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0. Step Ib > Antibiotics - Pencillins and Cephalosporins > Flashcards

Antibiotics - Pencillins and Cephalosporins Flashcards

1
Q

what does Penicillin, Cephalosporin, Monobactam, Carbapenem have in common?

A

ß lactam ring

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2
Q

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

A

inhibiting cell wall synthesis

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3
Q

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

A

ß lactamase enzymes - cleave the ß-lactam ring

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4
Q

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

A

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)

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5
Q

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

A

IgE Type I Hypersensitivity

rash, hives, angioedema, anaphylaxis

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6
Q

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

A

Cephalosporin, Monobactam, Carbapenem

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7
Q

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

A

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

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8
Q

Structure of penicillin?

A

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

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9
Q

MoA of penicillin?

A

bind covalently to Penicillin-binding proteins (PBP’s) at the active site, thereby interfering with the transpeptidase reaction
“bactericidal”

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10
Q

how does resistance develop against penicillin?

A

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

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11
Q

how does MRSA develop?

A

Modification of target PBP

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12
Q

What drugs are in the Benzopenicillin class?

A

Penicillin G

Penicillin V

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13
Q

sensitivity of penicillin G to ß lactamases?

A

sensitive

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14
Q

How is Penicillin G administered?

A

parenteral (poor oral bioavailability)
Procaine suspn (IM); duration 1-2 days
* Benzathine suspn (IV); duration 1-4 wks; great for kids

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15
Q

How is Penicillin V administered?

A

PO; very stable in stomach acid

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16
Q

Penicillins are effective in treating these bugs

A

Gram (+)

  • strep. pneumo
  • S. pyogenes
  • Actinomyces
  • N. meningitides
  • Spirochetes (T. pallidum)
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17
Q

what bugs are resistant to penicillin?

A

Staph (>85%)Pneumococcus (10-30%)bowel anaerobesgonorrhea (Pen G)most GNR’s

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18
Q

Contraindications of penicillin?

A

Pen-allergic patients

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19
Q

Side Effects of penicillins?

A

1) drug allergy especially rash, anaphylaxis
2) anemia (binds to RBC and induces hemolysis
3) Seizures following high doses

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20
Q

Drug interactions with penicillins?

A
  • synergy with gentamicin against staph and enterococcus

* probenecid inhibits renal active tubular secretion

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21
Q

What situations would warrant penicillin treatment?

A
  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)
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22
Q

Drugs in the Aminopenicillins class?

A

Ampicillin

Amoxicillin

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23
Q

sensitivity of aminopenicillins to ß lactamases?

A

sensitive (its nearly identical to penicillin)

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24
Q

mechanism of action of aminopenicillins?

A

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

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25
Q

How is ampicillin different than amoxicillin?

A

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

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26
Q

what bugs are sensitive to aminopenicillins?

A

extended spectrum of action

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

Amp HELPSS to kill enterococci

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27
Q

What bugs are resistant to aminopenicillins?

A
  • most staph
  • some pneumococcus (>30%)
  • some H. flu
  • bowel anaerobes
  • some GNRs
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28
Q

SE of aminopenicillins?

A
  • drug allergy especially rash, anaphylaxis
  • seizures following high doses
  • antibiotic-associated colitis
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29
Q

Contraindications of aminopenicillins?

A

Pen-allergic patients

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30
Q

drug interactions with aminopenicillins?

A

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

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31
Q

indications for aminopenicillins?

A
  • otitis media
  • neonatal sepsis
  • Lyme disease (early)
  • simple UTI’s (GNRs, such as E. coli, klebsiella, enterobacter, proteus)
  • meningitis with sensitive pathogens
  • URI
  • endocarditis w. sensitive pathogens
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32
Q

What are examples of“semi-synthetic”penicillins?

A
  • Nafcillin
  • Dicloxacillin
  • Oxacillin
  • Methicillin - original
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33
Q

sensitivity of nafcillin to ß lactmases?

A

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

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34
Q

MoA of nafcillin?

A

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

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35
Q

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

A

nafcillin or oxacillin - IV; serious infections with MSSA

dicloxacillin - PO; less severe infections

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36
Q

bugs sensitive to nafcillin?

