Sweatman Antimicrobial Reading Flashcards
(164 cards)
1
Q
What does mutations in penicillin binding proteins have in common with methylation of ribosomal subunits?
A
they are alterations that microbes have developed to subvert the target of antibiotics = 2 ways microbes have developed resistance
2
Q
How have microbes decreased the entry of a drug or forced the efflux of a drug?
A
altered their porin structure (to resist cell wall synthesis inhibitors) and they have developed efflux pumps to remove the drug (tetracylines)
3
Q
Microbes have become resistant to sulfa drugs by…
A
aquiring alternative metabolic pathways to bypass the pathway sulfa drugs block (they block folate synthesis)
4
Q
What are 2 ways that microbes can keep drugs inactive?
A
- cause a failure for the prodrug to convert to it’s active form (isoniazid)
- inactivate a drug (penicillin by B-lactamase)
5
Q
WHat are the 3 major factors to consider when selecting an anti-infective?
A
- microorganism factors
- host factors
- drug factors
6
Q
Factors to consider when selecting anti-microbial: Microorganism factors (2)
A
- ID organism
2. susceptibility of organism
7
Q
Factors to consider when selecting anti-microbial: Host factors (8)
A
- Drug allergies
- pharmacokinetic variables
- effect of food on drug
- effect of other drugs
- renal/hepatic function
- pregnancy/lactation
- signs and symptoms
- Fever, malaise, leukocytosis, pus
8
Q
Factors to consider when selecting anti-microbial: Drug factors (6)
A
- economics
- tissue penetration
- drug toxicity
- preventing resistance
- bad drug combos
9
Q
What are the 4 major mechanisms of action for antimicrobials?
A
- inhibition of cell wall synthesis (i.e. must have proliferating pop of microbes)
- inhibition of protein synthesis
- inhibition of folic acid biosynthetic pathways
- inhibition of DNA/RNA synthesis
10
Q
T or F: Sometimes, you need to combine drugs that work by different mechanisms of action to achieve synergistic killing effects
A
true
11
Q
What are the 5 classes that interfere with cell wall synthesis?
A
penicilins chephlasporins carbapenems monobactams vancomyosins
12
Q
Describe penicillin’s mechanism of action.
A
they bind to transpeptidase to inhibits the crosslinking of NAM and NAG
(they also activate the autolysins, carboxypeptidases, and endopeptidases that hydrolyze and destroy components of the cell wall)
13
Q
What are penicillin binding proteins?
A
bacterial proteins that penicillin binds
14
Q
T or F: for penicillins to function, they must penetrate the cell wall.
A
true
15
Q
What are the 4 ways bacteria may become resistant to penicillins?
A
- modification of their PBPs
- active pumping of drugs back out of cells
- developing B-lactamases to cleave of the B-lactam ring structure (this occurs w/in the periplasmic space)
- altered porins (gram - bac only) that prevent the drugs from reaching the PBPs
16
Q
What is the MIC?
A
minimum inhibitory concentration = lowest conc of an antimicrobial that will inhibit the visible growth of a microog after overnight incubation
17
Q
T or F: the lower the MIC, the better the antimicrobial agent.
A
true: a lower conc is needed to stop the growth the microbe
18
Q
What is the MBC?
A
minimum bactericidal concentration = lowest conc of antibiotic required to kill a particular bacterium
19
Q
What is the difference between MIC and MBC?
A
MIC is the lowest conc of drug needed to stop the bac from reproducing and MBC is the lowest conc of antibiotic needed to kill the microbe
20
Q
Describe the quantitative method of susceptibility testing.
A
a single colony of bacteria added into liquid cultures in varying antibiotic conc. The lowest conc in which there is no visible growth = MIC.
The remaining liquid cultures are plated onto agar that contains no antibiotic. The lowest dose/conc of the liquid antibiotic dilution in which bacteria does not grow on the petri dish = MBC.
