Nitrofurantoin antibacterial action

Nitrofurantoin is well absorbed after ingestion. It is metabolized and excreted so rapidly that no systemic antibacterial action is achieved. The drug is excreted into the urine by both glomerular filtration and tubular secretion. With average daily doses, concentrations of 200 mcg/mL are reached in urine. In renal failure, urine levels are insufficient for antibacterial action, but high blood levels may cause toxicity. Nitrofurantoin is contraindicated in patients with significant renal insufficiency. 

The mechanism of antibacterial action of the furan derivatives is unknown. However, the reduced forms of nitrofurans are highly reactive and are thought to inhibit many bacterial enzyme systems, including the oxidative decarboxylation of pyruvate to acetylcoenzyme A. Nitrofurans (see list in Table 1.7) are bacteriostatic but, at high concentrations, can be bactericidal to sensitive organisms. Both chromosomal and plasmid-mediated mechanisms of resistance to nitrofurantoin occur, and these most commonly involve the inhibition of nitrofuran reductase. 

It is not yet known whether magnesium trisilicate significantly reduces the antibacterial effectiveness of nitrofurantoin but the response should be monitored. While it is known that the antibacterial action of nitrofurantoin is increased by drugs that acidify the urine (so that reduced actions would be expected if the urine were made more alkaline by antacids) this again does not seem to have been confirmed. The results of the in vitro studies suggest that the possible effects of the other antacids are quite small, and aluminium hydroxide is reported not to interact. 

Reduction of nitro compounds occurs via the action of cyji450 in conjunction with NADPH in higher organisms, e.g. the inactivation of nitrazepam (Fig. 8.34) but an important pathway which is exploited in antibacterial compounds is the reduction of antibacterial compounds such as metronidazole (Fig. 8.34) and nitrofurantoin to their active forms by bacterial nitroreductases. 

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