Exam Two Flashcards

1
Q

Mechanism of action of beta lactam antibiotics

A

inhibitors of cell wall synthesis

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2
Q

mechanism of resistance of beta lactam antibiotics

A
  • destruction by beta lactamase enzymes
  • alteration in PBPs (not aztreonam)
  • decrease permeability of the outer cell membrane in gram negative bacteria
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3
Q

what are the pharmacodynamic properties of beta lactams

A

time dependent bactericidal activity (except against enterococcus)

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4
Q

What is the elimination half life of most beta lactams

A

< 2 hours

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5
Q

How are most beta lactams eliminated

A

renally

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6
Q

Which beta lactams are not eliminated renally?

A
  • nafcillin
  • oxacillin
  • ceftriaxone
  • cefoperazone
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7
Q

Are all beta lactams cross allergenic?

A

all except aztreonam

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8
Q

Natural Penicillins SOA

A
  • Most non beta lactamase producing gram positive cocci and bacilli
  • very little staphylococcus
  • gram negative cocci
  • anaerobes
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9
Q

Penicillinase-Resistant Penicillins (nafcillin, methicillin, oxacillin, dicloxacillin) SOA

A

MSSA

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10
Q

Aminopenicillins (ampicillin and amoxacillin) SOA

A
  • ineffective against staphylococcus aureus
  • better against enterococcus
  • excellent against listeria monocytogenes
  • Gram Negatives
  • anaerobes
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11
Q

What is ampicillin the drug of choice for

A

listeria monocytogenes and enterococcus

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12
Q

Carboxypenicillins (ticarcillin) SOA

A
  • weak gram positive activity (no activity against staphylococcus)
  • gram negative (including pseudomonas)
  • not active against klebsiella or serratia
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13
Q

Ureidopenicillins (piperacillin) SOA

A
  • good gram positive
  • no activity against staphylococcus
  • improved activity of gram negatives (including pseudomonas aeruginosa)
  • anaerobes similar to Pen G with some activity against B fragilis
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14
Q

Which penicillin has the most activity against pseudomonas

A

piperacillin

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15
Q

Beta lactamase inhibitor combination penicilllins SOA

A
  • staphylococcus aureus (MSSA)
  • enahnced activity of some gram negative
  • Anaerobes (B. fragilis and DOT organisms)
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16
Q

Are penicillins bactericidal or bacteriostatic against enterococcus

A

bacteriostatic

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17
Q

Does food delay the rate and/extent of absorption of penicillins?

A

Yes

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18
Q

Penicillin distribution to the CSF

A

only in the presence of inflamed meninges when high, maximal doses of parenteral penicillins are used

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19
Q

Where are nafcillin and oxacillin eliminated?

A

liver

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20
Q

Where is piperacillin eliminated

A

dual elimination

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21
Q

Which agents cause sodium load and must be considered in patients with CHF or renal dysfunction?

A
  • aqueous penicillin G
  • nafcillin
  • ticarcillin
  • piperacillin
  • carbenicillin
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22
Q

Natural penicillin use

A
  • streptococcus pneumonia (PSSP or PISP)
  • treponema pallidum (syphilis)
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23
Q

Penicillinase Resistant Penicillins (nafcillin, oxacillin)

