Efficacy and safety profile of long-term nitrofurantoin in urinary infections : 18 years' experience

• Published in: Journal of antimicrobial chemotherapy 1998-09, Vol.42 (3), p.363-371
• Main Authors: BRUMFITT, W, HAMILTON-MILLER, J. M. T
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Infective Agents, Urinary - adverse effects; Anti-Infective Agents, Urinary - therapeutic use; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteriuria - microbiology; Biological and medical sciences; Child; Feces - microbiology; Female; Humans; Medical sciences; Middle Aged; nitrofurantoin; Nitrofurantoin - adverse effects; Nitrofurantoin - therapeutic use; Pharmacology. Drug treatments; Treatment Outcome; Urinary Tract Infections - microbiology; Urinary Tract Infections - prevention & control
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/42.3.363

Case records from 219 female patients between 1975 and 1992 who were given long-term prophylaxis (1 year) with nitrofurantoin for the prevention of recurrent urinary infections have been reviewed. Patients' age ranged from 9 to 89 years (median 31-35 years, mode 26-30 years); most (61%) were < 40 years old. The median number of symptomatic episodes in the 12 months immediately before prophylaxis was six (mode 4, mean 6.9). 14.4% of the patients were allergic to an antibiotic, and 23.6% had an imaging abnormality. Three regimens were used: group A (43 patients), 50 mg microcrystalline nitrofurantoin, bd; group B (110 patients), 100 mg macrocrystalline nitrofurantoin (Macrodantin), od; group C (66 patients), 50 mg Macrodantin, od. There were no obvious differences in efficacy between the patient groups (173 assessable patients). The mean incidence of symptomatic episodes decreased 5.4-fold during prophylaxis. Four-fifths of the 43 breakthrough infections (mostly due to Escherichia coli), were caused by nitrofurantoin-sensitive strains. An important finding was that patients with an imaging abnormality responded as well as those with no such abnormalities. In 16% of patients, prophylaxis was not helpful, objectively or subjectively, for no obvious reasons. In most patients where prophylaxis was successful, clinical improvement was maintained for at least 6 months after the end of prophylaxis. Nausea was more common in group A (P < 0.001), as were 'all adverse events'. Of those in group A 25.6% stopped prematurely as a result of an adverse event of any type, compared with 13% of those taking Macrodantin (P < 0.01). Older patients (> 65 years) did not report more adverse events than younger patients. No adverse event was life-threatening. Faecal flora analysis showed neither overgrowth by nitrofurantoin-resistant bacteria nor elimination of sensitive coliforms. Thus, macrocrystalline nitrofurantoin 50 mg at bedtime is appropriate for use in the long-term (12 months) prophylaxis of recurrent urinary infections, in view of its efficacy and favourable safety and tolerability profile. Patients can be managed by their family doctor.