Bacterial Drugs Flashcards
1
Q
Trimethoprim action
A
inhibits Dihydrofolate reductase/ inhibits tetrahydrofolate synthesis resembles dihydrofolate (reactant) bacterstatic when used alone
2
Q
Sulfamethoxazole
A
inhibits dihydropteroate synthetase/ inhibits tetrahydroflolate synthesis resembles PABA (reactant)
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
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
5
Q
Clinical uses of TMP-SMX:
A
IV or PO
urinary infections (UTI)
Respiratory infections (Sinusitis, otitis media(
GI infections: bacterial diarrhea
6
Q
Can TMP-SMX penetrate immune privileged sites?
A
Yes- excellent tissue penetration
7
Q
What are resistance methods for TMP-SMX?
A
TMP and SMX: plasmid encoding alternative alleles for the enzymes
SMX: chromosomal mutations
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
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!
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
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
12
Q
What is the excretion method of TMP-SMX?
A
Urine, unchanged
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
14
Q
what is the excretion method of Quinolones?
What is the exception?
A
Urine
Exception: Moxifloxacin*
15
Q
What are the 4 types of Quinolones?
A
Nalidixic acid
Ciprofloxacin
Levofloxacin
Moxifloxacin
16
Q
Ciprofloxacin: target, uses, contraindications
A
target: Gyrase
used for: UTIs
not good against Streptococci (respiratory infections)
17
Q
Levofloxacin: target, uses
A
target: Topo IV
uses: better activity against Streptococci (respiratory infections)
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
19
Q
Quinolone resistance methods?
A
Mutations in target genes
Efflux pumps
plasmids
20
Q
what group of patients is Quinolone not approved for? Why?
A
Pregnancy and childhood
may cause arthropathy
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
22
Q
Nitrofurantion mechanism?
A
Unknown
23
Q
Nitrofurantion clinical uses? why?
A
UTI exclusively
doesn’t reach adequate serum levels, concentrates in urine
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
25
Rifamycins mechanism of action?
| Bactericidal or Bacteriostatic?
RNA inhibitor
binds to Beta subunit of RNA polymerase, blocks transcription
Bacteriostatic
26
General uses of Rifamycins?
Very broad spectrum: Gram positive, negative, mycobacterium, anaerobic
27
What are the 3 Rifamycins? important facts about each?
Rifampin- potent inducer
Rifabutin- not much of an inducer
Rifaximin- not absorbed (only used for GI infections)
28
Rifamycin resistance?
Mutations in target enzyme (mutations often preexist in the population limiting effectiveness)
29
Rifamycin uses:
PO
prophylaxis for Neisseria meningitis and Staph aureus
in combination with other antimicrobials for mycobacterium
GI infections (travelers diarrhea): Rifaximin only
30
Rifamycin adverse effects:
turns secretions orange
GI: pain, nausea, vomiting
Hem: mild thromocytopenia, leukopenia, anemia
hepatitis
31
Fidaxomicin mechanism
inhibits RNA polymerase by preventing DNA complex opening
32
Fidaxomicin general uses:
ONLY Gram positive bacteria
less drastic effect on fecal microbiome compared to other drugs
poor activity against gram negative enteric flora
33
Fidaxomicin clinical uses:
approved only for C. Difficile infections
PO
non-absorbable oral antimicrobial
34
Fidaxomicin adverse effects?
no side effects reported/minimal
35
Penicillin Mechanism of action?
B-lactam ring mimics D-Ala-D-ala, binds to Transpeptidase inactivating it, weakened cell wall, lysis
Bactericidal
36
Penicillin mechanism of resistance?
1. B-lactamases (penicillinases)
2. modified PBP
3. Efflux pumps
4. decreased outer membrane permeability
37
What is MRSA?
| What causes this resistance?
Methicillin-Resistant Staphylococcus aureus
| modified PBP: PBP2A encoded by mecA gene resulting in decrease affinity of PBP for B lactam antibiotics
38
General properties of Penicillin?
```
bactericidal
good tissue penetration- CNS for meningitis
Renal excretion
good therapeutic index
shot half life- frequent dosing
```
39
Common adverse effects of Penicillin?
Hypersensitivity**
| seizures at high doses
40
Penicillin G Bacterial Spectrum of activity?
Gram positive cocci and anaerobes
Gram negative cocci only
spirochetes
41
Clinical uses of Penicillin G?
