Lec 5-6 Micro Tx Staph Strep Flashcards

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1
Q

What is pharmacokinetics?

A

“what the body does to the drug”

- absorption, distribution, metabolism, elimination

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2
Q

What is pharmacodynamics?

A

“What the drug does to the body [or organism]”

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3
Q

What does it mean if an antimicrobial is concentration-dependent?

A
  • increase in concentration causes increase in rate of bacterial killing
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4
Q

3 examples of concentration-dependent antibiotics?

A
  • daptomycin [lipopeptides]
  • aminoglycosides
  • fluoroquinolones
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5
Q

What does it mean if an antimicrobial is time-dependent [concentration independent]?

A
  • killing is predicted by the amount of time that concentration in body is above certain level [MIC]
  • don’t get any more effectiveness by giving bigger dose at each time point, want to give doses more frequently
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6
Q

What are 2 examples of time-dependent drugs?

A
  • b lactams

- glycopeptides [vancomycin]

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7
Q

What is the minimum inhibitory concentration [MIC]?

A
  • lowest concentration of an antibiotic that will inhibit the visible growth of bacteria in vitro
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8
Q

What are 5 tests for antibiotic susceptibility

A
  • broth macrodilution
  • microdilution
  • E test
  • disk diffusion
  • automated systems
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9
Q

What is mech of broth macrodilution?

A
  • innoculate different concentrations of drug with same amount of bacteria
  • let incubate 24 hours
  • look for tubes with no turbidity [= no bacteria growth]
  • MIC is the lowest antibiotic conc that has no turbidity
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10
Q

What is broth microdilution?

A
  • uses idea of broth macrodilution but looking at multiple types of antibiotics as well as concentrations.
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11
Q

What is mech of E[psilometer] test?

A
  • plate inoculated with bacteria
  • lay down antibiotic-impregnanted strip with varying conc of antibiotic along the strip
  • wait 24 hours
    drug diffuses out from strip and inhibits bacterial growth
  • look for line where zone of inhibition ends to get min antibiotic conc that stops bacterial growth
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12
Q

What is mech of disk diffusion [kirby bauer] test?

A
  • plate innoculated with bacteria
  • put on antibiotic impregnated disk
  • measure size of zone of inhibition around the disk [large zone is susceptible, small or no zone is resistant]
  • qualitative not quantitative
  • does not give MIC
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13
Q

How do you calculate MIC from disk diffusion?

A
  • you can’t!

- you can only get qualitative information –> larger inhibition zone means more susceptible, smaller means resistant

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14
Q

What does bacteriostatic mean?

A
  • arrests bacterial growth

- allows host immune system to kill bacteria

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15
Q

What does bactericidal mean?

A
  • kills the bacteria

- eradicates infection in absence of host defense mech

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16
Q

Is linezolid bacteriostatic or bactericidal?

A

bacteriostatic

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17
Q

Are B lactams bacteriostatic or bactericidal?

A

bactericidal

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18
Q

Is vancomycin bacteriostatic or bactericidal?

A

both – it is bactericidal against some organisms and bacteriostatic against others

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19
Q

What is mech of action of B-lactams?

A
  • interfere with bacterial cell wall synthesis
  • bind penicillin binding proteins [PBPs] that are on cytoplasmic membrane
  • inhibit transpeptidases
  • prevent cross-linking of peptidoglycan
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20
Q

What are the 5 types of penicillins?

A
  • natural penicillins
  • anti-staphylococcal penicillins
  • extended-spectrum [amino] penicillins
  • anti-pseudomonal penicillins
  • B-lactamase inhibitor combinations
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21
Q

What is the route of administration of penicillin?

A
  • determined by how stable the drug is in presence of gastric acid –> if oral has to be stable
  • most incompletely absorbed after oral administration
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22
Q

What is the one type of penicillin that is completely absorbed after oral administration?

A

amoxicillin

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23
Q

What is the half life like for penicillin? What does this mean for dose timing?

