Other Antibacterials Questions Flashcards
1
Q
Name the glycopeptides and short-acting lipoglycopeptides.
A
- vancomycin
- telavancin
- teicoplanin (not available in the US)
2
Q
What is the general spectrum of activity of vancomycin?
A
Has activity against most things gram positive that haven’t learned to become resistant to it
- many enterococci have figured this out (especially E. faecium); VRE- vancomycin resistant enterococci
- few staphylococci have learned vancomycin resistance from the enterococci
3
Q
What is telavancin?
A
Lipoglycopeptide (structure modified from vancomycin)
-improved activity against MRSA that is less susceptible to vancomycin
4
Q
What is the MOA of vancomycin?
A
Glycopeptides bind to terminal D-ala-D-ala chains on peptidoglycan in the cell wall (preventing further elongation of peptidoglycan chains)
5
Q
What is the MOA of telavancin?
A
Vancomycin’s MOA plus:
Interferes with the cell membrane also (disrupting membrane function)
6
Q
What organisms do (lipo)glycopeptides have GOOD activity against?
A
- MSSA
- MRSA
- streptococci
- Clostridium difficile
7
Q
What organisms do (lipo)glycopeptides have MODERATE activity against?
A
-enterococci
8
Q
What organisms do (lipo)glycopeptides have POOR activity against?
A
-anything gram negative
9
Q
List the categories of adverse effects of vancomycin.
A
- infusion-related reactions
- ototoxicity
- renal
10
Q
What is red man syndrome?
A
Histamine-mediated reaction classically associated with vancomycin (not a true allergy)
Patient may feel:
- warm
- flushed
- may develop hypotension
11
Q
How can the risk of red man syndrome be decreased?
A
- can be prevented by slowing the infusion rate
- antihistamines can ameliorate the reaction
12
Q
Can telavancin cause red man syndrome?
A
Yes
-its core structure is essentially vancomycin
13
Q
Describe vancomycin’s ototoxicity.
A
Has historically been considered ototoxic
-evidence linking it with this toxicity is unclear
14
Q
Describe vancomycin’s nephrotoxicity.
A
- classically assigned to vancomycin
- historical evidence linking this with vancomycin is poor
- may be nephrotoxic in higher doses (including higher doses commonly used to treat MRSA in the 21st century)
15
Q
What is Mississippi Mud?
A
Nickname for vancomycin
- early formulation was brown
- current formulation is clear (lacks those potentially toxic excipients)
16
Q
Does telavancin have renal toxicity issues also?
A
Yes
17
Q
What are specific adverse effects associated with telavancin?
A
- taste disturbances
- foamy urine
18
Q
Should telavancin be used in pregnant women?
A
No, unless absolutely necessary
- is category C
- developmental issues seen in animal studies
19
Q
How is vancomycin pharmacokinetically monitored?
A
- trough concentrations used to monitor elimination (not being eliminated too quickly or slowly)
- different indications have different preferred trough ranges
- higher troughs may be associated with nephrotoxicity
20
Q
What are vancomycin peak levels used for?
A
For calculating patient specific PK parameters
- do not seem to predict efficacy or safety
- should NOT be drawn for most patients
21
Q
What is oral vancomycin used for?
A
Treatment of C. difficile-associated disease
- absorbed very poorly
- achieves sky-high gut concentrations (lowest dose is best for the majority of patients)
22
Q
Can IV vancomycin be used for C. difficile?
A
No
-does not reach high enough intracolonic concentrations to kill C. difficile
23
Q
What is the proper reaction to a too high vancomycin trough?
A
Ask if it was drawn correctly
-if so, increase the dosing interval
24
Q
Is vancomycin the preferred drug against MSSA?
A
No
- does not kill MSSA as quickly as beta-lactams
- use cefazolin or nafcillin
25
What is MIC creep in regards to staphylococci and vancomycin?
Susceptible range is <= 2mg/L
-patients receiving vancomycin for serious staphylococcal infections with an MIC = 2 mg/L have worse outcomes than those with lower MICs
26
Which (lipo)glycopeptide is more rapidly bactericidal?
Telavancin
- current clinical evidence that shows a benefit for this is lacking
- may be useful for patients not responding to other therapies for MRSA (may be an advantage in the treatment of some infections)
27
What is vancomycin good for?
- drug of choice for MRSA infections / empiric use when MRSA is a concern (ex: nosocomial pneumonia)
- other gram positive infections when patient has severe beta-lactam allergy
28
What is telavancin indicated for?
- skin and skin structure infections
- hospital-acquired pneumonia
It's role is still being defined
29
Name the long-acting glycopeptides.
- dalbavancin
| - oritavancin
30
What is unique about the long-acting glycopeptides?
- pharmacologically, have the base structure of a glycopeptide
- designed with PK characteristics that slow their elimination
31
What is the half life of long-acting glycopeptides?
Over a week
-can be dosed IV once for the equivalent of 2 weeks of therapy
32
What organisms do long-acting glycopeptides have GOOD activity against?
- MSSA
- MRSA
- streptococci
- enterococci (oritavancin)
33
What organisms do long-acting glycopeptides have MODERATE activity against?
-enterococci (dalbavancin)
34
What organisms do long-acting glycopeptides have POOR activity against?
-anything gram negative
35
What are the most common adverse effects of long-acting glycopeptides?
- nausea
- vomiting
- diarrhea
- rash
36
What are specific adverse effects of oritavancin?
Infusion related reactions if infused quickly
-given over 3 hours
Inhibits warfarin metabolism
-may increase risk of bleeding when given with it
37
What is something that can be overlooked with long-acting glycopeptides?
Prolonged elimination leads to easy outpatient options and compliance
- still need to be monitored for treatment success and adverse effects
- don't "set it and forget it"
38
Describe oritavancin's interaction with anticoagulants.
Interferes with assays for:
- prothrombin time (PT) for 24 hours: warfarin
- activated partial thromboplastin time (aPTT) for 48 hours: heparin
Do not use these drugs in combination with oritavancin during these time periods
-monitoring will be unreliable
39
How is dalbavancin dosed?
1000mg on day 1, then 500mg a week later
Or
1500mg once
The two dose regimen was studied first
40
What are long-acting glycopeptides good for?
Skin and skin structure infections
-either known or highly suspected to be caused by gram positive organisms
The paradigm for which patients are best for these drugs is still being defined
41
Name the fluoroquinolones (FQ).
- ciprofloxacin
- levofloxacin
- moxifloxacin
- gemifloxacin
42
Why are the FQ near ideal antibiotics?
Broad spectrum:
- gram positive
- gram negative
- atypical organisms
Excellent oral bioavailability
Distribute widely into tissues
43
How has resistance affected FQ?
