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Nitrofurantoin is an antibiotic. It is usually used in treating urinary tract infection.
Additional recommended knowledge
Organisms are said to be susceptible to nitrofurantoin if their Minimum inhibitory concentration (MIC) is 32μg/ml or less. The peak blood concentration of nitrofurantoin following an oral dose of nitrofurantoin 100mg, is less than 1 μg/ml and may be undetectable; tissue penetration is negligible; the drug is well concentrated in the urine: 75% of the dose is rapidly metabolised by the liver, but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 μg/ml or more. For this reason, nitrofurantoin cannot be used to treat anything other than simple cystitis.
At the concentrations achieved in urine, nitrofurantoin is bacteriocidal. The mechanism of action of nitrofurantoin is unique and complex. The drug works by damaging bacterial DNA, since its reduced form is highly reactive. This is made possible by the rapid reduction of nitrofurantoin inside the bacterial cell by flavoproteins (nitrofuran reductase) to multiple reactive intermediates that attack ribosomal proteins, DNA, respiration, pyruvate metabolism and other macromolecules within the cell. It is not known which of the actions of nitrofurantoin is primarily responsible for its bacteriocidal acitivity.
Nitrofurantoin and the quinolone antibiotics are mutually antagonistic in vitro. It is not known whether this is of clinical significance, but the combination should be avoided.
Resistance to nitrofurantoin may be chromosomal or plasmid mediated and involves inhibition of nitrofuran reductase. Acquired resistance in E. coli continues to be rare.
Nitrofurantoin and its metabolites are excreted mainly by the kidneys. In renal impairment, the concentration achieved in urine may be subtherapeutic. Nitrofurantoin should not be used in patients with a creatinine clearance of 60 ml/min or less.
The normal adult dose of nitrofurantoin is 50 to 100 mg four times daily for seven days. If a long-acting preparation (e.g., Macrobid®) is used then the dose is 100mg twice daily. The pediatric dose is 3mg/kg/day in four divided doses. Nitrofurantoin should be taken with food, as this improves the absorption of the drug by 45%.
Nitrofurantoin is only clinically proven for use against E. coli or Staph. saprophyticus. It may also have in vitro activity against:
and is used in the treatment of infections caused by these organisms. Only a minority of Enterobacter species and Klebsiella species are sensitive to nitrofurantoin; nitrofurantoin has no activity against
Nitrofurantoin must never be used to treat pyelonephritis, renal abscess, pyeloempyema or any urinary tract infection other than cystitis because of its extremely poor tissue penetration and low blood levels. Urinary catheter infections may be treated with nitrofurantoin if there are no systemic features; the catheter must be changed after 48 hours of antibiotics and treatment is ineffective if the catheter is not replaced or removed.
Nitrofurantoin can cause nausea and vomiting, fever, rash, hypersensitivity pneumonitis. When given for long periods of time, nitrofurantoin can cause progressive pulmonary interstitial fibrosis. All these side effects are much more common in the elderly.
Patients should be informed that nitrofurantoin colours urine a dark orange-brown; this is completely harmless.
Neonates (babies up to the age of one month) have immature enzyme systems in their red blood cells (glutathione instability) and nitrofurantoin must therefore not be used because it can cause haemolytic anaemia. For the same reason, nitrofurantoin should not be given to pregnant women after 38 weeks of pregnancy, or who are about to give birth.
Nitrofurantoin must be taken with food and can cause bleeding in the stomach, vomiting and other gastrointestinal disruptions if these warnings are not adhered to. Nitrofurantoin is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency because of risk of extravascular hemolysis resulting in anemia.
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Nitrofurantoin". A list of authors is available in Wikipedia.|