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Drugs > Bacterial Drugs > Flashcards

Bacterial Drugs Flashcards

1
Q

Trimethoprim action

A 
inhibits Dihydrofolate reductase/ inhibits tetrahydrofolate synthesis
resembles dihydrofolate (reactant)
bacterstatic when used alone
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2
Q

Sulfamethoxazole

A 
inhibits dihydropteroate synthetase/ inhibits tetrahydroflolate synthesis
resembles PABA (reactant)
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3
Q

What is the ratio of TMP: SMX used often?

why use combination compared to alone?

A

1:5 ratio
combination enhances activity and bactericidal
decreases emergence of resistance

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4
Q

TMP- SMX general uses:

A

broad spectrum (Gram negative and positive)
used for Staph aureus
used for Pneumocystisis Carnii/jirovecii fungi
resistant: pseudomonas, most enterococci, streptococci

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5
Q

Clinical uses of TMP-SMX:

A

IV or PO
urinary infections (UTI)
Respiratory infections (Sinusitis, otitis media(
GI infections: bacterial diarrhea

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6
Q

Can TMP-SMX penetrate immune privileged sites?

A

Yes- excellent tissue penetration

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7
Q

What are resistance methods for TMP-SMX?

A

TMP and SMX: plasmid encoding alternative alleles for the enzymes
SMX: chromosomal mutations

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8
Q

TMP-SMX side effects?

A

common: rash, nausea, vomiting, headache
less common: hyperkalemia, hepatitis, pancreatitis
severe: stevens-johnson syndrome, toxic epidermal necrolysis
pregnancy: kernicterus

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9
Q

Why does TMP-SMX cause kernicterus in pregnancy?

Why does TMP-SMX cause drug toxicities? which drugs?

A

sulfonamides displace bilirubin and other drugs (Warfarin) from albumin and increase bilirubin concentrations and drug concentrations in blood leading to kernicterus and warfarin toxicities (bleeding problems)

Dont give during pregnancy!

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10
Q

What is the action of Quinolones and Fluoroquinolones?

Bactericidal or bacteriostatic?

A

DNA inhibitors
stabilize the topoisomerase-DNA complex with the double stranded break
results in cell death=bactericidal

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11
Q

What is the action of the 2 topoisomerases?

what genes encode them?

A

Topoisomerase II (DNA gyrase): supercoils DNA, encoded by gyrA and gyrB

Topoisomerase IV: relaxes supercoils, encoded by parC and par E

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12
Q

What is the excretion method of TMP-SMX?

A

Urine, unchanged

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13
Q

General uses of Quinolones?

A

broad activity against Gram negative bacteria
Gyrase inhibition= gram negative bacteria
Topo IV inhibition= gram positive bacteria

other uses: “atypicals” and mycobacterium

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14
Q

what is the excretion method of Quinolones?

What is the exception?

A

Urine

Exception: Moxifloxacin*

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15
Q

What are the 4 types of Quinolones?

A

Nalidixic acid
Ciprofloxacin
Levofloxacin
Moxifloxacin

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16
Q

Ciprofloxacin: target, uses, contraindications

A

target: Gyrase
used for: UTIs
not good against Streptococci (respiratory infections)

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17
Q

Levofloxacin: target, uses

A

target: Topo IV
uses: better activity against Streptococci (respiratory infections)

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18
Q

What is unique about Moxifloxacin?

targets?

A

poor penetration into the urinary tract
don’t use for UTIs
not excreted in the urine
Targets: Gram positive, anaerobes

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19
Q

Quinolone resistance methods?

A

Mutations in target genes
Efflux pumps
plasmids

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20
Q

what group of patients is Quinolone not approved for? Why?

A

Pregnancy and childhood

may cause arthropathy

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21
Q

Adverse effects of Quinolone?

A 
considered pretty safe
headache, nausea, vomiting
prolonged QT time with other mediciations
tendon rupture
potential for arthropathy in children
risk factor for Clostridium Difficile
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22
Q

Nitrofurantion mechanism?

A

Unknown

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23
Q

Nitrofurantion clinical uses? why?

A

UTI exclusively

doesn’t reach adequate serum levels, concentrates in urine

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24
Q

Nitrofurantion general uses?

Not used for which bacteria?

A

used for: Gram positive and Gram negative

not used for: Proteus spp, Pseudomonas spp., Serratia marcescens

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25
Q

Rifamycins mechanism of action?

Bactericidal or Bacteriostatic?

A

RNA inhibitor
binds to Beta subunit of RNA polymerase, blocks transcription
Bacteriostatic

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26
Q

General uses of Rifamycins?

