4/9 Antibacterials I/II: Cell Wall Agents Flashcards Preview

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Flashcards in 4/9 Antibacterials I/II: Cell Wall Agents Deck (137)
1

what does Penicillin, Cephalosporin, Monobactam, Carbapenem have in common? What confers each specificity?

common structure: ß lactam ringspecificity

2

Penicillin, Cephalosporin, Monobactam, Carbapenem all have a common function:

Antimicrobial agents that work by inhibiting cell wall synthesis

3

in general, how are Penicillin, Cephalosporin, Monobactam, Carbapenem inactivated?

ß lactamase enzymes - cleave the ß-lactam ring (essential for activity)

4

Why do carbapenems additional stability (more resistant to ß lactamases) over the rest of the drugs?

the H next to the keto group is oriented ABOVE the plane, and this configuration seems to stabilize the molecule, and make it more resistant to ß-lactamases (others: below)

5

What type of hypersensitivity reaction does penicillin usually cause?What type of physical manifestations?

IgE Type I Hypersensitivity(rash, hives, angioedema, anaphylaxis).

6

If one is severely allergic to penicillin, what other drugs are they likely to be allergic too as well?

Cephalosporin, Monobactam, Carbapenem

7

Which one is the safest to use if if the patient had a mild allergic reaction? Why?

monobactam, since it looks the least like penicillin (it doesn’t have the second ring) and is least likely to trigger IgE compared to the other ones

8

Structure of penicillin?

all contain Ring A (thiazolidine ring) attached to Ring B (ß-lactam ring)

9

MoA of penicillin?

bind covalently to Penicillin-binding proteins (PBP’s) at the active site, thereby interfering with the transpeptidase reaction, a reaction that is critical in bacterial cell wall synthesis"bactericidal"

10

how does resistance develop against penicillin?

1) Inactivation by ß-lactamase

2) Modification of target PBP

3) Impaired penetration of the cell (ex: ∆ porin channel)

4) Presence of a new efflux pump

11

how does MRSA develop?

Modification of target PBP

12

What drugs are in the Benzopenicillin class?

Penicillin G

Penicillin V

13

sensitivity of penicillin G to ß lactamases?

sensitive

14

How is Penicillin G administered?

parenteral (poor oral bioavailability)


  • Procaine suspn (IM); duration 1-2 days
     

  • Benzathine suspn (IV); duration 1-4 wks; great for kids

15

How is Penicillin V administered?

PO; very stable in stomach acid

16

Penicillins are effective in treating these bugs

  • Gram (+)
    • strep. pneumo
    • S. pyogenes
    • Actinomyces
  • GNC
    • N. meningitides
  • Spirochetes (T. pallidum)





 

17

what bugs are resistant to penicillin?

Staph (>85%)

Pneumococcus (10-30%)

bowel anaerobes

gonorrhea (Pen G)

most GNR’s

18

Contraindications of penicillin?

Pen-allergic patients

19

Side Effects of penicillins?

1) drug allergy especially rash, anaphylaxis

2) anemia (binds to RBC and induces hemolysis)

3) Seizures following high doses

20

Drug interactions with penicillins?

  • synergy with gentamicin against staph and enterococcus
  • probenecid inhibits renal active tubular secretion

21

What situations would warrant penicillin treatment?

1. Streptococcal pharyngitis and skin infections

2. Pneumonia

3. Meningitis

4. Endocarditis - if organism is sensitive

5. Dental infection (by microaerophilic streptococcus)

6. Syphilis

7. Prevent rheumatic fever (GrpA ß hemolytic strep complication)

22

Drugs in the Aminopenicillins class?

Ampicillin

Amoxicillin

23

sensitivity of aminopenicillins to ß lactamases?

sensitive (its nearly identical to penicillin)

24

mechanism of action of aminopenicillins?

binds PBP’s and inhibits the assembly of the bacterial cell wall, bactericidal

25

How is ampicillin different than amoxicillin?

Ampicillin - PO or IV

Amoxicillin - PO (higher oral bioavailability) - newer version of ampicillin with slightly wider spectrum of action; less likely to cause diarrhea

26

what bugs are sensitive to aminopenicillins?

extended spectrum of action

  • Haemophilus influenza
  • E. coli
  • Listeria monocytogenes
  • Proteus mirabilis
  • Salmonella
  • Shigella
  • Enterococcus

Amp HELPSS to kill enterococci

27

What bugs are resistant to aminopenicillins?

  1. most staph
  2. some pneumococcus (>30%)
  3. some H. flu
  4. bowel anaerobes
  5. some GNRs

28

SE of aminopenicillins?

