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PDA antibacterials Flashcards

1
Q

What are infections where -cidal drugs have an advantage?

A 
pts with compromised immune system
following in immune-competent pts:
-meningitis
-endocarditis
-deep bone infections
-artificial device implants
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2
Q

What type of antibacterials are preferred for patients with competent immune systems with meningitis, endocarditis, deep bone infections, and artificial device implants?

A

-cidal drugs

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3
Q

What is time dependent killing?

A

amount of time about the MIC

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4
Q

What is concentration-dependent kkilling?

A

peak concentration matters most

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5
Q

What does it mean when drugs are concentration and time dependent?

A

area under curve of concentration over time vs MIC

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6
Q

When do time-dependent killing drugs work on epople?

A

drugs work best when conc. exceeds 4 times the MIC for greater than 50% of total time

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7
Q

What are beta-lactams dependent on for killing with respect to MIC?

A

Time-dependent

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8
Q

What type of depedency do amingolycosides have for killing?

A

concentration dependent and have persistent effect when levels fall below MIC

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9
Q

What type of dependenccy do quinolones have for killiing?

A

concentration x time (area under curve)

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10
Q

Why do beta-lactams requrie more frequent dosing?

A

time dependent killers and they have a shorter half life

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11
Q

Where do penicillins have low penetration?

A

into the csf; although increases during meningitis

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12
Q

How are penicillins eliminated?

A

renally; by anion transport

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13
Q

What are the half lives of penicillins?

A

short 30 minutes to 3 hours

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14
Q

How is penicillin V taken?

A

orally

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15
Q

How is penicllin G taken?

A

IV/IM

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16
Q

What are the spectrum of peniclin V and penicillin G?

A 
anaerobes (mainly gram positivie)
gram positive that are non-beta-lactamase producing
1st line for strep throat
very limited gram negative
-neisseria meningitidis
spirochetes
-syphillis
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17
Q

What penicillins are used for beta-lactamase positive staphylococci?

A

methicillin type drugs; ie oxacillin

MSSA(methicillin sensitive Staph aureus)

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18
Q

What is the spectrum for ampicillin and amoxicillin?

A

maitain gram postiive (Beta lactamase negative)
-enterococcus
expanded gram negative spectrum

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19
Q

What is the drug of choice for otitis media in otherwise healthy children?

A

high dose amoxicillin

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20
Q

What is amoxiciiln an althernate choice for in young children and pregnat/breat-feeding women?

A

Lyme disease

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21
Q

What are 2 important uses for ampicillin that amoxicillin doesnt?

A 
meningitis (neisseria, listeria)
bc available by IV
GI infections;
esp Shigella
bc less abosrbed in orally more avaiable in GI tract
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22
Q

What two penicilins have an extended gram-negative spectrum?

A

ticarcillin and piperacillin

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23
Q

What is the spectrumf or ticarcillin?

A

retain some gram-pos activity
good for some anaerobes
gram neg spectrum extended to include psuedomonas aeruginosa

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24
Q

What is the spectrum for piperacillin?

A

gram negative spectrum like ticarcillin but also some pseudomonas and klebsiella
include those that are ticarcillin-resistant

