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Host and Defense > EXAM 1 Antimicrobials I > Flashcards

EXAM 1 Antimicrobials I Flashcards

1
Q

what are the main antimicrobial targets of cell wall synthesis?

A
  • beta lactams
  • vancomycin
  • bacitracin
  • cell membrane
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2
Q

what are the 4 steps beta-lactam antimicrobials must take in order to be effective?

A
  1. evade bacterial defenses
  2. penetrate outer cell layers to reach inner cytoplasmic membrane
  3. keep their beta-lactam ring structure intact
  4. bind to the transpeptidase enzyme (penicillin-binding protein, PBP) on the bacteria’s cytoplasmic membrane
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3
Q

the beta-lactam region structurally resembles the D-Ala-D-Ala end of the peptide that serves as a substrate for ____

A

transpeptidase enzymes

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4
Q

what is the role of transpeptidase PBP in new bacterial cell wall synthesis?

A
  • clips off the terminal D-Ala residue and crosslink adjacent glycan chains
  • covalently bonded chains form rigid cell walls that prevent osmotic forces from rupturing bacterial cell walls
  • beta-lactam drugs bind to the transpeptidase PBP and prevent transpeptidation
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5
Q

what are the 3 characteristics common to all beta-lactam drugs?

A
  • require actively proliferating microorganisms to be maximally effective
  • inactive against organisms devoid of peptidoglycans
  • should be dosed to achieve serum concentrations (T) > MIC for at least 50% of the dosing interval (type II time-dependent PD)
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6
Q

what are the 2 forms of natural penicillins?

A

penicillin G and penicillin V

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7
Q

natural penicillins, aminopenicillins, penicillinase-resistant penicillins, anti-pseudonomal penicillins, cephalosporins, and carbapenems are all ___ antimicrobials

A

beta-lactam

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8
Q

what are the two forms of aminopenicillins?

A

ampicillin and amoxicillin

*aminopenicillins = extended spectrum penicillins

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9
Q

what are the 4 forms of penicillinase-resistant penicillins?

A

methicillin, nafcillin, oxacillin, and dicloxacicillin

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10
Q

which penicillinase-resistant penicillin is the first-line treatment of choise for staphylococcal endocarditis?

A

nafcillin

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11
Q

what are the 3 forms of anti-pseudomonoal penicillins, and what are examples of each?

A
  • monobactams (ex. aztreonam)
  • ureidopenicillins (ex. piperacillin)
  • carboxypenicillins (ex. ticarcillin, indanyl carbenicillum)
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12
Q

of all the anti-pseudomonal penicillins, ___ and then ___ have the broadest spectrums of activity

A

ticarcillin, piperacillin

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13
Q

describe the mechanism of cephalosporins

A
  • analogous to penicillin
    • bactericidal, so long as T > MIC maintained appropriately
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14
Q

what is the most important carbapenem, and why is it important?

A
  • impenem
  • it is the broadest antibacterial available
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15
Q

other than imipenem, what are two other forms of carbapenems?

A

meropenem and ertapenem

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16
Q

___ is the only true naturally occurring penicillin

A

penicillin G

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17
Q

penicillin is rapidly hydrolyzed by ___

A

penicillinase enzymes (beta-lactamase enzymes)

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18
Q

how is penicillin G usually administered?

A

IM or IV (sodium pen G injected every 6-12h)

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19
Q

is penicillin G a broad or narrow spectrum antimicrobial? describe

A
  • narrow
  • very active against gram +, but less active against gram -
  • 5-10x more active against gram - neisseria species and anaerobes than pen VK
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20
Q

describe penicillin V

A
  • acid stable
  • orally active
  • same spectrum as pen G, but less active
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21
Q

why are aminopenicillins considered “extended spectrum penecillins”?

A

better gram - coverage than either pen G or pen V; still sensitive to beta-lactamases

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22
Q

what class of drugs is the drug of choice for listeria monocytogenes, prophylaxis of infective endocarditis, and treatment of UTIs caused by susceptible enterococci?

A

aminopenicillins (ampicillin and amoxicillin)

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23
Q

aminopenicillins are usually administered with a ___

A
  • beta-lactamase inhibitor
    • ex. clavulanate, sulbactam, or tazobactam
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24
Q

what 2 drugs make up augmentin?