  1. drug allergy especially rash, anaphylaxis
  2. seizures following high doses
  3. antibiotic-associated colitis

29

Contraindications of aminopenicillins?

Pen-allergic patients 

30

drug interactions with aminopenicillins?

  • synergy with gentamicin against enterococcus
  • probenecid inhibits renal active tubular secretion of ampicillin
  • ampicillin may inhibit tubular secretion of MTX

31

indications for aminopenicillins?

  1. otitis media
  2. neonatal sepsis
  3. Lyme disease (early)
  4. simple UTI's (GNRs, such as E. coli, klebsiella, enterobacter, proteus)
  5. meningitis with sensitive pathogens
  6. URI
  7. endocarditis w. sensitive pathogens

32

What are examples of “semi-synthetic” penicillins?

  1. Nafcillin
  2. Dicloxacillin
  3. Oxacillin
  4. Methicillin - original

33

sensitivity of nafcillin to ß lactmases? 

more resistant to ß lactamases (have more complex side chains; more stable)

34

MoA of nafcillin?

binds PBP’s and inhibits the assembly of the bacterial cell wall, bactericidal 

35

There are various types of semi-synthetic penicillins. How would you use them clinically?

nafcillin or oxacillin - IV; serious infections with MSSA

dicloxacillin - PO; less severe infections

36

bugs sensitive to nafcillin?

Same as penicillin, but narrow spectrum

  • S. aureus (except MRSA, resistant due to altered PBP target site)

“use naf for staph”

37

bugs resistant to nafcillin or within the same class?

  1. MRSA (usually bc they have a different PBP)
  2. pneumococcus
  3. oral/bowel anaerobes
  4. GNR (most)

38

contraindications for semi-synthetic pencillins?

Pen-allergic patients

 

39

SE of semi-synthetic penicillins (ie nafcillin)?

  • drug allergy HSR
  • neprotoxic - allergic interstitial nephritis 
  • Methicillin – highly nephrotoxic (causes allergic interstitial nephritis) and resistant to ß-lactamase; not used anymore

40

drug interactions with nafcillin?

  • synergy with gentamicin against enterococcus
  • probenecid inhibits renal active tubular secretion

41

indications for nafcillin or semi-synthetic pencillins within the same class?

Staph aureus infections, especially if pathogen is sensitive (in skin, soft tissue, bone, lung, endocarditis)

42

Drugs in the Anti-Pseudomonas class?

  • Piperacillin
  • Carbenicillin 
  • Ticarcillin

43

Piperacillin - sensitivity to ß lactamases?

sensitive 

44

MoA of Piperacillin?

binds PBP’s and inhibits the assembly of the bacterial cell wall, bactericidal 

45

What is one thing that you have to consider when dosing Piperacillin and Carbenicillin? 

resistance w. monotherapy; given in combination therapy with gentamycin or tobramycin to decrease resistance

46

How is Piperacillin and Carbenicillin administered?

  • Piperacillin - IV
  • Carbenicillin - PO 

47

bugs sensitive to Piperacillin and Carbenicillin?

Same as penicillin, but with extended spectrum

  • Pseudomonas
  • GNR

48

bugs resistant to Piperacillin and Carbenicillin?

  1. GPC
  2. Anaerobes
  3. Enterococcus
  4. pneumococcus
  5. most S. aureus
  6. increasing # of resistant pseudomonas and GNRs

49

contraindications of anti-pseudomonal agents??

Pen-allergic patients 

50

SE of Piperacillin and Carbenicillin?

  1. drug allergy especially rash, anaphylaxis
  2. antibiotic-associated colitis

51

drug interactions of Piperacillin and Carbenicillin?

  1. synergy with gentamicin against Pseudomonas
  2. probenecid inhibits renal active tubular secretion of Piperacillin
  3. Piperacillin may inhibit tubular secretion of MTX

52

indications for Piperacillin and Carbenicillin?

  1. Pseudomonas infections (usually given in combination with gentamycin or tobramycin for synergy)
  2. Carbenicillin – used treat non-life threatning infections (ie UTI) caused by Pseudomonas)
  3. intra-abdominal infections (mixed GNR, anaerobes, and enterococcus)
  4. nosocomial pneumonia (because often caused by GNR in the ICU)

53

What are some ß-lactamase inhibitors that are manufactured with penicillins?

Clavulanic acid, sulbactam, and tazobactam 

54

How do ß-lactamase inhibitors work?

resemble ß lactam molecules and prevents cleavage of ß lactam rings, but have very weak antimicrobial activity themselves 

thus they are added to amoxicillin or ampicillin or pipercillin, whose “range” is extended by the inhibitor

55

3 types of Penicillins w. ß-lactamase inhibitors?



