Lecture 21- Principles Of Antimicrobial Therapeutics II

Question 1

Combination of antibiotics

Answer 1

Achieve synergism; e.g. B-lactam + aminoglycoside (gentamicin) for endocarditis

-slow down emergence of resistance e.g. sulphonamide + trimethoprim

-infections requiring prolonged treatment; e.g. multi-drug therapy for HIV/ TB

• mixed infections; e.g. peritonitis, leg ulcers in diabetic pts (mixture of anaerobes, aerobes, G+ve + G-ve organisms)

Question 2

Antibacterial drug interactions

Answer 2

Additive/indifferent- combined effects = sum of independent effects

Synergistic- combined effects > sum of independent effects

Antagonistic- combined effects < sum of independent effects

Question 3

Antibacterial drug interactions

Answer 3

Interactions= hard to predict;
- vary within species and strains
- occur over a narrow range of conc/ drug ratios

Method of detection;
- checkerboard
- killing curve

Question 4

Testing of antibiotic interactions

Answer 4

Activity of one drug = enhances that of a second drug synergy

Drugs may interfere with each other- Antagonism

Penicillins + Bacteriostatic drugs; tetracyclines = antagonistic, since penicillins require actively growing cells + static drugs prevent cell growth

Aminoglycosides = synergistic when used in combination with penicillins

Question 5

Synergism in antibiotic combinations

Answer 5

Sequential inhibition of successive steps in metabolism; sulphonamide-trimethoprim

Sequential inhibition of protein synthesis; syncercid

Facilitation of drug entry of one antibiotic by another; beta-lacam-aminoglycoside

Inhibition of inactivating enzymes; ampicillin- clavulanic acid

Prevention of emergence of resistant populations; triple therapy for TB

Treatment of systemic fungal infections; candidiasis, cryptococcosis; with amphotericin + flucytosine

Question 6

Antagonism of antibiotic combinations

Answer 6

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