Carol Winter

A prospective study of risk factors for symptomatic urinary tract infection in young women.

BACKGROUND Although acute urinary tract infections are common in young women, the associated risk factors have not been defined prospectively. METHODS We recruited sexually active young women who were starting a new method of contraception at a university health center or a health maintenance organization (HMO) and monitored them for six months for symptomatic urinary tract infections. Daily diaries and serial interviews were used to collect data on potential risk factors. RESULTS Among 796 women, the incidence of urinary tract infections per person-year was 0.7 in the university cohort (mean age, 23 years; n = 348) and 0.5 in the HMO cohort (mean age, 29; n = 448). In both cohorts, there were strong dose-response relations between the risk of infection and both recent use of a diaphragm with spermicide (respective relative risks for one, three, and five days of use in the past week, 1.42, 2.83, and 5.68 in the university cohort, P<0.001; and 1.29, 2.14, and 3.54 in the HMO cohort, P=0.04) and recent sexual intercourse (respective relative risks for one, three, and five days with intercourse in the past week, 1.37, 2.56, and 4.81 in the university cohort, P<0.001; and 1.24, 1.91, and 2.96 in the HMO cohort, P=0.002). The risk of acute infection was also associated with a history of recurrent infection (relative risk, 5.58 in the university group and 2.10 in the HMO group) but not with cervical-cap use, ABO-blood-group nonsecretor phenotype, or delayed postcoital voiding. CONCLUSIONS Among sexually active young women the incidence of symptomatic urinary tract infection is high, and the risk is strongly and independently associated with recent sexual intercourse, recent use of a diaphragm with spermicide, and a history of recurrent urinary tract infections.

A Double-Blind Study of Oral Acyclovir for Suppression of Recurrences of Genital Herpes Simplex Virus Infection

Patients with frequently recurring genital herpes were enrolled in a double-blind placebo-controlled trial comparing 200-mg acyclovir capsules, given five or two times daily, with placebo. Of 47 placebo recipients, 44 (94 per cent) had recurrences during the 120-day treatment period, compared with 13 (29 per cent) of 45 patients treated with acyclovir five times daily and 18 of 51 (35 per cent) treated with acyclovir twice daily (P less than 0.001 for each regimen compared with placebo). The median time to the first clinical recurrence was 18 days in placebo recipients, compared with over 120 days in both acyclovir-treated groups (P less than 0.001 for both groups compared with placebo). The mean monthly recurrence rate during the medication period was 0.86 in placebo recipients, compared with 0.13 in patients treated with acyclovir five times daily and 0.14 in patients treated with acyclovir twice daily (P less than 0.001 for both groups compared with placebo). While receiving therapy, 86 of 96 acyclovir-treated patients had over a 50 per cent reduction in their pretreatment recurrence rate. Breakthrough recurrences in acyclovir recipients were of shorter duration and associated with a lower frequency of viral shedding than recurrences in placebo recipients. After medication was discontinued, the subsequent recurrence rate returned to pretreatment frequencies. Daily oral acyclovir was well tolerated. We conclude that oral acyclovir given for four months markedly reduces but does not completely prevent recurrences of genital herpes and does not influence the long-term natural history of the disease.

A Prospective Study of Asymptomatic Bacteriuria in Sexually Active Young Women

BACKGROUND Asymptomatic bacteriuria is common in young women, but little is known about its pathogenesis, natural history, risk factors, and temporal association with symptomatic urinary tract infection. METHODS We prospectively evaluated 796 sexually active, nonpregnant women from 18 through 40 years of age over a period of six months for the occurrence of asymptomatic bacteriuria (defined as at least 10(5) colony-forming units of urinary tract pathogens per milliliter). The women were patients at either a university student health center or a health maintenance organization. Periodic urine cultures were taken, daily diaries were kept, and regularly scheduled interviews were performed. Escherichia coli strains were tested for hemolysin, the papG genotype, and the ribosomal RNA type. RESULTS The prevalence of asymptomatic bacteriuria (the proportion of urine cultures with bacteriuria in asymptomatic women) was 5 percent (95 percent confidence interval, 4 percent to 6 percent) among women in the university group and 6 percent (95 percent confidence interval, 5 percent to 8 percent) among women in the health-maintenance-organization group. Persistent asymptomatic bacteriuria with the same E. coli strain was rare. Symptomatic urinary tract infection developed within one week after 8 percent of occasions on which a culture showed asymptomatic bacteriuria, as compared with 1 percent of occasions when asymptomatic bacteriuria was not found (P<0.001). Asymptomatic bacteriuria was associated with the same risk factors as for symptomatic urinary tract infection, particularly the use of a diaphragm plus spermicide and sexual intercourse. CONCLUSIONS Asymptomatic bacteriuria in young women is common but rarely persists. It is a strong predictor of subsequent symptomatic urinary tract infection.

