Antibiotics Flashcards
1
Q
What is the structure of penicillin?
A
- Thiazolidine ring
- B-lactam ring
2
Q
What is the mechanism of action of B-lactams?
A
- interact with enzymes localized in cell membrane whose action is to build the cell wall
- prevents peptidoglycan synthesis (Gm +)
3
Q
What is the dose of antibiotics limited by?
A
Toxicity
4
Q
What is the minimum inhibitory concentration (MIC) of an antibiotic?
A
the lowest concentration of antibiotic that, under certain in vitro test conditions, inhibits further bacterial growth
5
Q
What is the minimum bactericidal concentration (MBC) of an antibiotic?
A
lowest concentration that kills bacteria
6
Q
In which diseases is the bactericidal effect thought to be important (relative to bacteriostatic effect)?
A
- endocarditis (only bacterial infection for which bacterial effect is absolutely necessary for a cure)
- meningitis or osteomylitis
- neutropenia
7
Q
What is Penicillin G?
A
- benzyl penicillin
- first form of penicillin used in humans
- aqueous
- most destroyed by gastric acid, so given IV
8
Q
What is penicillin V?
A
- add a phenoxy group to side chain of penicillin G
- can be given orally b/c it resists acid
9
Q
What does probenecid do?
A
- delays excretion of penicillin at renal tubules
- Musher has never used it, doesn’t think its necessary
10
Q
Where does penicillin go in the body (distribution)?
A
-distributes to EFC (22% of lean body weight)
11
Q
How rapidly is penicillin excreted (clearance)?
A
T1/2 = 20 minutes
-excreted via kidney
12
Q
By percentage of body weight, how much ECF do we have?
A
22% (15 liters)
13
Q
Why does penicillin only distribute to ECF?
A
- cell membranes exclude it
- polar molecule
14
Q
What conditions are associated with greatly increased ECF?
A
- Heart failure
- cirrhosis w/ ascites
- renal failure *doses of abx need to be adjusted to reflect this
15
Q
How is penicillin excreted?
A
100% Kidney
*keep creatinine clearance and kidney failure in mind
16
Q
Why is the peak concentration of penicillin much lower than expected?
A
- half life of 20 minutes
- infusion takes 20-30 minutes
17
Q
How should penicillin be administered? Why?
A
- IV at close intervals, usually 4hrs
- Keeps concentration above MIC about 2/3 of the time
18
Q
if you double the dose of IV penicillin, you only add ___________ of coverage
A
20 min (= one half-life)
19
Q
So, if you want to increase the concentration of penicillin, how do you do it?
A
- shorten the dosing interval
- doubling dose will only add 20 min of coverage
20
Q
How is nafcillin excreted?
A
-Kidney AND liver
21
Q
What are the pharmakinetic advantages and disadvantages of amoxicillin over penicillin?
A
- lower peak concentration
- level above MIC may be more sustained because drug is being absorbed in GI tract as its being excreted
- nearly 100% is absorbed in GI tract
22
Q
What are procaine and benzathine penicillin designed for?
A
-slow absorption from injection site
23
Q
What are the three factors that determine the outcome of treatment with antibiotics?
A
1) time that tissue levels exceed MIC
2) peak level of concentration (sometimes binding is irreversible above certain concentration)
3) area under the curve above MIC. (ex. both duration and height of level of quinolones)
24
Q
Beta-lactams. Must exceed MIC for ______ of treatment period.
A
>60%
25
Antibiotic resistance may arise by __________ or by acquisition of \_\_\_\_\_\_\_\_\_\_\_.
- point mutation
- genetic material
26
What are the general mechanisms of bacterial resistance to antibiotics?
1) make an enzyme that disrupts Abx at active site.
2) alter site at which abx act
3) generate new pathway that bypasses the one blocked by abx (MRSA)
4) alter entrance of antibiotic into bacterium (porins)
5) increase rate with which abx is pumped out of the bacterium
27
Resistance of pneumococci to beta-lactam antibiotics is of concern in \_\_\_\_\_\_\_\_\_\_\_\_\_\_, not in pneumonia, sinusitis or otitis media
meningitis (antibiotic passage across blood-brain barrier)
28
What are bacterial porins?
