Prospective, randomized, placebo-controlled trial of norfloxacin for the prophylaxis of recurrent urinary tract infection in women

Abstract

Thirty women were randomized in a double-blind, placebo-controlled study to receive either norfloxacin, 200 mg orally daily at bedtime, or placebo for the prevention of recurrent bladder infection. Subjects were followed monthly to monitor compliance and symptoms, for urine culture and periurethral and anal canal swabs to monitor colonization, and for blood specimens for hematologic and biochemical studies to monitor safety. During 1 year of follow-up, 10 of 15 placebo subjects and none of 15 norfloxacin subjects developed infection (P < 0.001). Adverse effects occurred with equal frequencies in the two groups. For norfloxacin subjects, only 2 (1.6%) of 129 periurethral and 4 (3.1%) of 129 anal canal swabs showed colonization with aerobic gram-negative organisms, while 16 (22%) of 73 periurethral and 47 (64%) of 73 anal canal swabs from placebo subjects showed colonization. Daily therapy with norfloxacin at bedtime is effective in preventing recurrent cystitis. During 1 year of norfloxacin therapy, colonization was infrequent and superinfection with norfloxacinresistant organisms did not occur.From 2 to 10% of all women experience recurrent symptomatic bladder infections due to reinfection from the fecal reservoir (13). Extended prophylaxis with a low dose of some antimicrobial agents is effective for the prevention of such infections (9, 10). The efficacy of prophylactic therapy is due to at least two mechanisms: the eradication of gut colonization with aerobic gram-negative organisms which are potential uropathogens, as occurs with trimethoprimsulfamethoxazole; and intermittent sterilization of the urine, as is observed with nitrofurantoin (14).The recently introduced quinolone antimicrobial agents have a wide spectrum of activity, including most uropathogens, and achieve high levels in urine for extended time periods. These agents have been extensively investigated for the treatment of urinary tract infections (8). With short courses of therapy, eradication of members of the family Enterobacteriaceae from the gut flora has been documented (11), an observation which has been exploited in the use of these agents for the prophylaxis of infection in granulocytopenic patients (3). Thus, these agents should constitute effective prophylaxis for the prevention of recurrent lower urinary tract infection in women. This study was undertaken to assess the effectiveness of norfloxacin for this clinical indication. antimicrobial agents. Informed written consent was obtained from all patients enrolled in the study. MATERIALSStudy design. The study was a double-blind, randomized, placebo-controlled trial comparing the efficacy of norfloxacin, 200 mg daily at bedtime, with that of placebo. Study subjects were treated for 12 months or until urinary tract infection recurred. When either symptomatic or asymptomatic urinary tract infection developed, subjects were withdrawn from the study without breaking the randomization code. Patients were monitored at monthly intervals for 12 months or until withdrawal and were questioned abo...

Prevention of Bacterial Resistance in Urinary Tract Infections

“…In the placebo group, 10 of 15 patients developed infection, and 22% of periurethral and 64% of anal canal swabs were colonized during the study period. The investigators con cluded that during norfloxacin therapy, 'colonization was infrequent and superinfection with norfloxacin-resistant organisms did not occur' [16].…”

“…Members of the same group [16] subsequently studied the efficacy of low-dose, once-daily norfloxacin compared with placebo for the prophylaxis of recurrent UTI in 30 women. None of the norfloxacin-treated women devel oped infection during the 1-year therapy.…”

“…The fluoroquinolones are considered excellent agents for the therapy of UTI in women because they achieve high fecal levels and penetrate vaginal secretions well, thereby preventing vaginal and periurethral colonization and subsequent recurrences of UTI [15,16].…”

Development and Validation of a Simple, Rapid and Stability-Indicating High Performance Liquid Chromatography Method for Quantification of Norfloxacin in a Pharmaceutical Product

“…It was developed for use in human and veterinary medicine [1]. Norfloxacin, occasionally used to treat common, as well complicated urinary tract infections, exhibits a broad spectrum of activity against Gram-positive and Gram-negative bacteria [2][3][4]. Chemically, it is 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinoline carboxylic acid ( Figure 1).…”

Long-term prophylaxis with norfloxacin versus nitrofurantoin in women with recurrent urinary tract infection

“…Numerous studies have shown their efficacy in the treatment of complicated and uncomplicated UTIs (1, 7), but few studies have evaluated their effectiveness as prophylactic agents (3,4 Forty-four (81%) women in the norfloxacin-treated group and 27 (65%) in the nitrofurantoin-treated group remained free of symptoms (P = 0.05), and the urine samples of 49 (92.4%) and 29 (70.7%) of the women, respectively, were sterile (P c 0.005). The incidence of UTIs after initiation of prophylaxis dropped dramatically in both groups, from 3.1 episodes per 6 months before treatment to 0.02 episode per 6 months after prophylaxis for the norfloxacin-treated women and from 3 episodes per 6 months to 0.3 episode per 6 months for the nitrofurantoin-treated women (P < 0.005) ( Table 2).…”