 

  1. Amoxicillin & clavulanate (Augmentin)
  2. Ampicillin & sulbactam (Unasyn)
  3. Piperacillin & Tazobactam (Zosyn)

56

bugs sensitive to Penicillins w. ß-lactamase inhibitors?

Augmentin (Amoxicillin & clavulanate): PO; broadest spectrum

Unasyn (Ampicillin & sulbactam): IV; broadest spectrum

Zosyn (Piperacillin & Tazobactam): IV; widest scope of activity

57

bugs resistant to Penicillins w. ß-lactamase inhibitors (ie clavulanic acids)?

ß-lactamases produced by

  1. enterobacter
  2. citrobacter
  3. serratia
  4. pseudomonas 

58

indications for augmentin?

otitis media, sinusitis, lung, skin, urine infections, bites

59

indications for unasyn?

skin, intra-abdominal, pelvic, bite, head/neck infections 

60

indications for Zosyn?

pneumonia, UTI, skin, gyn, bone, intra-abdominal, septicemia infections

61

How are cephalosporins similar than penicillins? different?

similar to penicillins in that they both have:

  • structure (A ring + ß lactam ring)
  • mechanism of action
  • toxicities/allergic reactions

different in that cephalosporins are:

  • more stable to many ß-lactamases
  • broader spectrum of activity (good for polymicrobial infections or infections where you don’t know what it is)
  • not as good as the penicillins against enterococcus and it is essentially worthless against listeria

62

What is the difference btwn the first generation cephalosporins and the later generations?

  • 1st generation - more active against GP organisms (e.g. staph, streptococci)
  • later drugs (2nd, 3rd, 4th gen) - are more active against GN aerobic organisms (e.g. E. coli, etc.)

63

Why is it bad to use cephalosporin if the bug is known?

bad to always use if the infection/pathogen is known because normal flora may be wiped out and cause c. diff, candidal infection, BV, or cause resistance! USE A MORE SPECIFIC ONE.

64

5 generations of cephalosporin? Which ones have good CSF penetration?

5 classes  (know the highlighted ones)

  • 1st gen: cefazolin iv, cephalexin po
  • 2nd gen: cefuroxime – not that impt to know
  • 3rd gen: ceftriaxone, ceftazidime, Cefotaxime, cefpodoxime
  • 4th generation: cefepime
  • 5th generation: ceftaroline

Good CSF penetration: 3rd, 4th, 5th

65

Drugs in the Cephalosporins 1st gen?

  • Cefazolin
  • cephalexin

66

MoA of Cefazolin?

binds PBP’s and inhibits the assembly of the bacterial cell wall, bactericidal

67

CSF penetration of Cephalosporins 1st gen?

poor

68

bugs sensitive to cefazolin?

broad spectrum of activity

  • GPC
  • Proteus mirabalis
  • E. coli
  • Klebsiella

PEcK

 

69

bugs resistant to cefazolin?

  • MRSA (about 30% and growing)
  • enterococcus,
  • Listeria
  • nosocomial GNRs
  • some pneumococcus
  • bowel anaerobes

70

contraindications of cefazolin?

Pen-allergic patients (cross-reactivity)

71

SE of cefazolin?

  • drug allergy especially rash, anaphylaxis
  • anemia
  • vitamin K deficiency 
  • antibiotic-associated colitis 

72

drug interactions of cefazolin?

  • probenecid inhibits renal active tubular secretion, prolongs half-life
  • increase nephrotoxicity of aminoglycosides

73

indications of cefazolin?

  • soft tissue infections (strep and staph)
  • UTI
  • patients with mild allergies (but not anaphylaxis) to penicillins
  • surgical prophylaxis (ie just before appendectomy or hysterectomy) to lower chance of developing wound infection against GNR

74

Rx in the Cephalosporins 3rd gen that we should know?

  • Ceftriaxone
  • Ceftazidime

75

MoA of Ceftriaxone?

binds PBP’s and inhibits the assembly of the bacterial cell wall, bactericidal

but it is more active against GNRs which produce ß-lactamases 

76

Why is Cefotaxime/cefpodoxime given to pediatric patients in lieu of the standard 3rd generation ceftriaxone?

 it is less likely to cause biliary sludging

77

bugs sensitive to ceftriaxone?

Given to serious GN infections that are resistant to other ß lactams

  • meningitis
  • gonorrhea

78

bugs resistant to ceftriaxone?

