From the Guidelines
Nitrofurantoin is effective against most gram-negative rod bacteria that cause urinary tract infections (UTIs), particularly Escherichia coli, but its efficacy against other gram-negative rods like Proteus, Pseudomonas, Serratia, or Acinetobacter species is limited. The typical dosing for acute uncomplicated UTIs is nitrofurantoin monohydrate/macrocrystals (Macrobid) 100 mg twice daily for 5 days, or nitrofurantoin macrocrystals (Macrodantin) 50-100 mg four times daily for 5-7 days, as recommended by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases 1. According to a 2021 study published in the Annals of Internal Medicine, nitrofurantoin is a suitable option for the treatment of uncomplicated bacterial cystitis, with a recommended treatment duration of 5 days 1.
Key Considerations
- Nitrofurantoin works by damaging bacterial DNA and inhibiting protein synthesis, and it achieves high concentrations in urine while maintaining low serum levels.
- The medication should be taken with food to enhance absorption and reduce gastrointestinal side effects.
- It should be avoided in patients with creatinine clearance below 30 ml/min, during pregnancy at term (38-42 weeks), and in infants under one month of age due to risk of hemolytic anemia.
- Local resistance patterns should be considered when prescribing nitrofurantoin, as its efficacy against certain gram-negative rods may be limited 1.
Treatment Recommendations
- For women with uncomplicated bacterial cystitis, clinicians should prescribe short-course antibiotics with either nitrofurantoin for 5 days, trimethoprim–sulfamethoxazole (TMP–SMZ) for 3 days, or fosfomycin as a single dose 1.
- In men and women with uncomplicated pyelonephritis, clinicians should prescribe short-course therapy either with fluoroquinolones (5 to 7 days) or TMP–SMZ (14 days) based on antibiotic susceptibility 1.
Resistance Patterns
- Local antimicrobial susceptibility patterns of E. coli should be considered in empirical antimicrobial selection for uncomplicated UTIs 1.
- Nitrofurantoin, fosfomycin, and mecillinam have good in vitro activity against E. coli in most regions, making them suitable options for empirical therapy 1.
From the Research
Nitrofurantoin Coverage for Gram-Negative Rod UTI
- Nitrofurantoin is effective against certain gram-negative rods, including Escherichia coli, with a susceptibility rate of 95.6% 2.
- The antibiotic is also effective against extended-spectrum β-lactamase (ESBL)-producing E. coli, with clinical and microbiological success rates of 69% and 68%, respectively 3.
- However, the effectiveness of nitrofurantoin against other gram-negative rods, such as Klebsiella pneumoniae and Pseudomonas spp., is not well established in the provided studies.
- Nitrofurantoin is recommended as a first-line treatment for acute uncomplicated bacterial cystitis in otherwise healthy adult nonpregnant females, particularly for infections caused by E. coli 4.
- The antibiotic is also considered a good alternative for the treatment of UTIs caused by ESBL-producing E. coli and other gram-negative rods, especially when other options are limited due to resistance 4, 3.
Limitations and Considerations
- The provided studies primarily focus on the effectiveness of nitrofurantoin against E. coli and ESBL-producing E. coli, with limited information on its effectiveness against other gram-negative rods.
- The use of nitrofurantoin should be guided by local susceptibility patterns and the specific characteristics of the infecting organism 2, 4.
- The antibiotic's long-term side effects, particularly in elderly patients, should be considered when prescribing nitrofurantoin for chronic UTIs 5.