A

Same as penicillin, but narrow spectrum
* S. aureus (except MRSA, resistant due to altered PBP target site)

“use naf for staph”

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37
Q

bugs resistant to nafcillin or within the same class?

A
  • MRSA (usually bc they have a different PBP)
  • pneumococcus
  • oral/bowel anaerobes
  • GNR (most)
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38
Q

contraindications for semi-synthetic pencillins?

A

Pen-allergic patients

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39
Q

SE of semi-synthetic penicillins (ie nafcillin)?

A
  • drug allergy HSR
  • neprotoxic - allergic interstitial nephritis
  • Methicillin – highly nephrotoxic (causes allergic interstitial nephritis) and resistant to ß-lactamase; not used anymore
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40
Q

drug interactions with nafcillin?

A
  • synergy with gentamicin against enterococcus

* probenecid inhibits renal active tubular secretion

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41
Q

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

A

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

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42
Q

Drugs in theAnti-Pseudomonas class?

A
  • Piperacillin
  • Carbenicillin
  • Ticarcillin
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43
Q

Piperacillin -sensitivity to ß lactamases?

A

sensitive

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44
Q

MoA ofPiperacillin?

A

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

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45
Q

What is one thing that you have to consider when dosingPiperacillin andCarbenicillin?

A

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

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46
Q

How isPiperacillin and Carbenicillin administered?

A
  • Piperacillin - IV

* Carbenicillin - PO

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47
Q

bugs sensitive toPiperacillin and Carbenicillin?

A

Same as penicillin, but with extended spectrum

  • Pseudomonas
  • GNR
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48
Q

bugs resistant toPiperacillin and Carbenicillin?

A
  • GPC
  • Anaerobes
  • Enterococcus
  • pneumococcus
  • most S. aureus
  • increasing # of resistant pseudomonas and GNRs
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49
Q

contraindications of anti-pseudomonal agents??

A

Pen-allergic patients

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50
Q

SE ofPiperacillin and Carbenicillin?

A
  • drug allergy especially rash, anaphylaxis

* antibiotic-associated colitis

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51
Q

drug interactions ofPiperacillin and Carbenicillin?

A
  • synergy with gentamicin against Pseudomonas
  • probenecid inhibits renal active tubular secretion of Piperacillin
  • Piperacillin may inhibit tubular secretion of MTX
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52
Q

indications forPiperacillin and Carbenicillin?

A
  • Pseudomonas infections (usually given in combination with gentamycin or tobramycin for synergy)
  • Carbenicillin – used treat non-life threatening infections (ie UTI) caused by Pseudomonas)
  • intra-abdominal infections (mixed GNR, anaerobes, and enterococcus)
    nosocomial pneumonia (because often caused by GNR in the ICU)
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53
Q

What are someß-lactamase inhibitors that are manufactured with penicillins?

A

Clavulanic acid, sulbactam, and tazobactam

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54
Q

How do ß-lactamase inhibitors work?

A

resemble ß lactam molecules andprevents cleavage of ß lactam rings, but havevery weak antimicrobial activity themselvesthus they areadded to amoxicillin or ampicillin or pipercillin,whose “range” is extended by the inhibitor

55
Q

3 types of Penicillins w.ß-lactamase inhibitors?

A
  • Amoxicillin & clavulanate (Augmentin)
  • Ampicillin & sulbactam (Unasyn)
  • Piperacillin & Tazobactam (Zosyn)
56
Q

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

A

ß-lactamases produced by

  • enterobacter
  • citrobacter
  • serratia
  • pseudomonas
57
Q

How are cephalosporins similar than penicillins? different?

A

similar to penicillins in that they both have:

  • structure (A ring + ß lactam ring)
  • mechanism of action
  • toxicities/allergic reactionsdifferent 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
58
Q

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

A
  • 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.)
59
Q

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

A

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.

60
Q

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

A

5 classes

  • 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: ceftarolineGood CSF penetration: 3rd, 4th, 5th
61
Q

Drugs in theCephalosporins1st gen?

A
  • Cefazolin

* cephalexin

62
Q

MoA ofCefazolin?

A

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

63
Q

CSF penetration of Cephalosporins1st gen?

A

poor

64
Q

bugs sensitive to cefazolin?