A
  • short half-life so need to dose frequently
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24
Q

How is penicillin excreted normally? what is the one exception?

A

renal elimination

nafcillin is the exception – is not eliminated by renal

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25
Q

What are 4 main types of infections penicillin is used to treat?

A
  • gram positive cocci, gram negative cocci, gram positive bacilli, spirochetes
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26
Q

What are 3 specific bacteria that penicillin is drug of choice for?

A
  • streptococcus pyogenes [GAS]
  • agalactiae [GBS]
  • treponema pallidum [syphilis]
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27
Q

What is penicillin G?

A

intravenous penicillin [most important]

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28
Q

What is penicillin V?

A

oral penicillin –> stable in presence of acid

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29
Q

What are penicillinases? Whats a bacteria that they are commonly found in?

A
  • penicillinases inactivate penicillin

- found in staphylococcus aureus

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30
Q

What are some examples of anti-staphylococal penicillins?

A

nafcillin [most important]
oxacillin
dicloxacillin

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31
Q

What is significant about anti-staphylococcal penicillins? How are they affected by penicillinase? what are they used to treat? are they active against gram negative?

A
  • penicillinase resistant
  • drug of choice for staph aureus skin or bloodstream infections
  • no gram-negative activity
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32
Q

What is MSSA?

A

methicillin susceptible staph aureus

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33
Q

What are some examples of extended spectrum [amino] penicillins?

A
  • ampicillin and amoxicillin [oral]
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34
Q

What is significant about extended spectrum penicillins? what are they used to treat? are they active against gram negative/positive/anaerobes?

A
  • treat gram-positive organisms [GAS and GBS]
  • better gram-negative activity than natural penicillin
  • some anaerobic activity
  • active against enterococci
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35
Q

What is ampicillin used to treat primarily?

A

listeria monocytogenes

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36
Q

What are two drugs of choice for strep throat [strep pyogenes]?

A
  • penicillin

- amoxicillin

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37
Q

What 3 main things confer penicillin resistance?

A
  • lack of peptidoglycan cell wall
  • B lactamases
  • decreased permeability to antibiotic
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38
Q

Why is mycoplasma inherently resistant to penicillin?

A

because mycoplasma lacks a cell wall –> penicillin works by attacking the cell wall so if no cell wall can’t attack

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39
Q

What do B-lactamases do? How can they be passed on?

A
  • hydrolyzed B-lactam ring
  • gene encoding enzyme transferred via plasmid from one bacteria to another
  • major causes of resistance in gram negatives
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40
Q

What are two mechs of decreased permeability in bacterial cell wall to antibiotic?

A
  • change in outer membrane porin so drug can’t enter

- efflux pump so drug is leaving get lower conc in cell

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41
Q

What is mech of altered penicillin target?

A
  • get mutation in PBP to reduce affinity

- in MRSA get altered PBP [PBP2a] that lowers affinity for all B-lactams

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42
Q

What are 3 B-lactamase inhibitors?

A
  • clavulanic acid
  • sulbactam
  • tazobactam
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43
Q

What do B-lactamase inhibitors do?

A
  • contain a B-lactam ring

- bind to B lactamases and prevent them binding antibiotic

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44
Q

Which B-lactamase inhibitor do you pair with ampicillin to increase gram negative activity?

A

ampicillin and sulbactam

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45
Q

Which B-lactamase inhibitor do you pair with amoxicillin to increase gram negative activity?

A

amoxicillin and clavulanic acid

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46
Q

What is mech of hypersensitivity rxn to penicillin?

A
  • penicilloic acid [penicillin metabolite] causes an immune rxn
  • get hives –> angioedema –> anaphylaxis
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47
Q

Which patients get maculopapular rash from amoxicillin?

A

pts with EBV associated mononucleosis

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48
Q

Why does penicillin cause diarrhea?

A
  • get alterations in commensal flora

- get clostridium difficile colitis

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49
Q

What is possible effect of penicillin on kidney

A
  • interstitial nephritis
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50
Q

What is effect of penicillin on neuro?

