Table. Features of nitrofurantoin and fosfomycin.
Characteristic | Nitrofurantoin | Fosfomycin |
---|---|---|
Year of discovery | 1953 | 1969 |
Formulations | Nitrofurantoin macrocrystal 50 mg, 100 mg capsules Slow-release formulation not available in Australia Older microcrystal formulation less available now (more adverse effects) |
Fosfomycin trometamol 3 g sachet containing granules to be dissolved in water Intravenous formulation available but for specialised use only |
Pharmacokinetics | High urinary concentrations Serum concentrations negligible |
Long half-life with high urinary concentrations Serum concentrations inadequate for treatment of systemic infection |
Mechanism of action | Not well understood, multifactorial, inhibits ribosomal protein synthesis | Inhibits pyruvyl transferase and therefore cell wall synthesis |
Spectrum of activity | Mostly susceptible: E. coli, Enterococcus Variably susceptible: Klebsiella, Enterobacter, Citrobacter and Providencia Typically resistant: Proteus, Serratia, Acinetobacter, Morganella and Pseudomonas |
Mostly susceptible: E. coli Variably susceptible: Klebsiella, Proteus, Citrobacter, Enterobacter, Pseudomonas and Enterococcus Typically resistant: Morganella and Acinetobacter |
Resistance | Uncommon | Uncommon |
Indications | Uncomplicated urinary tract infection in women | Uncomplicated urinary tract infection in women |
Dosing | 50–100 mg 4 times a day for 5 days | Single 3 g oral dose |
Adverse events | Infrequent, mainly gastrointestinal Rare reports of pulmonary or liver toxicity, peripheral neuropathy |
Infrequent, mainly gastrointestinal (9% diarrhoea, 4% nausea) |
Pregnancy and breastfeeding | Category A, although not recommended beyond 38 weeks gestation due to risk of haemolytic anaemia in neonates. For this reason it is also best to avoid during the first month of breastfeeding | Category B2, small amounts excreted in breast milk so not recommended in breastfeeding |
Children | Avoid <1 month of age | Avoid <12 years of age |
Interactions | Few significant drug interactions | Co-administration with metoclopramide can lower serum and urine concentrations |
Renal impairment | Contraindicated if CrCl <30 mL/min Cautious use between CrCl 30–60 mL/min if benefits outweigh risks |
Dose reduction required if CrCl <50 mL/min |
CrCl creatinine clearance