Lectures 4 and 5 anti-infectives Flashcards
What should the choice of antibiotic therapy be based on?
Culture and susceptibility test results (directed therapy) or known common pathogens in the condition and their current resistance patterns (empirical therapy).
What are the problems of broad spectrum therapy?
Selection of resistant organisms.
Superinfection with resistant organisms.
More likely to cause GI adverse effects.
Combination therapy is avoided, except in certain circumstances. When is combination therapy used?
To prevent the emergence of resistant microorganisms (e.g. treatment of TB, H Pylori, HAART).
To achieve synergy to improve outcomes.
Treat multiple simultaneous infections.
Treat a life-threatening infection empirically.
How have microbes developed antimicrobial resistance?
Production of Beta-lactamases by bacteria led to penicillins that were resistant to beta lactamase. Also development of beta lactamase inhibitors.
Alteration of penicillin-binding proteins.
Give an example of antibacterial synergy.
Penicillin and aminoglycoside for treatment of acute bacterial endocarditis.
The penicillin inhibits the cell wall biosynthesis, which allows the amino glycoside to penetrate the thick peptidoglycan layer of these organisms.
Give an example of an unfavourable antimicrobial combination, and explain.
Tetracyclines (bacteriostatic) with penicillins (bactericidal). Cells need to be growing for the penicillin to have bactericidal effect.
Bacteriostatic and bactericidal drugs are sometimes used when no good alternative exists.
How does combination therapy reduce toxicity? Give an example.
Combining drugs that have low TI reduces toxicity. For example, amphotericin B enhances uptake of flu cytosine by fungal cells. This combination reduces the dose of amphotericin B required to treat a systemic fungal infection.
Give an example of the use of combination therapy to treat multiple simultaneous infections.
Combination therapy extends spectrum of action. Eg after draining of abscess in appendix rupture, use an amino glycoside to kill aerobic G-, and clindamycin or metronidazole to kill aerobes.
Duplication of antibiotics that have the same spectrum of action should be avoided.
Why is it important to limit the duration of therapy?
To minimise selection of antibiotic resistant microorganisms.
Oral therapy should be used in preference to parenteral therapy, except in certain circumstances. When should parenteral therapy be considered?
If oral route is unavailable (unconscious, difficulty swallowing).
Unreliable absorption (vomiting, diarrhoea).
High doses required and are not readily achievable via oral route.
Oral antimicrobial with a suitable spectrum of activity is unavailable.
Urgent treatment is required.
Patient compliance is an issue.
Why must vancomycin be administered intravenously for systemic infections?
When is it given orally?
Vancomycin is a large hydrophobic molecule that partitions poorly across the GI mucosa and so is not well absorbed.
Given orally for serious cases of C difficile when unresponsive to metronidazole.
Discuss the use of antimicrobials for prophylaxis.
Restrict prophylactic use for when it has been shown to be effective, or if infection would be disastrous.
Base the choice of antimicrobial on known or likely target pathogen.
Duration should be as short as possible.
Surgical prophylaxis should be parenteral and commenced just before procedure.
When is non-surgical prophylaxis given?
Contact with menigococcal or H influenza Prevention of recurrent rheumatic fever Frequent recurrent UTI Prevention of endocarditis Contacts of active TB Opportunistic HIV infection Post needle stick injury
When is TDM of vancomycin warranted?
With concomitant amino glycoside therapy
Patients with altered pharmacokinetic parameters
Patients on haemodialysis, during high dose or prolonged treatment
Patients with impaired renal function.
What factors should be considered when choosing an antimicrobial?
Likely target organism, narrow spectrum of activity, safety, hypersensitivity, previous clinical experience, cheapest available alternative, potential resistance, risk of superinfection, patient factors.
Why is the drug being used? Prophylaxis, empirical therapy or directed therapy.