A

causes neurotoxicitiy –> decreases seizure threshold

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51
Q

How are cephalosporins categorized?

A
  • into 5 generations
  • increased gram negative activity with higher generations
  • 4th generation has good gram + and - activity
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52
Q

What is distribution volume of cephalosporins?

A
  • very big volume of distribution

- get into lungs, kidneys, joints, bone, cross placenta

53
Q

which cephalosporins can cross blood brain barrier?

A

3rd and 4th generations

54
Q

Is half life typically long or short for cephalosporins?

A

long half life, less frequent dosing [time dependent]

55
Q

How are cephalosporins eliminated?

A

via renal excretion –> means that with renal insufficiency need dose adjustment

56
Q

What is the exception to the rule that cephalosporins are all eliminated by kidney?

A

ceftriaxone

57
Q

What are the two first generation cephaslosporins?

A

cefazolin

cephalexin

58
Q

What are the 3 second generation cephalosporins

A

cefuroxime
cefoxitin
cefotetan

59
Q

What are the 3 third generation cephalosporins

A

cefotaxime
ceftriaxone
ceftazidime

60
Q

What are the 3 fourth generation cephalosporins

A

cefepime

61
Q

What are the 3 fifth generation cephalosporins

A

ceftaroline

62
Q

What do first generation cephalosporins treat?

A
  • gram posiitve cocci [MSSA, GBS]
  • e coli
  • k pneumoniae
  • p mirabilis
63
Q

Which cephalosporins treat enterococcus?

A

none

64
Q

Which cephalosporins treat listeria?

A

none

65
Q

which cephalosporins treat MRSA?

A

ceftaroline [5th gen]

66
Q

How is cefazolin normally administered?

A

IV/injection

67
Q

What is cephelexin?

A

oral form of cefazolin

68
Q

Which cephalosporin is most active against gram positive cocci?

A

cefazolin [first gen]

69
Q

What bacteria is cefazolin active against?

A

gram pos cocci

  • methicillin susceptible s. aureus [MSSA]
  • strep species [GAS, GBC, s. viridians]

some agasint gram neg bacilli
- proteus mirabilis, e coli, klebsiella pneumoniae

70
Q

Is cefazolin susceptible or resistant to penicillinase?

A

resistant to penicillinase

71
Q

What disease is cefazoline commonly used to treat?

A
  • urinary tract infections
  • skin infections
  • surgical prophylaxis
  • bloodstream infections
72
Q

What are adverse reactions to cephaolosporins?

A
  • hypersensitivity –> get rash, allergic interstitial nephritis
  • some cross reactivity with penicillins [avoid in pts with type 1 hypersensitivity rxn to penicillins]
73
Q

What are two best drugs you could use for pt with history of IV drug abuse, abscess on arm from recent injection, gram + cocci in clusters? Why?

A
  • cefazolin or nafcillin [assuming its methicillin susceptible]

because this is probably staph aureus and these two drugs are penicillinase resistant

74
Q

What are two drugs of choice for GAS pharyngitis?

A
  • penicillin

- amoxicillin

75
Q

What is mech of action of vancomycin?

A
  • inhibits bacterial cell wall synthesis

- binds peptidoglycan D-Ala-D-Ala and prevents elongation and cross-linking

76
Q

What is mech of vancomycin resistance?

A
  • thickened cell wall

- altered peptidoglycan binding site [replace D-Ala-D-Ala with D-Ala-D-lactate]

77
Q

Is vancomycin active against gram + or - or both?

A

only gram + organisms

78
Q

When might you use vancomycin instead of B-lactam?

A

in patient with severe B lactam allergy

79
Q

Is vancomycin bacteriostatic or bactericidal?

A

slowly bactericidal against strep and staph

bacteriostatic against enterococci

80
Q

What two things is vancomycin drug of choice for?

A
  • MRSA

- penicillin-resistant pneumococcus

81
Q

What can oral form of vancomycin treat? not treat?