A

broad spectrum of activity

  • GPC
  • Proteus mirabalis
  • E. coli
  • KlebsiellaPEcK
65
Q

bugs resistant to cefazolin?

A
  • MRSA (about 30% and growing)
  • enterococcus,
  • Listeria
  • nosocomial GNRs
  • some pneumococcus
  • bowel anaerobes
66
Q

contraindications of cefazolin?

A

Pen-allergic patients (cross-reactivity)

67
Q

SE of cefazolin?

A
  • drug allergy especially rash, anaphylaxis
  • anemia
  • vitamin K deficiency
  • antibiotic-associated colitis
68
Q

drug interactions of cefazolin?

A
  • probenecid inhibits renal active tubular secretion, prolongs half-life
  • increase nephrotoxicity of aminoglycosides
69
Q

indications of cefazolin?

A
  • 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
70
Q

Rx in the Cephalosporins3rd gen that we should know?

A
  • Ceftriaxone

* Ceftazidime

71
Q

MoA of Ceftriaxone?

A

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

72
Q

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

A

it is less likely to cause biliary sludging

73
Q

bugs sensitive to ceftriaxone?

A

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

  • meningitis
  • gonorrhea
74
Q

bugs resistant to ceftriaxone?

A
  • MRSA (~30% and growing)
  • pneumococcus (5-10%)
  • enterococcus
  • nosocomial GNRs
  • bowel anaerobes
  • pseudomonas
  • Listeria
75
Q

CI of ceftriaxone?

A

Pen-allergic patients

76
Q

SE of ceftriaxone?

A
  • drug allergy especially rash, anaphylaxis
  • anemia
  • antibiotic-associated colitis
  • vitamin k deficiency
77
Q

Drug interactions with ceftriaxone?

A
  • probenecid inhibits renal active tubular secretion
  • synergistic with gentamicin against some GNR
  • may enhance effects of warfarin increase nephrotoxicity of aminoglycosides
78
Q

indications for ceftriaxone?

A
  • meningitis
  • serious pneumonia
  • otitis
  • sinusitis
  • neisseria gonorrhea
  • GNR
  • lyme dz
79
Q

MoA forCeftazidime?

A

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

80
Q

bugs sensitive to ceftazidime?

A

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

81
Q

bugs resistant to ceftazidime?

A
  • large majority of staph
  • some pneumococcus
  • bowel anaerobes
82
Q

CI for ceftazidime?

A

Pen-allergic patients

83
Q

SE of ceftazidime?

A
  • drug allergy especially rash, anaphylaxis
  • antibiotic-associated colitis
  • vitamin k deficiency
84
Q

drug interactions withCeftazidime?

A
  • synergistic with gentamicin against some GNR, especially Pseudomonas
  • may enhance effects of warfarin
    increase nephrotoxicity of aminoglycosides
85
Q

indications for ceftazidime?

A
  • resistant GNRs and Pseudomonas
  • meningitis or sepsis where GNR is likely pathogen
  • bacteremia
  • UTI
  • urosepsis
  • empiric Rx of febrile neutropenic pts
86
Q

What generation isCeftaroline in?

A

Cephalosporins,5th gen

87
Q

MoA of ceftaroline?

A

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

88
Q

Why do you have to monitor ceftaroline in the elderly?

A

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

89
Q

bugs sensitive to ceftaroline?

A

Broadest spectrum of activity

  • GN
  • GP – strep pneumonia, staph aureus (MSSA and MRSA)
  • does not cover Pseudomonas
90
Q

bugs resistant to ceftaroline?

A

still being defined

91
Q

CI of ceftaroline?

A

Pen-allergic patients

92
Q

SE of ceftaroline?

A
  • drug allergy especially rash, anaphylaxis

* Clostridium difficile-associated diarrhea convert to a positive direct Coombs test (10% of patients)

93
Q

ceftaroline drug interactions?

A

none reported

94
Q

indications for ceftaroline use?

A
  • community acquired bacterial pneumonia (CABP)

* acute skin infectionbut only for pathogens likely to be sensitive, and only used when a broad spectrum drug is needed

95
Q

drugs in theCarbapenems class?

A
  • Meropenem
  • Imipenem
  • irbepenem
  • ertapenem
  • doripenem
96
Q

How are carbapenems different than penicillins?