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25
How can one predict severe allergic reaction to penicillin?
pt history PRE-PEN -skin test; 90-95% reliable at identifying those at risk for severe allergic reaction
26
What are the side effects of penicillins?
``` fever diarrhea(most common side effect) enterocolitis (all anti-biotics can causet his due to C diff infection) elevated liver enzymes hemolytic anemia seizures ```
27
What are some common properties of cephalosporins?
well distributed; although only 3rd gen reach CSF majority require injection same mechanism as penicillin
28
What is teh spectrum for 1st generation cephalosporins??
mostly gram positive spectrum uncomplicated outpatient skin infections surgical prophylaxis esp for skin flora
29
What are two cephalosporin 1st generation drugs?
cefazolin and cephalexin
30
What are two examples of second generation cephalosporins?
cefuroxime and cefoxitin
31
What is teh only second gen cephalosporin to penetrate CSF?
cefuroxime
32
What is cefuroxime used to treat?
best second for haemophilus but poor against enterics | good tolerance to many gram negative beta lactamases
33
What is cefotoxin used to treat?
similar to many second gen but also good for anaerobes including B. fragilis good tolerance to many gram-neg beta lactamases
34
What are two 3rd generation cephalosporins?
ceftriaxone and ceftazidime
35
What cephalosporin is a very good choice for common types of menigitis?
ceftriaxone
36
What is the therapy of choice for gonorrhea?
ceftriaxone
37
What is ceftriaxone used to treat?
``` common types of meningitis gonorrhea sever lyme disease typhoid fever surgical prophylaxis GI tract surgery ```
38
What is the half life comparison between 3rd generation cephalosporins?
ceftriaxone long half life 6-9 hours and ceftazidime shorter half life 90 minutes
39
What is ceftazimide used to treat?
meningitis, brain abcess pseudomonas aueruginosa esp those resistant ot aminoglycosides poorest for gram positive
40
What is the most active 3rd gen cephalosoporin for psuedomonas aeruginosa?
ceftazidime
41
What is teh poorest 3rd gen cephalosoporin for gram positive?
ceftazidime
42
What is a fourth generation cephalosporin?
cefepime
43
What is teh half life of cefepime?
2 hours
44
What is the spectrum of cefepime?
similar to ceftazidime except more resistant to inducible chromsomally endoced type 1 beta lactamases so covers mroe gram negative strain
45
What is cefepime used to treat
empirical treatment of serious inpatient infections where both gram positive and gram negative etiologies are possible
46
What are cephalosporins asa whole bad at treating?
``` camplobacter legionella C. Diff listeria Acinetobacter enterococcus penicillin resistant strep pneumoniae MRSA ```
47
How are cephalosporins excreted?
Renally: GFR and anion secretion
48
What are teh allergic reactions of cephalosporins?
2-10% ( 1-20% pts cross react with penicilin)
49
What are teh side effects for sephalosporins?
allergic rxns GI issues-generational differences hepatocellular damage
50
What do extended spectrum Beta-lactamases inactivate?
penicillins as well as drugs considered beta lactamase resistant such as 3rd gen cephalosporins and monobactams
51
What are the treatment of choice for ESBL (extended spectrum beta lactamase) organisms?
carbapenems
52
What is the spectrum of imipenem?
broad spepctrum gram pos and gram negative resistant to most beta lactamases including ESBLs
53
What is imipenem not for?
C. diff, MRSA, Enterococcoccus faecium, some psuedomonas, stenophomonas
54
What class is imipenem?
carbapenem
55
What is imipenem used for therapeutically?
ill-defined infections mixed infections non-responsive or resistant to other drugs (ESBLs)
56
Why is imipenem given with cilastatin?
to prevent hydrolysis by renal dipeptidases
57
What are teh side effects of imipenem?
allergic rxns seizures, dizziness, confusion nausea, vomitin, diarrhea, pseudomembranous colitis, superinfection thrombophlebitis
58
What is aztrenoam used to treat?
gram negative aerobic rods resistant to many beta lactamases
59
Does aztreonam have allergic cross-reactions with beta-lactams?
no
60
What are the side effects of aztreonam?
seizures, anaphylaxis, transient EKG changes - GI issues - hepatiits, jaudice, confusion
61
What is hte mechanism of action of vancomycin?
binds to free carboxl end of D-ala-Dala of the pentapetptide interferes with cross--linking of petidoglycan chain
62
What is vancomycin used to treat?
``` gram positives only staph, incl MRSA strep pneuomniae; hemolytic strep enterococcus (20-30% resistant VRE) C. dif enterocolitis ```
63
How is vancomycin administered?
IV for systemic infection limited pen into CSF oral for C. diff eneteroclitis
64
How is vanocmycin used to treat meningitis?
poor pen without inflamed meninges so used as a second line for cephalosporin resistant by combining 3rd gen cephalosporin and vancomycin together
65
What are the side effects of vancomycin?
``` nephrotoxicity red man syndrome ototoxicity phlebitis hypersensitivity, skin rashes, neutropenia ```
66
What is the use of fosfomycin?
uncomplicated UTIs caused by E. coli and enterococcus
67
What are the side effects of fosfomycin?
