Minimal inhibitory concentration exceeding

Pyrazinamide is distributed throughout the body. Peak plasma concentrations are reached 2 hours after oral administration. Excretion is primarily by glomerular filtration. Serum concentrations are generally 30-50 gg/ml with daily doses of 20-25 mg/kg. The maximum daily dose should not exceed 3 g, regardless of weight. At a pH of 5.5, the minimal inhibitory concentration of pyrazinamide for Mycobacterium tuberculosis is 20 pg/ml (1). 

The sulfones are distributed throughout total body water and are present in all tissues. They are retained in skin and muscle and especially in liver and kidney. The sulfones persist in the circulation for a long time because of reabsorption from the bile periodic interruption of treatment is advisable for this reason. Dapsone is acetylated in the liver by the same enzyme that acetylates isoniazid. Daily administration of50-100 mg results in serum levels exceeding the usual minimal inhibitory concentrations, even in rapid acetylators, in whom the serum t of dapsone is shorter than usual. 

Fosfomycin is excreted by the kidney, with urinary levels exceeding the minimal inhibitory concentrations (MiCs) for many urinaiy tract pathogens. In a single dose, the drug is less effective than a 7-day course of treatment with fluoroquinolones. With multiple dosing, resistance emerges rapidly and diarrhea is common. Fosfomycin may be synergistic with beta-lactam and quinolone antibiotics in specific infections. 

Substrate/Product Toxicity. Many volatile organic substrates such as terpenoids can be toxic to the organism and cannot exceed threshold concentration. Many end-products are secondary metabolites with intrinsic toxicological or inhibitory effects on the producing organisms. This can in some cases be minimized by the continuous stripping of finished product from the fermentation broth. 

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