A

has an additional ring structure to the ß lactam ring

97
Q

What do you often administer withImipenem and why?

A

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”

98
Q

CSF penetration of Meropenem?

A

good

99
Q

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

A

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

100
Q

bugs sensitive to carbapenem?

A

Broadest spectrum against the widest group of bacteria

  • most GPC (including staph)
  • most GNR (including pseumomonas)
  • Anaerobes
101
Q

bugs resistant to carbapenem?

A
  • MRSA
  • enterococcus
  • rare pneumococcus; but can develop resistance rapidly
102
Q

CI for using carbapenem?

A

Pen-allergic patients

103
Q

SE of carbapenem?

A
  • antibiotic-associated colitis
  • seizures (at high plasma levels)
  • GI distress
  • skin rash
104
Q

Rx interactions wtih carbapenem?

A
  • probenecid inhibits renal active tubular secretion
  • synergistic with gentamicin against some GNR
  • may enhance effects of warfarin
105
Q

Indications of carbapenem?

A
  • 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
106
Q

drugs in the monobactam class?

A

Azetreonam

107
Q

What is unique about Azetreonam?

A

resistant to ß lactamases

* NOcross-allergenicity with penicillin

108
Q

bugs sensitive to azetreonam?

A

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

109
Q

side effects of azetreonam?

A
  • Usually non-toxic

* Occasional GI upset

110
Q

drug interactions of azetronam?

A
  • synergistic with aminoglycosides
111
Q

When is azetreonam used??

A
  • penicillin allergic patients

* those with renal insufficiency who cannot tolerate aminoglycosides

112
Q

Example ofGlycopeptides?

A

Vancomycin

113
Q

MoA of vancomycin?

A

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

114
Q

How is vancomycin usually administered? CSF penetration?

A
  • IV, or PO only when it is used to treat a infection within the bowel lumen
  • FAIR CSF penetration if the meninges are inflamed
115
Q

How do VREs develop?

A

Remember the MoA of vancomycin isto bind the free carboxyl (COOH) end of the D-Ala-D-Ala chain, thereby preventing cross linking of peptidoglycanresistance in enterococci and S. aureus occurs because they convert D-Ala –> D-lactate, thereby reducing vancomycin efficacy (VRE)

116
Q

bugs sensitive to vancomycin

A

GPC only – serious MDR organisms, including

  • MSSA
  • MRSA
  • enterococcus
  • C. diff (only PO)
  • coagulase (-) staph
117
Q

bugs resistant to vancomycin?

A
  • All GNRs
  • anaerobes other than clostridia sp,
  • very rare S. aureus and enterococcus (VRE)
118
Q

Why should you give vancomycin very slowly?

A

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

119
Q

SE of vancomycin?

A
  • nephrotoxicity
  • neutropenia
  • ototoxicity
  • thrombophlebitis
  • red man syndrome
120
Q

Rx interactions with vancomycin?

A

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

121
Q

Indiations of vancomycin?

A
  • 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
122
Q

Example ofCyclic lipopeptides?

A

Daptomycin

123
Q

MoA ofDaptomycin?

A

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

124
Q

why is daptomycin not used for pneumonia?

A

because it is inactivated by pulmonary surfactant

125
Q

What must you do if you give a patient daptomycin?

A

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

126
Q

bugs sensitive to daptomycin?

A

most GPC (strep, staph, enterococcus)

127
Q

bugs resistant to daptomycin?

A

All GNR

128
Q

SE of daptomycin?

A
  • cardiac failure
  • pseudomembranous colitis
  • hypoglycemia
  • myopathy
129
Q

Drug interactions with daptomycin?

A
  • cautiously with statins (may increase risk of myopathy)
  • may alter levels of tobramycin
  • may alter response to warfarin
130
Q

indications for daptomycin?

A

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

131
Q

MRSA - drugs that it is resistant to? senstive?

A
  • 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).
132
Q

Pseudomonas treatments?

A

treatments = pipercillin or ceftazidimevery 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
133
Q

organisms typically not covered by cephalosporins?

A 
*organisms typically not covered by cephalosporins areLAME:
Listeria
Atypicals (Chlamydia, Mycoplasma)
MRSA
Enterococci

exception: ceftaroline covers MRSA

0. Step Ib (19 decks)

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