Lec 5-6 Micro Tx Staph Strep Flashcards
1
Q
What is pharmacokinetics?
A
“what the body does to the drug”
- absorption, distribution, metabolism, elimination
2
Q
What is pharmacodynamics?
A
“What the drug does to the body [or organism]”
3
Q
What does it mean if an antimicrobial is concentration-dependent?
A
- increase in concentration causes increase in rate of bacterial killing
4
Q
3 examples of concentration-dependent antibiotics?
A
- daptomycin [lipopeptides]
- aminoglycosides
- fluoroquinolones
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
6
Q
What are 2 examples of time-dependent drugs?
A
- b lactams
- glycopeptides [vancomycin]
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
8
Q
What are 5 tests for antibiotic susceptibility
A
- broth macrodilution
- microdilution
- E test
- disk diffusion
- automated systems
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
10
Q
What is broth microdilution?
A
- uses idea of broth macrodilution but looking at multiple types of antibiotics as well as concentrations.
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
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
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
14
Q
What does bacteriostatic mean?
A
- arrests bacterial growth
- allows host immune system to kill bacteria
15
Q
What does bactericidal mean?
A
- kills the bacteria
- eradicates infection in absence of host defense mech
16
Q
Is linezolid bacteriostatic or bactericidal?
A
bacteriostatic
17
Q
Are B lactams bacteriostatic or bactericidal?
A
bactericidal
18
Q
Is vancomycin bacteriostatic or bactericidal?
A
both – it is bactericidal against some organisms and bacteriostatic against others
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
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
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
22
Q
What is the one type of penicillin that is completely absorbed after oral administration?
A
amoxicillin
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
24
Q
How is penicillin excreted normally? what is the one exception?
A
renal elimination
nafcillin is the exception – is not eliminated by renal
25
What are 4 main types of infections penicillin is used to treat?
- gram positive cocci, gram negative cocci, gram positive bacilli, spirochetes
26
What are 3 specific bacteria that penicillin is drug of choice for?
- streptococcus pyogenes [GAS]
- agalactiae [GBS]
- treponema pallidum [syphilis]
27
What is penicillin G?
intravenous penicillin [most important]
28
What is penicillin V?
oral penicillin --> stable in presence of acid
29
What are penicillinases? Whats a bacteria that they are commonly found in?
- penicillinases inactivate penicillin
| - found in staphylococcus aureus
30
What are some examples of anti-staphylococal penicillins?
nafcillin [most important]
oxacillin
dicloxacillin
31
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?
- penicillinase resistant
- drug of choice for staph aureus skin or bloodstream infections
- no gram-negative activity
32
What is MSSA?
methicillin susceptible staph aureus
33
What are some examples of extended spectrum [amino] penicillins?
- ampicillin and amoxicillin [oral]
34
What is significant about extended spectrum penicillins? what are they used to treat? are they active against gram negative/positive/anaerobes?
- treat gram-positive organisms [GAS and GBS]
- better gram-negative activity than natural penicillin
- some anaerobic activity
- active against enterococci
35
What is ampicillin used to treat primarily?
listeria monocytogenes
36
What are two drugs of choice for strep throat [strep pyogenes]?
- penicillin
| - amoxicillin
37
What 3 main things confer penicillin resistance?
- lack of peptidoglycan cell wall
- B lactamases
- decreased permeability to antibiotic
38
Why is mycoplasma inherently resistant to penicillin?
because mycoplasma lacks a cell wall --> penicillin works by attacking the cell wall so if no cell wall can't attack
39
What do B-lactamases do? How can they be passed on?
- hydrolyzed B-lactam ring
- gene encoding enzyme transferred via plasmid from one bacteria to another
- major causes of resistance in gram negatives
40
What are two mechs of decreased permeability in bacterial cell wall to antibiotic?
- change in outer membrane porin so drug can't enter
| - efflux pump so drug is leaving get lower conc in cell
41
What is mech of altered penicillin target?
- get mutation in PBP to reduce affinity
| - in MRSA get altered PBP [PBP2a] that lowers affinity for all B-lactams
42
What are 3 B-lactamase inhibitors?
- clavulanic acid
- sulbactam
- tazobactam
43
What do B-lactamase inhibitors do?
- contain a B-lactam ring
| - bind to B lactamases and prevent them binding antibiotic
44
Which B-lactamase inhibitor do you pair with ampicillin to increase gram negative activity?
ampicillin and sulbactam
45
Which B-lactamase inhibitor do you pair with amoxicillin to increase gram negative activity?
amoxicillin and clavulanic acid
46
What is mech of hypersensitivity rxn to penicillin?