In some geographical regions and patient populations, lost much activity against enteric gram negatives:
- E. coli
- Klebsiella
No longer recommended 1st line in US for uncomplicated UTIs
44
How are the newer FQ different in spectrum of activity?
- gain increasing gram positive activity (mostly pneumococcal)
- lose some gram negative activity (mostly Pseudomonas)
45
What is the MOA of FQ?
Inhibit DNA topoisomerases (which are enzymes that are involved in the winding and unwinding of DNA)
-can lead to breaks in the DNA and death of the cell
46
What organisms do ciprofloxacin have GOOD activity against?
H. influenzae
Enteric GNRs (ex:)
- E. coli
- Proteus
- Klebsiella
47
What organisms do ciprofloxacin have MODERATE activity against?
Pseudomonas
Atypicals:
- Mycoplasma
- Chlamydia
- Legionella
48
What organisms do ciprofloxacin have POOR activity against?
- staphylococci
- S. pneumoniae
- anaerobes
- enterococci
49
What organisms do levo/moxi/gemifloxacin have GOOD activity against?
- enteric gram negatives
- S. pneumoniae
- atypicals
- H. influenzae
50
What organisms do levo/moxi/gemifloxacin have MODERATE activity against?
- MSSA
| - Pseudomonas (levofloxacin)
51
What organisms do levo/moxi/gemifloxacin have POOR activity against?
- anaerobes (moxifloxacin has moderate activity)
| - enterococci
52
List the categories of adverse effects of FQ
- nervous system
- cardiovascular
- musculoskeletal
- dermatologic
- developmental
53
Describe the nervous system adverse effects of FQ.
Central nervous system effects (elderly especially susceptible):
- dizziness
- confusion
- hallucinations
Younger patients may develop insomnia
Peripheral neuropathy
54
Describe the cardiovascular adverse effects of FQ.
Prolongation of the QT interval
Arrhythmias usually only occur patient has other risk factors:
- underlying arrhythmia
- concomitant pro-arrhythmic drug
- excessive dose
55
Describe the musculoskeletal adverse effects of FQ.
- arthralgias (uncommon)
- achilles tendon rupture (very rare)
- exacerbations of myasthenia gravis may occur (less common)
56
In what patients taking FQ is tendon rupture more common?
- elderly
- patients with renal dysfunction
- those taking corticosteroids
57
Why should complaints of tendon pain be taken seriously in patients talking FQ?
Tendonitis usually precedes rupture
58
Describe the dermatologic adverse effects of FQ.
Photosensitivity often seen
-avoid sun or use sunscreen
59
Describe the developmental adverse effects of FQ.
Toxicities seen in juvenile beagle dogs
Contraindicated in pregnant women
Relatively contraindicated in children
-experience with use in children suggests they may be used
60
How active are FQ against Pseudomonas?
- ciprofloxacin and levofloxacin are the only drugs that are well-absorbed and active against Pseudomonas
- MICs are typically higher than with other susceptible organisms
61
What is the antipseudomonal dose for ciprofloxacin?
- 400mg IV q8h
| - 750mg PO q12h
62
What is the antipseudomonal dose for levofloxacin?
-750 mg IV/PO daily
63
What is the bioavailabililty of FQ?
80-100%
IV dose = PO dose
-except ciprofloxacin: PO = ~1.25x IV dose
64
Which organism always requires susceptibility testing when using appropriate FQ?
Pseudomonas
-resistance common for this organism
65
What should be avoided when taking FQ?
FQ chelate cations (oral bioavailabililty significantly decreased)
- calcium
- iron
- antacids (calcium, magnesium, aluminum)
- milk
- multivitamins
Administration with tube feedings also problematic
-only oral formulations; IV forms avoid it
66
How should FQ-cation interaction be handled?
- separate by at least 2 hours
| - have patients take a week off of the supplements if possible
67
How are most FQ eliminated?
Cleared renally
-require dose reduction in renal dysfunction
68
How is moxifloxacin eliminated?
Not excreted into the urine
-not approved for treatment of UTIs
69
How is gemifloxacin eliminated?
Dual elimination
- DOES require dose adjustment in renal failure
- utility in treating UTIs not established (best to avoid for UTIs until there is supporting evidence)
70
What boxed warning do all FQ have in their package insert mandated by the FDA?
Possibility of tendon rupture
71
What additional warning in 2016 did the FDA require for all systemic FQ?
Risks outweigh benefits for most cases of (unless other options not available due to possibility of rare but serious adverse effects):
- sinusitis
- bronchitis
- uncomplicated UTIs
72
What is ciprofloxacin indicated for?
```
CAP, sinusitis, AECB: -
UTI: +
Intra-abdominal infection: +
Systemic Gram- infections: +
Skin/soft tissue infection: -
Pseudomonas (+/- beta lactam): +
Treatment/prophylaxis in bioterrorism scenario (active vs anthrax, plague, tularemia): +
```
```
+ = approved/studied/makes sense for this indication
? = should work/no clinical data
- = suboptimal
```
73
What is levofloxacin indicated for?
```
CAP, sinusitis, AECB: +
UTI: +
Intra-abdominal infection: +
Systemic Gram- infections: +
Skin/soft tissue infection: +
Pseudomonas (+/- beta lactam): +
Treatment/prophylaxis in bioterrorism scenario (active vs anthrax, plague, tularemia): +
```
74
What is moxifloxacin indicated for?
```
CAP, sinusitis, AECB: +
UTI: -
Intra-abdominal infection: +
Systemic Gram- infections: +
Skin/soft tissue infection: +
Pseudomonas (+/- beta lactam): -
Treatment/prophylaxis in bioterrorism scenario (active vs anthrax, plague, tularemia): ?
```
75
What is gemifloxacin indicated for?
```
CAP, sinusitis, AECB: +
UTI: ?
Intra-abdominal infection: ?
Systemic Gram- infections: ?
Skin/soft tissue infection: +
Pseudomonas (+/- beta lactam): -
Treatment/prophylaxis in bioterrorism scenario (active vs anthrax, plague, tularemia): ?
```
76
Name the aminoglycosides (AMG).
- Gentamicin
- Tobramycin
- Amikacin
- streptomycin
- spectinomycin
77
What are advantages of AMG?
- retain good activity against many problem pathogens (Pseudomonas, Acinetobacter) that have developed to more benign drug classes
- excellent at synergizing with the beta-lactams and glycopeptides to improve the efficiency of bacterial killing
78
What are disadvantages of AMG?
- narrow therapeutic window
- improper dosing has risk of inflicting significant toxicities
- nephrotoxicity
- ototoxicity
79
Which AMG are most commonly used?
- gentamicin
| - tobramycin
80
When is amikacin used?
Reserved for pathogens resistant to the first two
81
When is streptomycin used?
