Organisms are susceptible to nitrofurantoin if their minimum inhibitory concentration (MIC) is 32 μg/mL or less.
The peak blood concentration following an oral dose of nitrofurantoin 100 mg, is less than 1 μg/mL and may be undetectable.
Tissue penetration is negligible.
Well concentrated in the urine.
75% of the dose is rapidly metabolized by the liver.
25% of the drug is excreted in the urine unchanged, reliably achieving levels of 200 μg/ml or more, and at that concentrations achieved in urine, is bacteriocidal.
Should not be used to treat anything other than simple cystitis.
Resistance to other antibiotics has led to increased interest in this agent.
This agent and quinolone antibiotics are mutually antagonistic in vitro, and the combination should be avoided.
Resistance may be chromosomal or plasmid mediated and involves inhibition of nitrofuran reductase.
Acquired resistance by E. coli is rare.
Nitrofurantoin and its metabolites are excreted mainly by the kidneys, therefore in the presence of renal insufficiency, the concentration achieved in urine may be subtherapeutic.
Caution should be used in patients with a creatinine clearance of 60 mL/min or less.
The mechanism of action is that it works by damaging bacterial DNA, since its reduced form is highly reactive, and it undergoesrapid reduction of inside the bacterial cell by flavoproteins to multiple reactive intermediates that attack ribosomal proteins, DNA, respiration, pyruvate metabolism and other macromolecules within the cell.
Normal adult dose of nitrofurantoin is 50 to 100 mg four times daily for seven days, but with long-acting preparation ii is 100 mg twice daily.
The pediatric dose is 5–7 mg/kg/day in four divided doses or when in 25 mg/5ml oral suspension then pediatric dose is 3 mg/kg/day in four divided doses.
Should be taken with food, as this improves the absorption of the drug by 45%.
Only clinically proven for use against E. coli or Staph. saprophyticus.
May also have in vitro activity against: Citrobacter species, Coagulase-negative staphylococci,Enterococcus faecalis, Klebsiella species, Staphylococcus aureus, Streptococcus agalactiae,and is used in the treatment of infections caused by these organisms.
Only a minority of Enterobacter species and Klebsiella species are sensitive to this agent.
This agent is not efficacious for: Acinetobacter species, Morganella species, Proteus species, Providentia species, S2242atia species, or Pseudomonas species.
Not indicated for pyelonephritis, or renal abscess, because of extremely poor tissue penetration and low blood levels.
Urinary catheter infections may be treated with nitrofurantoin in the absence of systemic symptoms, and if the catheter is not replaced or removed.
Side effects include: nausea and vomiting, fever, rash, hypersensitivity pneumonitis, and pulmonary fibrosis and these side effects are much more common in the elderly.
Colors urine a dark orange-brown.
It can cause haemolytic anemia in newborns and the drug should not be given to pregnant women after 38 weeks of pregnancy, or who are about to give birth.
Must be taken with food or it is associated with gastrointestinal symptoms.
Its use is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency because of risk of extravascular hemolysis resulting in anemia.
Most urinary isolates have remained sensitive to this agent after decades of use.
Has minimal gastrointestinal excretion and is used almost exclusively for UTIs.
Poor activity against Proteus, S2242atia, and Pseudomonas species.
Associated with nausea and headache.
Long-term use associated with pulmonary fibrosis.
Safe to use in pregnancy.
Rarely associated with C. difficile colitis.
Associated with hemolytic anemia in patients with glucose-6-phosphate dehydrogenase deficiency.
Rare serious adverse effects include: hepatitis, hypersensitivity pneumonitis, and peripheral neuropathy.