2. Antimicrobial agents II Flashcards
How may misuse of antibiotics occur?
No infection present, selection of incorrect drug, inadequate or excessive dose, inappropriate drug therapy (inappropriate use of empirical antibiotics is responsible for a lot of complications), expensive agent used when cheaper is available. (about 50% of people with bacteraemia would get better by themselves)
What percentage of those given an antimicrobial will experience an adverse event? And what adverse events occur?
About 5% will experience an adverse event. This can result in GI upset, fever and rash, renal dysfunction, acute anaphylaxis (if someone says they have penicillin allergy, clarify exactly how bad the allergy is) and hepatitis
What to consider when prescribing antibiotics? CHAOS
CHAOS. Choice of the correct antimicrobial depends on: Host characteristics (e.g. age, pregnancy, renal/liver failure, other medications); Antimicrobial susceptibilities; Organism itself; and Site of infection (e.g. bone, CSF, urine).
What to consider when prescribing antimicrobials, in terms of more specific guidelines for the choice of drug
- Use NARROW SPECTRUM if possible
- Use BACTERICIDAL drugs if possible.
- Ideally the choice should be based on bacteriological diagnosis (or the best guess based upon the differential diagnosis).
- Consider local sensitivity patterns.
- Patient characteristics.
- Cost.
What other factors must be considered when prescribing antimicrobials? *
- Pharmacokinetics (absorption, distribution, elimination).
- Route of administration: NOTE: in patients who are septic, their blood pressure is likely to be low, hence perfusion of their intestines will be low and so drug absorption per orally may be compromised. IV is recommended if the infection is serious or if the patient is not absorbing orally. IV is also recommended for deep infections and for CNS infections.
- Dosage (age, renal/hepatic function, drug monitoring)
How can susceptibility be tested?**
Minimum inhibitory concentration (MIC), using agar disc diffusion method (?)
What is MIC?
Minimum inhibitory concentration. This is the minimum drug concentration that is required to inhibit the growth of the organism in a culture. There are regulatory bodies that set an MIC cut-off (i.e. if the MIC is higher than X the organism is resistant, if it is lower than X it is sensitive).
What is agar disc diffusion method?
The disc is impregnated with antibiotic which diffuses out from the disc. As the distance from the disc increases, the concentration of antibiotic decreases logarithmically. The border of the clear zone is the MIC. This is a time-consuming method.
Through what method can MIC be determined?
Agar Disc Diffusion method
What is important to do before starting empirical antibiotic therapy?
It is important to collect specimens for culture BEFORE starting empirical antibiotic therapy if possible. Empirical cover can then be changed based on the culture results. Empirical therapy covers the most likely organism.
What are important indications for broad-spectrum antibiotics?
In patients with nosocomial infections, appropriate initial antimicrobial therapy is associated with higher survival rates. So broad spectrum antibiotics are an optimal initial choice for nosocomial pneumonia and severe sepsis. Septic shock is a particularly important indication for broad-spectrum antibiotics.
How does preliminary identification of organisms occur?
Gram-staining, send as much specimen as possible (higher volume of sample means higher sensitivity), and rapid antigen detection (immunofluorescence, PCR).
What must be considered with the site of infection?
Local concentration of the antimicrobial will be affected by factors such as: pH at the infection site, lipid-solubility of the drug, and ability to penetrate the blood-brain barrier. Special considerations needed for endocarditis and osteomyelitis.
How do you decide if the patient needs an antimicrobial?
- Check for evidence of a systemic response i.e. fever, raised CRP, high WBC (mainly neutrophils) NOTE: in severe infections you can get a low WBC.
- Duration of symptoms
- Underlying risk factors
- Likely source of infection
- Exclude other pro-inflammatory diseases
How do you decide the route of administration of an antimicrobial?
- i.v. - Used for serious (or deep-seated) infection.
- p.o. - Usually easy, but avoid if poor GI function or vomiting. Different classes of antimicrobial have different oral bioavailabilities.
- i.m. - Not an option for long-term use. Avoid if bleeding tendency or drug is locally irritant.
- topical - limited application and may cause local sensitisation
- NOTE: putting topical antibiotics on sloughing tissue will not be very effective.
When may you switch from IV to PO?
- IV to PO switch is recommended in hospital for most infections if the patient has stabilised after 48 hours of IV treatment.
- In CNS infections and severe infections such as osteomyelitis, you may NOT switch to PO.
Draw a graph showing pharmacokinetics and pharmacodynamics of antibiotics.
See notes. Include Cmax, area under curve, MIC, Time>MIC, Peak/MIC(?), 24 AUC/MIC(?), x axis: time (hours), y axis: (concentration).
What are the different patterns of activity of antibiotics?
Type I, type II and type III
What is type I pattern of activity?
Concentration dependent killing and prolonged persistent effects
What are examples of antibiotics that have type I pattern of activity?
Aminoglycosides, daptomycin, fluoroquinolones, ketolides
What is the goal of therapy of type I antibiotics?
Maximise concentrations
What PK/PD parameters are used in type I pattern of activity?
24h-AUC/MIC, Peak/MIC
What is type II pattern of activity?
Time-dependent killing and minimal persistent effects
What are examples of antibiotics that have type II pattern of activity?
Carbapenems, cephalosporins, erythromycin, linezolid, penicillins
What is the goal of therapy of type II antibiotics?
Maximise duration of exposure
What PK/PD parameters are used in type II pattern of activity?
T>MIC