Limited uses
- Enterococcus
- tuberculosis
- plague
82
What is the MOA for AMG?
Bind to the bacterial ribosome (30S subunit)
- causes misreading of the genetic code
- leads to incorrect protein formation and interruption of protein synthesis
83
What organisms do AMG have GOOD activity against?
Gram negatives
- E. coli
- Klebsiella
- Pseudomonas
- Acinetobacter
- most others
84
What organisms do AMG have MODERATE activity against?
In combination with a beta-lactam or glycopeptide:
- staphylococci (including MRSA)
- viridans streptococci
- enterococci (gentamicin and streptomycin are best)
85
What organisms do AMG have POOR activity against?
- atypicals
- anaerobes
- gram positive organisms (as monotherapy)
86
What AMG are best for enterococci?
- gentamicin
| - streptomycin
87
List the categories of adverse effects of AMG.
- nephrotoxicity
- ototoxicity
- neurologic
88
Describe AMG nephrotoxicity.
Oliguric acute renal failure
- preceded by a rising serum creatinine
- dose related adverse effect
89
How can the risk of AMG nephrotoxicity be reduced?
Correct dosing (including the use of extended-interval dosing)
Avoidance of coadministration of other nephrotoxins:
- cyclosporine
- cisplatin
- foscarnet, etc.
90
Describe AMG ototoxicity?
Dose related adverse effect:
- cochlear toxicity (hearing loss)
- vestibular toxicity (balance problems)
- not reversible and can significantly quality of life
91
When is baseline and follow up audiology necessary with AMG?
For patients anticipated to receive long term therapy
-greater than 2 weeks
92
Describe AMG neurologic toxicity.
Neuromuscular blockade
-especially when high doses are given to patients who are receiving therapeutic paralysis
93
What is the benefit of once daily/extended-interval AMG dosing?
Leverages the concentration-dependent killing of AMG to create a dosing regimen that is:
- equally effective
- more convenient
- possibly safer
94
In which patient populations has once daily dosing had less study?
- pregnant
- critically ill
- significant renal dysfunction
- morbidly obese
Use QD dosing cautiously if at all in these populations
95
What is the pregnancy category of AMG?
Category D
-avoid if possible
96
How should AMG serum levels be drawn for traditional dosing?
Peak level:
-30 minutes after the end of infusion
Trough level:
-within 30 minutes of the next dose
97
How is AMG QD dosing monitored?
Published nomograms
-number of potential monitoring points
98
Describe AMG distribution into tissues.
Relatively poor distribution into many tissues (including lungs and CNS)
-makes them less than optimal as monotherapy for many severe infections
99
Based on what weight should AMG be dosed?
On patient's ideal or adjusted body weight
-NOT on total body weight (serious overdose can occur)
100
Which AMG are best for Pseudomonas?
Amikacin
>
Tobramycin
>
Gentamicin
101
Which AMG are best for Klebsiella?
Amikacin
=
Gentamicin
>
Tobramycin
102
Which AMG is used for resistant tuberculosis?
Streptomycin
- some older references incorrectly list it as 1st line for TB
- it was the first drug available but now safer and more effective 1st line drugs exist
103
What are AMG good for?
Treatment of serious gram negative infections:
- febrile neutropenia
- sepsis
- exacerbations of cystic fibrosis
- ventilator associated pneumonia
In combination with a beta-lactam or glycopeptide for serious gram positive infections (primarily gentamicin):
- endocarditis
- osteomyelitis
- sepsis
In combination with other antimycobacterials (streptomycin and amikacin):
-drug resistant infections with Mycobacterium tuberculosis or other mycobacteria
104
Why is correct AMG dosing so important?
Because most toxicity is dose-related
- adjust for renal dysfunction
- use ideal or adjusted body weight
PK concentrations are useful if drawn correctly
- monitoring
- dosing
105
Name the tetracyclines and glycylcyclins.
- doxycycline
- minocycline
- tetracycline
- tigecycline (glycylcycline)
106
What are the tetracyclines?
- once considered broad spectrum agents
- useful (but not highly studied) alternatives for common respiratory tract infections
- drugs of choice for a variety of uncommon infections
107
Which tetracycline is preferred in most situations?
Doxycycline
108
What is tigecycline?
Glycylcycline
- evades most tetracycline resistance mechanisms
- has a broad spectrum of activity
109
What is the MOA of (tetra)glycylcyclines?
Bind to the bacterial ribosome at the 30S subunit
-prevents the docking of tRNA carrying new amino acids for addition to the elongating protein chain
110
What organisms do tetracyclines have GOOD activity against?
- atypicals
- rickettsia
- Plasmodium species (malaria)
Spirochetes (ex:)
- Borrelia burgdorferi
- H. pylori
111
What organisms do tetracyclines have MODERATE activity against?
- staphylococci (including MRSA)
| - S. pneumoniae
112
What organisms do tetracyclines have POOR activity against?
- most GNRs
- anaerobes
- enterococci
113
What organisms does tigecycline have GOOD activity against?
- atypicals
- enterococci (including VRE)
- staphylococci (including MRSA)
- S. pneumoniae
114
What organisms does tigecycline have ACCEPTABLE activity against?
- most GNRs
| - anaerobes
115
What organisms does tigecycline have POOR activity against?
- Pseudomonas
- Proteus
- Providencia
116
List the categories of adverse effects of (tetra)glycylcyclines?
- GI
- dermatologic
- sensory
- developmental
117
Describe (tetra)glycylcycline GI toxicity.
Tetracyclines can cause esophageal irritation
-take the drug with water while standing up
Tigecycline (severe):
- nausea
- vomiting
- diarrhea
118
Describe (tetra)glycylcycline dermatologic toxicity.
Photosensitivity often seen
-avoid the sun or use sunscreen
119
Describe (tetra)glycylcycline sensory toxicity.
Minocycline:
- dizziness
- vertigo
120
Describe (tetra)glycylcycline developmental toxicity.
Discoloration of developing teeth
Contraindicated in:
- pregnant women
- children younger than 8 years old
121
Describe (tetra)glycylcycline GI bioavailabililty.
Doxycycline and minocycline
-100%
Tigecycline
-IV only
122
What should be avoided when taking tetracyclines?
Chelate cations (oral bioavailabililty significantly decreased)
- calcium
- iron
- antacids (calcium, magnesium, aluminum)
- milk
- multivitamins
123
How should the tetracycline-cation interaction be handled?
- separate by at least 2 hours
| - have patients take a week off of the supplements if possible
124
How does food affect tetracyclines?
Tetracycline
-decreases absorption substantially
Minocycline/Doxycycline
-minimally
125
How should tetracyclines be dosed in renal dysfunction?