- penicilloic acid [penicillin metabolite] causes an immune rxn
- get hives --> angioedema --> anaphylaxis
47
Which patients get maculopapular rash from amoxicillin?
pts with EBV associated mononucleosis
48
Why does penicillin cause diarrhea?
- get alterations in commensal flora
| - get clostridium difficile colitis
49
What is possible effect of penicillin on kidney
- interstitial nephritis
50
What is effect of penicillin on neuro?
causes neurotoxicitiy --> decreases seizure threshold
51
How are cephalosporins categorized?
- into 5 generations
- increased gram negative activity with higher generations
- 4th generation has good gram + and - activity
52
What is distribution volume of cephalosporins?
- very big volume of distribution
| - get into lungs, kidneys, joints, bone, cross placenta
53
which cephalosporins can cross blood brain barrier?
3rd and 4th generations
54
Is half life typically long or short for cephalosporins?
long half life, less frequent dosing [time dependent]
55
How are cephalosporins eliminated?
via renal excretion --> means that with renal insufficiency need dose adjustment
56
What is the exception to the rule that cephalosporins are all eliminated by kidney?
ceftriaxone
57
What are the two first generation cephaslosporins?
cefazolin
| cephalexin
58
What are the 3 second generation cephalosporins
cefuroxime
cefoxitin
cefotetan
59
What are the 3 third generation cephalosporins
cefotaxime
ceftriaxone
ceftazidime
60
What are the 3 fourth generation cephalosporins
cefepime
61
What are the 3 fifth generation cephalosporins
ceftaroline
62
What do first generation cephalosporins treat?
- gram posiitve cocci [MSSA, GBS]
- e coli
- k pneumoniae
- p mirabilis
63
Which cephalosporins treat enterococcus?
none
64
Which cephalosporins treat listeria?
none
65
which cephalosporins treat MRSA?
ceftaroline [5th gen]
66
How is cefazolin normally administered?
IV/injection
67
What is cephelexin?
oral form of cefazolin
68
Which cephalosporin is most active against gram positive cocci?
cefazolin [first gen]
69
What bacteria is cefazolin active against?
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
Is cefazolin susceptible or resistant to penicillinase?
resistant to penicillinase
71
What disease is cefazoline commonly used to treat?
- urinary tract infections
- skin infections
- surgical prophylaxis
- bloodstream infections
72
What are adverse reactions to cephaolosporins?
- hypersensitivity --> get rash, allergic interstitial nephritis
- some cross reactivity with penicillins [avoid in pts with type 1 hypersensitivity rxn to penicillins]
73
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?
- cefazolin or nafcillin [assuming its methicillin susceptible]
because this is probably staph aureus and these two drugs are penicillinase resistant
74
What are two drugs of choice for GAS pharyngitis?
- penicillin
| - amoxicillin
75
What is mech of action of vancomycin?
- inhibits bacterial cell wall synthesis
| - binds peptidoglycan D-Ala-D-Ala and prevents elongation and cross-linking
76
What is mech of vancomycin resistance?
- thickened cell wall
| - altered peptidoglycan binding site [replace D-Ala-D-Ala with D-Ala-D-lactate]
77
Is vancomycin active against gram + or - or both?
only gram + organisms
78
When might you use vancomycin instead of B-lactam?
in patient with severe B lactam allergy
79
Is vancomycin bacteriostatic or bactericidal?
slowly bactericidal against strep and staph
| bacteriostatic against enterococci
80
What two things is vancomycin drug of choice for?
- MRSA
| - penicillin-resistant pneumococcus
81
What can oral form of vancomycin treat? not treat?
- can treat c difficile colitis
| - not absorbed by GI tract so can't be used to treat systemic infections
82
What are toxicities associated with vancomycin?
- acute kidney injury [mostly when other nephrotoxic agents + unstable renal function]
- hypersensitivity [red man syndrome, anaphylaxis]
83
What is red man syndrome? What causes it?
- 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
What bugs does daptomycin treat? not treat?
- treats gram-pos organisms: MSSA, MRSA, enterococcus, VRE
| - does not treat gram neg organisms
85
What is mech of daptomycin action?
- uses Ca to bind cytoplasmic membrane
- depolarized membrane
- leads to release of intracellular ions and cell death
86
Is daptomycin bactericidal or bacteriostatic?
rapidly bactericidal --> kills bugs in minutes
87
Is daptomycin type or concentration dependent?
concentration dependent
88
Can you use daptomycin for pneumonia?
No -- because it is inactivated by pulmonary surfactant
89
What infections does daptomycin treat?
- skin or strep skin/soft tissue infections
- MSSA or MRSA bloodstream infections
- enterocci [including vancomycin-resistant ones]
90
What are adverse reactions of daptomycin?
