this form as the beta-lactamase inhibitor combination versions are used instead

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24
Q

Describe possible uses of extended spectrum penicillins

A

Pseudomonas, polymicrobial infections, nosocomial infections

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25
Q

List four penicillin + beta lactamase inhibitor combinations

A

Oral: amoxicillin-clavulanic acid
IV: ampicillin- sulbactam; ticarcillin-clavulanic acid; pipercillin-tazobactam

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26
Q

Describe the spectrum of penicillin + beta lactamase inhibitor combinations

A

Same as parent penicillin PLUS

S aureus, E coli, H influenzae, Moraxella, Klebsiella, Bacteriodes, etc

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27
Q

Describe clinical uses of penicillin + beta lactamase inhibitor combinations

A

Upper and lower respiratory tract infections, head and neck, cellulitis, abscess, pasteurella, intra-abdominal infections, nosocomial infections, Pseudomonas

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28
Q

Describe adverse effects of penicillins

A

Rash, hypersensitivity, diarrhea, interstitial nephritis

  • nafcillin- neutropenia, phlebitis
  • ticarcillin/ piperacillin- high salt load
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29
Q

List two first generation cephalosporins

A

cephalexin (oral)

cefazolin (IV)

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30
Q

Describe the spectrum of coverage of cephalexin

A

First generation cephaolsporin

Gram positive cocci, strep, staph, E coli, Klebsiella

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31
Q

Describe the spectrum of coverage of cefazolin

A

First generation cephaolsporin

Gram positive cocci, strep, staph, E coli, Klebsiella

32
Q

Describe clinical uses of Cephalexin

A

First generation cephalosporin

SSTI, UTI, surgical prophylaxis

33
Q

Describe clinical uses of cefazolin

A

First generation cephalosporin

SSTI, UTI, surgical prophylaxis

34
Q

List two groups within the second generation cephalosporins and the drugs within those groups

A

Cefuroxime group- oral or IV cefuroxime

Cephamycin group- cefoxitin

35
Q

Describe the coverage of cefuroxime

A

Second generation cephalosporin, cefuroxime group
Gram positive cocci, strep, staph, E coli, Klebsiella
PLUS Hemophilus, Moraxella

36
Q

Describe the coverage of cefoxitin

A

Second generation cyclosporin, cephamycin group
Gram positive cocci, strep, staph, E coli, Klebsiella
PLUS more anaerobes and aerobic GNR

37
Q

Describe the clinical uses of cefuroxime

A

Second generation cephalosporin

Upper and lower respiratory tract infections

38
Q

Describe the clinical uses of cefoxitin

A

Second generation cephalosporin

Intra-abdominal and pelvic infections

39
Q

List four third generation cephalosporins

A

Oral: cefixime, cefpodoxime
IV: ceftriaxone, cefazadime

40
Q

Describe the coverage of cefixime

A

Third generation cephalosporin

Gram negative aerobes, strep

41
Q

Describe the clinical uses of cefixime

A

Third generation cephalosporin

Gonorrhea, others

42
Q

Describe the coverage of cefpodoxime

A

Third generation cephalosporin

Gram negative aerobes, strep

43
Q

Describe the clinical uses of cefpodoxime

A

Third generation cephalosporin

Infection with gram negative aerobes

44
Q

Describe the coverage of ceftriaxone

A

Third generation cephalosporin

Gram negative aerobes, strep, N. gonorrheae

45
Q

Describe the clinical uses of ceftriaxone

A

Third generation cephalosporin DOC for meningitis, COP, viridans strep endocarditis, UTI, gonorrhea, intra-abdominal infection (plus something for anaerobes)

46
Q

Describe the coverage of ceftazadime

A

Third generation cephalosporin

Gram negative aerobes, Pseudomonas (but poor staph and strep)

47
Q

Describe the clinical uses of ceftazadime

A

Third generation cephalosporin

Pseudomonas

48
Q

List one fourth generation cephalosporin

49
Q

Describe the coverage of cefepime

A

Fourth generation cephalosporin
Excellent S aureus, strep, GNR aerobes, Pseudomonas
No anaerobe coverage