21
Q
Describe the qualitative method of susceptibility testing.
A
Disks with “impregnated” drugs are placed onto a petri dish that has been swabbed with bacteria. After incubation, the size of zones of inhibition around the disks indicate the bacterial susceptibility of the drug
22
Q
What drugs target cell wall synthesis?
A
B-lactams (penicillin, cepthalasporins, carbapenems, monobactams) and Vancomyosin
23
Q
What drugs inhibit folic acid synthesis?
A
trimethoprim
sulfonamides
24
Q
What 2 enzymes are targeted to inhibit DNA/RNA synthesis?
A
DNA gyrase
DNA-directed RNA polymerase
25
What drug targets DNA gyrase?
quinolones
26
What drug targets DNA-directed RNA polymerase?
rifampin
27
What drugs inhibit protein syntheis by binding the 50S ribosomal subunit?
```
chloramphenicol
macrolides
lincosamides
ketolides
Retapamulin
linezolid
```
28
What drugs target the 30S ribosomal subunit?
tetracylines
| aminoglycosides
29
Should penicillin be combined with tetracycline?
No. Tetracycline is bacteriostatic so it woud antagonize the penicillin
30
Why are oral contraceptives less effective when taken with an antibiotic?
Gut flora becomes disrupted and the enterohepatic recirculation of estrogenic components becomes impaired--> decreasing t1/2 of the OC --> less duration of action --> betta wrap that junk!
**Under normal circumstances, gut flora cleave estrogen-glucuronide conjugates to allow the estrogenic component to be absorbed. This cleavage decreases with decreasing gut flora function during antibiotic therapy
31
What are the 4 subclasses of penicillins?
1. natural penicillins
2. aminopenicillins
3. penicillinase-resistant penicillins
4. antipseudomonal penicillins
32
Why would you want to co-administer penicillin with an irreversible B-lactamase inhibitor?
broadens the antimicrobial spectrum to include coverage of B-lactasmase producing organisms
33
What types of penicillin is used to treat gram positive microorganisms?
natural penicillins and penicillinase-resistant penicillins
34
What cell wall synthesis inhibitors are used to fight infections with gram - bacteria?
Aminopenicillins
Antipseudomonal
Cycloserine
Polymixin B
35
What are examples of natural penicillins?
penicillin G and penicillin V
36
Why must penicillin ___ must be administered by IV. Why?
G: it is readily destroyed in acidic environments (i.e. digestive tract)
37
IM injections of penicillin G are used to prevent ____ and treat ____
rheumatic fever
| syphilis
38
How is penicillin V be administered?
orally but on an empty stomach (1 hr before meals or 2-3 hrs after meals for maximal efficacy)
39
What are examples of aminopenicillins?
ampicillin and amoxicillin
40
How is ampicillin administered?
enterally or parenterally; if oral, must be on an empty stomach
41
Which aminopenicillin can be taken with or without food?
amoxicililin
42
What are examples of penicillinase-resistant penicillins?
dicloxacillin
methicillin
oxacillin
nafcillin
43
What is the MOA for penicillinase-resistant penicillins?
they contain side groups that protect the drugs from being inactivated by B-lactamases
44
How is methicillin usually administered?
parenterally
45
How is dicloxacillin usually administered?
orally
46
How is oxacillin usually administered?
parenterally
47
How is nafcillin usually administered?
parenterally
48
Where do B-lactamases reside?
periplasmic space
49
What are the 2 effects penicllin binding PBPs has?
1. blocks transpeptidase of peptidoglycan to prevent cell wall syntheis
2. activates autolytic enzymes in the cell wall that cause lesions --> bacterial cell death
50
What are examples of antipseudomonal penicillins?
carbenicillin
ticarcillin
mezlocillin
piperacillin
51
How are antipseudomonal penicillins usually administered?
parenterally
carbenicillin the the only one to be administered orally (but therapeutic levels are only found in the uninary tract = treatment only for UTIs and prostate infections
52
What penicillin is restricted to treating UTIs an prostate infections?
carbenicillin
53
T or F: Irreversible B-lactamases can be administered as a stand alone antimicrobial therapy.
