Antimicrobials (2) Flashcards
How are antibiotics misused?
- No infection present
- Selection of incorrect drug
- Inadequate or excessive dose
- Inappropriate duration of therapy
• Expensive agent used when cheaper is available
Name adverse events from antibiotics.
- GI upset
- Fever & rash
- Renal dysfunction
- Acute anaphylaxis
- Hepatitis
What should be considered when prescribing antimicrobials?
C Choice of correct antimicrobial depends upon the…
H Host characteristics (i.e. renal failure, pregnancy, allergy, age, genetics, hepatic function)
A Antimicrobial susceptibilities of the…
O Organism itself and also the…
S Site of infection (i.e. bone, CSF, urine)
What pharmacological aspects need to be considered when choosing antimicrobials?
- Use NARROW SPECTRUM if possible
- Ideally choice should be based upon abacteriological diagnosis (otherwise, “best guess” based upon likely differential diagnosis refer to local policy)
- Consider local sensitivity patterns
- Patient characteristics •Cost
What are the different types of sensitivity testing?
- 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)
- Gradient MIC method – agar
- Agar Disc Diffusion Method
- Time-consuming
- The disc is impregnated with antibiotic which diffuses out from the disc
- As distance from disc increases, concentration of the antibiotic decreases logarithmically
- The border of the clear zone is the MIC
- MIC>breakpoint – resistant
- MIC
What is the guidance when giving empirical treatment?
- 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 (even before you know the exact one)
- In patients with nosocomial infections, appropriate initial ABx is associated with higher survival rates
- So, broad spectrum ABx are an optimal initial choice for nosocomial pneumonia and severe sepsis
- Septic shock is a particularly important indication for broad-spectrum antibiotics
How can organisms be identified?
Gram stain:
CSF
Joint aspirate
Pus
Rapid antigen detection
- Immunofluorescence
- PCR
How are local concentrations of antimicrobials affected by the site of infection?
The local concentration of the antimicrobial will be affected by factors such as
- pH at the infection site
- Lipid-solubility of the drug
- Ability to penetrate the blood- brain barrier (CNS infections)
Special considerations required for Rx endocarditis or osteomyelitis
Does the patient actually require an antimicrobial? - what should be considered here?
How do you choose the route of administration?
i.v. to p.o. switch is recommended in hospital for most infections if the patient has stabilised after 48 hours i.v. therapy
What are the Type I antibiotic pharmacokinetics?
- Peak above the MIC (Cmax) is the MOST IMPORTANT factor (these drugs have concentration-dependent effects)
- Therefore, aminoglycosides are given as one big dose once a day, to try and get the Cmax as high as possible
- The higher the Cmax the better the clinical outcome for infections treated with aminoglycosides
- However, achieving high Cmax must be balanced with the risk of adverse effects (ototoxicity and nephrotoxicity)
- You also measure the trough concentration to ensure that the drug is being eliminated
- Accumulation of the drug is associated with toxicity
- If the trough is too high, you will adjust the frequency of the doses being given so that you do not compromise the Cmax but do reduce accumulation of the drug
- I.E. the peak will influence the dose of the drug given, whereas the trough will determine the frequency
- NOTE: if a patient has renal failure than you may be worried about giving a full dose of aminoglycosides however, if their renal failure is caused by the sepsis then you would want to start off with the full dose and worry about the nephrotoxicity and accumulation later
What are the Type II antibiotic pharmacokinetics?
- These are time-dependent, so you want to maximise the time above the MIC
- The concentration above the MIC is NOT very important
- So, with penicillins, you tend to take them quite frequently (3-4 times per week)
What are the Type III antibiotic pharmacokinetics?
Type III (e.g. Vancomycin)
Sort of a combination of Type I and Type II
The AUC above the MIC is the MOST IMPORTANT factor (both concentration and time-dependent effects)
Infusions can maintain an AUC above the MIC
Recommended treatment duration for specific infections:
N. meningitidis
Acute osteomyelitis (adult)
Bacterial endocarditis
Group A Strep Pharyngitis
Simple cystitis
If there is no response 48 hrs after administration of antibiotics, what should be done?
Does the patient have a bacterial infection?
Is there a persistent focus present (e.g. urinary catheter)?
Is there a deep-seated collection (e.g. intra-abdominal) that requires drainage?
Could the patient have bacterial endocarditis?
Am I using the correct dose of antimicrobial?
Is there another infection present (consider Candida)?