headache, diarrhea, nausea, vaginitis | dizziness, rash
68
What is the mechanism of bacitracin?
interferes with cell wall syntehsis by interfereing with carrier that moves early wall components through membrane
69
What is bacitracin used for?
topical only and used only against the gram positive spectrum
70
What is the side effect of bacitracin?
allergic dermatitis
71
What are drugs that target cell membrane?
polmyxin B and E | daptomycin
72
What is the mechanism of polymyxin B?
branched chain decapeptides; act as cationic detergents taht binds LPS in outer membrane of gram negatives
73
What are the side effects of polymyxin B?
topical use-few probelms, allergies | systemic use-potential for serious nephrotoxicity and neurotoxicity
74
What is the mechanism of daptomycin?
binds to bacterial cytoplasmic membrane causing rapid membrane depolarization stops essential metabolic and catabolic steps rapidly bactericidal
75
What is the spectrum of daptomycin?
gram positive spectrum | no cross resistance
76
What is the use of daptomycin?
for complicated skin and skin structure infections MRSA Streptococcus Enterococcus (vancomycin-susceptile only) bacteremia not for pneumonia
77
What are the side effects of daptomycin?
nausea, diarrhea, GI flora alterations including C. Diff enterocolitis muscle pain and weakness fever, headache, rash, dizziness, injection site rxn
78
What is the mechanism of action of quinolones?
inhibits alpha and possibly beta subunit of DNA gyrase, thereby interfering with control of DNA winding bactericidal
79
How is killing by quinolones best predicted?
AUC24/MIC more frequent doses more drug per dose longer half life
80
What is the norfloxacin used for?
prototype quinolone for urinary infections | limited use at other sites
81
What is ciprofloxacin used for?
``` useful for infections at many sites UTI infectious diarrhea bone and joint infections skin infections not best choice for gram positive infections chlamydia haemophilus anthrax ```
82
What is better against gram positive than cirpofloxacin used for?
moxifloxacin and levofloxacin
83
Quinolones administered how?
oral some also IV
84
How is quinolones distributed?
many fluorinated drugs are well-distributed | some and the nonfluorinated agents achieve therapeutic concentration onsly in urinary tract
85
What are the quinolones side effects?
``` nausea, vomitting, abdominal paiin rare seizure dizziness, headache, restlesness, depression rashes, some serious potentially fatal EKG iregullariteies, arrythmias peripheral neuropathy; rapid onset children cartilage damage cautioned precautions those with seizure disorder and pregnancy arthropathy-tendon rupture ```
86
What is the mechanism of nitrofurantoin?
itroreductase enzyme converts tehse drugs to reactive compounts whch ccan damage DNA
87
What does nitrofurantoi treat?
UTI lower only not renal
88
What are teh side effects of nitrofurantoin?
``` nausea, vomiting, diarrhea hypersensitivity, fever, chills peripheral neuropathy acute and chronic pulmonary reaction acute and chronic liver damage granulocytopenia, leukopenia, megaloblatic anemia acute hemolytic anemai ```
89
What is the mechanism of rifampin?
binds to and inhibits RNA pollymerase Beta inhibits RNA synteshis bacteriacidal
90
What is rifampin used for?
tuberculosis meningitis prophylaxis difficult infections
91
Wha are the side effects of rifampin?
serious hepatotoxicity strongly induces many other enzymes including CYP3A orange color to excrement may others
92
What is the mechanism of fidaxomicin?
non competitive inhibitor of RNA polymerase
93
What is fidaxomicin used for?
clostridium dif infxn; 3rd line | bacteria cidal
94
What is the spectrum of fidaxomicin?
narrow gram pos mainly clostridium oral admin, poorly absorbed limited impact on normal GI flora
95
What are fidaxomicin side effects?
GI upset, GI bleed, neutropenia
96
What is the mechanism of action of metronidazole?
anaerobes reduce the nitro group resuting produc damages and disrrupts DNA bacteriacidal
97
What are the uses of metronidazole?
anaerobes C. diff enterocolitis H. pylori combo therapy bacterial vaginosis
98
What are the side effects of metronidazole?
nausea, vomiting, anorexia, diarrhea transient leukopenia, neutropenia thrombophlebitis after IV infusion bacteria and fungal superinfection
99
Aminoglycosides are unique how?
only protein synthesis inhibitors that are bactericidal
100
What is teh mechanism of aminoglycosides?
transported into bacteria by energy-requirng aerobic procesc | bind to several ribosomal sites; stop initiation, cause mRNA misreading
101
What is the primary use of aminoglycosides?
primarily for gram negative aerobic bacilli | poor activity against anaerobes
102
How do you use aminoglycosides with gram positive bacteria?
cell wall inhibitors plus aminoglycosides lead to increased permeability and death of aminoglycosides
103
Aminoglycosides have post-antibiotic effect?
sustained activity for several hours after aminoglycoside concentraion ahd dropped below effective levels concentration dependent killing
104
Aminoglycosides are restricted to what type of infections?
serious infections
105
What are teh three aminoglycosides?
gentamicin, tobramycin, amikacin
106