False: they are have no anti-microbial activity by themselves. They need to be co-administered with penicillins to expand coverage against B-lactamase resistant microorgs
54
Cephlophlasporins structurally resemble ____ because they possess _____
penicillins bc they have a B-lactam chemical backbone
55
How are cephalopsorins different than penicillins?
cephalosporins are relatively stable to pH changes and may be taken with or without food
56
What drugs are irreversible inhibitors of B-lactamases?
clavulanic acid
sulbactam
tazobactam
57
Why can penicillin-allergic patients also be hypersensitive to cephalosporins?
bc of their structural similarities
58
T or F: As a rule, it is wise to refrain from prescribing ______ to patients with a well documented history of anaphylactic reactions to penicillins.
cephalosporins
59
Other than allergic reactions, what are some adverse effects of cephalosporins? (7)
1. GI irritation
2. local irritation at the site of injection
3. renal toxicity (bc excreted by kidneys) = trouble for pt. with kidney disease
4. disulfriam-like reactions
5. hypoprothrombinemia
6. seizures in pt with impaired kidney function (bc drug accumulates)
7. 2ndary infections (disrupt normal flora)
60
What are examples of carbapenems?
imipenem/cilastatin
doripenem
ertapenem
meropenem
61
T or F: Carbapenems are bacteriostatic and inhibit cell wall synthesis.
False: they are bactericidal
62
How are carbapenems different then penicillin and cephalosporins?
they have a different stereochemical structure in their B-lactam ring that renders them resistant to B-lactamases
63
What drugs interfere with cell wall synthesis by blocking polymerization and crosslinking by binding to D-ala D-ala portion of the cell walls?
telavancin
| vancomycin
64
What are the MOA for telavancin?
1. blocking polymerization and cross-linking by binding D-ala pair
2. disruption of the cell membrane potential and changes in cell permeability bc of the presence of a lipophillic side chain moiety
65
WHat is the MOA for cycloserine?
inhibits cell wall synthesis in gram-NEG microbes but is usually reserved for treating TB infections resistant to first line anti-tubercular drugs
66
What is the MOA for polymyxin B? What kind of microbes does it target?
It is a cationic detergent that disrupts the lipoproteins in bacterial cell walls --> inc membrane permeability
bactericidal to nearly all gram-neg bacilli with the exception of Proteus
67
What are examples of aminoglycosides?
```
amikacin
gentamicin
kanamycin
netilmicin
streptomycin
tobramycin
neomycin
```
68
What is the MOA for aminoglycosides?
Bind to bacterial 30s and interferes with protein synthesis in at least 3 ways:
1. formation of the initiation complex
2. misread mRNA and miscode aa in the growing peptides
3. cause ribosomes to separate from mRNA--> monosome = inefficient protein synthesis
69
How are aminoglycosides typically administered? Why?
parenterally because they are too water soluble to be given orally
70
Where do aminoglycosides accumulate?
inner ear and renal cortex
| *accounts for nephrotoxic and ototoxic side effects
71
What is the postantibiotic effect?
microbes continue to die even as plasma levels of the drug decline
72
T or F: aminoglycosides exhibit the post-antibiotic effect.
true
73
What type of microbes are aminoglycosides used to treat?
ONLY gram-negative
74
What general type of bacteria have developed a resistance to aminoglycosides?
anaerobes (they have altered receptor proteins on their ribosomes that prevent the drug from binding
or any bacteria that have enzymatically or postranslationally altered the drug (via phosphorylation, acetylation, etc.) which interferes with the drug's ability to efficiently bind the ribosomal subunits
75
What are examples of tetracycline?