50
Q

Describe the clinical uses of cefepime

A

Fourth generation cephalosporin
Nosocomial infection, febrile neutropenia, Pseudomonas, ESBL producing GNR, mixed infections (plus something for anaerobes)

51
Q

List one fifth generation cephalosporin

A

Ceftaroline

52
Q

Describe the coverage of ceftaroline

A

Fifth generation cephalosporin
Excellent S aureus, MRSE, MRSA, strep, Gram negatives
No Pseudomonas

53
Q

Describe the clinical uses of ceftaroline

A

Fifth generation cephalosporin

CAP, SSTI, MRSA infection

54
Q

List four organisms that NONE of the current cephalosporins have activity against

A

Enterococci
Listeria
Chlamydia
Mycoplasma

55
Q

Distinguish which of the cephalosporins have good vs bad CNS penetration

A

No CNS penetration: all first generation and most second generation

Excellent CNS penetration: ceftriaxone, ceftazadime, cefepime

56
Q

Mention adverse effects of cephalosporins

A

Rash- low cross reactivity with penicillins, diarrhea

  • ceftriaxone- biliary sludging
  • cefepime- mental status changes (gets into CNS easily)
57
Q

List four carbapenems

A

Imipenem
Meropenem
Doripenem
Ertapenem

58
Q

Describe the coverage of the carbapenems

A

Excellent Gram positive, excellent Gram negative including ESBL, excellent Pseudomonas (doripenem is best), excellent anaerobes

59
Q

List three explanations for why carbapenems are so effective

A
  1. small molecules- get through porins in gram -
  2. resistant to many beta lactamases
  3. affinity for PBPs from a wide range of organisms, even if altered slightly
60
Q

List organisms that all carbapenems do NOT have coverage for

A 
MRSA
MRSE
E faecium
C diff
Stenotrophomonas
Burkholderia
61
Q

List some clinical uses of carbapenems

A

Serious infections in very ill patients- nosocomial, pseudomonas, meningitis, mixed intra-abdominal or SSTI

62
Q

Describe the adverse effects of carbapenems

A

Rash, diarrhea (anaerobe activity)

*imipenem- seizure

63
Q

List one monobactam

64
Q

Describe the spectrum of coverage of aztreonam

A

Gram negatives including Pseudomonas

NO Gram positives or anaerobes

65
Q

Describe clinical uses of aztreonam

A

Niche role for Pseudomonas in people with penicillin allergy

could also be used for other GNR aerobes

66
Q

Explain why it is safe to use aztreonam in patients with penicillin allergy

A

No beta lactam ring so no cross reactive hypersensitivity with IgE-mediated penicllin allergy

67
Q

Describe the mechanism of action of vancomycin

A

Glycopeptide
Prevents formation of peptidoglycan cross linds, binds to different part of precursor unit than beta lactams
Causes slow autolysis

68
Q

Describe the spectrum of vancomycin

A

Gram positive aerobic and anaerobic GPC, most GPR

MRSA, MRSE, enterococci, streptococci

69
Q

Vancomycin is a large molecule that is poorly absorbed in the GI tract, so its oral form is used only to treat __________

70
Q

Vancomycin is difficult to get into the _____ because it is a very large molecule

71
Q

List adverse effects of vancomycin

A

Neutropenia
Nephrotoxicity
Ototoxicity (rare)
Red man syndrome: histamine release, itching and rash but not IgE mediated

72
Q

Describe clinical uses of vancomycin

A

MRSE, MRSA, enterococci, alternative to beta lactam if severe allergy present, meningitis, C. diff

73
Q

Describe the mechanism of action of daptomycin

A

Cyclic lipopeptide

Rapid cidal activity- lipid portion inserts into bacterial membrane, loss of membrane potential and ion conductance

74
Q

Describe the spectrum of daptomycin

A

Gram positives including MRSA, MRSE, VRE, pneumococci, streptococci.

75
Q

List a significant side effect of daptomycin

76
Q

Describe clinical uses of daptomycin

A

Severe infections due to MRSA, MRSE, VRE

77
Q

There is one condition daptomycin is NEVER used to treat. Identify this condition and explain why.

A

Pneumonia- daptomycin is inactivated by pulmonary surfactant

FM2 (11 decks)

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