Urinary antiseptics are oral agents that exert antibacterial activity in the urine but have little or no systemic antibacterial effect. Their usefulness is limited to lower urinary tract infections. Prolonged suppression of bacteriuria with urinary antiseptics may be desirable in chronic or recurrent urinary tract infections in which eradication of infection by short-term systemic therapy has not been possible.
At therapeutic doses, nitrofurantoin is bactericidal for many gram-positive and gram-negative bacteria; however, P aeruginosa and many strains of Proteus are inherently resistant. Nitrofurantoin has a complex mechanism of action that is not fully understood. Antibacterial activity appears to correlate with rapid intracellular conversion of nitrofurantoin to highly reactive intermediates by bacterial reductases. These intermediates react nonspecifically with many ribosomal proteins and disrupt the synthesis of pro-teins, RNA, DNA, and metabolic processes. It is not known which of the multiple actions of nitrofurantoin is primarily responsible for its bactericidal activity.There is no cross-resistance between nitrofurantoin and other antimicrobial agents, and resistance emerges slowly. As resistance to trimethoprim-sulfamethoxazole and fluoroquinolones has become more common in Escherichia coli, nitrofurantoin has become an important alternative oral agent for treatment of uncomplicated urinary tract infection.
Nitrofurantoin is well absorbed after ingestion. It is metabo-lized 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, concen-trations 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 (creatinine clearance 60 mL/min).
The dosage for urinary tract infection in adults is 100 mg orally taken four times daily. The drug should not be used to treat upper urinary tract infection. Oral nitrofurantoin can be given for months for the suppression of chronic urinary tract infection. It is desirable to keep urinary pH below 5.5, which greatly enhances drug activity. A single daily dose of nitrofurantoin, 100 mg, can prevent recurrent urinary tract infections in some women.
Anorexia, nausea, and vomiting are the principal side effects of nitrofurantoin. Neuropathies and hemolytic anemia occur in patients with glucose-6-phosphate dehydrogenase deficiency. Nitrofurantoin antagonizes the action of nalidixic acid. Rashes, pulmonary infiltration and fibrosis, and other hypersensitivity reactions have been reported.
Methenamine mandelate is the salt of mandelic acid and methe-namine and possesses properties of both of these urinary antisep-tics. Methenamine hippurate is the salt of hippuric acid and methenamine. Below pH 5.5, methenamine releases formalde-hyde, which is antibacterial (see Aldehydes, below). Mandelic acid or hippuric acid taken orally is excreted unchanged in the urine, in which these drugs are bactericidal for some gram-negative bacteria when pH is less than 5.5. Methenamine mandelate, 1 g four times daily, or methenamine hippurate, 1 g twice daily by mouth (children, 50 mg/kg/d or 30 mg/kg/d, respectively), is used only as a urinary antiseptic to sup-press, not treat, urinary tract infection. Acidifying agents (eg, ascorbic acid, 4–12 g/d) may be given to lower urinary pH below 5.5. Sulfonamides should not be given at the same time because they may form an insoluble compound with the formaldehyde released by methenamine. Persons taking methenamine mandelate may exhibit falsely elevated tests for catecholamine metabolites.