1. Porins are protein channels of outer membrane
2. Transport polar molecules into periplasmic space; from there, diffuse through cell wall into cytoplasm
3. Mechanism only for gram **_negative_** rods; Gram positive bacteria do not have them
29
Which -cillins are resistant to B-lactamase?
- Methicillin
- Nafcillin
- oxacillin
30
What drug is usually used against methicillin-susceptible S. aureus?
Nafcillin
31
Which drugs is MRSA resistant to?
- all penicilins
- cephalosporins (except ceftaroline)
- carbapenems
32
What is the half life of Amoxicillin?
45-60 minutes
33
What types of organisms is ampicillin good against?
Gm (-) organisms
34
What is piperacillin used against?
- Gm (-) rods
- pseudomonas
\*\*widely used in TMC, especially with B-lactamase inhibitor (tazobactam)
35
What are the B-lactamase inhibitors?
- clavulanic acid
- sulbactam
- tazobactam
36
What is Augmentin made of?
-Amoxicillin + Clavulanic acid (b-lactamase blocker)
37
Can Augmentin be used against MRSA?
no
38
What is Unasyn?
-Ampicillin + sulbactam
39
What is Zosyn?
Piperacililn + tazobactam
40
What are the adverse effects of penicillin?
- skin rash (10%)
- anaphylaxis (0.01%)
41
What is the structure of cephalospornis?
- four membered ring attached to a six membered ring
- side chain on four-membered ring
42
What are the first generation cephalosporins?
- Cefazolin
- Cephalexin (oral cefazolin)
43
What is Cefazolin used against?
- non-MRSA Staph aureus
- Group A strep, & other soft tissue infections
- Gm (-) rods
\*\*no effect against enterococcus
44
What is antibiotic prophylaxis for surgery?
-give abx before surgery so that it is in the tissues at the time of surgery
45
What is cephalexin?
-oral version of cefazolin
46
What are the third generation of cephalosporins?
- cefotaxime (Claforan)
- ceftriaxone (Rocephin)
- cefpodoxime (Vantin) = oral
- ceftazidime (pseudo)
47
What are third generation cephalosporins effective against?
- Strep
- pneumo
- Haemophilus
- Moraxella
- Gonococci
- Lyme disease
- Gram negative rods (except Pseudomonas)
48
What is the half life of Ceftriaxone?
6-8 hours
\*can be given every 24 hours
49
What cephalosporins are good against pseudomonas?
- Ceftazidime (3G)
- Cefepime (4G)
- ceftaroline (5G) (MRSA)
50
Does penicillin cross the blood brain barrier?
Not very well
51
Inflammation decreases the rate at which the choroid plexus pump removes _________ from CSF, so, during meningitis, antibiotic levels persist whereas in the absence of meningitis they are rapidly cleared.
antibiotics
52
Does ceftriaxone cross the blood-brain barrier?
- yes
- good for meningitis
53
What is Cefpodoxime?
-Oral 3rd generation cephalosporin
54
What are the fourth generation cephalosporins?
-cefepime
55
When is cefepime used?
-like ceftriaxone, but with a good effect against pseudomonas
\*really only used for pseudomonas
56
What is ceftaroline?
- "fifth generation" cephalosporin
- has all properties of cefepime, but ALSO active against MRSA
57
What are ESBL bacteria?
- extended spectrum beta lactamase
- resistant to all beta-lactamases (penicillins & cephalosporins)
\*big problem
58
Many cephalosporins have capacity to induce bacterial production of \_\_\_\_\_\_\_\_\_\_\_\_\_.
cephalosporinases
59
What are the side effects and drug reactions of cephalosporins?
- most common is skin rash
- drug fever is #2
- don't give ceph if pt has had life threatening rxn to penicillin)
60
Which penicillins are good against pseudomonas?
- piperacillin
- ticarcillin
61
How do we treat syphilis?
benzathine penicillin
62
How do we know which antibiotics are carbapenems?
-they all end in penem
63
What is Primaxin?
-Compination of imipenem and cilastatin
64
How do carbapenems work?
-bind all known penicillin binding proteins EXCEPT PBP2a (MRSA)
65
Are carbapenems effective against bacteria with beta-lactamases?
-yes
\*carbapenemases have appeared though
66
Are carbapenems effective against E. faecalis?
Yes
67
Are carbapenems effective against MRSA?
No
68
Are carbapenems effective against pseudomonas?
yes
69
What is Aztreonam useful against?