A

Very broad spectrum: Gram positive, negative, mycobacterium, anaerobic

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27
Q

What are the 3 Rifamycins? important facts about each?

A

Rifampin- potent inducer
Rifabutin- not much of an inducer
Rifaximin- not absorbed (only used for GI infections)

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28
Q

Rifamycin resistance?

A

Mutations in target enzyme (mutations often preexist in the population limiting effectiveness)

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29
Q

Rifamycin uses:

A

PO
prophylaxis for Neisseria meningitis and Staph aureus
in combination with other antimicrobials for mycobacterium
GI infections (travelers diarrhea): Rifaximin only

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30
Q

Rifamycin adverse effects:

A

turns secretions orange
GI: pain, nausea, vomiting
Hem: mild thromocytopenia, leukopenia, anemia
hepatitis

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31
Q

Fidaxomicin mechanism

A

inhibits RNA polymerase by preventing DNA complex opening

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32
Q

Fidaxomicin general uses:

A

ONLY Gram positive bacteria
less drastic effect on fecal microbiome compared to other drugs
poor activity against gram negative enteric flora

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33
Q

Fidaxomicin clinical uses:

A

approved only for C. Difficile infections
PO
non-absorbable oral antimicrobial

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34
Q

Fidaxomicin adverse effects?

A

no side effects reported/minimal

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35
Q

Penicillin Mechanism of action?

A

B-lactam ring mimics D-Ala-D-ala, binds to Transpeptidase inactivating it, weakened cell wall, lysis
Bactericidal

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36
Q

Penicillin mechanism of resistance?

A
  1. B-lactamases (penicillinases)
  2. modified PBP
  3. Efflux pumps
  4. decreased outer membrane permeability
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37
Q

What is MRSA?

What causes this resistance?

A

Methicillin-Resistant Staphylococcus aureus

modified PBP: PBP2A encoded by mecA gene resulting in decrease affinity of PBP for B lactam antibiotics

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38
Q

General properties of Penicillin?

A 
bactericidal
good tissue penetration- CNS for meningitis 
Renal excretion
good therapeutic index
shot half life- frequent dosing
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39
Q

Common adverse effects of Penicillin?

A

Hypersensitivity**

seizures at high doses

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40
Q

Penicillin G Bacterial Spectrum of activity?

A

Gram positive cocci and anaerobes
Gram negative cocci only
spirochetes

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41
Q

Clinical uses of Penicillin G?

A

IV
Streptococci (Group A, group B, pneumoniae)
Anaerobic infection (dental abscesses, human bites)
Sphyillis

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42
Q

Aminopenicillins? IV or PO?

A

Ampicillin (IV)

Amoxicillin (PO)

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43
Q

Aminopenicillins: Adverse effects?

A

Hypersensitive
seizures at high doses
GI distress
patients with mononucleosis treated with amoxicillin will get a maculopapular rash (not an allergic reaction)

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44
Q

Aminopenicillins: Bacterial spectrum?

A

same as penicillin G except:
improved activity for Gram negative bacilli (H.flu, Ecoli)
NOT pseudomonas

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45
Q

Aminopenicillins: Clinical uses?

A

community acquired HEENT and upper respiratory infections

community acquired UTIs

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46
Q

Semi-synthetic penicillins? IV or PO?

A

Penicillinase-resistant penicillins
Nafcillin (IV)
Decloxacillin (PO)

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47
Q

What is the prototype of semi-synthetic penicillins? why is it no longer used

A

Methicillin

no longer used due to toxicity

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48
Q

Nafcillin and Dicloxacillin: Bacterial spectrum of activity?

A

Gram positive ONLY

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49
Q

Nafcillin and Dicloxacillin: Clinical uses?

A

infections due to methicillin-susceptible Staphylococcus aureus

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50
Q

Piperacillin: bacterial spectrum?

A

Pseudomonas

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51
Q

B-Lactamase Inhibitors:

A

Clavulanic acid
Taxobactum
Sulbactam

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52
Q

What are B-lactamases? How are they used?

A

enzymes produced by bacteria that hydrolyze B-lactam antibiotics
used in fixed combinations with B-lactam antibiotics

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53
Q

What are Expanded-spectrum B-lactamases (ESBL)?