What ist he choice agent for gentamicin and tobramycin resistant straing?
amikacin
107
What are the two classic side effects of aminoglycoides?
nephrotoxicity-mostly reversible ototoxicity-mostly irreversible neuromuscular blockade-less common; associated with intraabdominal infection
108
Tetracyclines are what type of mechanism?
transported into cells by protein carrier binds aminoacyl-tRNA to 30S ribosomal subunit
109
What is teh most common for of resistance to tetracyclines?
drug efflux pumps, resistance to one tetracycline implies resistance to all
110
Use of tetracycline is the preffered agent for what?
``` unusual bugs rickettsia lyme disease chlamdia, mycoplasma, ureaplasma(atypical) chancroid (haemophilus ducreyi) ```
111
What are the two tetracyline examples?
doxycycline and minocycline
112
What is doxycycline used for?
alternative for penG-sens syphilis | uncomplicated N. gonorrheae
113
What is unique about doxycycline among tetracyclines?
has the least affinity for calcium
114
Binding calcium does what to tetracycline?
inhibits it's absorption
115
What are the side efffects of tetracycline?
``` GI disturbance photosensitization cadida infection teeth discoloration- avoid use in you children contraindicated in pregnancy ```
116
Tigecycline is used when?
increased risk of death makes it a last line drug when nothing else is working
117
Chloramphenicol has what mechanism of action?
binds 50S subunits to prevent protein use
118
Chloramphenicol has what major side effect and used for what?
very serious can result in bone marrow suppression alternative in those with serious cephalosporin meningitis brain abcesses (often anaerobes)
119
What are the major side effects of chloramphenicol?
Gray baby bone marrow suppression -fatal aplastic anemia (1 in 30000) optic neuritis and blindness
120
What are the macrolides?
erythromycin, clarithromycin, azithromycin
121
What is the mechanism of macrolides?
bind 50S subunit and blocks translocation
122
What is erythromycin used for?
primarily against gram positive 2nd line against strep in allergic also effective against atypical bugs -mycoplasma, chlamydia, brdetella, legionella
123
What is erythromycin side effects?
rapid vomitting and nausea from enhacned GI motility inhibits CyP3A metabolism increased risk of arrythmias and cardiac arrest -doubles risk on its own 5 fold on other CYP3A inhibitors
124
What is Clarithromycin role?
most expensive macrolide; similar mechanism also some CV risk prolongs QT interval but less GI motility, wider antibacterial spectrum
125
What is the use of clarithromycin?
``` same as erythromycin plus: haemophilus influenzae, moraaxella pneicillin resistant strep pneuoniae atypical mycobacteria liscened for heliobacter pylori 3 drug combos are becoming standard ```
126
Heliobacter approved eradication include what?
combination with 2 antibiotcs + acid blocker most efective combination
127
What is the role of azithromycin
very common for outpatient respiratory tract infections | also genita infections-chlamydia and 2nd line for N. gonorrhea
128
Azithromycin has what adverse reactions?
fewer still QT prolongation fewer effects on CYP3A4
129
What is clindamycin mechanism of action?
binds to 50S ribosomal subunit
130
What is clindamycin famous for?
causing C. diff infections
131
What is the use for clindamycin?
Strep and MSSA (gram pos cocci) suppresses bacterial toxin production many anaerobes including bacteroides flragiles
132
What are the side effects of clindamycin?
liver damage colitis GI problems
133
What is the mechanism of linezolid?
binds to 50S ribosomal subunit and interferes with formation of 70S initiation complex
134
Linezolid is used for what?
``` gram positive spectrum Vancomycin resistant Enterococcus Staph Aureus including MRSA Strep Nosocomial pneuomniae ```
135
What are the side effects of linezolid?
non-selective inhibitor of MAO diarrhea, eneterocolitis headache, nausea/vomiting bone marrow suppresion
136
What are the anti-folates?
inhibit folate synthesis sulfamethoxazole sulfadiazine trimethoprim
137
What is mechanism of action of sulfonamides?
competitive analogs of p-aminobenzoic acid, a precursor in folate synthesis
138
Sulfonamides are used how?
wide spectrum but high resistance | used in combination with others
139
What is silver sulfadiazine used for?
used topically for infection prevention in burn pts | large amount of its effect is silver
140
What are the side effects of sulfonamides?
``` hypersensitivity sunlight makes rashes worse renal damage (crystalluria) potentiate actions of other drugs inhibit CYP2C9 therefore ave an effect on warfarin ```
141
Sulfonamides plus trimethorpim has waht sort of effect
-cidal effect; unusual bc its two statics
142
what is trimethorprim used for?
``` in combo wit sulfamethoxazole used for uncomplicated UTIs -E.coli and coagulase negative staph upper respiratory tract, ear infections GI infections 1st line in pneumocytis jiroveci ```
143
What are the side effects of the TMP/SMX side effects?
all of the sulfa side effects bone marrow suppression GI effects
144
What is one common use of empiric therapy?
uncomplicated cstitis in nonpregnant women

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