  • MRSA (~30% and growing)
  • pneumococcus (5-10%)
  • enterococcus
  • nosocomial GNRs
  • bowel anaerobes
  • pseudomonas
  • Listeria

79

CI of ceftriaxone?

Pen-allergic patients 

80

SE of ceftriaxone?

  • drug allergy especially rash, anaphylaxis
  • anemia
  • antibiotic-associated colitis
  • vitamin k deficiency

81

Drug interactions with ceftriaxone?

  • probenecid inhibits renal active tubular secretion
  • synergistic with gentamicin against some GNR
  • may enhance effects of warfarin

  • increase nephrotoxicity of aminoglycosides
     

82

indications for ceftriaxone?

  • meningitis
  • serious pneumonia
  • otitis
  • sinusitis
  • neisseria gonorrhea
  • GNR
  • lyme dz

83

MoA for Ceftazidime?

binds PBP’s and inhibits the assembly of the bacterial cell wall, bactericidal, but more activae against GNRs which produce ß-lactamases 

84

bugs sensitive to ceftazidime?

Given to serious GN infections that are resistant to other ß lactams

  • Pseudomonas

85

bugs resistant to ceftazidime?

  • large majority of staph
  • some pneumococcus
  • bowel anaerobes

86

CI for ceftazidime?

Pen-allergic patients 

87

SE of ceftazidime?

  • drug allergy especially rash, anaphylaxis
  • antibiotic-associated colitis
  • vitamin k deficiency

88

drug interactions with Ceftazidime?

  • synergistic with gentamicin against some GNR, especially Pseudomonas
  • may enhance effects of warfarin

  • increase nephrotoxicity of aminoglycosides
     

89

indications for ceftazidime?

  • infections where resistant GNRs and Pseudomonas are likely
  • meningitis or sepsis where GNR is likely pathogen
  • bacteremia
  • UTI
  • urosepsis
  • empiric Rx of febrile neutropenic pts 

90

What generation is Ceftaroline in?

Cephalosporins, 5th gen

91

MoA of ceftaroline?

binds PBP’s and inhibits the assembly of the bacterial cell wall, bactericidal, but more activae against GNRs which produce ß-lactamases 

92

Why do you have to monitor ceftaroline in the elderly?

renal excretion – must monitor in elderly, who have reduced GFR

93

bugs sensitive to ceftaroline?

Broadest spectrum of activity

  • GN
  • GP – strep pneumonia, staph aureus (MSSA and MRSA)
  • does not cover Pseudomonas

94

bugs resistant to ceftaroline?

still being defined

95

CI of ceftaroline?

Pen-allergic patients 

96

SE of ceftaroline?

  • drug allergy especially rash, anaphylaxis
  • Clostridium difficile-associated diarrhea 
  • convert to a positive direct Coombs test (10% of patients)

97

ceftaroline drug interactions?

none reported

98

indications for ceftaroline use?

  • community acquired bacterial pneumonia (CABP)
  • acute skin infection

but only for pathogens likely to be sensitive, and only used when a broad spectrum drug is needed

99

drugs in the Carbapenems class?

  • Meropenem
  • Imipenem
  • irbepenem
  • ertapenem
  • doripenem

100

How are carbapenems different than penicillins?

has an additional ring structure to the ß lactam ring

101

What do you often administer with Imipenem and why?


Imipenem - RESISTANT to ß lactamases; often given with cilastatin inhibitor of renal dehydropeptidase I) to reduce inactivation of drug in renal tubules   “with imipenem, the kill is ‘lastin with cilastatin”
 

102

CSF penetration of Meropenem?

good

103

Why would you not use carbapenems as a first-line tx?

significant side effects and $$$ (not used as a first-line tx; use limited to life-threatening infections or after other drugs have failed)

104

bugs sensitive to carbapenem?

Broadest spectrum against the widest group of bacteria

  • most GPC (including staph)
  • most GNR (including pseumomonas)
  • Anaerobes

105

bugs resistant to carbapenem?

  • MRSA
  • enterococcus
  • rare pneumococcus; but can develop resistance rapidly

106

CI for using carbapenem?

Pen-allergic patients 

107

SE of carbapenem?

  • antibiotic-associated colitis
  • seizures (at high plasma levels)
  • GI distress
  • skin rash

108

Rx interactions wtih carbapenem?

  • probenecid inhibits renal active tubular secretion
  • synergistic with gentamicin against some GNR
  • may enhance effects of warfarin

109

Indications of carbapenem?

  • mixed nosocomial infections with resistant GNRs (do not use for single-organism infections or when the infection is unknown (ie patient comes in with septic shock))
  • complicated meningitis
  • peritonitis
  • serious pneumonia
  • sepsis

110

drugs in the monobactam class?