IV
Streptococci (Group A, group B, pneumoniae)
Anaerobic infection (dental abscesses, human bites)
Sphyillis
42
Aminopenicillins? IV or PO?
Ampicillin (IV)
| Amoxicillin (PO)
43
Aminopenicillins: Adverse effects?
Hypersensitive
seizures at high doses
GI distress
patients with mononucleosis treated with amoxicillin will get a maculopapular rash (not an allergic reaction)
44
Aminopenicillins: Bacterial spectrum?
same as penicillin G except:
improved activity for Gram negative bacilli (H.flu, Ecoli)
NOT pseudomonas
45
Aminopenicillins: Clinical uses?
community acquired HEENT and upper respiratory infections
| community acquired UTIs
46
Semi-synthetic penicillins? IV or PO?
Penicillinase-resistant penicillins
Nafcillin (IV)
Decloxacillin (PO)
47
What is the prototype of semi-synthetic penicillins? why is it no longer used
Methicillin
| no longer used due to toxicity
48
Nafcillin and Dicloxacillin: Bacterial spectrum of activity?
Gram positive ONLY
49
Nafcillin and Dicloxacillin: Clinical uses?
infections due to methicillin-susceptible Staphylococcus aureus
50
Piperacillin: bacterial spectrum?
Pseudomonas
51
B-Lactamase Inhibitors:
Clavulanic acid
Taxobactum
Sulbactam
52
What are B-lactamases? How are they used?
enzymes produced by bacteria that hydrolyze B-lactam antibiotics
used in fixed combinations with B-lactam antibiotics
53
What are Expanded-spectrum B-lactamases (ESBL)?
B-lactamases that have mutations that enable them to degrade some antibiotics that are design to resist B-lactamase cleavage (semi-synthetic penicillins)
54
B-lactamase use:
broad spectrum
| should not be used if narrow spectrum agents are available
55
Cephalosporin: Mechanism of action
B-lactam
| similar mechanism to penicillin- bind and inhibit PBPs, weakening cell wall, cell death
56
Cephalosporins do not work against what type of bacteria (generalization)
Enterococci
| Cephalosporins have no activity against enterococci due to intrinsic resistance
57
What is the only cephalosporin with activity against MRSA?
Ceftaroline
58
Cephalosporins: Side Effects
generally well tolerated
| Hypersensitivity (cross reactivity with penicillin allergy exists)
59
Cephalosporins: Mechanism of resistance
Intrinsic resistance (Enterococci, pseudomonas)
Altered membrane permeability
altered PBPs
B-lactamases
60
Cephalosporins: generalizations on bacterial spectrum?
Gram negative activity increase with increasing generations
all have some Gram positive activity
NO activity against Enterococci
only 1 agent against MRSA
61
1st generation Cephalosporins? IV or PO?
Cefazolin (IV)
| Cephalexin (PO)
62
Cefazolin and Cephalexin: Bacterial spectrum
Gram negative
good Gram positive
Broad spectrum
63
Cefazolin and Cephalexin: Clinical uses?
Cefazolin: Surgical prophylaxis
Cephalexin: skin/soft tissue infections (streptococci and staphylococci)
64
2nd generation Cephalosporins?
Bacterial spectrum?
Clinical Use?
Cefoxitin (IV)
increased Gram negative activity
good anaerobic activity*
Intra-abdominal infections, prophylaxis for intra-abdominal surgery
65
3rd generation Cephalosporins?
unique feature about this group (tissue penetration)?
Bacterial Spectrum
Ceftriaxone (IV)
Ceftazidime (IV)
high degree of CNS penetration
excellent Gram negative cocci and bacilli
66
Ceftriazone: clinical use
| Unique excretion?
community acquired pneumonia
Meningitis due to N. meningitis and S. pneumonia
serious infections
Excretion: Biliary tract
67
Ceftazidime specific bacterial spectrum
Pseudomonas
68
4th generation cephalosporins?
bacterial spectrum
clinical uses
Cefepime (IV)
excellent Gram negative (including pseudomonas)
Gram positive
Serious or resistant infections (highly resistant to B-lactamases)
69
5th general cephalosporins?