- Pseudomonas
- NOT enterococcus
70
What element do aminoglycosides require?
oxygen
71
How do aminoglycosides work?
Irreversibly bind to 30s ribosomal subunit at interface of 30s and 50s subunits
72
What is an example of synergism involving aminoglycosides?
- Aminoglycosides + B-lactams
- B-lactam alters cell wall, allows high concentrations of aminoglycoside to enter cell
- fights Enterococcus and other Gm (+) bacteria
73
What class of abx is streptomycin?
Aminoglycoside
74
What was streptomycin first developed as?
an antituberculosis agent
75
What kind of bacteria is streptomycin good against?
Gm (-) rods
\*limited by rapid selection to resistance
76
What are the adverse effects of all aminoglycosides?
- Nephrotoxicity
- CN 8 damage
\*\*\*dosage must be reduced in renal insufficiency
77
What organ clears aminoglycosides?
Kidneys
78
What bugs is gentamicin good against?
- nearly all communit Gm (-) rods and most nosocomial
- pseudomonas
79
What is a good initial therapy for serious UTI?
Gentamicin
80
What class of drug is gentamicin?
Aminoglycoside
81
Why is it ok if aminoglycoside levels are not above the MIC for the majority of time?
- irreverisbly binds ribosome
- bacteriocidial capability depends on peak concentration, NOT time above MIC
82
What class of drug is Amikacin?
Aminoglycoside
83
What is Amikacin used for?
-nosocomial or comm acquired Gm (-) infection
84
When are aminoglycosides used?
-againsed Gm (-) rod infections but generally only if not susceptible to other drugs (fear of toxicity)
85
Vancomycin resistant bacteria have gene ______ which encodes formation of terminal ________ instead of D-ala; thus vancomcyin does not bind.
- VanA
- lactate
86
What is vancomycin good against?
- MRSA
- NOT better than penicillins in staph infection s that are methicillin susceptible
- works on pretty much everything except VRE
87
Why do we need to measure Vancomycin levels when giving to patients?
- It distributes to fat as well
- need to base dosage on TOTAL body mass, not just lean mass
88
What drug is added to vancomycin for synergy against Staph aureus?
gentamicin
89
Do not use vancomycin for "empiric" therapy unless:
- infection is serious AND
- there is good reason to believe that it is due to an organism that will be resistant to other Abx
90
(T/F) Every pneumococcus is susceptible to vancomycin.
True
\*but still give ceftriaxone b/c vanc can't cross BBB as well
91
What is Panton-Valentine Toxin?
- seen in CA-MRSA
- causes necrotic lesions of skin and mucos
\*\*produced from genetic material of a bacteriophage
92
PNEUMOLYSIN
- know that all pneumococci produce it
- if we block its production, pneumococci are no longer virulent
- animal studies show cure to pneumococcal disease if they have antibody to it
- inhibits PMN function
93
What toxicities do we watch for with Polymyxins?
-Nephro and neurotoxic
94
What are Polymyxins good against?
Gm (-) rods, especially ones that are resistant to other abx
95
What drugs are Polymyxins?
- Polymyxin
- colistin
96
What drugs are the advanced macrolides?
- clarithromycin (Biaxin)
- azithromycin (Zithromax/Z-pack)
97
Macrolides are \_\_\_\_\_\_\_\_for Staph aureus. \_\_\_\_\_\_\_\_\_\_for pneumococcus, Haemophilus
- bacteriostatic
- Bactericidal
98
How do macrolides prevent biofilm production by pseudomonas?
-block alginate
99
Why are macrolides used in CF patients?
-it prevents biofilm production by pseudomonas
100
What are the two clinically important forms of resistance to macrolides?
- efflux pump (**mef** gene)
- Erythromycin ribosome methylation, alters attachment site (**erm** gene)
101
What is azithromycin useful against?
- Haemophilus
- Moraxella
- N. gonorrhoeae
- Legionella
- Mycoplasma
- Chlamydia
- Mycobacterium avium-intracellulare (MAC)
102
Why are macrolides good against intracellular pathogens?
-they are taken up by macrophages
103
What are the adverse effects of Macrolides?
- nausea
- vomiting
- prolonged Q-T interval
- sudden death (VERY rare)
104
What class of drug is Clindamycin?