(all ending with -cycline)
76
What is the MOA of tetracycline?
inhibit protein synthesis by reversibly bindind the 30S subunit to prevent the binding of new/incoming aa = interferes with peptide growth
*blocks the A site
77
What are glycyclines?
antibiotics derived from tetracycline that are designed to overcome resistance medated by efflux pumps and ribosomal protection
78
What tetracycline derivative most closely structurally resembles minocycline?
tigecycline
79
T or F: tetracyclines are bactericidal only to gram negatives microbes.
False: they are BACTERIOSTATIC to both gram neg and gram pos
80
How does tetracycline enter a gram neg cell? gram positive?
neg: passive diffusion
pos: active transport
81
What limits gastric absorption of tetracycline?
chelation due to divalent cations (iron, Al, Mg, CALCIUM CONTAINING ANTACIDS and MILK or bile acid resins
82
What tetracycline is the safest option for patients in renal dysfunction? Why?
doxycycline bc it is metabolized hepatically and excreted in the feces
83
What mech of resistance do gram positives use against tetracycline?
efflux pump
84
What mech of resistance do gram negatives use against tetracycline?
changes to outer membrane that prevent tetracylines from entering.
85
T or F: Minocycline is not affected by tetracycline resistance mechanisms?
False: tigecycline is not affected by resistance to prevent tetracyclines from entering but microbes have developed resistance to minocycline
86
Chloraphenicol is (bacteriostatic or bactericidal).
bacteriostatic
87
Describe the MOA of chloramphenicol.
binds to the 50S ribosomal subunit and interferes with the enzyme peptidyl transferase to block the linkage of incoming aa
88
What type of phase II reaction metabolizes chloramphenicol?
glucuronidation
89
What can happen to infants and adults with hepatic disease that also are taking chloramphenicol?
the drug accumulates and is inefficiently glucuronidated resulting i n "gray baby/adult' syndrome (fail to eat, thrive, pallor, cyanotic, abd distension, and may die of respiratory or vasomotor collapse)
90
What type of drug is clindamycin?
lincosamides
91
What is the MOA of clindamycin?
binds 50S subunit and prevents TRANSLOCATION of aa from A site to P site
92
What are examples of macrolides?
```
drugs that have erythromycin base:
erythromycin estolate
erythromycin sterate
erythromycin ethylsuccinate
clarithromycin
azithromycin
```
93
Describe the MOA for macrolides.
bind to the 50S subunit to prevent translocation of the amino acids from the A site to the P site
94
What drugs prevent the translocation of amino acids from the P to A site? What is a possible consequence of this?
clindamycin
chloramphenicol
macrolides
they may interfere with one another and cross-resistance may develop between them
95
Macrolides are (bacteriostatic or bactericidal)
both, it depends on drug conc
96
Microbes become resistant to macrolides in the following circumstances (3):
1. when their permeability for macrolides is altered
2. when the microbes methylate the 50S subunit
3. When the bacteria develop mechanisms to enzymatically destroy the drugs
97
What are some adverse effects associated with erythromycin? (4)
1. GI distress
2. cholestatic hepatitis (elevated liver enzymes, malaise, nausea, vomiting, abd cramps, jaundice, and fever)
3. inhibit CYP34A --> toxicity
4. fatal arrhythmia (from prolong the QT interval)
98
T or F: clarithromycin is associted with more GI distress than erythromycin.
False: less
99
How is azithromycin different than erythromycin and clarithromycin?
- does not prolong QT interval
| - does not inhibit hepatic microsomal P450s
100
What is an example of ketolides?
telithromycin
101
What is the MOA of telithromycin?
inhibits 50S by binding at TWO locations
102
Why is it difficult for bacteria to develop resistance to telithromycin?
must have mutations in 2 diff domains of 50S and this drug is a poor substrate for eflux pumps
103
What is the MOA for retapamulin? How is it administered?