| Bacterial spectrum
Ceftaroline (IV)
Only cephalosporin with MRSA activity
bacterial activity resembles 3rd generation activity
70
5 Carbapenems, IV or PO?
```
Doripenem
Meropenem
Imipenem
Ertapenem
ALL IV
```
71
Carbapenems: mechanism of action
similar to Penicillins: binds and inhibits PBP, weakening cell wall, cell lysing
72
Carbapenems: mechanism of resistant
B-lactamases: Carbapenases
KPCs: Klebsiella producing carbapenases
metallo-B-lactamases
73
Carbapenems: Adverse reaction
Hypersenitivity
| Cross reactivity with penicillin allergy
74
Carbapenems: Spectrum of activity
very broad: Gram negative, Gram positive, Anaerobes
including Pseudomonas
Ertapenem does NOT work for Pseudomonas or Acinetobacter
75
Carbapenems; Spectrum of activity
Empiric treatment of serious infections (because IV only and very broad)
Resistant infections
76
Aztreonam: Mechanism of Action
Monobactam
similar mechanism to penicillins: binds, inhibits PBPs and lysis cell
IV only
77
Aztreonam: adverse effects
limited immunogenic potential
| hypersensitivy or cross reactivity to penicillin less common
78
Aztreonam Bacterial spectrum
| Clinical Uses
Gram negative ONLY
| limited use: life threatening infections, alternative for penicillin/cephalosporin allergy
79
Vancomycin: Mechanism of action
| IV or PO
glycopeptide
binds to D-ala-D-ala on peptidoglycan
inhibits both transglycosylase and transpeptiase
IV
PO- nonabsorbable
80
Vancomycin resistance
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
Vancomycin Adverse events
Red Man syndrome
Nephrotoxicity
Dose related ototoxicity
82
What is Red man syndrome? What antibiotic?
Vancomycin
infusion reaction, NOT hypersensitivty
histamine release from mast cells, independent of IgE
not a true allergy, prevented by slowing infusion rate
83
Vancomycin bacterial spectrum
Gram positive ONLY
Strep, Staph, Enterococci, GP anaerobes
including MRSA
84
Vancomycin clinical uses
inferior to B-lactams
Empiric treatment for serious infection
PO- C. Difficile
85
Daptomycin mechanism of action
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
Daptomycin resistance
failure associated with increased MIC
87
Daptomycin adverse effects
Elevated creatinine phosphokinase (CPK)
Rhabdomyolysis (avoid concurrent use of statin drugs)
GI upset, rash, headache
88
Daptomycin bacterial spectrum
| Clinical uses
Gram positive ONLY (including MRSA and VRE)
Staph, Enterococci, GP anaerobes
complicated Gram positive infections: bacteremia, endocarditis, skin/soft tissue infections
89
Bacitracin
Topical
Gram positive ONLY (S.aureus, Strep pyogenes)
clinical use: superficial skin infections
90
Polymixin B and Polymixin E (Colistin)
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
Fosomycin
oral powder
| Exclusively UTIs
92
Cell envelope antibiotics:Gram positive only antibiotics?
Nafcillin, Vancomycin, Daptomycin, Bacitracin
93
Cell envelope antibiotics: Gram negative only antibiotics?
Aztreonam, Polymyxins
94
Cell envelop antibiotics with MSRA activity
Ceftaroline, Vancomycin, Daptomycin
95
What cell envelope antibiotic does have any enterococci activity?
Cephalosporins
96
4 Aminolgycosides
Gentamycin
Amikacin
Streptomycin
tobramycin
97
Aminoglycosides mechanism of action?
| IV or PO
binds to 30S subunit, inhibits protein synthesis
alone cannot penetrate cell wall of Gram positive bacteria- synergy with B-lactams
IV
98
Aminoglycosides adverse side effects
Nephrotoxicity: tubular necrosis, damage
Ototoxicity: hearing loss, loss of balance
Neuromuscular blockade: dont use in patients with Myasthenia gravis
99
Amingoglycoside spectrum of activity
predominantly Gram negative, including pseudomonas
No activity against Gram positive alone
No activity against anaerobes
100
Aminoglycosides Clinical use
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
3 Tetracyclines
Docycyclins
Tetracyclins
Minocyclin
102
Tetracyclines mechanism of action
Binds to 30S ribosomal subunit, preventing tRNA binding, inhibiting protein synthesis
lipophilic nature allows penetration through GN and GP bacterial cell wall
103
Tetracycline resistance
common
| Plasmid mediated: active efflux, ribosomal protective proteins
104
Tetracyclines PK/PD
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
Tetracycline Adverse effects
Bone problems- stained teeth, teeth hypoplasia, stunted growth
Photosensitivity
106
Tetracycline Bacterial spectrum
```
broad range
Gram negative, NOT pseudomonas
Gram positive
some anaerobes
atypicals: chlamydia, mycoplasma
```
107
Tetracycline clinical uses
Community acquired pneumonia
Bronchitis
STI: Chlamydia
do NOT use in children or pregnant woman
108
Tigecycline, mechanisms of action, spectrum, clinical uses
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
Macrolides
| Mechanism of action?
