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. Traditional recommendations are to avoid use in patients with creatinine clearance <60 mL/min; however, some data suggest short-term nitrofurantoin treatment is acceptable in patients with creatinine clearance >30 mL/min.
The dosage for urinary tract infection in adults is 100 mg orally taken four times daily. A long-acting formulation (Macrobid) can be taken twice daily. Each long-acting capsule contains two forms of nitrofurantoin. Macrocrystalline nitrofurantoin, which has slower dissolution and absorption than nitrofurantoin monohydrate, constitutes 25%. The remaining 75% is nitrofurantoin monohydrate contained in a powder blend, which, upon exposure to gastric and intestinal fluids, forms a gel matrix that releases nitrofurantoin over time.
The drug should not be used to treat upper 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 pulmonary toxicities may occur, particularly with prolonged use or in patients with renal impairment. Hemolytic anemia can 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 methenamine and possesses properties of both of these urinary antiseptics. Methenamine hippurate is the salt of hippuric acid and methenamine. Below pH 5.5, methenamine releases formaldehyde, which is antibacterial (see Aldehydes, below). Oral mandelic acid or hippuric acid is absorbed and excreted unchanged in the urine. These drugs are bactericidal for some Gram-negative bacteria when urine pH is less than 5.5.
Methenamine mandelate, 1 g four times daily, or methenamine hippurate, 1 g twice daily by mouth (in children age 6 to 12 years, 500 mg four times daily or twice daily, respectively), is used only as a urinary antiseptic to prevent, not treat, symptomatic 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.
■ DISINFECTANTS, ANTISEPTICS, & STERILANTS
Disinfectants are chemical agents or physical procedures that inhibit or kill microorganisms (Table 50–1). Antiseptics are disinfecting chemical agents with sufficiently low toxicity for host cells that they can be used directly on skin, mucous membranes, or wounds. Sterilants kill both vegetative cells and spores when applied to materials for appropriate times and temperatures. Some of the terms used in this context are defined in Table 50–2.