Antibacterial Concepts & Antibiotic Stewardship Flashcards
What drug can be used for MRSA bacteraemia?
What is the recommended therapeutic blood level for this drug?
Teicoplanin
the recommmended therapeutic blood level is > 20 mg / L
If someone has an MRSA bacteraemia and has therapeutic levels of teicoplanin below the recommended, what should be done if he is getting better?
- Continue the same dose of 400mg once daily
- increase the dose to 800mg daily
- give the same dose (400mg) but twice daily
- reduce the dose
each of these could be a reasonable option depending on the circumstances
In general, what are the roles of antibiotics?
Bacterial infections are treated with antibiotics that inhibit bacterial growth
bacteriocidal antibiotics will kill bacteria, but most will just inhibit growth
the immune system can then intervene and macrophages will engulf the bacteria
How can you test how susceptible to an antibiotic a bacteria is?
By determining the minimum amount of antibiotic that stops the bacteria from growing
this is the minimum inhibitory concentration (MIC)
What is the MIC?
How can it be worked out?
Minimum inhibitory concentration:
- the minimum concentration of antibiotic which inhibits bacterial growth
- the same amount of culture medium and bacteria are placed in each test tube
- varying concentrations of antibiotics in doubling dilutions are placed in the test tubes
- these are left to grow overnight
- you can see which test tubes contain bacteria
- they may still be present - the bacteria are not killed but their growth has been inhibited
Why are antibiotics given in different doses?
We dose antibiotics to try and ensure all patients get blood concentrations of antibiotic that are associated with increased survival
There is a % of time at which the blood level of antibiotic is above the MIC and is inhibiting growth
How do MIC values vary within species?
There is intra-species variations in MIC values
e.g. e coli
different concentrations of antibiotic are needed to inhibit growth within a population of bacteria
What are the following features on the blood antibiotic profile?
C max - the highest concentration of antibiotic that is achieved in the blood
AUC/MIC - the area under the curve divided by the MIC
T > MIC -
Why does the MIC concentration need to be considered?
The MIC needs to be considered in relation to serum concentrations of antibiotic
How can dosage vary depending on how different drugs are effective in different ways?
Some drugs are dosed infrequently but with higher doses
some drugs are dosed frequently but with lower doses
this depends on the time above the MIC
What is meant by the pharmacodynamic target?
For all antibiotics there is a pharmacodynamic target that is associated with increased clinical cure
after the PD target has been acheived, there is no additional efficacy benefit
so antibiotics are dosed to the PD target, but not to exceed the PD target
you should give enough drug, not more and more drug
What is meant by antibiotic pharmacokinetics?
There is a lot of variation between patients in how antibiotic is:
- Distributed in the body
- Cleared from the body
antibiotic treatment must consider human populations and the variation within it
Why are multiple doses of antibiotics given during the day?
To keep the blood concentration of antibiotic above the MIC for as long as possible
or
continuous infusions of antibiotics are given where the concentration is kept just above the MIC
What can be summarised about the MIC and antibiotic use?
- MIC is relatively important in relation to cure
- the antibiotic pharmacokinetics are relatively important to clinical cure
- MIC and PK values vary
- the PD target is fixed
What information is used in simulations to predict optimal antibiotic doses?
- MIC value
- PK
- PD targets
these are used to help decide what is the best dose of an antibiotic for a population of patients
How can the data for simulations be described?
The MIC and PK data can be described using probabilities
The PD target will be fixed
What is the purpose of statistical simulations?
they can be used to determine the probability that, if treated with a certain antibiotic dose, for a certain infection, they will attain the desired pharmacodynamic target
this is the probability of target attainment
How is the cure rate calculated?
What dose should be used?
1 - cure / probability of target attainment
with a dose of 2X - there may be a cure rate of 100%
if this dose of 2X has an acceptable toxicity profile, the antibiotic can be used to treat patients
What is meant by the probability of target attainment?
Simulations can be used to determine what dose of antibiotic will be able to achieve a high PTA
if the recommended dose has an acceptable toxicity profile, the antibiotic can be used to treat patients
Why are differences in different patients important to consider when prescribing antibiotics?
The same dose is given to people with the same condition and is usually sufficient
some patients may get too much antibiotic and have toxicity
some patients may get too little antibiotic
the dose needs to be changed to adapt to differences in different patients
What is the difference in action of IV and oral antibiotics in the long term?
When the drug has reached systemic circulation, IV and PO antibiotics can be considered equal
someone who is very ill may be given their initial dose IV so the drug gets into the bloodstream immediately to have an effect
What are the characteristics of oral antibiotics?
- Slower absorption
- antibiotic associated diarrhoea
- absorption may vary
- requires small bowel for absorption (cannot be used in small bowel resection)
- no intravenous (IV) access required, and no IV access side effects
- self administration
- cheaper
What are the properties of intravenous antibiotics?
- Faster / instantaneous absorption
- antibiotic associated diarrhoea
- no bowel required for absorption
- absorption rate can be varied
- IV access is required and there may be side effects such as thrombophlebitis, thrombosis and infection
- medical staff required for administration
- more expensive
In what types of infections have oral antibiotics been shown to be comparable to intravenous antibiotics?