Azetreonam

111

What is unique about Azetreonam?

  • resistant to ß lactamases
  • NO cross-allergenicity with penicillin 

112

bugs sensitive to azetreonam?

  • NARROW coverage - only aerobic GNR (e. coli, pseudomonas


     

113

side effects of azetreonam?

  • Usually non-toxic
  • Occasional GI upset

114

drug interactions of azetronam?

  • synergistic with aminoglycosides 

115

When is azetreonam used??


  • penicillin allergic patients
     
  • those with renal insufficiency who cannot tolerate aminoglycosides

116

Example of Glycopeptides?

Vancomycin

117

MoA of vancomycin?

binds to free carboxyl (COOH) end of the D-Ala-D-Ala chain, thereby preventing cross linking of peptidoglycan

118

How is vancomycin usually administered?

CSF penetration?

  • IV, or PO only when it is used to treat a infection within the bowel lumen
  • FAIR CSF penetration if the meninges are inflamed

119

How do VREs develop?

Remember the MoA of vancomycin is to bind the free carboxyl (COOH) end of the D-Ala-D-Ala chain, thereby preventing cross linking of peptidoglycan

resistance in enterococci and S. aureus occurs because they convert D-Ala --> D-lactate, thereby reducing vancomycin efficacy (VRE)

120

bugs sensitive to vancomycin

GPC only – serious MDR organisms, including

  • MSSA
  • MRSA
  • enterococcus
  • C. diff (only PO)
  • coagulase (-) staph

121

bugs resistant to vancomycin?

  • All GNRs
  • anaerobes other than clostridia sp,
  • very rare S. aureus and enterococcus (VRE)

122

Why should you give vancomycin very slowly?

if given too fast, it can cause the red man syndrome (rapid rate of infusion can cause histamine release; trmt: slow infusion over 60min)

123

SE of vancomycin?

  • nephrotoxicity
  • neutropenia
  • ototoxicity
  • thrombophlebitis
  • red man syndrome 

124

Rx interactions with vancomycin?

  • additive nephrotoxicity if given with other nephrotoxic drugs, including aminoglycosides, amphotericin
  • synergistic when given with gentamicin against staph aureus, enterococcus, and staphylococci

125

Indiations of vancomycin?

  • Empiric treatment of serious infections likely caused by GPC pending culture results (e.g meningitis, sepsis, pneumonia, endocarditis)
  • treatment of serious infections caused by GPC resistant to other drugs (e.g. MRSA)
  • oral treatment of C. difficile colitis 

126

Example of Cyclic lipopeptides?

Daptomycin

127

MoA of Daptomycin?

antibacterial - binds to cell membrane, depolarizes the cell, which inhibits protein, DNA, and RNA synthesis, leading to cell death; does not enter the cytoplasm itself

128

why is daptomycin not used for pneumonia?

because it is inactivated by pulmonary surfactant 

129

What must you do if you give a patient daptomycin?

check CPK weekly due to myopathy risk; stop Rx if CPK rise to 10x normal limit 

130

bugs sensitive to daptomycin?

most GPC (strep, staph, enterococcus)

131

bugs resistant to daptomycin?

All GNR

132

SE of daptomycin?

  • cardiac failure
  • pseudomembranous colitis
  • hypoglycemia
  • myopathy

133

Drug interactions with daptomycin?

  • cautiously with statins (may increase risk of myopathy)
  • may alter levels of tobramycin
  • may alter response to warfarin

134

indications for daptomycin?

serious infections caused by resistant GPC (ie MRSA, VRE) such as bacteremia, endocarditis, skin and soft tissue infections

135

MRSA - drugs that it is resistant to? senstive?

  • resistant to all penicillins (penicillin, methacillin, nafcillin, oxacillin, and Dicloxacillin) and cephalosporins (except ceftaroline, 5th generation)
  • sensitive to Ceftaroline, Vancomycin – use vanco because it is cheaper and it is more specific (wont encourage other bugs to develop resistance).

136

Pseudomonas treatments?

treatments = pipercillin or ceftazidime

very good at becoming resistant at every drug; can cause life threatening infections in compromised patients in a setting where antibiotics or chemotherapy are used; classic cases

  • little old lady with indwelling foley who lives in a nursing home where antibiotics are widely used
  • cancer patients on chemotherapy

137

organisms typically not covered by cephalosporins?

*organisms typically not covered by cephalosporins are LAME:

Listeria

Atypicals (Chlamydia, Mycoplasma)

MRSA

Enterococci

exception: ceftaroline covers MRSA