Hypothesis / aims of study
Nitrofurantoin (NF) is commonly used to treat recurrent urinary tract infections (RUTI). Despite minimal data, the Beers criteria has cautioned against long-term use of NF in geriatric patients. This study reviews the safety and efficacy of chronic suppressive therapy with NF in neurogenic and non-neurogenic peri-menopausal and post-menopausal women.
Study design, materials and methods
A query of the electronic medical record at a tertiary care institution yielded 11,200 charts of women aged 50-95 prescribed NF by over 75 providers from 2006 to 2018 in outpatient clinics. Charts from the two primary urology providers prescribing NF therapy for at least 3 consecutive months were further analyzed. Demographics, reason for initiation of NF, dose of NF, duration of therapy, explanation of chronic therapy interruptions, resistance to NF, occurrence of adverse effects of NF (liver disease, pulmonary fibrosis, and neuropathy), comorbid conditions, urine culture, and relevant lab/imaging results were recorded. The start and stop dates of chronic suppressive therapy were tallied from the medication lists and cross-referenced with notes documented by the provider for accuracy. Recorded number of months on chronic suppressive therapy were summed.
Of the 221 patients included, 167 (77%) were prescribed 100mg of NF. The most common indication for chronic NF therapy was RUTI prophylaxis. 104 (47%) patients developed cultures resistant to NF but only 4 were switched to an alternative suppressive therapy. 88 (40%) patients on chronic NF therapy developed breakthrough UTI but only 10 were not restarted on NF again (4 patients due to NF resistance). Neurogenic patients had a higher occurrence of catheter use (p=0.0008) but non-neurogenic patients had an increased incidence of breakthrough UTI (p=0.0134). There was no difference in resistance rates between neurogenic and non-neurogenic groups (p=0.4361). None of the patients developed neuropathy, 1 developed liver dysfunction (elevated LFTs) after 3.5 years of therapy, and 4 developed lung symptoms after a mean use of NF for 3.5 years. Of the 5 women who developed side effects to NF, 3 of them were under the age of 65 years (all 3 developed lung symptoms). One of these women was noted to have baseline lung disease and had to discontinue NF after 6.6 years. No other patients with neuropathy, lung disease, or liver disease at baseline had to stop NF due to worsening of their chronic underlying disease. None of the patients who developed chronic cough had changes seen on chest x-ray. 8 patients in the cohort were found to have chronic changes on chest x-rays for various reasons, but none of these patients stopped NF therapy.
Interpretation of results
NF is narrow-spectrum, has a low likelihood of developing drug-resistant bacteria, and is primarily used to treat cystitis unlike other antibiotics such as fluoroquinolones and TMP-SMX which are often used to treat other conditions as well. Therefore, NF should be considered for prolonged therapy in order to avoid cycling through different antibiotics with every RUTI and risking the formation of multi-drug resistant bacteria. Though we recorded a high rate of resistance to NF in our results, we can cannot conclude that there was increased NF resistance due to long-term NF use as all culture results found in the patients’ charts, irrespective of whether the patient was on NF at the time of urine collection, were recorded. Moreover, most patients with a culture result showing a pathogen resistant to NF were temporarily switched to an alternative antibiotic before resuming their suppressive NF therapy. As such, it is likely that many of these patients had RUTI with some organisms that were resistant to NF and others that were susceptible to NF. Therefore, breakthrough UTIs may have occurred with NF resistant pathogens but RUTI frequency was still decreased overall as UTIs from susceptible pathogens were prevented.
Despite a paucity of data, the 2015 Beers Criteria has suggested physicians avoid using NF for longer than 90 days due to concerns for pulmonary fibrosis, neuropathy, and hepatotoxicity. A recent review of all literature from 1968 to 2014 reporting adverse effects to NF revealed that the rate of NF adverse effects compared to total NF prescriptions remained quite small for pulmonary (0.001%), neuropathic (0.0007%), and hepatic (0.0003%) adverse effect. This retrospective study corroborates that data, as most women in this cohort tolerated prolonged NF suppressive therapy well without developing adverse effects. In addition, most of the women who developed side effects to NF (hepatotoxicity and lung symptoms) were under the age of 65 years.