A

B-lactamases that have mutations that enable them to degrade some antibiotics that are design to resist B-lactamase cleavage (semi-synthetic penicillins)

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54
Q

B-lactamase use:

A

broad spectrum

should not be used if narrow spectrum agents are available

55
Q

Cephalosporin: Mechanism of action

A

B-lactam

similar mechanism to penicillin- bind and inhibit PBPs, weakening cell wall, cell death

56
Q

Cephalosporins do not work against what type of bacteria (generalization)

A

Enterococci

Cephalosporins have no activity against enterococci due to intrinsic resistance

57
Q

What is the only cephalosporin with activity against MRSA?

A

Ceftaroline

58
Q

Cephalosporins: Side Effects

A

generally well tolerated

Hypersensitivity (cross reactivity with penicillin allergy exists)

59
Q

Cephalosporins: Mechanism of resistance

A

Intrinsic resistance (Enterococci, pseudomonas)
Altered membrane permeability
altered PBPs
B-lactamases

60
Q

Cephalosporins: generalizations on bacterial spectrum?

A

Gram negative activity increase with increasing generations
all have some Gram positive activity
NO activity against Enterococci
only 1 agent against MRSA

61
Q

1st generation Cephalosporins? IV or PO?

A

Cefazolin (IV)

Cephalexin (PO)

62
Q

Cefazolin and Cephalexin: Bacterial spectrum

A

Gram negative
good Gram positive
Broad spectrum

63
Q

Cefazolin and Cephalexin: Clinical uses?

A

Cefazolin: Surgical prophylaxis
Cephalexin: skin/soft tissue infections (streptococci and staphylococci)

64
Q

2nd generation Cephalosporins?
Bacterial spectrum?
Clinical Use?

A

Cefoxitin (IV)
increased Gram negative activity
good anaerobic activity*
Intra-abdominal infections, prophylaxis for intra-abdominal surgery

65
Q

3rd generation Cephalosporins?
unique feature about this group (tissue penetration)?
Bacterial Spectrum

A

Ceftriaxone (IV)
Ceftazidime (IV)
high degree of CNS penetration
excellent Gram negative cocci and bacilli

66
Q

Ceftriazone: clinical use

Unique excretion?

A

community acquired pneumonia
Meningitis due to N. meningitis and S. pneumonia
serious infections
Excretion: Biliary tract

67
Q

Ceftazidime specific bacterial spectrum

A

Pseudomonas

68
Q

4th generation cephalosporins?
bacterial spectrum
clinical uses

A

Cefepime (IV)
excellent Gram negative (including pseudomonas)
Gram positive
Serious or resistant infections (highly resistant to B-lactamases)

69
Q

5th general cephalosporins?

Bacterial spectrum

A

Ceftaroline (IV)
Only cephalosporin with MRSA activity
bacterial activity resembles 3rd generation activity

70
Q

5 Carbapenems, IV or PO?

A 
Doripenem
Meropenem
Imipenem
Ertapenem
ALL IV
71
Q

Carbapenems: mechanism of action

A

similar to Penicillins: binds and inhibits PBP, weakening cell wall, cell lysing

72
Q

Carbapenems: mechanism of resistant

A

B-lactamases: Carbapenases
KPCs: Klebsiella producing carbapenases
metallo-B-lactamases

73
Q

Carbapenems: Adverse reaction

A

Hypersenitivity

Cross reactivity with penicillin allergy

74
Q

Carbapenems: Spectrum of activity

A

very broad: Gram negative, Gram positive, Anaerobes
including Pseudomonas
Ertapenem does NOT work for Pseudomonas or Acinetobacter

75
Q

Carbapenems; Spectrum of activity

A

Empiric treatment of serious infections (because IV only and very broad)
Resistant infections

76
Q

Aztreonam: Mechanism of Action

A

Monobactam
similar mechanism to penicillins: binds, inhibits PBPs and lysis cell
IV only

77
Q

Aztreonam: adverse effects

A

limited immunogenic potential

hypersensitivy or cross reactivity to penicillin less common

78
Q

Aztreonam Bacterial spectrum

Clinical Uses

A

Gram negative ONLY

limited use: life threatening infections, alternative for penicillin/cephalosporin allergy

79
Q

Vancomycin: Mechanism of action

IV or PO

A

glycopeptide
binds to D-ala-D-ala on peptidoglycan
inhibits both transglycosylase and transpeptiase

IV
PO- nonabsorbable

80
Q

Vancomycin resistance

A

altering binding site: change from D-ala-D-ala to D-ala-D-lactic acid
VanA-E genes
VRE- vancomyosin resistant enterococci
VRSA- vancomyosin resistant S. aureus

Thickened cell wall- decreases penetration

81
Q

Vancomycin Adverse events

A

Red Man syndrome
Nephrotoxicity
Dose related ototoxicity

82
Q

What is Red man syndrome? What antibiotic?