A
  • MSSA
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24
Q

Aminopenicillin use

A

Enterococcal infections and listeria monocytogenes

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25
Ureidopenicillins (piperacillin) use
pseudomonas aeruginosa
26
beta lactamase inhibitor combination product use
- Augmentin useful for above the diaphragm infections - Unasyn and Zosyn for polymicrobial infections such as intraabdominal, gynecological, and adiabetic foot - Zosyn covers pseudomonas aeruginosa like HAP
27
Adverse Effects of penicillins
- hypersensitivity - direct neurologic toxic effect (seizures) - leukopenia, neutropenia, thrombocytopenia - C diff - interstitial nephritis
28
What are the characteristics of interstitial nephritis in penicillin use?
- fever - eosinophiluria and eosinophilia - an abrupt increase in serum creatinine - associated with methicillin and nafcillin
29
Nafcillin specific advere effect
- phlebitis - interstitial nephritis
30
ticarcillin specific adverse effect
- hypokalemia - sodium overload and fluid retention
31
piperacillin specific adverse effect
- sodium overload and fluid retention
32
MOA of cefiderocol
binds to extracellular free ferric iron and actively transported across the outer cell membrane of bacteria into periplasmic space using a siderophore iron uptake mechanism
33
First generation cephalosporins SOA
- best activity against gram positive aerobes (PSSP, MSSA) - Gram negative aerobes (PEK)
34
PEK
- proteus mirabilis - escherichia coli - klebsiella pneumoniae
35
Second generation cephalosporins SOA
- gram positive aerobes - gram negative aerobes (HENPEK) - anaerobes (bacteroides fragilis) only with cefoxitin, cefotetan, cefmetazole
36
HENPEK
- haemophilus influenzae - moraxella catarrhalis - neisseria - enterobacter
37
Which second generation cephalosporins cover anaerobes like bacteroides fragilis
- cefoxitin - cefotetan - cefmetazole
38
What are the most commonly used first generation cephalosporins
- cefazolin - cephalexin (oral)
39
What are the most commonly used second gen cephalosporins
- cefuroxime - cefprozil - cefoxitin
40
Third Generation cephalosporin SOA
- Gram positive aerobes like PRSP (ceftriaxone and cefotaxime) - gram negative aerobes (HENPECKSSS with Pseudomonas) - limited anaerobes
41
Which cephalosporin is a strong inducer of ESBLs in gram negative bacteria
ceftazidime
42
HENPECKSSS
- haemophilus influenzae - moraxella catarrhalis - neisseria - enterobacter - citrobacter - morganella - providencia - Serratia - Salmonella - Shigella
43
What are the most commonly used third generation cephalosporin agents
- ceftriazone - ceftazidime - cefpodoxime
44
Fourth generation cephalosporin SOA
- gram positive aerobes - gram negative aerobes including pseudomonas and b-lactamase producing enterobacter
45
which cephalosporin is a poor inducer of ESBLs in gram negative aerobic bacteria
cefepime
46
Ceftaroline SOA
- coverage against staphylococci and streptococci including PRSP and MRSA (ceftriaxone w/ MRSA activity) - gram negative aerobes (HENPEK)
47
Does ceftaroline cover pseudomonas?
No
48
Cefiderocol SOA
- no gram positive - gram negative aerobes (HENPECKSSS w/ pseudomonas and MDR carbapenamase strains)
49
Ceftolazane-tazobactam SOA
- gram positive streptococci - gram negative coverage like cefepime including ESBL and some AmpC pseudomonas
50
Ceftazidime-avibactam SOA
- gram positive streptococci - gram negative coverage like cefepime incljuding ESBLs, some AmpC enterobacterales and pseudomonas - some KPC producing and OXA producing enterobacterales
51
What are cephalosporins mostly unactive against
- MRSA (except ceftaroline) - enterococcus - Legionella
52
Which cephalosporins achieve concentrations in the CSF
- cefuroxime (2nd gen) - IV third gen - IV fourth gen
53
Which cephalosprins are not eliminated in the kidneys
- ceftriaxone (biliary) - cefoperazone (liver)