Doxycycline
-does NOT need to be adjusted in renal or hepatic dysfunction
Tetracycline
- eliminated renally
- should NOT be used in cases of renal insufficiency (can worsen renal dysfunction)
126
Describe tigecycline distribution.
Very large volume of distribution
- distributes highly into many tissues
- extensive distribution leads to low bloodstream concentrations (not ideal choice for treating primary bloodstream infections)
127
How is tigecycline eliminated?
Hepatically
- achieves low urinary concentrations
- probably should not be used for UTIs
128
What did an FDA analysis of tigecycline across all indications show?
Mortality DISadvantage compared to other antibiotics
- driven largely by a study of hospital acquired pneumonia
- still may be useful because it has activity against many highly drug resistant organisms in which there are few (or no) alternatives
- those hard to treat infections usually don't make it into analyses
129
What are tetracyclines good for?
Uncomplicated respiratory tract infections
- acute exacerbations of chronic bronchitis
- sinusitis
- community acquired pneumonia
Drugs of choice for many tick-borne diseases
Use as alternative for:
- skin/soft-tissue infections
- syphilis
- pelvic inflammatory disease (with cefoxitin)
Alternative to ciprofloxacin in bioterrorism scenarios
- anthrax
- plague
- tularemia
Malaria
- prophylaxis
- treatment
130
What is tigecycline good for?
May have role in treatment of complicated polymicrobial infections
- intra-abdominal infections
- complicated skin/skin-structure infections
131
Name the macrolides and ketolides.
- Clarithromycin
- Azithromycin
- Erythromycin
- telithromycin
132
What antibiotics are used most frequently in the outpatient setting?
Macrolides
- broad (not deep) coverage of respiratory pathogens
- increasing resistance (especially in S. pneumoniae)
133
What is telithromycin?
Ketolide derivative
- better coverage of resistant S. pneumoniae
- significant risk of hepatotoxicity
134
What is the class patriarch of macrolides?
Erythromycin
Has little use (except as GI stimulant) because:
- adverse effects
- drug interactions
- frequent doses
135
What is the MOA of (macro)ketolides?
Bind to the 50S subunit of bacterial ribosomes
-prevents the ribosome from shuffling along and adding a new amino acid to the elongating protein chain
136
What organisms do (macro)ketolides have GOOD activity against?
- atypicals
- H. influenzae
- Moraxella catarrhalis
- H. pylori
- Mycobacterium avium
137
What organisms do (macro)ketolides have MODERATE activity against?
S. pneumoniae
-telithromycin > macrolides
S. pyogenes
138
What organisms do (macro)ketolides have POOR activity against?
- staphylococci
- anaerobes
- enterococci
Enteric GNRs
-azithromycin > clarithromycin
139
List the categories of adverse effects of (macro)ketolides?
- GI
- hepatic
- cardiac
140
Describe macrolide GI toxicity.
Significant GI adverse effects
- nausea
- vomiting
- diarrhea
141
Which macrolide has the worst GI adverse effects?
Erythromycin
-employed as a prokinetic agent for patients with impaired GI motility
142
Describe macrolide hepatic toxicity.
Rare but serious adverse hepatic events
Telithromycin:
Associated with hepatic failure leading to
- death
- need for transplantation
143
Describe macrolide cardiac toxicity.
Prolongation of the QT interval
144
Which macrolide has the greatest risk of QT prolongation?
Erythromycin
145
In which patients on macrolides is the risk of QT prolongation greatest?
- pre-existing heart conditions
- on anti-arrhythmic drugs
- on interacting drugs
146
Which macrolide is not a potent inhibitor of drug-metabolizing cytochrome P450 enzymes?
Azithromycin
147
Which macrolide has a prolonged half-life?
Azithromycin
- short course may be adequate for most infections
- Z-pak
- extended-release single dose Z-max
148
Do macrolides kill bacteria or just inhibit growth?
Bacteriostatic
Not appropriate for infections in which cidal activity is usually required
- meningitis
- endocarditis, etc.
149
What is Prevpac used for?
Combination of drugs prescribed for eradication of H. pylori and treatment of peptic ulcer disease
-screen patients for beta-lactam allergies and drug interactions before administering
150
What drugs make up Prevpac?
- clarithromycin
- lansoprazole
- amoxicillin
151
What type of infection is a macrolide ideal for?
Spectrum of activity makes them ideal for treatment of mild community acquired pneumonia
- risky choice for monotherapy if infection is worse than mild due to high rates of resistance for S. pneumoniae
- treat more fragile patients with something else or add a beta-lactam active against S. pneumoniae
152
What are macrolides good for?
- upper and lower respiratory tract infections
- chlamydia
- atypical mycobacterial infections
- traveler's diarrhea (azithromycin)
- H. pylori-induced GI ulcer disease (clarithromycin plus other drugs and acid-suppressive agents)
153
Name the oxazolidinones.
- Linezolid (dosed twice daily)
| - tedizolid (dosed once daily)
154
What are some general characteristics of oxazolidinones?
- broad gram positive activity
- excellent oral bioavailability
- linezolid has an advantage over other agents active against MRSA in its clinical trial data supporting its use for MRSA pneumonia
155
What is the MOA of oxazolidinones?
Protein synthesis inhibitors that bind to 50S ribosomal subunit
- blocks the formation of a stable 70S initiation complex
- prevents translation
- this binding site is distinct from other protein synthesis inhibitors
156
What organisms do oxazolidinones have GOOD activity against?
- MSSA
- MRSA
Streptococci
-including multi-drug resistant S. pneumoniae
Enterococci
-including VRE
-Nocardia
157
What organisms do oxazolidinones have MODERATE activity against?
- some atypicals
| - Mycobacterium tuberculosis
158
What organisms do oxazolidinones have POOR activity against?
- all gram negatives
| - anaerobes
159
What are the adverse effects of oxazolidinones?
Generally well tolerated
Can cause bone marrow suppression
-most commonly thrombocytopenia
160
Describe linezolid bone marrow suppression.
Tends to occur after 2 or more weeks
- warrants monitoring
- tedizolid seems to have the same effects
161
What adverse effects can occur with prolonged linezolid therapy?
Occur after months because of mitochondrial toxicity
- peripheral neuropathy
- lactic acidosis
162
What is the bioavailability of oxazolidinones?
Over 90%
-have oral formulations that greatly increase their utility
163
What does linezolid inhibit?
Monoamine oxidase (MAO)
- can cause serotonin syndrome when given concurrently with serotonergic drugs
- avoid concurrent use if possible
- uncommon but does occur
164
Does tedizolid cause MAO inhibition?
Animal models show minimal to no inhibition
-human data is limited
165
How is linezolid eliminated?
Dual hepatic and renal elimination
-does NOT need to be adjusted in renal or hepatic dysfunction
166
How is tedizolid eliminated?
