M9: CC2: Practical Aspects of Antibiotic Therapy Flashcards
What different types of antibiotic prescribing are there?
Prophylaxis is the use of _ agents to _
Types (4)
antimicrobial
prevent infection
perioperative
endocarditis
travel
opportunistic infection
What different types of antibiotic prescribing are there?
Perioperative prophylaxis is used to prevent _ infections
Clean wound:
No _ encountered
_, _, and _ not entered
Clean-contaminated wound:
_, _, or _ entered without significant _
Contaminated wound:
Gross spillage from _
Entrance into _ or _ with infected _ or _
Traumatic wounds or any wound with _
surgical site
inflammation
Respiratory, GI and GU tract
GI, GU or respiratory tracts
spillage
GI tract
GU or biliary tract, urine or bile
pus
What different types of antibiotic prescribing are there?
Endocarditis prophylaxis is used to prevent _ (infections of _) with procedures that induce _
Travel prophylaxis may be taken by travelers to prevent _
Opportunistic infection prophylaxis may be taken by _ patients to prevent infections such as _
endocarditis
heart valves
bacteremia
malaria
immunocompromised Pneumocystis jiroveci (carinii)
What different types of antibiotic prescribing are there?
Pre-emptive therapy is the use of antibiotics in case of an _ infection which is likely to become _ with serious consequences unless treated.
The treatment decision is mostly based on _.
ex. Starting _ in a transplant patient with evidence of _ reactivation by increased viral load per PCR in serum
asymptomatic
symptomatic
laboratory markers
valganciclovir
cytomegalovirus (CMV)
What different types of antibiotic prescribing are there?
Empiric therapy is the use of antibiotics for a _ infection but before the _ of the infection is known
Common infections for which empiric therapy is given include fever in _ patients, _-acquired pneumonia and _-associated pneumonia.
In general, delaying the antibiotic therapy until the microbiological diagnosis is made can be (beneficial / detrimental) to the patient in case of a rapidly progressing infection
The antibiotics chosen for empiric therapy depend on individual patient factors, exposures and local epidemiology
Empiric antibiotic therapy is by necessity “(broad / narrow)” in many instances
In some suspected infections it may be better to wait for _ or _ rather than give empiric antibiotics.
Many infections resolve due to the _ and do not justify the use of antibiotics.
presumed
etiology
neutropenic
community
ventilator
detrimental
broad
clinical progress or the results of cultures and susceptibilities
immune system of the host
What different types of antibiotic prescribing are there?
Pathogen-directed therapy is when the organism is _, but antibiotic susceptibility is _
Appropriate antibiotics can be selected based on the local _ of antimicrobial susceptibility, but are (broader / narrower) than when the susceptibility of the infecting organism is known.
known
awaited
epidemiology
broader
What different types of antibiotic prescribing are there?
Susceptibility-guided therapy is when the organism and the antibiotic susceptibility are both _
This allows for “_” of antibiotic therapy.
In general the antibiotic with the (broadest / narrowest) spectrum, the most _, least _ and _ is chosen.
known
streamlining
narrowest
effective
toxic
cheapest
On which occasions are no antibiotics required?
_ (for example, rhinitis) for which no effective antimicrobial medications exist.
_ (for example, one of two sets of blood cultures with coagulase-negative staphylococci)
_ (for example, the finding of vancomycin resistant Enterococcus faecium from a rectal swab)
_ (for example, bronchitis) even if bacteria are the cause.
Also, adequate _ obviates the need for antibiotics
Suspected viral infection
Contamination of the sample
Colonization in the absence of infection
Treatment has not shown to hasten the resolution of the infection
surgical drainage of an abscess
How do microbiology laboratories perform antibiotic susceptibility testing?
Disk diffusion:
Disks containing _ are placed on an agar plate and _ of bacterial growth is measured.
The greater the zone, the more _.
Method which determines the MIC? (y/n)
antibiotics
zone of inhibition
susceptible the bacteria are to the antibiotics diffused from the disk
n
How do microbiology laboratories perform antibiotic susceptibility testing?