54
Which cephalosporin has a long half life
ceftriaxone
55
What is cefazolin the drug of choice for?
surgical prophylaxis
56
first gen cephalosporin use
- MSSA
57
Should first gen cephalosporins be used for meningitis?
no
58
Second gen cephalosporin use
- polymicrobial infections of anaerobes and aerobes (intraabdominal, cefazolin not great, use second gen) - B fragilis
59
Third generation use
- pseudomonas (ceftazidime or cefoperazone) - ceftriaxone for uncomplicated gonorrhea - PRSP with cefotaxime and ceftriaxone
60
Fourth generation cephalosporin use
- CAP and HAP - pseudomonas
61
Ceftaroline use
MRSA
62
Cefiderocol
MDR gram negative bacteria who have limited or no therapeutic options
63
Clinical signficance of 5-NMTT side chain
- hypoprothrombinemia - disulfiram reaction
64
Which agents have 5-NMTT side chain
- cefamandole - cefotetan - cefmetazole - cefoperazone - moxalactam
65
Which cephalosporins have a reaction with alcohol?
- cephamycins and 5-NMTT side chains
66
Adverse effects of cephalosporins
- hypersensitvity - leukopenia, neutropenia, thrombocytopenia - biliary sludging (ceftriaxone) - C-diff - nonconvulsive status epilepticus
67
Which cephalosporins cause nonconvulsive status epilepticus in renal insufficiency
- cefepime - ceftazidime - cefiderocol
68
Which cephalosporin precipitates with calcium
ceftriaxone
69
Carbapenems SOA
- gram positive aerobes including MSSA and enterococcus faecalis (imipenem) - gram negative aerobes HENPECKSSS w/ pseudomonas (not ertapenem) - gram negative aerobes
70
What are carbapenems the drug of choice for
ESBL and AmpC producing bacteria
71
Which carbapenems are best for gram positive aerobes
imipenem and doripenem
72
which carbapenems are the best for gram negative aerobes
doripenem and meropenem
73
Which carbapenem does not cover pseudomonas
ertapenem
74
Carbapenems do not cover what
- MRSA - C diff - Stenotrophomonas - Atypicals
75
CSF penetration of carbapenems
meropenem penetrates into the CSF better
76
Elimination of carbapenems
renal
77
Which carbapenems require dose adjustments
all of them
78
purpose of cilastatin
prevent renal metabolism and protect against potential nephrotoxicity due to DHP
79
Clinical uses of carbapenems
- polymicrobial infections including pseudomonas - infections due to ESBLs/AmpCs - KPC producing enterobacterales (combination drugs)
80
Major side effect of carbapenems
CNS toxicity (seizures) in patients that have CNS disorders, high doses, and presence of renal dysfunction
81
Aztreonam SOA
gram negative aerobes (HENPECKSSS + pseudomonas)
82
Does aztreonam penetrate in into the CSF
yes
83
Elimination of aztreonam
renal (dose adjsutment needed)
84
Use of aztreonam
- gram negative aerobes including pseudomonas - penicillin allergy infections
85
Use of aztreonam in pen allergic patients
- low to negligible cross reactivity - can be used in patients
86
Carbapenem and Monobactam general adverse effects
- neutropenia/thrombocytopenia - transient LFT increases - drug fever - phlebitis
87
FQ MOA
inhibition of DNA synthesis by binding to and inhibiting bacterial topoisomerases
88
FQ resistance mechanisms
- mutation in the genes that code for DNA gyrase or topoisomerase IV (change in binding site) - efflux - alteration in cell wall permeability
89
FQ Activity
concentration dependent bactericidal activity
90
FQ SOA
- new FQs have enhanced activity including PRSP (not cipro) and MSSA - delafloxacin against MRSA - HENPECKSSS + against gram negative aerobes + pseudomonas - Legionella - Mycobacterium
91
Which FQ is least active against gram negatives
moxifloxacin)
92
Which FQs cover pseudomonas
cipro, levo, dela
93
PK advantages of FQs
- penetration into prostate - display PAE against both gram positive and negative aerobes - well absorbed after oral administration
94
How are FQs eliminated
- levo cipro and dela renally, need dose adjustments - moxifloxacin is hepatic
