Nitrofurantoin: Preferred Empiric Therapy for Community-Acquired Lower Urinary Tract Infections

To the Editor: I read with great interest the article on nitrofurantoin for uncomplicated urinary tract infections (UTIs) by McKinnell et al.¹ Although their study primarily focused on pharmacoeconomics, comparing nitrofurantoin to trimethoprim/sulfamethoxazole (TMP-SMX) and fluoroquinolones, it has important clinical implications.

Nitrofurantoin is an underused antimicrobial for empiric therapy for community-acquired and nosocomial lower UTIs. Among susceptible uropathogens after extensive use worldwide for more than 50 years, there has been virtually no acquired resistance to nitrofurantoin.^2,3 Most physicians are acquainted with the adverse effects of nitrofurantoin but are unfamiliar with its virtues. Nitrofurantoin has a unique mechanism of action by interfering with bacterial growth at 3 different locations in the Kreb’s cycle. Although approximately 25% of nitrofurantoin is excreted renally, some is eliminated via the gastrointestinal tract. Unlike “high resistance potential” antibiotics, nitrofurantoin does not predispose to resistance.⁴ Pharmacokinetically, nitrofurantoin reabsorption is pH dependent and at normal urinary pH (approximately 5.5 pH); nitrofurantoin is preferentially excreted into the lower urinary tract, ie, bladder urine, making it is useful to treat lower UTIs.^3,5-7

Nitrofurantoin is active against most common uropathogens, but most Proteus species, Serratia marcescens, and Pseudomonas aeruginosa are naturally resistant.^4,8 Nitrofurantoin is useful against Escherichia coli and Enterococci, the most frequent causes of nosocomial lower UTIs, ie, catheter-associated bacteriuria. Nitrofurantoin is also active against most strains of multidrug-resistant gram-negative bacilli, including most extended spectrum β lactamase-producing strains.⁸ Nitrofurantoin is also active against vancomycin-sensitive enterococci and vancomycin-resistant enterococci.^3,7,8

During the past 3 decades, I have had extensive experience with nitrofurantoin therapy for nosocomial and community-acquired lower UTIs. Nitrofurantoin, 100 mg orally every 12 hours is well tolerated. The adverse effects of nitrofurantoin are relatively uncommon and benign.^4,8 Occasional nausea may occur but is uncommon with macrocrystalline formulations. In patients with intact renal function, nitrofurantoin urinary concentrations are 50 to 300 mg/mL.⁸ With creatinine clearances lower than 30 mL/min, therapeutic urinary concentrations are unlikely to be obtained, and therapeutic failure may result.^4,8 For this reason, nitrofurantoin should be avoided in patients with a creatinine clearance lower than 30 mL/min.^7,8 Acute toxicity is limited to acute/reversible migratory pulmonary infiltrates/eosinophilia. Long-term nitrofurantoin toxicity includes peripheral neuropathy, interstitial lung disease, or hepatotoxicity, which may occur in patients treated long term who have chronic renal insufficiency.^6,8 Nitrofurantoin has advantages over TMP-SMX and fluoroquinolones for initial empiric therapy of community-acquired and nosocomial lower UTIs. Against gram-negative bacilli uropathogens, nitrofurantoin has a “low resistance potential” vs the “high resistance potential” of TMP-SMX and ciprofloxacin. Unlike TMP-SMX and fluoroquinolones, nitrofurantoin has activity against vancomycin-resistant enterococci^3,8 (Table).

TABLE.

Antibiotic Activities Against Selected Gram-Negative and Gram-Positive Uropathogens^a

In my experience-based opinion, nitrofurantoin should be the preferred empiric therapy for community-acquired and nosocomial lower UTIs. Nitrofurantoin has remained effective after more than 50 years of extensive use worldwide with essentially no resistance, and for initial empiric therapy for uncomplicated community-acquired or nosocomial UTIs, nitrofurantoin is an ideal antibiotic. If urine cultures are positive for Proteus species, S marcescens, or P aeruginosa, an alternate agent should be selected. I agree with the authors that nitrofurantoin should be the preferred antibiotic for the initial empiric treatment of community-acquired lower UTIs.