Theodore G. Sacks

Recurrent urinary tract infections in premenopausal women: prophylaxis based on an understanding of the pathogenesis.

We studied 56 sexually active premenopausal women with a normal genitourinary tract but with persistent introital colonization by enteric gram-negative bacteria who were prone to suffer recurrent urinary tract infections. Sexual intercourse was revealed as a major factor in inducing recurrent urinary tract infections, usually within 24 hours, by transferring the pre-existing introital bacteria into the bladder. Abstention from sexual activity without any additional treatment prevented the development of new urinary tract infections in these women despite persistent introital enteric bacterial flora. Urinary tract infections occurred after onset of sexual activity in all but 2 of the premenopausal women in this study. The 25 premenopausal women with recurrent urinary tract infections were subjected to early postcoital prophylaxis consisting of bladder voiding and the administration of a single tablet of either cotrimoxazole (80 mg. trimethoprim plus 400 mg. sulfamethoxazole), nalidixic acid (500 mg.), nitrofurantoin (50 or 100 mg.) or sulfonamides (500 mg. sulfisoxazole or 250 mg. sulfamethizole). Whereas 70 urinary tract infections occurred during a mean 8-month followup before treatment only 4 occurred during the mean 12.5-month followup after introduction of post-coital prophylaxis (none occurred on co-trimoxazole or nalidixic acid therapy and only 1 infection occurred on nitrofurantoin therapy). Sulfonamides are not recommended as post-coital prophylaxis because of the higher incidence of breakthrough infections. Post-coital prophylaxis with co-trimoxazole, nalidixic acid or nitrofurantoin proved to be simple, economical and efficient, and is recommended in the prevention of recurrent urinary tract infections in otherwise normal premenopausal women.

The Bacterial Flora of the Vaginal Vestibule, Urethra and Vagina in Premenopausal Women with Recurrent Urinary Tract Infections

Gram-negative enteric bacteria, mainly Escherichia coli, form the predominant microbial flora of the introitus, vagina and urethra in women with a normal genitourinary tract but who are prone to suffer recurrent urinary infections. The infections in these women tend to occur in greater numbers and persist for long intervals, compared to normal control women who never experience urinary infections and in whom the main introital, vaginal and urethral microbial flora consists of lactobacilli and staphylococci. The appearance of gram-negative enterobacteria in the normal and control subjects usually is a rare and transitory event. The majority of urinary tract infections that developed in our population during this study was preceded by a persistent similar gram-negative vulvovaginal and urethral microbial flora. However, prolonged spontaneous intervals occurred occasionally during which the introital, vaginal and urethral cultures were free of gram-negative bacteria, with simultaneous intervals free of infection. Nevertheless, all of these intervals ended with documented urinary tract infections. The introital culture is a reliable mirror of the vulvovaginal and urethral microbial flora and, therefore, it is adequate in the study of urinary infections in women.

The Bacterial Flora of the Vaginal Vestibule, Urethra and Vagina in the Normal Premenopausal Woman

A study of 100 healthy, premenopausal women demonstrated that lactobacilli and staphylococci are the predominant normal bacterial flora in the vaginal vestibule, urethra and vagina, with diphtheroids, streptococci and micrococci occurring in decreasing order. Gram-negative enterobacteria are a rare occurrence in the normal bacterial flora of the vaginal vestibule (7 per cent), urethra (9 per cent) and vagina (6 per cent). A second study of 10 healthy premenopausal women in whom serial examinations were done confirmed the findings of the first study and revealed that when gram-negative enterobacteria do colonize the normal vaginal vestibule, urethra and vagina colonization is of a transitory nature since enterobacteria tend to disappear spontaneously.

Effective Postcoital Quinolone Prophylaxis of Recurrent Urinary Tract Infections in Women

A total of 33 sexually active, premenopausal and postmenopausal women, suffering from recurrent urinary tract infections was randomized to receive postcoital prophylaxis with a dose of either 100 mg. ofloxacin (12), 200 mg. norfloxacin (11) or 125 mg. ciprofloxacin (10). While 130 urinary tract infections occurred in these patients during a mean of 8 months before postcoital quinolone prophylaxis, only 1 occurred during a mean of 15 months following prophylaxis. This difference was statistically highly significant. Each of these patients ingested a mean of 117 quinolone doses per year of postcoital prophylaxis. Before prophylaxis 74% of the introital cultures yielded gram-negative enterobacteria (mainly Escherichia coli), whereas only 11% yielded the same bacteria following prophylaxis. Postcoital oral prophylaxis with minimal quinolone doses is highly effective in the prevention of recurrent urinary tract infections in women, because it achieves high urinary bactericidal concentrations, and clears the majority of the introital and urethral Enterobacteriaceae without inducing resistance to the quinolones despite long-term treatment. This prophylaxis is highly recommended because of its ease of compliance, preservation of drug efficacy, lack of toxicity and cost-effectiveness. Postcoital quinolone prophylaxis is as good as or better than daily quinolone prophylaxis and uses only a third of the amount of drug consumed in daily prophylaxis.