95
Which FQ does not have to be dose adjusted renally
moxi
96
FQ clinical uses
- prostatitis - pseudomonas - respiratory infections
97
FQ adverse effects
- peripheral neuropathy - hepatotoxicity (trova) - QTc prolongation - articular damage (contraindicated in pregnancy) - tendonitis
98
Which class of antibiotics cause QTc prolongation
FQs
99
Should FQs be taken during pregnancy
no
100
Drug interactions of FQs
- warfarin - divalent and trivalent
101
Macrolide MOA
- reversibly bind to 50s ribosomal subunit to induce dissociation of peptidyl transferase RNA from the ribosome
102
Macrolide activity
bacteriostatic (reversibly binds)
103
Macrolide MOR
- active efflux by mef gene confers low level resistance - alteration in the binding site by erm confers high level resistance
104
Macrolide SOA
- gram positive aerobes (C>E>A) including PSSP and MSSA - Gram Negative aerobes (A>C>E) - Legionella and mycobacterium avium complex (azithro and clarithro)
105
do macrolides distribute into the CSF
No
106
Which macrolides reqiuire renal dosage adjustment
clarithromycin in patients with CrCl < 30 mL/min
107
Which macrolide is inhibited by CYP3A4 and 2C9
- clarithromycin and erythromycin
108
Clinical uses of macrolides
- CAP especially for atypical coverage - chlamydia (azithromycin) - MAC (clarihtyromycin)
109
Major adverse effects of macrolides
- GI distress - thrombophelbitis and infusion site irritaiton - QTc prolongation
110
Drug interactions with macrolides
- warfarin - theophylline - carbamazepine - valproate - cyclosporine - digoxin - phenytoin
111
Vancomycin MOA
- inhibits the synthesis of the bacterial cell wall during the second stage (D-Ala D-Ala)
112
Mechanism of Resistance of Vancomycin
- modification of D-Ala D-Ala binding site into D-Lactate by VanA - thickening of peptidoglycan wall in VISA
113
Vancomycin SOA
- gram positve aerobic and anaerobic - MRSA - PRSP - C diff
114
Vancomycin activity
slowly bactericidal in a time dependent manner
115
Vancomycin penetration into CSF?
Yes
116
What is the drug of choice for MRSA
vancomycin
117
What dosage form of vancomycin is used for C diff
oral
118
How is vancomycin eliminated
renaly, need dose adjustment
119
Clinical uses of Vancomycin
- MRSA (the drug of choice) - PRSP - Cdiff
120
Adverse effects of vancomycin
- red man syndrome related to the rate of infusion - reversible nephrotoxicity - irreversible ototoxicity
121
Synercid MOA
inhibit protein synthesis by binding to 50S ribosomal subunit
122
Synercid MOR
alteration of ribosomal binding site by erm gene
123
Synercid activity
time dependent bacteristatic
124
Synercid SOA
- VRE (faecium) - PRSP - MSSA and MRSA
125
When to consider Synercid for VRE
Enterococcus faecium VRE
126
Elimination of synercid
hepatic clerance
127
Renally adjust synercid?
NO
128
Drug interactions Synercid
- HMG-CoA reductase - immunosuppressive agents - carbamazepine
129
Synercid adverse effects
- myalgias, arthralgia - venus irritation
130
Linezolid MOA
inhibits protein synthesis by binding to 50s near 30S interface, producing inhibition of the 70S initiation complex
131
Linezolid activity
bacteriostatic
132
linezolid MOR
alteration of the ribosomal subunit (rare)
133
Linezolid SOA
- VRE faecium AND faecalis - MSSA, MRSA - VISA, VRSA - inactive against gram negatives and atypicals
134
PK characteristics of linezolid
- PAE - rapidly and orally abosrbed 100%
135
Linezolid distribution into CSF
limited data
136
Elimination of linezolid
- both renal and nonrenal - does not require renal dosage adjustment
137
When is linezolid used?
- Both Faecalis and faecium VRE - MRSA, VISA, VRSA
138
Drug interactions Linezolid
- MOAi - serotonergic agents
139
Adverse Effects linezolid
- peripheral neuropathy - thrombocytopenia and anemia
140
Daptomycin MOA
binds to bacterial membranes and inserts lipophilic tail into cell wall to cause leakage
141