A

amoxicillin and clavulanate

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25
Q

___ has higher oral absorption, higher CPmax, longer 1/2 life, and less likely to cause adverse GI effects than ___.

A

amoxicillin, ampicillin

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26
Q

what is the interaction warning for amoxicillin?

A

it dose-dependently inhibits renal tubular excretion of methotrexate, resulting in prolonged/high serum levels of methotrexate

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27
Q

what is the drug of choice for standard prophylactic prevention of bacterial endocarditis?

A

amoxicillin (PO)

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28
Q

as an alternative to amoxicillin, in the case of non-anaphylactic allergy, what drug can be given for prophylactic prevention of bacterial endocarditis?

A

cephalexin - 1st generation cephalosporin

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29
Q

as an alternative to amoxicillin, in cases of serious allergy requiring non-beta-lactams, what 2 drugs can be given for prophylaxis for the prevention of bacterial endocarditis?

A
  • clindamycin
    • lincosamide protein synthesis inhibitor
  • azithromycin or clarithromycin
    • macrolide protein synthesis inhibitors
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30
Q

what drug is active against all organisms sensitive to pen G, plus many gram - bacilli?

A

ampicillin

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31
Q

amoxicillin is better absorbed through which route? why is this important

A

orally

it is not influenced by food consumption, and thus produces higher plasma concentrations

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32
Q

describe the parenteral use of ampicillin

A

drug of choice in pateints unable to take oral medications so long as they are not allergic to penicillin

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33
Q

what are the adverse effects of ampicillin?

A
  • diarrhea
    • pseudomembranous colitis (c. dificile overgrowth)
  • rashes
  • hypersensitivity
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34
Q

___ inactivates ampicillin if mixed in IV solution

A

hydrocortisone

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35
Q

what can occur if probenecid (given for gout) is taken with ampicillin?

A

slows renal excretion of ampicillin

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36
Q

describe how penicillinase-resistant penicillins are “anti-staphylococcal penicillins”

A

active against staphylococci and streptococci but not enterococci, anaerobic bacteria, or gram - cocci and rods

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37
Q

penicillnase-resistant penicillins are less potent than ___, but are agents of first choice for treatment of which 2 penicillinase-producing bacteria that are not methicillin-resistant?

A
  • pen G
  • s. aureus and s. epidermidis
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38
Q

which 2 penicillinase-resistant penicillins have activity similar to methacillin and beta-lactamase resistance, but are acid stable with reduced risk of interstitial nephritis?

A

oxacillin and dicloxacillin

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39
Q

what is the drug of choice for serious s. aureus infections (non-MRSA), such as in cellulitis, endocarditis, and sepsis? why?

A
  • nafcillin
    • think “use naf for staph”
  • they are resistant to staphylococcal beta-lactamases
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40
Q

why does probenecid not interact with nafcillin, oxacillin, and dicloxacillin?

A

they are lipophilic and undergo biliary excretion (not renal excretion)

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41
Q

describe probenecid

A

it is a uric acid reducer used to treat gout and to increase plasma levels of some antibiotics

42
Q

___ inhibits organic anion transporter’s (OAT) in the renal proximal tubule, reducing clearance, and thus increasing plasma levels of drugs normally secreted by this mechanism

A

probenacid

43
Q

since most beta-lactams are renally excreted, their ___ levels are increase, and ___ are prolonged if given with probenecid

A
  • serum levels
  • half-lives
44
Q

anti-pseudomonal penicillins are clinically used for treating serious bacteremias, pneumonias, post-burn infections, and UTIs, due to what?

A

bacteria resistant to pen G and ampicillin

45
Q

how are anti-pseudomonal penicillins administered?

A

IM or IV

not PO

46
Q

the recent emergence of ___ is threatening the utility of anti-pseudonomal penicillins

A

broad-spectrum beta-lactamases

47
Q

carboxypenicillins (indanyl carbenicillin and ticarcillin) are more or less active than piperacillin against pseudonomas?

A

less

48
Q

which carboxypenicillin is orally active and is used clinically for management of UTIs caused by p. aerugenosa or proteus sp?

A

indanyl carbenicillin

49
Q

___ is 2-4x more active than indanyl carbenicillin

A

ticarcillin

50
Q

what is the main cilinical use of ticarcillin?

A
  • injectable agent against gram - bacteria, particularly p. aeruginosa
    • it is one of the few antibiotics capable of treating stenotrophomonas maltophilia infections in/on indwelling mechanical devices
51
Q

ticarcilin is no longer available in the US. what was it replaced with?