Azithromycin, Erythromycin, Clarithromycin
| binds to 50S ribosomal subunit, inhibit protein synthesis
110
Macrolides resistance
```
may mechanism limit use
efflux pumps
alteration of target site (erm genes)
decrease cell wall permeability
enzymatic drug interactions
```
111
Macrolides adverse effects
```
Epigastric distress (N/V/abdominal pain)
prolonged Q-T
```
112
Macrolides bacterial spectrum
```
Broad activity
GN (NOT pseudomonas)
GP: Staph and strep
some anaerobes
atypicals: chlamydia, mycoplasma, legionella
```
113
Azithromycin clinical uses
Community acquired pneumonia
bronchitis
STI: Chlamydia
atypical pneumonia
114
Erythromycin clinical uses
not usually used as an antibiotic
promote gut motility
not used due to adverse events (GI distress) and frequent dosing
115
Clarithromycin Clinical uses
Helicobacter pylori
Mycobacterium avium
**not usually used for bacterial infections
116
Clindamycin: mechanism of action
Lincosamide
| mechanism same as macrolides: binds 50S ribosomal subunit
117
Clindamycin Resistance
Clindamycin inducible resistance
mediated by erm gene
suspect with S. aureus with clindamycin sensitivity and erythromycin resistance
test this with D test
118
Clindamycin adverse effects
Clostridium difficile infection**
119
Clindamycin bacterial spectrum
NO GN activity
GP: Strep and Staph
Anaerobes
Parasites
120
Clindamycin clinical uses
Community acquired aspiration pneumonia
above the diaphragm infections
skin and soft tissue infections
toxic shock syndeome due to Group A strep
121
2 Oxazolidinones; IV or PO?
Linezolid
Tedizolid
both IV and PO
122
Oxazolidinones resistance
uncommon
123
Oxazolidinones Adverse effects
```
Bone marrow supression: thrombocytopenia
Serotonin syndrome (inhibits monoamine oxidase)
lactic acidosis
```
124
Oxazolidinones Bacterial spectrum
Gram positive ONLY
| Strep, Staph, Enterococci (including VRE)
125
```
Mupirocin
mechanism of action
how is it applied?
Resistance?
Adverse events
```
binds to tRNA synthetase
topical
MRSA display high or low levels of resistance
no significant adverse events, contact dermititis
126
Muriocin
Bacterial spectrum
clinical uses
Gram Positive ONLY (not enterococci)
uncomplicated soft tissue infections
MRSA decolonization of anterior snares
prophylaxis against catheter related infections
127
Imidazoles (2)
| mechanism of action
Metronidazole
Tinidazole
enters through diffusion, production of free radicals, cytotoxic effect
128
Imidazoles (Metronidazole, Tinidazole) adverse effects
metallic taste
| Disulfram-like effect with alcohol (vomiting, flushing)
129
Imidazoles Bacterial spectrum, clinical uses
Anaerobes (below the diaphragm)
protozoas
cllinical uses: anaerobic infections below the diaphragm (C-diff, intra-abdominal infections(
130
```
Adverse effects of Protein synthesis inhibitors;
Aminoglycosides
Tetracyclines
Ery/Azithromycin
Clindamycin
Linezolid
```
Aminoglycosides: Oto/nephrotoxicity, NMJ blockade
Tetracyclines: Photosensitivity, Bone/teeth
Ery/Azithromycin: GI, prolonged QT
Clindamycin: C,diff
Linezolid: BM suppression, Serotonin syndrome
131
Protein synthesis inhibitors: Cover anaerobes only
Clindamycin, Tetracyclines, Tigecycline, macrolids, imidazoles
132
Protein synthesis inhibitors: Gram positive only
Linezolid/tedizolid (including Enterococci
| Mupirocin (no enterococci
133
TB drugs
```
Isoniazid
Strepomycin
Rifampin
Ethambutol
Pyrazinamide
```
134
Leprosy drugs
Dapsone
Rifampin
Clofazamine