A

Vancomycin
infusion reaction, NOT hypersensitivty
histamine release from mast cells, independent of IgE
not a true allergy, prevented by slowing infusion rate

83
Q

Vancomycin bacterial spectrum

A

Gram positive ONLY
Strep, Staph, Enterococci, GP anaerobes
including MRSA

84
Q

Vancomycin clinical uses

A

inferior to B-lactams
Empiric treatment for serious infection
PO- C. Difficile

85
Q

Daptomycin mechanism of action

A

Cyclic lipopeptide
IV only
lipophilic tail inserts into membrane, depolarization, K efflux, cessation of cellular activity, cell death without lysis
*activity not dependent on actively growing cells

86
Q

Daptomycin resistance

A

failure associated with increased MIC

87
Q

Daptomycin adverse effects

A

Elevated creatinine phosphokinase (CPK)
Rhabdomyolysis (avoid concurrent use of statin drugs)

GI upset, rash, headache

88
Q

Daptomycin bacterial spectrum

Clinical uses

A

Gram positive ONLY (including MRSA and VRE)
Staph, Enterococci, GP anaerobes
complicated Gram positive infections: bacteremia, endocarditis, skin/soft tissue infections

89
Q

Bacitracin

A

Topical
Gram positive ONLY (S.aureus, Strep pyogenes)
clinical use: superficial skin infections

90
Q

Polymixin B and Polymixin E (Colistin)

A

Gram negative Bacilli ONLY
IV, topica, inhalation
serious toxicities: Nephrotoxicity, neurotoxicity, inhaled bronchospasm
only used for serious resistant GN infections when no other drugs available- last resort

91
Q

Fosomycin

A

oral powder

Exclusively UTIs

92
Q

Cell envelope antibiotics:Gram positive only antibiotics?

A

Nafcillin, Vancomycin, Daptomycin, Bacitracin

93
Q

Cell envelope antibiotics: Gram negative only antibiotics?

A

Aztreonam, Polymyxins

94
Q

Cell envelop antibiotics with MSRA activity

A

Ceftaroline, Vancomycin, Daptomycin

95
Q

What cell envelope antibiotic does have any enterococci activity?

A

Cephalosporins

96
Q

4 Aminolgycosides

A

Gentamycin
Amikacin
Streptomycin
tobramycin

97
Q

Aminoglycosides mechanism of action?

IV or PO

A

binds to 30S subunit, inhibits protein synthesis
alone cannot penetrate cell wall of Gram positive bacteria- synergy with B-lactams
IV

98
Q

Aminoglycosides adverse side effects

A

Nephrotoxicity: tubular necrosis, damage
Ototoxicity: hearing loss, loss of balance
Neuromuscular blockade: dont use in patients with Myasthenia gravis

99
Q

Amingoglycoside spectrum of activity

A

predominantly Gram negative, including pseudomonas
No activity against Gram positive alone
No activity against anaerobes

100
Q

Aminoglycosides Clinical use

A

UTIs- reaches high levels in kidneys
Serious Gram negative Infections
usually used in combination with another drug (except for UTIs)
Amikacin and Streptomycin used for resistant Mycobacterium TB
NOT used for PNA because inactivated by acidic pH

101
Q

3 Tetracyclines

A

Docycyclins
Tetracyclins
Minocyclin

102
Q

Tetracyclines mechanism of action

A

Binds to 30S ribosomal subunit, preventing tRNA binding, inhibiting protein synthesis
lipophilic nature allows penetration through GN and GP bacterial cell wall

103
Q

Tetracycline resistance

A

common

Plasmid mediated: active efflux, ribosomal protective proteins

104
Q

Tetracyclines PK/PD

A

decreased absorption with Ca and Dairy
binds to calcified tissues, bone and teeth- teeth staining, teeth hypoplasia and stunted growth of long bone
crosses placenta barrier- dont use in pregnant woman

105
Q

Tetracycline Adverse effects

A

Bone problems- stained teeth, teeth hypoplasia, stunted growth
Photosensitivity

106
Q

Tetracycline Bacterial spectrum

A 
broad range
Gram negative, NOT pseudomonas
Gram positive
some anaerobes
atypicals: chlamydia, mycoplasma
107
Q

Tetracycline clinical uses

A

Community acquired pneumonia
Bronchitis
STI: Chlamydia

do NOT use in children or pregnant woman

108
Q

Tigecycline, mechanisms of action, spectrum, clinical uses

A

semi-synthetic derivative of tetracycline, same mechanism
spectrum- even broader spectrum then Tetracyclines (NO Psuedomonas)
clinical use- IV, high resistance, increased mortality with use for serious infections including pneumonia

109
Q

Macrolides

Mechanism of action?