- binds 50S to prevent formation of active 50S subunit
- inhibits peptidyl trasferase
- blocks P site interactions
-topical ointment
104
What is the MOA of mupirocin?
inhibits tRNA that transports isoleucine
105
T or F: Mupirocin can partake cross-resistance to other antimicrobials.
False: to does not (bc it is a unique MOA)
106
What is cross resistance in antimicrobials?
resistance to a particular antibiotic that often results in resistance to other antibiotics
107
What is the MOA of linezolid?
binds to a unique RNA site on the 50S to prevent formation of the 70S complex.
108
What type of drug is a combination of quinupristin and dalfopristin?
streptogramins
109
What is the MOA of the quinupristin/dalfopristin?
quinupristin irreversible blocks ribosomes to inhibit the late phase of protein synthesis.
Dalfopristin inhibits early phases of protein synthesis.
110
What is the quinupristin/dalfopristin combination used to treat?
to treat life-threatening infections caused by vancomycin-resistant enterococci and complicated skin infections caused by MRSA
111
Folic acid is a ____ vitamin
B
112
T or F: bacteria can use folic acid obtained from the environment.
false: they cannot use it
113
What drugs target dihydropteroate synthetase?
sulfonamides
114
What drugs target dihydrofolate reductase?
trimethoprim
115
What are examples of sulfonamides?
```
sulfadiazine
silver sulfadiazine
sulfamethoxazole
sulfacetaminde
sulfasalazine
```
116
Describe the MOA for sulfonamides
compete with para-aminobenzoic acid (PABA) for binding to dihydropteroate synthetase (1st step in pathway) --> if it binds the pathway is blocked
117
Sulfonamides are highly bound to ______
plasma proteins
118
What are complications that can arises from concurrent administration of sulfonamides and warfarin, NSAIDs, and sulfonylurases
if they outcompete these drugs for binding to plasma proteins, the conc of these drugs will drastically rise and potentially become toxic
119
Why are sulfonamides contraindicated for pregnant women in later term and infants less that 2 mo old?
they displace bilirubin from protein binding sites in neonates and hyperbilirubinemia in neonates may cause kernicterus (CNS disorder)
120
What are the 4 ways bacteria develop resistance to sulfonamides?
1. reduce uptake of drug
2. develop alt pathways to make folic acid
3. produce excess PABA to outcompete sulfonamides
4. mutated dihydropteroate synthetase (rate limiting enzyme)
121
How are sulfonamides metabolized?
hepatically by acetylation, oxidation, and/or glucuronidation
122
Who are at an increased risk of hypersensitivity reactions to sulfonamides?
slow acetylators
123
____(type of metabolic reaction) ___ of sulfonamides likely is responsible for many of the adverse affects associated with sulfonamides.
oxidation
124
How are sulfonamide metabolites excreted?
renally
125
Trimethoprim inhibits ____
dihydrofolate reductase (last set of folic acid synthesis)
126
Bacteria may become resistant to trimethoprim by...
1. reduced uptake of drug
2. mutations in dihydrofolate reductase
3. overproduction of dihydrofolate reductase
127
What are some examples of fluoroquinolones?
all ending in "-floxacin"
128
What is the MOA of fluoroquinolones?
inhibit DNA gyrase or topoisomerase IV
129
What is the function of DNA gyrase?
relaxes supercoiled DNA and is essential in replication, Tx, and DNA repair
130
What is the role of topoisomerase IV?
seperating DNA into daughter cells during replication
131
What must bacteria become resistant to evade the effects of fluoroquinolone or gemifloxacin?
must acquire mutations in both DNA gyrase and topoisomerase IV
132
What can impair the absorption of fluoroquinolones?
food or cations (Ca, Fe, Al, Mg, Zn) or sucralfate
133
T or F: Fluoroquinolones penetrates and distributes mainly to the CNS.
false: they do not penetrate CNS and they distribute to nearly all other body compartments
134
What type of drug is Daptomycin?
lipopeptide
135
What is the MOA of daptomycin?
binds bacterial membranes and cuases rapid depolarization of the cell --> stops DNA, RNA, and protein synthesis => cell death
136
T or F: cross resistance between daptomycin and rifaximin has developed.
false: daptomycin has not developed cross resistance with any other antibiotics
137
T or F: Datomycin metabolites are excreted in the urine.