Broth macrodilution, microdilution and agar dilution:
Test-tubes, microtiter plates or agar plates containing varying _ of the antibiotic are inoculated with the organism.
These are the classic methods for determining the _ of the antibiotic against that particular organism.
This is the lowest concentration of antibiotic at which there is _
Method which determines the MIC? (y/n)
concentrations
minimum inhibitory concentration (MIC)
no visible growth in the test-tube
y
How do microbiology laboratories perform antibiotic susceptibility testing?
E-test:
A _ is impregnated with different concentrations of antibiotics along its gradient.
The strip is placed directly on an _ inoculated with the organism.
The zone of inhibition can be read as the _
Method which determines the MIC? (y/n)
patented strip
agar plate
MIC
y
How do microbiology laboratories perform antibiotic susceptibility testing?
Commercial semi-automated methods:
These have a small number of _ containing varying concentrations of the antibiotic to be tested.
Usually only the concentrations around the “breakpoint” differentiating _ from _ organisms are tested.
Method which determines the MIC? (y/n)
wells
susceptible
resistant
n
How do microbiology laboratories perform antibiotic susceptibility testing?
Genetic testing:
PCR amplification can identify the presence of _ (rifampin resistant TB) or _ encoding enzymes conferring resistance to antimicrobials (HIV genotyping).
Method which determines the MIC? (y/n)
antimicrobial resistance genes
mutations in genes
n
What are some of the pharmacodynamic considerations in prescribing antibiotics?
2 types of antibiotics
concentration-dependent
time-dependent
What are some of the pharmacodynamic considerations in prescribing antibiotics?
Concentration-dependent antibiotics:
- Achieve maximal efficacy at _
- The upper concentration limit in the patient is limited by the concentrations that will produce _
(Examples include _ and _)
- Knowledge of the MIC is important because the ratio of _ to MIC is a predictor of efficacy of _
maximal concentrations
toxicity
aminoglycosides
fluoroquinolones
peak concentration
aminoglycosides
What are some of the pharmacodynamic considerations in prescribing antibiotics?
Time-dependent antibiotics:
- Do not result in better efficacy at concentrations of more than _
- The time the concentration of drug at the site of infection _ is the major determinant of clinical efficacy
(Examples include _ and _)
- Continuous _ or multiple _ optimizes the time above the MIC
4 times the MIC
exceeds the MIC
beta-lactams
vancomycin
infusion
daily doses
What are other determinants in choosing antibiotics?
Route of administration:
Most antibiotics are available in _ form. This is especially helpful if the patient is too sick or if the _ system is not capable of _ the antibiotic.
Some antibiotics are absorbed very well and the intravenous formulation can be exchanged to an _ if the patient has improved
(Examples include _, _, and _).
intravenous
gastro-intestinal
absorbing
oral pill
azithromycin
trimethoprim-sulfamethoxazole
fluoroquinolones
What are other determinants in choosing antibiotics?
Anatomic site where the infection needs treatment:
Most IV antibiotics reach sufficient levels in the _, so bacteremias are treatable as long as the drug levels exceed the _ of the bacteria.
However, due to the _ it is very difficult for antibiotics to reach adequate levels in the _ compartment and high doses need to be used.
Also, antibiotics may not reach adequate concentrations in _ and other poorly _ sites (foreign materials implanted, necrotic bone).
blood stream
MIC
blood-brain barrier
cerebrospinal
pus (abscess)
perfused
What are other determinants in choosing antibiotics?
Combination therapy:
Used as _, when a wide range of organisms are suspected, that cannot be covered by _. Ex. _.
Used for _, when the efficacy of a combination is expected to be more than the summation of the efficacy of each antibiotic alone. Ex.Enterococcal endocarditis where a combination of _ and _ is more efficacious than either agent alone.
To prevent emergence of _. Ex. _ therapy for active tuberculosis, which combines _, _, _, and _. Another example is _ for which 3 active drugs must be used simultaneously to attain durable viral suppression.
empiric therapy
monotherapy
Bacterial meninigitis
synergy
ampicillin and gentamicin
resistance
Induction
rifampin, isoniazid, pyrazinamide and ethambutol (RIPE)
HIV
What are other determinants in choosing antibiotics?
