INDEX combination drug therapy

Two methods are used to determine the expected effects of combination antibiotic therapy. For the most part, both methods are not used commonly in the clinical microbiology laboratory owing to the substantial labor involved with these tests and the lack of strong correlation with clinical outcome in the majority of infections. The first method is the microtiter fractional inhibitory concentration (FlC, or checkerboard method). The FlC is performed in a similar manner to the microtiter broth MIC except that two antibiotics are tested in the same microtiter plate. Twofold serial dilutions of one antibiotic are made in one direction on the plate (e.g., from right to left), whereas dilutions of the second antibiotic are made from the other direction on the same plate (e.g., from top to bottom). This method produces all possible combinations of twofold concentrations for the two drugs being tested. An inoculum of test bacteria is added to all wells, and the results are read in a similar manner as the MIC test. The FlC is expressed mathematically by calculation of the FlC index. The FlC index is calculated as... 

AMPHETAMINES BUPROPION 1. t plasma concentrations of these substrates, with risk of toxic effects 2. t risk of seizures. This risk is marked in elderly people, patients with a history of seizures, those with an addiction to opiates/ cocaine/stimulants, and those with diabetes treated with oral hypoglycaemics or insulin 1. Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 2. Bupropion is associated with a dose-related risk of seizures. These drugs that lower seizure threshold are individually epileptogenic. They have additive effects when combined 1. Initiate therapy with these drugs, particularly those with a narrow therapeutic index, at the lowest effective dose. Interaction is likely to be important with substrates for which CYP2D6 is considered the only metabolic pathway (e.g. amphetamines) 2. Extreme caution. The dose of bupropion should not exceed 450 mg/day (or 150 mg/day in those with severe hepatic cirrhosis)... 

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