Primarily by the liver
-may not be sufficiently concentrated in the urine to treat UTIs
167
What is the oxazolidinone dosing for skin and skin structure infections?
Tedizolid
- studied as a 6 day therapy
- comparable to 10 days of linezolid
- possible that shorter courses would work with other drugs too
168
What is a convenience of linezolid?
Oral formulations are less expensive and more convenient than home infusion vancomycin and a nurse
169
What are oxazolidinones good for?
Infections caused by resistant gram positive organisms
- MRSA
- VRE, etc.
170
What is linezolid useful for?
- pneumonia
- skin and skin structure infections
- UTIs
- other uses
171
What is tedizolid indicated for?
- skin and skin structure infections
| - may be useful for other types
172
What are some quick monitoring tips for linezolid?
Bone marrow suppression
-particularly during long term therapy
If possible avoid concurrent serotonergic drugs
- many SSRIs have long half lives (simply discontinuing an SSRI does not avoid a potential interaction)
- monitor for serotonin syndrome
173
Name the nitroimidazoles.
- Metronidazole
| - tinidazole
174
What is a general overview of the nitroimidazoles?
Clean up organisms that the big drug classes miss
- gut anaerobes
- parasites in patients with diarrhea
- mild C. difficile colitis after going overboard with antibiotics
- do not have adequate activity against aerobic bacteria
175
What is tinidazole?
Cousin of metronidazole
- similar spectrum
- approved only for parasitic infections
176
What is the MOA of nitroimidazoles?
A part of the nitroimidazole molecule is activated by anaerobic bacteria and protozoa (but not aerobic bacteria)
- forms free radicals
- thought to damage DNA
- leads to cell death
177
What organisms do nitroimidazoles have GOOD activity against?
Gram negative and positive anaerobes, including (species):
- Bacteroides
- Fusobacterium
- Clostridium
Protozoa:
- Trichomonas
- Entamoeba
- Giardia
178
What organisms do nitroimidazoles have MODERATE activity against?
H. pylori
179
What organisms do nitroimidazoles have POOR activity against?
Aerobic anything
Anaerobes that reside in the mouth
- Peptostreptococcus
- Actinomyces
- Propionibacterium
180
Name the categories of nitroimidazole toxicity.
- GI
| - neurologic
181
Describe nitroimidazole GI toxicity.
Not uncommon
- nausea
- vomiting
- diarrhea
- metallic taste
More severe adverse reactions (rare)
- hepatitis
- pancreatitis
182
Describe nitroimidazole neurologic toxicity.
Occasionally reported
-peripheral neuropathy (dose-related, reversible)
Very rare
- confusion
- seizures
183
What type of reaction can metronidazole cause?
Disulfiram-like reaction with consumption of alcohol
- inhibits aldehyde dehydrogenase
- abstain from alcohol
184
What drug has a severe interaction with metronidazole?
Warfarin
- warfarin metabolism inhibited
- anticoagulant properties are significantly potentiated
- careful monitoring
- warfarin dose reduction likely necessary
185
Describe metronidazole bioavailability?
Excellent (~100%)
-switch from IV to PO as soon as oral medications tolerated
186
Does metronidazole have drug-chelating concerns?
No
187
Describe metronidazole treatment failure against C. difficile.
Resistance among isolates of C. difficile uncommon but treatment failure is not
- organism can exist as antibiotic-resistant spore
- can cause relapses after the end of treatment
188
When should metronidazole NOT be used for C. difficile infection?
- moderate to severe C. difficile infection
- more than one relapse of mild disease
Use oral vancomycin or fidaxomicin
189
What are nitroimidazoles good for?
Infections with documented/suspected abdominal anaerobic bacteria
-use second drug for adjunctive coverage of aerobes if necessary
Vaginal trichomoniasis
GI infections caused by susceptible protozoa
- amebiasis
- giardiasis, etc.
H. pylori GI ulcer disease in combination with other antibacterials and acid-suppressive drugs (metronidazole)
Option for mild-moderate C. difficile infection
190
What is an important tip for when to use metronidazole?
Determine whether you really need anaerobic coverage
- metronidazole's effect on the normal (primarily anaerobic) GI flora can set up patients for colonization with nasty organisms
- VRE, etc.
191
Name a nitrofurans.
Nitrofurantoin
192
What two drugs are an alternative to treat patients with uncomplicated cystitis due to the rise in resistance among common urinary tract pathogens (primarily E. coli)
Nitrofurantoin and fosfomycin
- structurally dissimilar with different MOA
- similar clinical niches
- have retained excellent activity against E. coli (>90% in most studies)
- have adequate coverage of other community-acquired urinary tract pathogens
193
What infections should nitrofurantoin and fosfomycin NOT be used for?
More severe UTIs
- pyelonephritis, urosepsis, etc.
- utility limited to infections of the lower urinary tract because of PK limitations
IV fosfomycin available in other countries for more severe GNR infections
194
What is the MOA of fosfomycin?
Inhibits bacterial cell wall synthesis
- different way from beta-lactams and glycopeptides
- prevents the production of the building blocks of peptidoglycan
195
What is the MOA of nitrofurantoin?
Not well characterized
196
What organisms do nitrofurantoin and fosfomycin have GOOD activity against?
- E. coli
| - S. saprophyticus
197
What organisms do nitrofurantoin and fosfomycin have MODERATE activity against?
- Citrobacter
- Klebsiella
- Proteus
- enterococci
- Pseudomonas (fosfomycin)
- Serratia (fosfomycin)
198
What organisms do nitrofurantoin and fosfomycin have POOR activity against?
-Acinetobacter
199
Describe the GI toxicity of nitrofurantoin and fosfomycin.
Occasionally reported
- nausea
- vomiting
Taking the drugs with food may decrease these effects
200
Describe nitrofurantoin pulmonary toxicity.
Can cause very rare but serious pulmonary toxicity of two forms
201
Describe acute nitrofurantoin pulmonary toxicity.
Acute pneumonitis
- cough
- fever
- dyspnea
- typically resolves soon after drug discontinuation
202
Describe chronic nitrofurantoin pulmonary toxicity.
Chronic pulmonary fibrosis
- most commonly with prolonged therapy
- recovery of lung function limited after drug discontinuation
203
Why are nitrofurantoin and fosfomycin NOT effective for infections outside of the lower urinary tract in US formulations?
Require high concentrations for antimicrobial activity
-only reached where they concentrate in the urine
204
In what patients should nitrofurantoin be avoided?
Patients who have significant renal dysfunction
- CrCL <50 mL/min
- may be insufficient accumulation of drug in the urine for activity
205
What formulations is nitrofurantoin available in?
- Macrodantin
| - Macrobid
206
What is Macrodantin?