Daptomycin activity
concentration dependent bactericidal activity
142
Daptomycin MOR
- rarely reported - altered cell membrane
143
Daptomycin SOA
- gram positive aerobes - PRSP - VRE (both) - MSSA - MRSA - VISA -VRSA - LRSA
144
When to use daptomycin
- When vancomycin or linezolid cannot be used - enterococcus faecium and faecalis including VRE - MSSA, MRSA - VISA, VRSA - linezolid resistant staphylococcus aureus
145
Elimination of daptomycin
renal dose adjustment needed
146
When should daptomycin not be used
treatment of pneumonia
147
clinical uses for daptomycin
Staphylococcus aureus bacteremia and endocardidits
148
Drug interactions daptomycin
- statins
149
adverse effects daptomycin
- myopathy and CPK elevation - acute eosinophllic pneumonia
150
Lipoglycopeptides MOA
- inhibit second stage of protein synthesis - oritavancin and telavancin bind to bacterial cell membranes and insert lipophilic tails
151
lipoglycopeptides MOR
- alteration of D-ala D-ala binding site
152
lipoglycopeptides activity
concentration dependent bactericidal
153
lipoglycopeptides SOA
- gram positive aerobes including both VRE (oritavancin) and MRSA, VISA, VRSA (oritavancin)
154
CSF penetration lipoglycopeptides
No
155
Which lipoglycopeptide requires renal adjustment
- telavancin and dalbavancin
156
lipoglycopeptides adverse effects
- infusion syndrome - nephrotoxicity - QTc prolongation - taste disturbances
157
Which lipoglycopeptide should not be used in pregnancy
telavancin
158
aminoglycosides MOA
irreversibly bind to the 30s ribosomal subunit
159
aminoglycoside activity
concentration dependent bactericidal
160
aminoglycoside MOR
- alteration in aminoglycoside uptake - synthesis of aminoglycoside modifying enzymes - alteration in ribosomal binding site (strepto)
161
aminoglycosides SOA gram positives
- never use alone - always use with low doses with cell wall agents - most strains of staphy aureus (never use alone for MSSA and MRSA)
162
aminoglycosides SOA gram negatives
- often use with cell wall active agents to provide synergy - higher doses uses - PPPEEACKSSS - Pseudomonas!
163
Which aminoglycoside is used in gram positives
gentamicin, low dose with other agents
164
Which aminoglycoside is active against atypicals
streptomycin - mycobacteria
165
PK of aminoglycosides
- interpatient variability exists in the PK parameters of Vd and clearance - influences dosing for each individual patient
166
distribution of aminoglycosides
- poorly in the CSF - ideal body weight should be used - volume differences must be taken into account because they are concentration dependent agents
167
When is it important to achieve therapeutic concentrations in aminoglycoside
within 24 hours for gram negative sepsis
168
Standard dosing principles
- smaller doses (1-2.5 mg/kg/dose) - for gram negative and gram positive synergy
169
Gram negative moderate infections PK paramenters aminoglycosides
- Peak 4-6 - Trough 0.5-1.5
170
Gram negative moderate to severe infections PK paramenters aminoglycosides
- Peak 6-8 - trough 1.0-1.5 - soft tissue, bacteremia
171
Gram negative severe infections PK paramenters aminoglycosides
- Peak 8-10 - trough <2 - pneumonia, life threatening, burn
172
Gram positive moderate PK aminoglycosides
- gent only - peak 3-5 - trough 1
173
Aminoglycoside extended dosing
5-7 mg/kg as single daily dose (use IBW or ADW)
174
When should extended dosing be considered
- urospesis - intraabdominal - skin and soft tissue
175
Extended dosing used in caution with aminoglycosides
- immunocompromised patients - patient with large or small Vd - patients with high clearance (young,burn)
176
When should serum concentrations be taken in extended dosing
- 2 and 10 hours after the end of infusion - 8-12 hours after the first dose
177
Extending dosing PK paramenters
- gram negatives only - peak 13-20 - trough < 0.5
178
use of aminoglycosides