- musculoskeletal --> muscle weakness, cramping, particularly at risk for patients on statins
91
How do you monitor patient son daptomycin to check for musculoskeletal rxn?
- monitor serum creatine phsophokinase [CPK] = breakdown of muscle breakdown
- look for clinical signs of weakness
92
Are inhibitors of protein synthesis active against gram + cocci? are they bacteriocidal? Are they active against MRSA?
yes, no , yes
they are active against gram + cocci
they are bacteriostatic
they are active against MRSA
93
What are the 5 steps where protein synthesis can be inhibited?
- initiation
- elongation
- transpeptidation
- translocation
- termination
94
What drug inhibits protein synthesis initiation [ribosome starts reading mRNA]?
linezolid
95
what drug inhibits protein synthesis elongation [new tRNA brought to ribosome]?
doxycycline
96
what drug inhibits protein synthesis transpeptidation [formation peptide bond]?
clindamycin
97
Are tetracyclines bacteriocidal or bacteriostatic? What types of bacteria are they active against?
- bacteriostatic
- active against gram + and -
- also active against intracellular bacteria
98
What types of diseases do tetracyclines treat?
- skin and soft tissue infections
| - atypical pneumonia, cholera, RMSA, chlamydia
99
What is the major tetracycline?
doxycycline
100
Is doxycycline given orally or in IV?
either
101
What are a few things that patient should not consume when on oral doxycycline?
- dairy [Ca], Na, Al, Fe, antacids
| - because doxy forms chelate with cations that makes unabsorbable
102
Where does doxycline concentrate? how big is vol of distribution? can it cross placenta?
- 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
How is doxycycline eliminated?
- hepatic metabolism, urinary excretion
104
What are adverse affects of doxycycline?
- GI discomfort
- discoloration of teeth
- hepatoxicity
- photosensitivity
105
Is clindamycin given oral or IV?
either
106
What is clindamycin active against?
- against anaerobic bacteria
- non-enterococcal gram + cocci [potentially active against strep or staph]
- no activity against enterococcus
107
does clindamycin get into CSF?
not really -- not in therapeutic level
108
side effects clindamycin?
- rash
| - clostridium difficile colitis [has reputation for having this effect relatively commonly]
109
If you have gram + cocci in pairs and chains in pt and no rxn to vancomycin and ampicillin-sulbactam what could the bug be?
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
What can you use to treat E. faecalis?
penicillin/ampicillin or vancomycin assuming susceptible, if not susceptible to one try treating with the other
111
What can you use to treat E. faecium?
most are penicillin/ampicillin resistant so need to treat with other drug
- linezolid
- daptomycin
- quinupristin/dalfopristin [rare to use]
112
What drugs available to treat vancomycin resistant enterococci [VRE]?
- linezolid
- daptomycin
- [rarely] quinupristin/dalfopristin for E. faecium only
113
What is bioavailability of the oral form of linezolid?
high bioavailability = 100%
114
Do you need to alter linezolid dosage for renal or hepatic disease?
NOPE -- makes it good treatment for people with renal or hepatic disease
115
What does linezolid treat?
- skin and soft tissue infections
- pneumonia
- blood stream infections
- gram + organisms including VRE, staph, strep
- nocardia
- non-TB myobacteria
- TB
116
What are the toxicities associated with linezolid?
- thrombocytopenia and neutropenia after prolonged used [decreased platelets]
- metabolic acidosis
- serotonin syndrome in combo with SSRIs
117
What is serotonin syndrome?
- 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
What are the 5 names for the primary folic acid antagonist used?
- trimethoprim-sulfamethoxazole
- co-trimoxazole
- TMP-SMZ
- bactrim
- septra
119
How do folic acid antagonists work?
- 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
What is TMP-SMZ? bacteriostatic or bacteriocidal? what does it treat?
- 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
How is TMP-SMZ absorbed? what is volume of distribution like?
- oral or IV
- intestinal absorption
- large volume of distribution including CSF
122
What is significance of TMP-SMZ entering CSF?
- it is drug of choice for treating listeria infection in patient with B-lactam allergy
123
What are side effects of TMP-SMZ?
- hypersensitivity
- rashes
- hemolytic anemia
- kernicterus
124
Is TMP-SMZ safe for neonates and pregnant women?
no becuase it causes kernicterus [brain dysfunction]
125
What are some drugs that can treat MRSA
- vancomycin [drug of choice]
- daptomycin
- clindamycin
- doxycycline
- linezolid
- TMP-SMZ
126
Can vancomycin be used in patient with B-lactam hypersensitivity?
yes
127
Is doxy safe for young children/pregnant women?
nope
128
Does TMP-SMZ treat strep?
not reliable for strep-- if you can't tell whether a person has strep or staph infection might want to use another drug