Toxicity:
(Aminoglycosides / Cephalosporins) are more toxic (nephrotoxic, ototoxic) than (Aminoglycosides / Cephalosporins).
As soon as the causative _ is identified and _ are determined you should use the least toxic drug.
Aminoglycosides
cephalosporins
micro-organism
susceptibilities
What are other determinants in choosing antibiotics?
Costs:
(Linezolid / Nafcillin) is much cheaper than (Linezolid / Nafcillin) so the latter should only be used in specific circumstances justifying the much higher costs.
Nafcillin
linezolid
Example of the interpretation of MIC’s in treatment of Streptococcus pneumoniae:
PCN MIC ≤2 µg/ml is reported as (susceptible / intermediate / resistant) (92% at PUH):
Treat with IV _ 18 million units/24 hours
susceptible
Penicillin
Example of the interpretation of MIC’s in treatment of Streptococcus pneumoniae:
PCN MIC =4 µg/ml is reported as (susceptible / intermediate / resistant) (5% PUH):
Treat with IV _ 24 million units/24 hours or _
Higher dose of _ (PCN or ceftriaxone) overcome the resistance mediated by PCN binding proteins (PBPs)
There is no benefit of adding _ (clavunalate, sulbactam, tazobactam) since the resistance to beta-lactams is due to _ and not beta-lactamases.
intermediate
Penicillin
Ceftriaxone
beta-lactams
beta-lactamase inhibitors
PBPs
Example of the interpretation of MIC’s in treatment of Streptococcus pneumoniae:
PCN MIC ≥8 µg/ml is reported as (susceptible / intermediate / resistant) (3% PUH):
Treat with _
Even very high doses of _ (PCN or ceftriaxone) cannot overcome the PBP mediated resistance.
There is no benefit of adding _ (clavunalate, sulbactam, tazobactam) since the resistance to beta-lactams is due to _ and not beta-lactamases.
resistant
Vancomycin
beta-lactams
beta-lactamase inhibitors
PBPs
Example of the interpretation of MIC’s in treatment of Streptococcus pneumoniae:
These new PCN MIC breakpoints for the interpretation of susceptibilities of Streptococcus pneumoniae are NOT applicable for _ due to the blood brain barrier.
PCN has lower achievable concentrations in _ than in other compartments and although in theory a Streptococcus pneumoniae isolate with MIC=4 from _ (reported as resistant) could be treated with high dose _ alone, additional highly dosed _ is required.
meningitis
cerebrospinal fluid
CSF
beta-lactams
vancomycin
Example of the interpretation of MIC’s in treatment of Streptococcus pneumoniae:
1) The MIC of bacteria such as Strep pneumo for a certain antimicrobial can be determined by _ or by _.
The higher the MIC, the higher the _.
2) The MIC itself is not affected by the _ from where the bacteria is isolated.
3) However, the interpretation of the MIC calling the bacteria susceptible, intermediate or resistant to an antimicrobial is dependent upon the .
4) So if the MIC of a bacterium is lower than the concentration attained by the antimicrobial in the infected compartment, we call it “.”
broth dilution
Etest
concentration of that antimicrobial is required to inhibit its growth
location /body site
compartment from where the isolate is obtained i.e. the location of the infection
resistant
Example:
A certain E.coli strain isolated has a MIC of 32 for cefepime. A safe IV dose of cefepime attains a serum level of 25 and a urine level of 100.
So if the E. coli was isolated from blood (bacteremia) it was reported as _ to cefepime.
But if the E. coli was isolated from urine (in case of bladder infection) it could have been reported as _ to cefepime.
resistant
susceptible
Example:
Strep pneumoniae isolated has a MIC of 1 for PCN. A safe IV dose of PCN attains a serum level of 30 and CSF level of 0.5
So if the Strep pneumo was isolated from blood it was reported as _ to PCN.
But if the Strep pneumo was isolated from CSF (case of meningitis) it was reported as _ to PCN.
susceptible
resistant