- crystalline form
| - dosed QID
207
What is Macrobid?
- macrocrystalline/monohydrate form
| - dosed BID
208
How is fosfomycin available in the US?
Only as a powder
-add to water before taking
209
What is the duration of nitrofurantoin therapy for UTIs?
A study showed it can be used for 5 days instead of the traditional 7 day therapy
-many patients used to 3 day courses of SMX/TMP and FQ for UTIs
210
What is the approved regimen of fosfomycin therapy for uncomplicated cystitis?
Single dose
211
What are nitrofurantoin and fosfomycin good for?
Treatment of uncomplicated cystitis in patients with adequate renal function
Nitrofurantoin only
-prophylaxis against recurrent uncomplicated lower UTIs
212
What is a major caution when using nitrofuran and fosfomycin?
Do not use these drugs in anything but cystitis
-if used in pyelonephritis or urosepsis, will be a treatment failure
213
What are the streptogramins?
Quinupristin/dalfopristin
-other streptogramins have been developed and used in animals as growth promoters (>50% of US antibiotics are used for this purpose)
214
What is Synercid?
Quinupristin/dalfopristin
-each separately is bacteriostatic, but combined act synergistically to give bactericidal activity against some gram positive cocci (MRSA, VRE)
215
What is the MOA of streptogramins?
Each streptogramin of Synercid binds to a different site on the 50S subunit of the bacterial ribosome
-prevents bacterial protein synthesis
216
What organisms do quinupristin/dalfopristin have GOOD activity against?
- MSSA
- MRSA
- streptococci
- E. faecium (including VRE strains)
217
What organisms do quinupristin/dalfopristin have POOR activity against?
- E. faecalis
| - anything gram negative
218
What are the adverse effects of quinupristin/dalfopristin?
Can cause phlebitis
-ideally should be administered via a central line
High incidence of myalgias and arthralgias
-can limit tolerance to therapy
219
Does quinupristin/dalfopristin have any drug interactions?
Inhibits cytochrome P450 3A4
220
What does quinupristin/dalfopristin have to be mixed and administered with?
5% dextrose in water (D5W) solutions only
221
What happens when quinupristin/dalfopristin is mixed with normal saline?
Drug becomes insoluble and can crystallize
- happens even when IV line is flushed with saline
- make sure nurse is aware how to flush the line with D5W or another saline-free diluent
222
Is it possible to decrease the arthralgias and myalgias associated with quinupristin/dalfopristin?
They can be significant
-decreasing the dose may decrease the severity (but may compromise efficacy)
223
For which organism was the indication removed for quinupristin/dalfopristin?
Vancomycin-resistant E. faecium infections
- indication removed from labeling due to a lack of follow up data after the initial approval
- no longer considered first line for VRE infections
224
What is quinupristin/dalfopristin good for?
Infections in patients not responding to or intolerant of other medications caused by:
- MRSA
- E. faecium
225
Which type of Enterococcus is quinupristin/dalfopristin NOT active against?
E. faecalis
226
Which type of Enterococcus is is more common in most hospitals?
E. faecalis
227
Which type of Enterococcus is LESS likely to be resistant to vancomycin?
E. faecalis
228
Which medications do not have the Enterococcus issue that quinupristin/dalfopristin has and are generally better therapy options?
- linezolid
| - daptomycin
229
Name a cyclic lipopeptide.
Daptomycin
230
How does daptomycin work?
Binds to the cell membrane of gram positive bacteria
- weakens the cell membrane
- allows essential ions to leak out of the organism
- leads to a rapid depolarization of the membrane potential and cessation of needed cell process
- leads to cell death
231
What is the major difference in end results between the MOA of daptomycin and beta-lactams?
- daptomycin leaves the dead bacteria intact
| - beta-lactams blow the bacteria apart
232
What is the MOA of daptomycin?
Inserts into the cell membrane of gram positive bacteria
- leads to leakage of intracellular cations that maintain membrane polarization
- results in rapid depolarization and cell death
233
What organisms does daptomycin have GOOD activity against?
- MSSA
- MRSA
- streptococci
234
What organisms does daptomycin have MODERATE to GOOD activity against?
Enterococci
-including VRE
235
What organisms does daptomycin have POOR activity against?
-anything gram negative
236
What is the major adverse effect of daptomycin?
Has effects on skeletal muscle
-can manifest as muscle pain or weakness
or
-possibly rhabdomyolysis
237
How are the skeletal muscle effects of daptomycin monitored?
CK (creatine kinase) concentrations should be checked weekly while on therapy
238
How can the skeletal muscle effects of daptomycin be decreased?
- do NOT administer the drug more than once daily
| - adjust the interval in renal dysfunction
239
What is another adverse effect reported in patients on daptomycin therapy?
Eosinophilic pneumonia
240
What resistant gram positive organisms is daptomycin active against?
- VRE
| - MRSA
241
What is an indication that daptomycin has that few antibiotics have?
Staphylococcal endocarditis
-specifically right-sided endocarditis
242
Is resistance to daptomycin reported?
Yes, but is uncommon
243
What is the MIC for daptomycin?
Standard MIC for resistance has not yet been defined
-labs may report isolates as "nonsusceptibile"
or
- not at all if they do not fall into the susceptible range
- ask your lab for specifics
244
Can daptomycin be used to treat pneumonia?
No
- penetrates lung tissue well, but:
- human pulmonary surfactant binds to it
- renders it inactive
- poor outcomes in daptomycin-treated pneumonia patients
245
What is daptomycin's FDA approved dosing?
4-6 mg/kg/day
246
Why is off-label dosing used with daptomycin?
Studies suggest higher doses may be more effective without causing substantially more toxicity
-may see doses as high as 12 mg/kg/day in difficult-to-treat infections
247
What drug class may daptomycin be synergistic with?
Some beta-lactams
- even in beta-lactam resistant organisms like:
- MRSA
- VRE
248
What is daptomycin good for?
Skin and skin structure infections caused by:
-resistant gram positive organisms
Staphylococcal bacteremia
-including right-sided endocarditis
Also has utility in enterococcal bacteremia
-not indicated or well studied for this use
249
What are important monitoring parameters for daptomycin?
- CK concentrations
- renal function
Especially if on other drugs toxic to skeletal muscle
-HMG-CoA reductase inhibitors
250
Name some folate antagonists.
- trimethoprim/sulfamethoxazole (TMP/SMX)
- dapsone
- pyrimethamine
- sulfadiazine
- sulfadoxine
251
What is TMP/SMX?
- most widely used folate antagonist
- active against both bacterial and parasitic/fungal infections
- once considered broad-spectrum antibacterial
- resistance varies largely by geographic region (consider local antibiogram before using)
- other agents in this class used against parasitic/fungal infections
252
What is the MOA of folate antagonists?