-lincosamide
105
What is clyindamycin effective against?
- Gm (+) bacteria
- Most CA-MRSA
- most anaerobic bacteria
106
In which clinical scenarios is clindamycin useful?
- Intraabdominal infection
- aspiration pneumonia
- w/ penicillin in Streptococcal gangrene (necrotizing fasciitis (group A))
107
What drug is most likely to cause C. diff colitis?
Clindamycin
108
What is the black box warning on Ketolides for?
Liver failure
109
What is linezolid effective against?
- Gm (+) organisms
- S. aureus & MRSA
- Coag (-) staph
- pneumococci
- enterococci
\*\*expensive
110
What are the adverse effects of linezolid?
-bone marrow suppression, especially platelets
111
What drug is used for N. meningitis prophylaxis of nasal carriage in an outbreak situation?
Rifampin
112
Why can't rifampin be used as a single drug?
rapid emergence of resistance
113
What is Rifabutin used for?
Mycobacterium avium/intracellular (MAC)
114
When is rifampin used?
- TB
- Meningococci prophylaxis
- Difficult staph associated with foreign body (prosthetics)
- Coating of impregnating implantable devices
115
What are the adverse effects of rifampin?
- turns urine and tears orange
- Stains soft contact lenses
116
What are the tetracyclines?
- doxycycline
- minocycline
117
What are tetracyclines effective against?
- pneumococci
- Haemophilus & moraxella
- Staph aureus including MRSA
- Legionella, mycoplasma, chlamydia
- brucella
- Rickettsiae, ehrlichia, anaplasma
118
What is Septra/Bactrim?
-combination of sulfamethoxazole plus trimethoprim
119
How does sulfamethoxazole work?
-inhibits synthesis of tetrahydrofolic acid (needed for synthesis of thymidine)
120
What bugs are sulfa drugs and trimethoprim effective against?
- S. aureus soft tissue infections (including MRSA)
- Group A strep in vitro, poor in vivo though (strep break down human tissue to get thymidine)
121
What are the recommended clinical uses for sulfa/trimethoprim?
- uncomplicated UTI
- pneumonia caused by Pneumocystis jiroveci
- Nocardosis
122
What are the adverse effects of sulfa/trimethoprim?
- Stevens Johnson syndrome (idiosyncratic)
- Renal insufficiency (dose-related)
123
How are quinolones given?
-orally, they are well absorbed
\*except in surgical pt's who cannot swallow
124
What bugs are quinolones good against?
- Gram (-) rods
- good against biofilms
125
What clinical scenarios are quinolones used?
- UTI
- CA-intraabdominal infection
- biofilm
- Atypical pneumonia
126
What antibiotic is causing problems because farmers are adding it to animal feed?
quinolones
127
What's a super awesome treatment against biofilm formation?
-combination of quinolone with rifampin
128
What are the adverse effects of quinolones?
- prolonged Q-T interval (be careful in conjunction w/ Ca channel blockers)
- Tendonitis & achilles rupture
- Drug-drug interaction; increased risk of bleeding in pt's on warfarin (vitamin K)
\*\*prophylaxis in pt's w/ prolonged neutropenia or cirrhosis, ascites, and prior spont. bacterial peritonitis
129
What drug is in the class of Lipopeptides?
Daptomycin
130
What class of drug is Daptomycin?
Lipopeptide
131
What class of drug is Daptomycin?
Lipopeptide
132
Why can't we use daptomycin to treat pneumonia?
-it is inactivated by surfactant
133
What is Daptomycin good against?
-S. aureus and MRSA
134
What are the adverse effects of Daptomycin?
- muscle pain
- elevation of enzymes indicating muscle damage (Cr. phosphokinase)
135
What class of antibiotics ends in "-vancin"?
Lipoglycopeptides
136
What is the mechanism of action of Lipoglycopeptides?
1) block peptidoglycan synthesis (same as vanc)
2) alter cell membrane (dame as daptomycin)
137
What is metronidazole good against?
- intraabdominal infections
- Trichomonas vaginalis
138
What are the adverse effects of metronidazole?
- relatively nontoxic
- causes a bad taste in the mouth
139
What is fidaxomycin used to treat?
- C. diff ONLY
- better than vanc (lower rate of relapse)
140
What are the two topical antibiotics?
- Bacitracin
- Mupurocin
