What two purposes can antibiotics be used for?
a) prophylaxis
- peri-operative
- immunocompromised host
- exposure to certain bacteria
- dental prcedures
b) treatment
What factors could guide the choice of antibiotic?
What are the important areas of antibiotic resistance?
• MRSA - Methicillin Resistant Staphylococcus aureus (Resistant to all beta-lactam antibiotics)
• VRE - Vancomycin Resistant Enterococci
(Enterococci are inherently resistant to most antibiotics and treatment of serious infection has been limited to amoxycillin or vancomycin)
• ESBLs - Extended Spectrum Beta-lactamases
(Beta-lactamases produced by some Enterobacteriaceae which destroy 3rd generation cephalosporins and other beta lactam antibiotics)
• CREs - Carbapenem Resistant Enterobacteriaceae
(Carbapenems - imipenem & meropenem are very broad spectrum antibiotics, often used in serious infections as a last resort)
What is the difference between empiric and directed antibiotic treatment?
What would be appropriate empiric antibiotic prescribing?
What guidelines assist antibiotic choice?
Australian Therapeutic Guidelines
What is the MIC of an antibiotic?
Minimum inhibitory concentration (MIC) is the lowest concentration of an antibiotic that will inhibit the growth of an organism
What is the difference between concentration and time dependent drugs in terms of dosage?
What factors determine appropriate route of administration?
Why would you need therapeutic drug monitoring for antibiotics?
• Required for antibiotics with a narrow therapeutic index
=ratio of toxic to therapeutic dose/level – Eg vancomycin, gentamycin
How does antibiotic resistance develop?
• De novo chromosomal mutation
– eg ciprofloxacin resistance point mutation occurs in 1:108 bacteria
• Acquired
– Clonal expansion (vertical transmission)
– Mobile genetic elements (horizontal transmission)
What are two strategies to reduce antibiotic resistance?
FRONT END:
– Restricted formulary - Limited range of antibiotics available in pharmacy
– Restricted approval of antibiotic initiation
– Selective antibiotic susceptibility reporting
– Guidelines and protocols
– Education, audit and feedback
BACK END:
– Ward based patient/chart review by IDPhysician/pharmacist
– Biomarkers
2. Prevent the secondary spread of resistance – Hygiene and cleaning - patient isolation - personal protective equipment - cleaning - decolonisation
What are some of the downsides to screening?
What can screening identify?
What is the aim of screening?
Reduce the burden of the disease in the community, including:
a) incidence
b) morbidity
c) mortality
Why does early detection from screening not necessarily mean good prognosis?
a) Lead time bias – there is a delay between the time when the disease is detected and when it is likely to produce symptoms and be diagnosed without screening. Because patient is diagnosed earlier, it may seem like they are living longer – apparent increase in life expectancy (lead time). ‘Disease time’ is increased
b) Length-time bias - Slowly progressing variants of disease remain in a pre-symptomatic (but screen-detectable) stage for longer than rapidly progressing variants of the same disease. Hence, screening is more likely to detect slowly progressing cases. Screen detected cases appear to live longer because they have a slower progression.
c) Overdiagnosis
The equity of screening – what are some of the factors to consider?
What is the number-needed-to-screen?
The number of people that need to be screened for a given duration to prevent one death or adverse event.
What are the 2 measures that tell us how valid (accurate) as diagnostic test is?
a) Sensitivity – probability of those with the disease correctly detected by the rest
- the true positive ‘rate’
- high sensitivity = few people are missed
- ΣTP/Σcondition present = a/a+c
- if high, negative result will ‘rule out’ disease
b) Specificity – probability of those without the disease correctly excluded by the test
- the true negative ‘rate’
- high specificity = rarely test positive when person doesn’t have disease
- ΣTN/Σcondition absent = d/b+d
- if high, positive will rule in disease
What are the 2 measurements that are used to evaluate the result for an individual?
a) Positive Predictive Value
- given a positive test, probability that the patient ahs the disease
- ΣTP/ΣAll Positives = a/a+b
b) Negative Predictive Value
- given a negative test, the probability that the patient doesn’t have the disease
- ΣTN/ΣAll Negatives = d/c+d
What is the triple test approach to diagnosis?
Three diagnostic components:
It is positive if any component is indeterminate, suspicious or malignant.
The sensitivity of the triple test is greater than any of the individual components alone.
What are the issues to consider with placebos?
Cons:
Pros:
NOTE: the doctor in question can impact the placebo effect - how well dressed they are, tone of voice, professional appearance etc.
What are the issues with therapeutic adherence?
Why are some people noncompliant?