Inhibit steps in the folate biosynthesis pathway
- depletes the pool of nucleosides
- ultimately leads to inhibition of DNA synthesis in susceptible organisms
253
What organisms does TMP/SMX have GOOD activity against?
- S. aureus (including many MRSA strains)
- H. influenzae
- Stenotrophomonas maltophilia
- Listeria
- Pneumocystis jirovecii (formerly known as P. carinii)
- Toxoplasma gondii (pyrimethamine and sulfadiazine)
254
What organisms does TMP/SMX have MODERATE activity against?
- enteric GNRs
- S. pneumoniae
- Salmonella
- Shigella
- Nocardia
- S. pyogenes
255
What organisms does TMP/SMX have POOR activity against?
- Pseudomonas
- enterococci
- anaerobes
256
List the categories of adverse effects of TMP/SMX.
- dermatologic
- hematologic
- renal
257
Describe TMP/SMX dermatologic toxicity.
Frequently causes rash (SMX component)
- rashes usually not severe
- rash more common in HIV/AIDS patients
Life threatening dermatologic reactions can occur
- Stevens-Johnson syndrome
- toxic epidermal necrolysis
258
Describe TMP/SMX hematologic toxicity.
Primarily dose dependent bone-marrow suppression
-especially at higher doses used to treat Pneumocystis infections
259
Describe TMP/SMX true renal failure.
SMX component can lead to acute renal failure by:
- crystalluria
- AIN
260
Describe TMP/SMX pseudo-renal failure.
TMP causes a blockade of creatinine secretion
-can cause an increase in SCr without a true decline in GFR
TMP can also cause hyperkalemia
-in a similar way to the potassium sparing diuretics (ex: triamterene)
261
What was TMP/SMX a standard first line therapy for before increasing resistance?
Treatment of acute uncomplicated cystitis in women
-use alternative drug (nitrofurantoin) in areas with local resistance rates > 15-20% in E. coli
At a minimum do not use for empiric therapy of complicated UTI:
- pyelonephritis
- urosepsis
262
What is the ratio of TMP:SMX?
Fixed 1:5 ratio
Oral tablet comes in two strengths:
- single strength: 80:400
- double strength: 160:800
263
Which part of TMP/SMX is the dosing based on?
TMP component
264
How is TMP/SMX bioavailability?
Excellent bioavailability
-convert to oral therapy as soon as patients are tolerating oral medications
265
What interaction does TMP/SMX have a significant interaction with?
Warfarin
- leads to higher than anticipated prothrombin times
- avoid the combination if possible
- if not possible, carefully monitor patient's INR (international normalized ratio)
266
How soluble is TMP/SMX in IV solutions?
Fairly insoluble
- relatively large volumes of diluent needed for it to go into solution
- fluid may be considerable for volume overloaded patients (ex: heart failure)
267
Is TMP/SMX active against MRSA
Yes
- predominant strain of MRSA that causes outpatient MRSA infections is very susceptible to TMP/SMX
- likes to cause skin infections with abscesses (often large ones)
- good choice for staphylococcal skin infections (abscesses must be drained)
268
What is TMP/SMX primarily good for?
Treatment of uncomplicated lower UTIs
- empirically in areas with low local resistance
- definitively whenever susceptible -prophylaxis against recurrent UTIs
- treatment of listeria meningitis
- treatment/prophylaxis for P. jirovecii pneumonia
- treatment of Toxoplasma encephalitis
269
What is TMP/SMX an alternative for?
- bacterial prostatitis
- typhoid fever
- MRSA infections
270
What is sulfadiazine used for?
Treatment of toxoplasmosis
271
Patients allergic to TMP/SMX may have cross-reactions to what other drugs containing sulfonamide moieties?
- furosemide
- HCTZ
- sulfadiazine
- acetazolamide
- glipizide
272
Name a lincosamide.
Clindamycin
273
From which drugs does clindamycin contain attributes?
A mix of vancomycin and metronidazole
- has attributes of each
- not quite as good as either alone
274
How is clindamycin against gram positive organisms?
An alternative when treatment requires gram positive activity
-as with beta-lactam allergies
Has more variable activity than vancomycin against certain pathogens
- MRSA
- S. pyogenes
275
How is clindamycin against anaerobes?
Covers many anaerobic organisms
-higher level of resistance among gram negative anaerobes (ex: B. fragilis) than with metronidazole
276
What is clindamycin's most common tendency?
Causes GI toxicity
277
When is clindamycin best empirically?
Nonsevere infections of the skin and oral cavity
278
What is the MOA of clindamycin?
Binds at a site on the 50S ribosome right next to where the macrolides bind
- acts similarly in preventing protein synthesis
- prevents the ribosome from moving on to adding another amino acid in the protein chain
279
What organisms does clindamycin have GOOD activity against?
- many gram positive anaerobes
- Plasmodium species (malaria)
- S. pyogenes
280
What organisms does clindamycin have MODERATE activity against?
- S. aureus (including many MRSA)
- gram negative anaerobes
- Chlamydia trachomatis
- P. jirovecii
- Actinomyces
- Toxoplasma
281
What organisms does clindamycin have POOR activity against?
- enterococci
- C. difficile
- gram negative aerobes
282
What is the most common adverse effect associated with clindamycin?
Diarrhea
283
Describe clindamycin GI toxicity?
-relatively benign, self-limited diarrhea
or
-can result in more severe diarrhea resulting from superinfection with C. difficile (can be life threatening)
Some studies suggest clindamycin may confer an especially high risk for causing C. difficile disease compared to other antibiotics
-almost all antibiotics have been associated with an increased risk of C. difficile disease
284
When can C. difficile diarrhea and colitis occur with clindamycin therapy?
During or after therapy
285
When do patients with diarrhea need evaluation for C. difficile disease?
- if diarrhea is severe
- associated with fever
- persists after clindamycin therapy
286
Describe clindamycin dermatologic toxicity.
Rash may occur
-severe manifestations like SJS are very rare
287
Clindamycin is a reasonable alternative for what types of infections?
Staphylococcal infections
288
Why must care be taken when interpreting clindamycin susceptibility testing?
Significant proportion of organisms that are reported as clindamycin-susceptible but erythromycin-resistant may harbor a gene for resistance leading to high level clindamycin resistance during therapy
289
What susceptibility test is used to check for resistance before using clindamycin?
D-test
-used to screen erythromycin-resistant, clindamycin susceptible strains before using clindamycin
290
How is a D-test interpreted?
If D-test is positive:
- inducible clindamycin resistance is present
- clindamycin should not be used
291
What types of infections does clindamycin have a unique role in?