False: Daptomycin (UNCHANGED) is excreted in urine
138
What antibiotic is selcetively absorbed by anaerobic bac and sensitive protozoa?
metronidazole
139
Describe the MOA for metronidazole in anaerobes.
taken up and non-enzymatically reduced by reacting with reduced ferredoxin --> produces metabolites that are toxic --> DNA and nucleic acid synthesis is inhibited and existing DNA is degraded or strand breaks are introduced --> CELL DEATH
140
What is the MOA for nitazonxanide?
inferfeeres with pyruvate/ferredoxin oxidoreductase enzyme dept e- transfer (necessary for anaerobic bacteria metabolism)
141
WHat is the MOA for tinidazole?
causes DNA damage--> inhibiting DNA synthesis
142
What antibiotics can be mutagenic and possibly carcinogenic?
metronidazole
nitazoxanide
tinidazole
143
When are metronidazole and tinidazole contraindicated?
first timester of pregnancy
144
T or F: Metronidazole penetrate the CNS and therefore can be used to treat meningitis and brain abscesses caused by aerobic bacteria.
False: All is true except it must be caused by an anaerobic bactera
145
What is the MOA of rifaximin?
inhibits bacterial RNA synthesis by binding bacterial DNA dept RNA polymerase
146
How is rifaximin excreted?
It is NOT abs in GI tract and therefore it is excreted in feces
147
What are the difference between rifaximin and rifampin?
- rifaximin does not interfere with CYP450s while rifampin does
- rifaximin is excreted in feces
148
What are mycobacteria?
gram positive rod-like bacteria that are aerobic and can form filamentous branching structures
149
Why are mycobacterial infections (like TB and leprosy) hard to treat? (5)
1. mycobac grows slowly
2. they can lie dormant
3. they have thick cell walls that are relatively impermeable
4. they can reside n host cells
5. become resistant quickly
150
What is the MOA for isoniazid?
inhibits synthesis of mycolic acids (essental component of mycobacterial cell wall)
151
T or F: Isoniazid diffuses throughout total body water, even the CNS.
true
152
Metabolism of isoniazid occurs by _____
acetylation
153
What consequences do "fast acetylators" have on the use of isoniazid as a treatment?
isoniazid may not reach therapeutic levels because they have a short plasma half life
154
Will fast or slow acetylators be at a greater risk for drug-related toxicity with izoniazid?
slow
155
What is the MOA of rifampin?
binds upstream of RNA pol binding site to physically prevent the Tx of a gene (inhibits RNA pol)
156
Rifampin is a potent inducer of _____
CYP450s --> DRUG-DRUG INXS are a major concern.
157
What is the MOA of pyrazinamide?
unclear but thought that it lowers the pH in the tubercle cavity and inhibits growth of mycobacterium
158
What is the MOA of ethambutol?
inhibits RNA synthesis and decreases replication of the tubercle bacilli
159
What is the MOA of clofazimine?
binds to mycobacterial DNA to inhibit RNA pol actions. Tx is very slow and requires pt to be treated for a min of 2 yrs and possible for life
160
What antibiotics are used to treat mycobacterial infections?
```
isoniazid
rifampin
pyrazinamide
ethambutol
clofazimine
```
161
T/F: Aminopenicillin is unaffected by B-lactamase.
F
162
What type of bacteria can become resistant by altering their porin structure?
gram -
163
Where in the bacterial cell do B lactams work?
periplasmic space
164
What cell wall inhibitors (other than penicillin) are used to treat gram - infections?
- polymyxin B (proteus resistant)
| - (cycloserines, but these are usually reserved for TB)