A
  • can treat c difficile colitis

- not absorbed by GI tract so can’t be used to treat systemic infections

82
Q

What are toxicities associated with vancomycin?

A
  • acute kidney injury [mostly when other nephrotoxic agents + unstable renal function]
  • hypersensitivity [red man syndrome, anaphylaxis]
83
Q

What is red man syndrome? What causes it?

A
  • side effect of vancomycin hypersensitivity
  • occurs with quick administration, can improve by slowing the infusion rate or pre-treatment wtih antihistamine
  • turn bright red from lots of histamine release
84
Q

What bugs does daptomycin treat? not treat?

A
  • treats gram-pos organisms: MSSA, MRSA, enterococcus, VRE

- does not treat gram neg organisms

85
Q

What is mech of daptomycin action?

A
  • uses Ca to bind cytoplasmic membrane
  • depolarized membrane
  • leads to release of intracellular ions and cell death
86
Q

Is daptomycin bactericidal or bacteriostatic?

A

rapidly bactericidal –> kills bugs in minutes

87
Q

Is daptomycin type or concentration dependent?

A

concentration dependent

88
Q

Can you use daptomycin for pneumonia?

A

No – because it is inactivated by pulmonary surfactant

89
Q

What infections does daptomycin treat?

A
  • skin or strep skin/soft tissue infections
  • MSSA or MRSA bloodstream infections
  • enterocci [including vancomycin-resistant ones]
90
Q

What are adverse reactions of daptomycin?

A
  • musculoskeletal –> muscle weakness, cramping, particularly at risk for patients on statins
91
Q

How do you monitor patient son daptomycin to check for musculoskeletal rxn?

A
  • monitor serum creatine phsophokinase [CPK] = breakdown of muscle breakdown
  • look for clinical signs of weakness
92
Q

Are inhibitors of protein synthesis active against gram + cocci? are they bacteriocidal? Are they active against MRSA?

A

yes, no , yes
they are active against gram + cocci
they are bacteriostatic
they are active against MRSA

93
Q

What are the 5 steps where protein synthesis can be inhibited?

A
  • initiation
  • elongation
  • transpeptidation
  • translocation
  • termination
94
Q

What drug inhibits protein synthesis initiation [ribosome starts reading mRNA]?

A

linezolid

95
Q

what drug inhibits protein synthesis elongation [new tRNA brought to ribosome]?

A

doxycycline

96
Q

what drug inhibits protein synthesis transpeptidation [formation peptide bond]?

A

clindamycin

97
Q

Are tetracyclines bacteriocidal or bacteriostatic? What types of bacteria are they active against?

A
  • bacteriostatic
  • active against gram + and -
  • also active against intracellular bacteria
98
Q

What types of diseases do tetracyclines treat?

A
  • skin and soft tissue infections

- atypical pneumonia, cholera, RMSA, chlamydia

99
Q

What is the major tetracycline?

A

doxycycline

100
Q

Is doxycycline given orally or in IV?

A

either

101
Q

What are a few things that patient should not consume when on oral doxycycline?

A
  • dairy [Ca], Na, Al, Fe, antacids

- because doxy forms chelate with cations that makes unabsorbable

102
Q

Where does doxycline concentrate? how big is vol of distribution? can it cross placenta?

A
  • concentrates in liver, kideny, skin, spleen
  • large volumed of D
  • can cross to placenta
  • can get into CSF
  • binds to teeth and bones undergoing calcification
103
Q

How is doxycycline eliminated?

A
  • hepatic metabolism, urinary excretion
104
Q

What are adverse affects of doxycycline?

A
  • GI discomfort
  • discoloration of teeth
  • hepatoxicity
  • photosensitivity
105
Q

Is clindamycin given oral or IV?

A

either

106
Q

What is clindamycin active against?

A
  • against anaerobic bacteria
  • non-enterococcal gram + cocci [potentially active against strep or staph]
  • no activity against enterococcus
107
Q

does clindamycin get into CSF?