Treatment of necrotizing fasciitis and other toxin-mediated diseases
-due to clindamycin's inhibition of protein synthesis
and
-activity against organisms in stationary-phase growth
Consider adding clindamycin to beta-lactam based therapy for these types of infections
292
How is clindamycin bioavailability?
Nearly 100% orally bioavailable
-oral doses generally lower than IV to improve GI tolerance
293
Which drug has greater activity against community acquired MRSA infections: clindamycin or TMP/SMX?
TMP/SMX
-more community acquired MRSA infections are susceptible to TMP/SMX vs clindamycin
294
What is clindamycin primarily good for?
- treatment of skin and soft-tissue infections
- infections of the oral cavity
- anaerobic intra-abdominal infections
295
What is clindamycin used topically for?
Treatment of acne
296
What is clindamycin a second line agent for?
Treatment of P. jirovecii pneumonia
-in combination with primaquine
297
What are some other uses of clindamycin?
Treatment of bacterial vaginosis
Prophylaxis of bacterial endocarditis
Treatment of malaria
-in combination with other drugs
298
Name the polymixins.
- colistin (colistimethate sodium)
| - polymixin B
299
What are polymixins used for?
Highly resistant gram negative infections caused by:
- A. baumannii
- P. aeruginosa
- carbapenem-resistant Enterobacteriaceae (CRE), such as K. pneumoniae
300
Why is the use of polymixins problematic?
- have not been evaluated with the rigor of the modern drug approval process
- PK and efficacy dat on their use are limited
301
What is the MOA of polymixins?
Bind to the outer membrane of gram negative bacteria
- leads to disruption of membrane stability
- leads to leakage of cellular contents
302
What organisms do polymixins have GOOD activity against?
Many GNRs, multi-drug resistant:
- A. baumannii
- P. aeruginosa
- K. pneumoniae
303
What organisms do polymixins have MODERATE activity against?
Stenotrophomonas maltophilia
304
What organisms do polymixins have POOR activity against?
- all gram positive organisms
- anaerobes
- Proteus
- Providencia
- Burkholderia
- Serratia
- gram negative cocci
305
What is the most common adverse effect of polymixins?
Nephrotoxicity
-due to acute tubular necrosis
306
How common is the incidence of polymixin induced acute kidney injury?
Commonly occurs in clinical use
- incidence is hard to estimate but is substantial (especially in critically ill patients who may not be able to tolerate the renal insult)
- monitor renal function closely
- most recent studies of polymixins are noncomparative evaluations of salvage therapies in very ill patients
307
Which polymixin is less nephrotoxic?
Polymixin B
-several studies suggest polymixin B is less nephrotoxic than colistin
308
What drugs should be avoided while on polymixins?
Concomitant nephrotoxins if possible, including vancomycin
309
How common is polymixin neurotoxicity?
Less common
310
Describe polymixin neurotoxicity.
Can manifest as:
- dizziness
- weakness
- paresthesias
- mental status changes
Neuromuscular blockade
- can also occur
- may lead to fatal respiratory arrest
311
How is colistin administered as?
To be given systemically, must be administered as colistimethate sodium
-colistimethate converted into active colistin in the body
312
How is colistimethate cleared?
Renally
-only the proportion not cleared is converted to colistin
313
How is colistin typically dosed in the US?
Milligrams of "colistin base activity"
- (~400mg colistimethate = 150mg colistin base activity)
- actual amount that is systemically active differs in each patient
314
Is colistin itself used systemically?
No
-when references refer to "colistin," they are referring to "colistimethate sodium"
315
How is colistin given?
As a renally eliminated prodrug
316
How is polymixin B given?
Given in its active form
-has more predictable PK
317
Should polymixins be given with loading doses?
Yes
318
How is polymixin B cleared?
NOT eliminated renally
- modern PK studies suggest it should NOT be dose adjusted in renal dysfunction
- unlikely to be successful in treating UTIs
319
How do Europe and many other countries dose colistin?
International units
- 1mg of colistin base activity is equivalent to ~30,000 units
- actually calculates to ~33,333 units but many references round this number
320
What are two ways to summarize colistin dosing?
1,000,000 units ~ 80mg colistimethate ~ 30mg colistin base activity
1mg colistin base activity ~ 2.7mg colistimethate ~ 30,000 units
321
How should colistin NEVER be prescribed or recommended?
NEVER in terms of mg of colistimethate
-misinterpretation can be fatal
322
How is polymixin B dosed?
Either mg or international units
-1mg = 10,000 units
323
What drugs are polymixins used in combination with?
Generally last line antibiotics
- various combinations of colistin with other drugs may be better than colistin alone
- rifampin
- meropenem
324
What is oral colistin used for?
Only for bowel decontamination
- ex: before GI surgery
- do not convert from IV to PO to treat a systemic infection
325
What are aerosolized polymixins used for?
Decrease colonization with gram negative bacteria (primarily Pseudomonas) in some patients
- particularly those with cystic fibrosis
- prepare just before administration
Aerosolized drugs have been used to treat pneumonia
-evidence for this not very strong
326
What are polymixins good for?
Treatment of multi-drug resistant gram negative infections including:
- pneumonia
- bacteremia
- sepsis
- complicated UTIs
Use other drugs if pathogens susceptible
-polymixins are poorly studied in many of these disease states
327
What is fidaxomicin's use?
Only one use
-C. difficile infections
328
What is fidaxomicin?
Nonabsorbed macrocyclic antibiotic with a narrow spectrum
329
Why is fidaxomicin ideal for treating C. difficile infections?
Sparing to the normal flora of the GI tract
-allows it to be restored during therapy
330
What organisms does fidaxomicin have GOOD activity against?
C. difficile
331
What organisms does fidaxomicin have POOR activity against?
Anything else, including:
- Bacteroides species
- enteric GNRs
332
What are the adverse effects of fidaxomicin?
Most are associated with C. difficile infection
- nausea
- diarrhea
- abdominal pain
- cramping
333
How did fidaxomicin compare to oral vancomycin capsules in one trial?
- showed similar clinical efficacy
- superior in preventing recurrences of C. difficile infection
- may be preferred for patients at high risk of recurrence
334
Should fidaxomicin be combined with other drugs?
Two drugs are not always better than one; should probably be avoided
-when coadministered with oral vancomycin or metronidazole, the advantages of fidaxomicin in sparing the normal GI tract flora are likely negated
335
What is a disadvantage of fidaxomicin?
Expensive
- patient assistance programs available
- cheaper than an admission for C. difficile relapse
- challenging to determine who are the best candidates for fidaxomicin use
336
What is fidaxomicin good for?
C. difficile infection
-ranging from diarrhea to pseudomembranous colitis
337
What is a predicament with fidaxomicin use?
Has important benefit in lowering C. difficile infection RECURRENCE
-high cost necessitates careful determination of which patients are most likely to benefit from it