- Bone and joint infections
- pyelonephritis
- empyema (lung abscess)
- febrile neutropenia in cancer patients
When are intravenous antibiotics preferred to be used?
IV antibiotics are important to quickly and reliably achieve targeted serum antibiotic concentrations
some drugs are not available intravenously
some antibiotics are not well absorbed orally
When is ciprofloxacin used?
What are the IV and PO disease and which is more effective?
It is used against E. coli in kidney infections
IV dose = 400mg 12 hourly
PO dose = 500mg 12 hourly with 80% oral bioavailability
Both IV and PO antibiotics have 400mg BD bio available
Both IV and PO administrations have the same PTA
What is shown in these graphs about antibiotic durations?
Positive correlations:
- as durations increase, adverse events increase
Negative correlations:
- as durations increase, failure rates decrease
- but there are diminishing returns
How are antibiotic durations chosen?
Antibiotic durations are chosen to try and maximise cure while minimising adverse effects
What are the problems involved when looking at antibiotic durations?
To reduce antibiotic resistance, shorter courses of antibiotics tend to be given
this means there is an increased risk in some patients that the infection will come back, but they can be retreated
guidelines give recommended durations but there is no fixed answer as the duration needed depends on the patient
What does the choice of antibiotic duration depend upon?
- Evidence
- clinical factors
- social factors
- costs
- resources available
When are antibiotics started?
When the benefits or starting antibiotics are greater than the disadvantages
individual patient factors may mean antibiotics may or may not be started
Under which conditions should antibiotics always / never be started?
There are times when antibiotics should always be started
e.g. Patients with sepsis
there are times when antibiotics should never be started
e.g. Patients with no evidence of infection such as auto-immune inflammation
What factors should be considered when choosing not to start antibiotics in a patient with an infection?
It can be reasonable to not start antibiotics in a patient with an infection, but it must be done in the context of an overall management plan
e.g. A patient with a skin abscess may not be given antibiotics if there is a plan for surgical drainage of the abscess
What are the benefits of early antibiotic therapy?
- Early treatment has a mortality and morbidity benefit
- narrow spectrum antibiotics can be given earlier, whereas if you wait and the patient becomes more ill, then broader spectrum antibiotics may be needed
- if clinically stable, an oral antibiotic may be administered and the response assessed
- prevention of infection metastases
What are the disadvantages of early antibiotic therapy?
- May reduce time available to do cultures so there is reduced chance of giving targeted therapy and getting a diagnosis
- may reduce time to do investigations so patient may be “overtreated”
- may increase the chance of giving the wrong antibiotic or not enough antibiotic
- insufficient time to check allergies
What are the 4 different strategies used when starting antibiotic therapy?
- Start antibiotics early and look to stop / de-escalate early
- Delay antibiotics with a plan for how / when to access / start antibiotics e.g. delayed prescription
- Start with broad spectrum and aim to narrow
- Start with narrow spectrum and have a plan for how / when to broaden
What is meant by the therapeutic window?
Why do certain drugs need to be monitored?
Maintaining the concentration within the therapeutic window ensures a safe but sufficient dose is being given
gentamicin is nephrotoxic and ototoxic so patients must be monitored to ensure levels don’t enter the toxic range
monitoring for efficacy is also important as there needs to be high enough levels in order for the drug to be effective
What is meant by surgical antibiotic prophylaxis?
Antibiotics are given at least an hour before surgery
this gives enough time for the antibiotics to reach high concentrations within the wounds
any time after an hour, and there is less benefit from the antibiotics
What is meant by antibiotic stewardship?
A coherent set of actions which promote using antimicrobials responsibility
What is meant by the 30% rule in antimicrobials prescribing?
- 30% of all hospitalised inpatients at any given time receive antibiotics
- over 30% of antibiotics are prescribed inappropriately in the community
- up to 30% of all surgical prophylaxis is inappropriate
- 30% of hospital pharmacy costs are due to antimicrobials use
- 10-30% of pharmacy costs can be saved by antimicrobial stewardship programs
What are the factors that must be considered in antibiotic stewardship?
- Involves timely and optimal selection, dose and duration of an antimicrobial
- for the best clinical outcome for the treatment or prevention of infection
- minimal toxicity to the patient
- minimal impact on resistance and other adverse effects such as C. Difficile
What % of patients have a penicllin allergy?
What types of antibiotics should not be used in people with this allergy?
10% of patients have a penicillin allergy
they may also cross-react to other beta-lactam antibiotics such as cephalosporins and carbapenems
What are the 4 main limitations of antibiotics?
- They will not treat non-infectious disease
e. g. A lot of people naturally have E.coli in the urine which is asymptomatic - They will not treat contaminated samples
- They may only be the supporting factor in some infections that require surgical intervention
- They damage the microbiome
Why can antibiotics not be used to treat infections that require surgical intervention?
Antibiotics need to get into the site of infection in order to be effective
they can only reach a site of infection if there is a vascular supply to this site
e.g. A large abscess of pus will not have a blood supply so the antibiotics wont actually clear the infection and surgery may be needed