A

not really – not in therapeutic level

108
Q

side effects clindamycin?

A
  • rash

- clostridium difficile colitis [has reputation for having this effect relatively commonly]

109
Q

If you have gram + cocci in pairs and chains in pt and no rxn to vancomycin and ampicillin-sulbactam what could the bug be?

A

some sort of enterococci that is resistant to ampicillin and to vancomycin – there is increasing vancomycin resistance

ampicillin: active against enterococci, gram + cocci susceptible to penicillin
vancomycin: gram + cocci, MRSA, penicillin resistant pneumococus, enterococcus

110
Q

What can you use to treat E. faecalis?

A

penicillin/ampicillin or vancomycin assuming susceptible, if not susceptible to one try treating with the other

111
Q

What can you use to treat E. faecium?

A

most are penicillin/ampicillin resistant so need to treat with other drug

  • linezolid
  • daptomycin
  • quinupristin/dalfopristin [rare to use]
112
Q

What drugs available to treat vancomycin resistant enterococci [VRE]?

A
  • linezolid
  • daptomycin
  • [rarely] quinupristin/dalfopristin for E. faecium only
113
Q

What is bioavailability of the oral form of linezolid?

A

high bioavailability = 100%

114
Q

Do you need to alter linezolid dosage for renal or hepatic disease?

A

NOPE – makes it good treatment for people with renal or hepatic disease

115
Q

What does linezolid treat?

A
  • skin and soft tissue infections
  • pneumonia
  • blood stream infections
  • gram + organisms including VRE, staph, strep
  • nocardia
  • non-TB myobacteria
  • TB
116
Q

What are the toxicities associated with linezolid?

A
  • thrombocytopenia and neutropenia after prolonged used [decreased platelets]
  • metabolic acidosis
  • serotonin syndrome in combo with SSRIs
117
Q

What is serotonin syndrome?

A
  • side effect of linezolid in combo with SSRI
  • 3 symptoms
    1. cognitivie: changes in metnal status
    2. autonomic: fever, hypertension, tachycardia
    3. somatic: tremor, hyperreflexia
118
Q

What are the 5 names for the primary folic acid antagonist used?

A
  • trimethoprim-sulfamethoxazole
  • co-trimoxazole
  • TMP-SMZ
  • bactrim
  • septra
119
Q

How do folic acid antagonists work?

A
  • cells cannot grow and divide without folate
  • bacteria synthesize folate, we get folate from our diet
  • folic acid antagonists inhibit steps along the folate synthesis pathway
120
Q

What is TMP-SMZ? bacteriostatic or bacteriocidal? what does it treat?

A
  • combo of sulfamethozaole and trimethoprim
  • bacteriostatic
  • treat MSSA/MRSA skin and soft tissue infections
  • can treat gram - activity
  • primarily used to treat UTIs
  • can treat pneumocystis jiroveci and nocardia spp
121
Q

How is TMP-SMZ absorbed? what is volume of distribution like?

A
  • oral or IV
  • intestinal absorption
  • large volume of distribution including CSF
122
Q

What is significance of TMP-SMZ entering CSF?

A
  • it is drug of choice for treating listeria infection in patient with B-lactam allergy
123
Q

What are side effects of TMP-SMZ?

A
  • hypersensitivity
  • rashes
  • hemolytic anemia
  • kernicterus
124
Q

Is TMP-SMZ safe for neonates and pregnant women?

A

no becuase it causes kernicterus [brain dysfunction]

125
Q

What are some drugs that can treat MRSA

A
  • vancomycin [drug of choice]
  • daptomycin
  • clindamycin
  • doxycycline
  • linezolid
  • TMP-SMZ
126
Q

Can vancomycin be used in patient with B-lactam hypersensitivity?

A

yes

127
Q

Is doxy safe for young children/pregnant women?

A

nope

128
Q

Does TMP-SMZ treat strep?

A

not reliable for strep– if you can’t tell whether a person has strep or staph infection might want to use another drug