A

Azithromycin, Erythromycin, Clarithromycin

binds to 50S ribosomal subunit, inhibit protein synthesis

110
Q

Macrolides resistance

A 
may mechanism limit use
efflux pumps
alteration of target site (erm genes)
decrease cell wall permeability
enzymatic drug interactions
111
Q

Macrolides adverse effects

A 
Epigastric distress (N/V/abdominal pain)
prolonged Q-T
112
Q

Macrolides bacterial spectrum

A 
Broad activity
GN (NOT pseudomonas)
GP: Staph and strep
some anaerobes
atypicals: chlamydia, mycoplasma, legionella
113
Q

Azithromycin clinical uses

A

Community acquired pneumonia
bronchitis
STI: Chlamydia
atypical pneumonia

114
Q

Erythromycin clinical uses

A

not usually used as an antibiotic
promote gut motility
not used due to adverse events (GI distress) and frequent dosing

115
Q

Clarithromycin Clinical uses

A

Helicobacter pylori
Mycobacterium avium
**not usually used for bacterial infections

116
Q

Clindamycin: mechanism of action

A

Lincosamide

mechanism same as macrolides: binds 50S ribosomal subunit

117
Q

Clindamycin Resistance

A

Clindamycin inducible resistance
mediated by erm gene
suspect with S. aureus with clindamycin sensitivity and erythromycin resistance
test this with D test

118
Q

Clindamycin adverse effects

A

Clostridium difficile infection**

119
Q

Clindamycin bacterial spectrum

A

NO GN activity
GP: Strep and Staph
Anaerobes
Parasites

120
Q

Clindamycin clinical uses

A

Community acquired aspiration pneumonia
above the diaphragm infections
skin and soft tissue infections
toxic shock syndeome due to Group A strep

121
Q

2 Oxazolidinones; IV or PO?

A

Linezolid
Tedizolid
both IV and PO

122
Q

Oxazolidinones resistance

A

uncommon

123
Q

Oxazolidinones Adverse effects

A 
Bone marrow supression: thrombocytopenia
Serotonin syndrome (inhibits monoamine oxidase)
lactic acidosis
124
Q

Oxazolidinones Bacterial spectrum

A

Gram positive ONLY

Strep, Staph, Enterococci (including VRE)

125
Q 
Mupirocin 
mechanism of action
how is it applied?
Resistance?
Adverse events
A

binds to tRNA synthetase
topical
MRSA display high or low levels of resistance
no significant adverse events, contact dermititis

126
Q

Muriocin
Bacterial spectrum
clinical uses

A

Gram Positive ONLY (not enterococci)
uncomplicated soft tissue infections
MRSA decolonization of anterior snares
prophylaxis against catheter related infections

127
Q

Imidazoles (2)

mechanism of action

A

Metronidazole
Tinidazole
enters through diffusion, production of free radicals, cytotoxic effect

128
Q

Imidazoles (Metronidazole, Tinidazole) adverse effects

A

metallic taste

Disulfram-like effect with alcohol (vomiting, flushing)

129
Q

Imidazoles Bacterial spectrum, clinical uses

A

Anaerobes (below the diaphragm)
protozoas

cllinical uses: anaerobic infections below the diaphragm (C-diff, intra-abdominal infections(

130
Q 
Adverse effects of Protein synthesis inhibitors;
Aminoglycosides
Tetracyclines
Ery/Azithromycin
Clindamycin
Linezolid
A

Aminoglycosides: Oto/nephrotoxicity, NMJ blockade
Tetracyclines: Photosensitivity, Bone/teeth
Ery/Azithromycin: GI, prolonged QT
Clindamycin: C,diff
Linezolid: BM suppression, Serotonin syndrome

131
Q

Protein synthesis inhibitors: Cover anaerobes only

A

Clindamycin, Tetracyclines, Tigecycline, macrolids, imidazoles

132
Q

Protein synthesis inhibitors: Gram positive only

A

Linezolid/tedizolid (including Enterococci

Mupirocin (no enterococci

133
Q

TB drugs

A 
Isoniazid
Strepomycin
Rifampin
Ethambutol
Pyrazinamide
134
Q

Leprosy drugs

A

Dapsone
Rifampin
Clofazamine

Drugs (5 decks)

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