Single Dose Quinolone Treatment in Acute Uncomplicated Urinary Tract Infection in Women

A total of 125 ambulatory women (85 premenopausal and 40 postmenopausal) who experienced 174 acute urinary tract infections with mainly gram-negative bacteria (99%) was randomized to receive a single dose, 2-tablet treatment with either ofloxacin (400 mg.), norfloxacin (800 mg.) or ciprofloxacin (500 mg.). Cure was achieved in 163 of the 174 acute episodes (94%). More specifically, the cure rates were 97% (57 of 59 infections) with ofloxacin, 96.5% (56 of 58) with ciprofloxacin and 88% (50 of 57) with norfloxacin. While the initial cure rate of the acute urinary tract infections was 96% (112 of 117) in the premenopausal group, it reached only 90% (51 of 57) in the postmenopausal group. The 17 urinary tract infections that followed the initial 2-tablet quinolone treatment were cured by either an additional single dose, 2-tablet treatment with a different quinolone in 6 cases, a 1-day treatment with other adequate antibacterials in 9 and a 7-day treatment in 2. The 2-tablet quinolone treatment proved to be an effective, easy and cost-effective treatment for acute urinary tract infections in premenopausal and postmenopausal women.

Effective Prophylaxis of Recurrent Urinary Tract Infections in Premenopausal Women by Postcoital Administration of Cephalexin

A total of 31 sexually active premenopausal women, prone to have recurrent urinary tract infections but who otherwise were healthy, underwent postcoital prophylaxis consisting of a single oral dose of 250 mg. cephalexin. While 127 urinary tract infections occurred in these patients during a mean of 6 months before treatment, only 1 occurred during a mean of 12 months after postcoital cephalexin prophylaxis. This difference was statistically highly significant. Each of these patients ingested approximately 120 cephalexin tablets per year of postcoital prophylaxis. Postcoital oral cephalexin prophylaxis is highly effective in the prevention of recurrent urinary tract infection in the nonpregnant as well as pregnant premenopausal women because of easy compliance, the high urine concentration achieved and the minimal induction of resistance to cephalexin in the introital gram-negative bacterial flora. Postcoital cephalexin prophylaxis achieves identical results to daily cephalexin prophylaxis but uses only a third of the tablets required in the daily regimens. Finally, cephalexin represents an additional valuable antibacterial drug in postcoital prophylaxis along with cotrimoxazole, nitrofurantoin and cinoxacin.

A Randomized Comparison of 1-Day versus 10-Day Antibacterial Treatment of Documented Lower Urinary Tract Infection

We randomized 58 women with lower urinary tract infection diagnosed on bilateral ureteral catheterization studies to a 1-day or 10-day treatment regimen. The study revealed that 1-day adequate antibacterial treatment was as effective as 10-day treatment for lower urinary tract infection. Sterile urine was obtained in all 27 women (100 per cent) given 1-day treatment and in 30 of 31 (97 per cent) given 10-day therapy. Three weeks after the 1-day treatment significantly more postmenopausal women had infected urine than premenopausal women. This difference was not seen in the 10-day group. We conclude that 1-day treatment is sufficient for the cure of lower urinary tract infection in women.

Prevention of Recurrent Urinary Tract Infections in Premenopausal Women by Post-coital Administration of Cinoxacin

A total of 21 sexually active premenopausal women, prone to recurrent urinary tract infections but who otherwise were healthy, underwent post-coital prophylaxis consisting of bladder voiding and a single 250 mg. tablet of cinoxacin. While 94 urinary tract infections occurred during a mean of 7.5 months before treatment, only 8 occurred during a mean of 12.5 months after prophylaxis. This difference was statistically highly significant. A mean of 106 cinoxacin tablets per patient were administered during post-coital prophylaxis. Cinoxacin represents an additional valuable and effective antibacterial in post-coital prophylaxis of recurrent urinary tract infection in otherwise healthy premenopausal women, although it is slightly less effective than cotrimoxazole or nitrofurantoin. Effective post-coital prophylaxis requires the use of much smaller quantities of antibacterial agents than the daily use of a single tablet and in women with a high incidence of recurrent urinary tract infections it is superior to intermittent self-administered antibacterial therapy.