Nitrofurantoin is Bactericidal, Not Bacteriostatic
Nitrofurantoin is a broad-spectrum bactericidal antibiotic, not bacteriostatic. 1, 2
Mechanism of Action and Bactericidal Properties
- Nitrofurantoin has a complex mode of action that is not completely understood but results in bactericidal effects against both Gram-negative and Gram-positive bacteria 1
- It is a prodrug that requires activation by bacterial nitroreductases, after which it inhibits multiple bacterial cellular processes including DNA, RNA, cell wall, and protein synthesis 3
- Once activated, nitrofurantoin demonstrates bactericidal activity against common urinary pathogens, particularly at concentrations ≥2× MIC 4
Time-Kill Studies Confirming Bactericidal Activity
- Time-kill studies have demonstrated bactericidal activity against ESBL-producing organisms with complete killing observed at ≥2× MIC for:
- Enterobacter cloacae after 4-8 hours
- Klebsiella pneumoniae after 8-10 hours
- Escherichia coli after 12-16 hours 4
- The drug exhibits differential patterns of bactericidal activity: concentration-dependent killing against E. cloacae and time-dependent killing against E. coli 4
Clinical Efficacy Supporting Bactericidal Activity
- Nitrofurantoin has been successfully used for decades for both treatment and prophylaxis of urinary tract infections, with clinical cure rates ranging from 88-93% 5
- Bacterial cure rates with nitrofurantoin range from 81-92% for uncomplicated urinary tract infections in women 5
- The 5-day regimen of nitrofurantoin monohydrate/macrocrystals (100 mg twice daily) shows equivalent clinical and microbiological cure rates to other bactericidal antibiotics like trimethoprim-sulfamethoxazole 5
In Vivo Bactericidal Activity
- In mouse urinary tract infection models, nitrofurantoin at doses of 30 mg/kg and 100 mg/kg significantly reduced viable bacterial cell counts in the kidney, demonstrating effective in vivo bactericidal activity 6
- This bactericidal activity was maintained even against ciprofloxacin-resistant E. coli strains 6
Clinical Applications Based on Bactericidal Properties
- Nitrofurantoin is recommended as a first-line agent for uncomplicated UTIs by multiple guidelines including the Infectious Diseases Society of America and the European Association of Urology 7, 5
- Its bactericidal activity makes it particularly valuable in the era of increasing antibiotic resistance, as it maintains effectiveness against many multidrug-resistant urinary pathogens 1
Important Considerations
- The bactericidal activity of nitrofurantoin is dependent on active bacterial metabolism, which explains why it may have reduced activity against non-growing or stationary-phase bacteria 3
- Nitrofurantoin is contraindicated in patients with creatinine clearance <60 mL/min due to inadequate urinary drug concentrations that would prevent bactericidal activity 8
- Despite over 60 years of clinical use, nitrofurantoin has maintained its bactericidal effectiveness with minimal development of resistance, likely due to its complex and multi-targeted mechanism of action 2