Nitrofurans

Agent: nitrofurantoin

With the rise in resistance among common urinary tract pathogens (primarily  E. coli), first among TMP/SMX and more recently among the fluoro-quinolones, clinicians are left searching for an alternative to treat their patients with uncomplicated cystitis. Nitrofurantoin fits nicely into this niche, because it has retained excellent activity against E. coli (< 90% in most studies) and also has adequate coverage of other common community-acquired urinary tract pathogens. Its utility is limited to infections of the lower urinary tract,  however, because of its pharmacokinetic limitations. Thus, nitrofurantoin should not be used for more severe infections such as pyelonephritis and urosepsis.

Spectrum

Good: E. coli, Staphylococcus saprophyticus

Moderate: Citrobacter, Klebsiella, enterococci

Poor : Pseudomonas, Proteus, Acinetobacter, Serratia

Adverse Effects

Gastrointestinal: Nausea and vomiting are occasionally reported. Taking the drug with food may decrease these effects.

Pulmonary: Nitrofurantoin can cause very rare but serious pulmonary toxicity of two forms. First is an acute pneumonitis manifesting as cough, fever, and dyspnea. This form typically resolves soon after drug discontinuation. A chronic pulmonary fibrosis can occur, most commonly with prolonged nitrofurantoin  therapy;  recovery of lung function is limited after drug discontinuation.

Peripheral neuropathy may also occur.

Important Facts

• It bears repeating: nitrofurantoin is ineffective for infections outside of the lower urinary tract.  The drug requires high concentrations for antimicrobial activity, and these are reached only where it concentrates in the urine. Note this also means that in patients who have significant renal dysfunction (e.g., a creatinine clearance of less than 50 ml/min), there is insufficient accumulation of the drug in the urine for activity.

• Nitrofurantoin comes in two formulations: a crystalline form (Macrodantin®) and a macro-crystalline/monohydrate form (Macrobid®). The former is dosed 4 times daily, the latter BID.

Guess which one patients prefer?

• A recent study of nitrofurantoin showed that it can be used for 5 days instead of the traditional 7-day regimen. This shorter regimen may make nitrofurantoin therapy more palatable for patients who are used to 3-day courses of other UTI drugs (TMP/SMX and fluoroquinolones).

What It’s Good For

Treatment of uncomplicated cystitis in patients with adequate renal function and prophylaxis against recurrent uncomplicated lower UTI.

Don’t Forget!

To repeat: do not use this drug in anything but un-complicated cystitis. Nitrofurantoin use in pyelonephritis or urosepsis is a treatment failure waiting to happen .

References

Gallagher ,J.C. and MacDougall ,c. (2012). Antibiotics Simplified. Second Edition. Jones & Bartlett Learning, LLC.