- serious infections due to gram negative aerobic bacteria includihng pseudomonas
179
Adverse effects aminoglycosides
- neprotoxicity for prolonged high trough concentrations - ototoxocity irreversible
180
180
tetracycline MOA
reversibly bind to the 30s blocking the A site
181
tetracycline activity
bacteriostatic time dependent
182
tetracycline MOR
- decreased accumulation due to tetracycline specific efflux pumps - decreased access due to robosomal protection proteins - enzymatic inactivation
183
tetracycline analogs MOR
multidrug efflux pump
184
Tetracycllines SOA
- gram positive aerobes (mino and doxy) including PSSP and MSSA - gram negative aerobes , not enterobacteraales
185
tetracycline analogs SOAA
- MSSA and MRSA - garam negative aerobes EEACKSS - anaerobes bacteroides - atypicals mycobacterium
186
drug interctions tetracyclines
- divalent or trivalent cations
187
distribution of tetracyclines
- prostataic - small amounts in CSF
188
Which tetracyclines required renal dose adjustments
demecycline and tetracycline
189
Which tetracyclines require hepatic adjustments
tigecycline eraavacycline
190
Uses of doxycyline
- CAP - chlamydial infectiosn and nongonococcal urethritis
191
adverse effects tetracyclines
- GI - photosensitivity - pregnancy contraindication
192
TMP SMX MOA
- block microbial folic acid synthesis - SMX block dihydropteroate synthetase - TMP blocks DHFR
193
activity of TMP SMX
- bactericidal time dependent
194
MOR TMP SMX
- point mutations in dihydropteroatre synthase or altered production of DHFR
195
TMP SMX SOA
- gram positive aerobes (MRSA, CA-MRSA) - gram negative aerobes (most including stenotrophomoas and HENPEACKSSS)
196
What is TMP SMX the drug of choice for
pneumocystis carinii/jirovecci
197
Does TMP SMX cover anaerobes
NO
198
distribution of TMP SMX
urine, prostatic tissue
199
Dose adjustment of TMP SMX
CrCl < 30
200
Clinical uses TMP SMX
- UTI - pneumocystis carinii jirovecci pneumonia - CA MRSA - stenotrophomonas
201
TMP SMX Adverse effects
- leukopenia - rash - crystalluria - renal insufficiency - pregancy (kernicterus in newborns)
202
Drug interactions TMP SMX
warfarin
203
Polymyxins MOA
displacement of calcium and magnesium causing leakage of cellular contents
204
polymyxins activity
concentration-dependent bactericidal
205
CMS vs Colisitin
- less toxicic and is a prodrug
206
polymyxin MOR
- alteration of the outer cell membrane - decreased lipopolysaccharide content and calciium and magnesium
207
polymyxins SOA
Gram negative AEROBES - acintobacter - pseudomonas
208
Dose adjustments for polymyxins
CMS renal adjustment when CrCl is < 80 mL /min
209
clinical uses of polymyxins
gram negative aerobic infections including pseudomonas
210
adverse effects of polymyxins
- nephrotoxicity - neurotoxicity
211
clindamycin MOA
binds reversibly to 50S subunit
212
activity clindamycin
primarily bacteriostatic time dependent
213
Clindamycin MOR
alteration in ribosomal binding site
214
clindamycin SOA
Gram positives aerobes (MSSA and CA-MRSA) - gram negative above the diaphragm anaerobes (bacteroides)
215
Does clindamycin penetrate the CSF
no
216
clinical uses clindamycin
- infections due to anaerobes outside the CNS - CA MRSA
217
adverse efffects of clindamycin
C diff hepatotoxicity
218
metronidazole MOA
inhibit nucleic acid synthesis
219
metronidazole activity
bactericidal in concentration dependent manner
220
Metronidazole MOR
- altered growth requirements (higher oxygen) - altered levels of ferredoxin gene, decreasing electron donating
221
metronidazole SOA
- gram negative anaerobes - b frag and bdot organisms - gram positive anerobes including cdiff
222
Does metronidazole penetrate into the CSf
yes
223
Metronidazole uses
- infections due to anaerobes (need additional coverage for aerobes) - c diff - trichomoas vaginalis
224
Metronidazole adverse effects
- metallic taste - CNS disorders (seizures/peripheral neuropathy)