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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
List four penicillin + beta lactamase inhibitor combinations
Oral: amoxicillin-clavulanic acid IV: ampicillin- sulbactam; ticarcillin-clavulanic acid; pipercillin-tazobactam
26
Describe the spectrum of penicillin + beta lactamase inhibitor combinations
Same as parent penicillin PLUS | S aureus, E coli, H influenzae, Moraxella, Klebsiella, Bacteriodes, etc
27
Describe clinical uses of penicillin + beta lactamase inhibitor combinations
Upper and lower respiratory tract infections, head and neck, cellulitis, abscess, pasteurella, intra-abdominal infections, nosocomial infections, Pseudomonas
28
Describe adverse effects of penicillins
Rash, hypersensitivity, diarrhea, interstitial nephritis * nafcillin- neutropenia, phlebitis * ticarcillin/ piperacillin- high salt load
29
List two first generation cephalosporins
cephalexin (oral) | cefazolin (IV)
30
Describe the spectrum of coverage of cephalexin
First generation cephaolsporin | Gram positive cocci, strep, staph, E coli, Klebsiella
31
Describe the spectrum of coverage of cefazolin
First generation cephaolsporin | Gram positive cocci, strep, staph, E coli, Klebsiella
32
Describe clinical uses of Cephalexin
First generation cephalosporin | SSTI, UTI, surgical prophylaxis
33
Describe clinical uses of cefazolin
First generation cephalosporin | SSTI, UTI, surgical prophylaxis
34
List two groups within the second generation cephalosporins and the drugs within those groups
Cefuroxime group- oral or IV cefuroxime Cephamycin group- cefoxitin
35
Describe the coverage of cefuroxime
Second generation cephalosporin, cefuroxime group Gram positive cocci, strep, staph, E coli, Klebsiella PLUS Hemophilus, Moraxella
36
Describe the coverage of cefoxitin
Second generation cyclosporin, cephamycin group Gram positive cocci, strep, staph, E coli, Klebsiella PLUS more anaerobes and aerobic GNR
37
Describe the clinical uses of cefuroxime
Second generation cephalosporin | Upper and lower respiratory tract infections
38
Describe the clinical uses of cefoxitin
Second generation cephalosporin | Intra-abdominal and pelvic infections
39
List four third generation cephalosporins
Oral: cefixime, cefpodoxime IV: ceftriaxone, cefazadime
40
Describe the coverage of cefixime
Third generation cephalosporin | Gram negative aerobes, strep
41
Describe the clinical uses of cefixime
Third generation cephalosporin | Gonorrhea, others
42
Describe the coverage of cefpodoxime
Third generation cephalosporin | Gram negative aerobes, strep
43
Describe the clinical uses of cefpodoxime
Third generation cephalosporin | Infection with gram negative aerobes
44
Describe the coverage of ceftriaxone
Third generation cephalosporin | Gram negative aerobes, strep, N. gonorrheae
45
Describe the clinical uses of ceftriaxone
Third generation cephalosporin DOC for meningitis, COP, viridans strep endocarditis, UTI, gonorrhea, intra-abdominal infection (plus something for anaerobes)
46
Describe the coverage of ceftazadime
Third generation cephalosporin | Gram negative aerobes, Pseudomonas (but poor staph and strep)
47
Describe the clinical uses of ceftazadime
Third generation cephalosporin | Pseudomonas
48
List one fourth generation cephalosporin
Cefepime
49
Describe the coverage of cefepime
Fourth generation cephalosporin Excellent S aureus, strep, GNR aerobes, Pseudomonas No anaerobe coverage
50
Describe the clinical uses of cefepime
Fourth generation cephalosporin Nosocomial infection, febrile neutropenia, Pseudomonas, ESBL producing GNR, mixed infections (plus something for anaerobes)
51
List one fifth generation cephalosporin
Ceftaroline
52
Describe the coverage of ceftaroline
Fifth generation cephalosporin Excellent S aureus, MRSE, MRSA, strep, Gram negatives No Pseudomonas
53
Describe the clinical uses of ceftaroline
Fifth generation cephalosporin | CAP, SSTI, MRSA infection
54
List four organisms that NONE of the current cephalosporins have activity against
Enterococci Listeria Chlamydia Mycoplasma
55
Distinguish which of the cephalosporins have good vs bad CNS penetration
No CNS penetration: all first generation and most second generation Excellent CNS penetration: ceftriaxone, ceftazadime, cefepime
56
Mention adverse effects of cephalosporins
Rash- low cross reactivity with penicillins, diarrhea * ceftriaxone- biliary sludging * cefepime- mental status changes (gets into CNS easily)
57
List four carbapenems
Imipenem Meropenem Doripenem Ertapenem
58
Describe the coverage of the carbapenems
Excellent Gram positive, excellent Gram negative including ESBL, excellent Pseudomonas (doripenem is best), excellent anaerobes
59
List three explanations for why carbapenems are so effective
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
List organisms that all carbapenems do NOT have coverage for
``` MRSA MRSE E faecium C diff Stenotrophomonas Burkholderia ```
61
List some clinical uses of carbapenems
Serious infections in very ill patients- nosocomial, pseudomonas, meningitis, mixed intra-abdominal or SSTI
62
Describe the adverse effects of carbapenems
Rash, diarrhea (anaerobe activity) | *imipenem- seizure
63
List one monobactam
Aztreonam
64
Describe the spectrum of coverage of aztreonam
Gram negatives including Pseudomonas | NO Gram positives or anaerobes
65
Describe clinical uses of aztreonam
Niche role for Pseudomonas in people with penicillin allergy | could also be used for other GNR aerobes
66
Explain why it is safe to use aztreonam in patients with penicillin allergy
No beta lactam ring so no cross reactive hypersensitivity with IgE-mediated penicllin allergy
67
Describe the mechanism of action of vancomycin
Glycopeptide Prevents formation of peptidoglycan cross linds, binds to different part of precursor unit than beta lactams Causes slow autolysis
68
Describe the spectrum of vancomycin
Gram positive aerobic and anaerobic GPC, most GPR | MRSA, MRSE, enterococci, streptococci
69
Vancomycin is a large molecule that is poorly absorbed in the GI tract, so its oral form is used only to treat __________
C diff
70
Vancomycin is difficult to get into the _____ because it is a very large molecule
CNS
71
List adverse effects of vancomycin
Neutropenia Nephrotoxicity Ototoxicity (rare) Red man syndrome: histamine release, itching and rash but not IgE mediated
72
Describe clinical uses of vancomycin
MRSE, MRSA, enterococci, alternative to beta lactam if severe allergy present, meningitis, C. diff
73
Describe the mechanism of action of daptomycin
Cyclic lipopeptide | Rapid cidal activity- lipid portion inserts into bacterial membrane, loss of membrane potential and ion conductance
74
Describe the spectrum of daptomycin
Gram positives including MRSA, MRSE, VRE, pneumococci, streptococci.
75
List a significant side effect of daptomycin
myopathy
76
Describe clinical uses of daptomycin
Severe infections due to MRSA, MRSE, VRE
77
There is one condition daptomycin is NEVER used to treat. Identify this condition and explain why.
Pneumonia- daptomycin is inactivated by pulmonary surfactant

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