A

timentin (ticarcillin/clavulanate combination)

52
Q

piperacillin retains all the activity of ampicillin against gram + cocci and l. monocytogenes, plus has excellent activity against what?

A

pseudomonas, klebsiella, and other gram - microorganisms

53
Q

___ is the broadest spectrum of the antipseudomonal penicillins

A

piperacillin

54
Q

what is preferred over piperacillin to combat beta-lactamases?

A

zosyn (piperacillin/tazobactam)

55
Q

___ is great for patients with IgE-mediated penicillin allergy

A

aztreonam (IV)

56
Q

aztreonam is resistant to some ___, but not ___

A
  • beta-lactamases
  • extended-spectrum lactamases
57
Q

describe the toxicity of aztreonam

A
  • pseudomonas colitis (c. dificile overgrowth)
  • cellulitis
  • hematologic disorders
58
Q

describe the common side effects of penicillins

A
  • hypersensitivity/anaphylaxis
  • local effects
  • large doses of pen G may produce lethargy, confusion, twitching, seizures, kidney failure, and coma
  • low superinfection risk for narrower spectrum drugs
59
Q

cephalosporins are resistant to what?

A

many older penicillinases (beta-lactamases)

60
Q

like most penicillins, cephalosporins are ___ excreted, and may cause toxicity in patients with ___

A
  • renally
  • renal insufficiency
61
Q

cephalosporin cross allergy with penicillins is ___%. patients with mild, delayed penicillin allergy can often tolerate cephalosporins, but patients with history of ___ cannot.

A
  • 5%
  • anaphylaxis
62
Q

name the 1st-5th generation cephalosporins

A
  • 1st generation - cephalexin, cefazolin
  • 2nd generation - cefaclor, cefuroxime, cefoxitin
  • 3rd generation - cefdinir, cefotaxime, ceftazidime, ceftriaxone
  • 4th generation - cefepime
  • 5th generation - ceftaroline
63
Q

describe the spectrum of activity of 1st generation cephalosporins

A
  • moderate spectrum
    • active against gram +, modest gram - activity
  • most active against s. aureus, streptococci, and pneumococcus
64
Q

describe the spectrum of activity of 2nd generation cephalosporins

A
  • moderate/broad spectrum
    • not as active against gram + organisms as 1st generation, but also possess good activity against e. coli, h. influenzae, and klebsiella
  • not active against pseudomonas
65
Q

describe the spectrum of activity of 3rd generation cephalosporins

A
  • have broadest spectrum of all the cephalosporins and are extremely effective against gram - organisms
  • most can cross the blood brain barrier (exception is cefoperazone)
    • important for the treatment of meningitis
66
Q

describe the spectrum of activity of 4th generation cephalosporins

A

broad spectrum, less gram +, but more gram - activity and resistance to beta-lactamase

67
Q

describe the spectrum of activity of 5th generation cephalosporins

A

broad spectrum, same as 4th generation plus active against MRSA

68
Q

because 2nd, 3rd, and 4th generation cephalosporins have reduced gram + activity, ___ with these may occur

A

superinfection

69
Q

___ has the broadest spectrum coverage (IV or IM) available to man

A

imipenem

70
Q

___ is a non-beta-lactam antibacterial, blycopeptide, bactericidal, covers all gram + bacteria (not gram -), and is used to treat endocarditis in penicillin-allergic patients (IV)

A

vancomycin (IV)

71
Q

none of the 1st generation cephalosporins penetrate the ___

A

CNS

72
Q

___ generation cephalosporins are not the first drug of choice for any active infections

A

1st

73
Q

___ is a ___ generation cephalosporin used for prophylaxis prior to surgery

A

cefazolin, 1st

74
Q

___ is a ___ generation cephalosporin used to treat oral sinusitis and otitis media caused by H. influenzae

A

cefaclor, 2nd

75
Q

___ is a ___ generation cephalosporin that has enhanced anaerobe activity and extended beta-lactamase resistance

A

cefoxitin, 2nd

76
Q

why is cefuroxime a unique 2nd generation cephalosporin?

A

it can cross the blood brain barrier

77
Q

___ or ___ are both ___ generation cephalosporins (both IV) used for gram - bacterial sepsis and meningitis

A
  • cefotaxime or ceftriaxone
  • 3rd
78
Q

___ is a ___ generation cephalosporin that is active against pseudomonas aeruginosa

A
  • ceftazidime
  • 3rd
79
Q

___ is a ___ generation cephalosporin, the highest selling cephalosporin, and is used for the treatment of otitis, soft tissue infections, respiratory tract infections, including sinitis, strep throat, CAP, and acute bronchitis.

A
  • cefdinir
  • 3rd
80
Q

___ is a ___ generation cephalosporin that has activity greater than ceftazidime against streptococci and methicillin-susceptible staph, and has comparable activity to ceftazidime against pseudomonas aeruginosa

A
  • cefepime
  • 4th
81
Q

___ is a ___ generation cephalosporin that is active against MRSA, gram + bacteria, and gram - bacteria

A
  • ceftaroline
  • 5th
82
Q

___ is a carbapenem that is active against gram + organisms, gram - rods, and anaerobes

A

imipenem

83
Q

___ and ___ are both resistant to imipenem

A

MRSA and mycoplasma

84
Q

carbapenems are very stable in the presence of beta-lactamases, including ___ and ___ that are resistant to most beta-lactam antibiotics

A

penicillinase and cephalosporinase

85
Q

what are the adverse effects of carbapenems?

A
  • similar to penicillins
  • renal clearance is critical
    • levels in patients with renal insufficiency is known to cause seizures
86
Q

why is impenem always coadministered with cilistatin (renal dehydropeptidase 1 inhibitor)?

A

imipenem is rapidly degraded by the renal enzyme dehydropeptidase-1, so it is always coadministered with cilistatin, the inhibitor of this enzyme

87
Q

name 2 newer carbapenems that are not inactivated by renal dipeptidases so do not require silistatin coadministration

A

meropenem and ertapenem

88
Q

what are the 4 non-beta-lactam antibacterials?

A
  • bacitracin (topical)
  • vancomycin (IV)
  • polymyxins
  • daptomycin (IV)
89
Q

___ is a non-beta-lactam antibacterial, polypeptide from bacillus subtillus, bactericidal, disrupts both gram + and gram - bacteria, and can cause kidney damage when used internally?

A

bacitracin

90
Q

___ inhibits cell wall synthesis in gram + bacteria at an earlier stage of the peptidoglycan synthetic pathway than beta-lactams, and is not active against most gram - bacteria

A

vancomycin

91
Q

___ is the first line IV treatment for complicated skin infections, bloodstream infections, endocarditis, bone and joint infections, and meningitis caused by MRSA

A

vancomycin

92
Q

why should vancomycin not be used to treat methicillin-sensitive s. aureus?

A

vancomycin is inferior to nafcillin

93
Q

vancomycin is poorly absorbed PO. how can this be advantageous?

A

for the treatment of clostridium difficile colitis

94
Q

vancomycin is a good alternative for the treatment of infections caused by gram + microorganisms in patients with ___

A

serious allergies to beta-lactam antimicrobials

95
Q

what are 3 adverse effects of vancomycin?

A

thrombophlebitis, skin rashes, leukopenia

96
Q

vancomycin has traditionally been considered a ___ and ___ drug, especially when given in patients on aminoglycosides

A

nephrotoxic and ototoxic drug

97
Q

what is red man syndrome?

A
  • can be an adverse effect of vancomycin
  • rapid infusion induced non-immunological release of histamine
98
Q

___ are non-beta-lactam antibacterials that are bactericidal against gram - bacteria, used clinically against multidrug resistant gram - bacteria, and are associated with neurotoxicity and acute renal tubular necrosis

A

polymyxins

99
Q

___ is a non-beta-lactam antibacterial that is a cyclic lipopeptide, bactericidal against gram + bacteria, is inactivated by pulmonary surfactants (so it is not indicated for pneumonia), and has adverse effects that include myopathy, arthralgia, and eosinophylic pneumonia

A

daptomycin (IV)

100
Q

describe immediate/acute onset allergic reactions to penicillins/beta-lactams

A
  • reactions within 30 minutes (anaphylaxis)
  • IgE mediated - life-threatening
101
Q

describe accelerated onset allergic reactions to penicillins/beta-lactams

A
  • arise 30min to 48hr after administration
  • urticaria, pruitis, wheezing, local inflammatory response
102
Q

describe delayed onset allergic reactions to penicillins/beta-lactams

A
  • reactions that take longer than 2 days to develop
  • 80-90% of penicillin reactions are of this type

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