Influence of the Normal Menstrual Cycle on Vaginal Tissue, Discharge, and Microflora

The objective of this study was to examine genital tissue, vaginal fluid, and vaginal microbial flora at 3 phases of the menstrual cycle in asymptomatic women. Vaginal examinations were performed 3 times in 74 women: at the menstrual phase (days 1-5), the preovulatory phase (days 7-12), and the postovulatory phase (days 19-24). Flora of 50 women without bacterial vaginosis (BV) was analyzed separately from flora of 24 women with BV. The volume of vaginal discharge increased and the amount of cervical mucus decreased over the menstrual cycle. Among subjects without BV, the rate of recovery of any Lactobacillus changed little (range, 82% to 98%; P = .2); however, a small increase occurred in the rate of recovery of heavy (3+ to 4+ semiquantitative) growth of Lactobacillus over the menstrual cycle (P = .04). A linear decrease occurred in the rate of recovery of heavy growth of any non-Lactobacillus species, from 72% at days 1-5 to 40% at days 19-24 (P = .002). A linear decrease also occurred in the rate of recovery of Prevotella species, from 56% on days 1-5 to 28% on days 19-24 (P =. 007), while a small linear increase occurred in the rate of recovery of Bacteroides fragilis (P=.05). Among subjects with BV, the only significant change was an increase in the rate of recovery of Lactobacillus, from 33% at days 1-5 to 54% at days 19-24 (P = .008). Among all subjects, the rate of recovery of heavy growth of Lactobacillus increased over the menstrual cycle and, in contrast, the concentration of non-Lactobacillus species tended to be higher at menses, which is evidence that the vaginal flora becomes less stable at this time.

Development of Clinically Recognizable Genital Lesions among Women Previously Identified as Having Asymptomatic Herpes Simplex Virus Type 2 Infection

Abstract Study Objective:To determine if patients initially identified by history, clinical examination, and serologic status as having asymptomatic herpes simplex virus type 2 infection report cli...

Intravenous acyclovir for the treatment of primary genital herpes.

Thirty-one patients with first episodes of genital herpes were randomized in a double-blind fashion to intravenous treatment with saline placebo or acyclovir, 5 mg/kg body weight at 8-hour intervals, for 5 days. The median duration of viral shedding from genital lesions after the onset of therapy was significantly shorter for patients given acyclovir (2 days) than for those given placebo (13 days), p less than 0.001. Viral shedding from the pharynx, cervix, urethra, and urine were also shorter in acyclovir-treated patients. (p less than or equal to 0.01 for each comparison). Local and systemic symptoms were shortened by a mean of 5 days and healing of genital lesions by a mean of 12 days in acyclovir-treated patients. (p less than 0.01). Complications during treatment, such as extragenital lesions or urinary retention requiring catheterization, developed in four patients given placebo and in none given acyclovir. (p less than 0.05). Intravenous acyclovir substantially decreases the symptoms, duration of lesions, and complications of primary genital herpes.

Single-dose and three-day regimens of ofloxacin versus trimethoprim-sulfamethoxazole for acute cystitis in women.

We compared the safety and efficacy of a single 400-mg dose of ofloxacin, ofloxacin (200 mg) once daily for 3 days, and trimethoprim-sulfamethoxazole (160:800 mg) twice daily for 7 days for the treatment of acute uncomplicated cystitis (urinary tract infection [UTI]) in women. At 5 weeks posttreatment, 35 (81%) of 43 patients treated with single-dose ofloxacin, 40 (89%) of 45 treated with 3 days of ofloxacin, and 41 (98%) of 42 treated with trimethoprim-sulfamethoxazole were cured (P = 0.03, single-dose ofloxacin group versus trimethoprim-sulfamethoxazole group). Retreatment for symptomatic recurrent UTI was given to 7 (16%) of 43 patients initially treated with single-dose ofloxacin, 3 (7%) of 45 patients treated with 3 days of ofloxacin, and 0 of 42 patients treated with trimethoprim-sulfamethoxazole (P = 0.01, single-dose ofloxacin group versus trimethoprim-sulfamethoxazole group). There was a trend in each of the three treatment groups toward an association between persistent or recurrent episodes of significant bacteriuria and a history of UTI in the past year and with diaphragm use. Ofloxacin was more effective than trimethoprim-sulfamethoxazole in eradicating Escherichia coli from rectal cultures during or soon after therapy, but there were no differences at later follow-up visits. Adverse effects were equally common among the three treatment groups. We conclude that single-dose ofloxacin was less effective than 7 days of trimethoprim-sulfamethoxazole for treatment of uncomplicated cystitis in women, while the 3-day ofloxacin regimen and the trimethoprim-sulfamethoxazole regimen were not significantly different in efficacy.

Double-blind controlled trial of topical acyclovir in genital herpes simplex virus infections☆

Sixty-nine patients with first episodes and 111 with recurrent episodes of genital herpes simplex virus (HSV) infection were enrolled in a double-blind trial comparing a 5 percent topical acyclovir ointment versus placebo, polyethylene glycol (PEG). Among acyclovir recipients with first episodes of genital herpes, the mean duration of viral shedding from genital lesions, 2.0 days, mean duration of local pain or itching, 3.6 days, and mean time to healing of lesions, 11.2 days, were less than in placebo recipients 4.6, 6.7, and 15.8 days, respectively (p less than 0.05 for each comparison). Among patients with recurrent genital herpes, the mean duration of viral shedding from genital lesions was 0.8 days in acyclovir recipients compared with 1.7 days in placebo recipients (p less than 0.001). Among men with recurrent genital herpes, the mean time to crusting and healing of lesions was 3.5 and 7.5 days in acyclovir recipients compared with 5.0 and 9.7 days in placebo recipients, p = 0.03 and 0.07, respectively. No significant differences in the duration of symptoms or healing times were noted between acyclovir- and placebo-treated women with recurrent genital herpes. Acyclovir therapy was not associated with a decrease in frequency of clinical recurrences or an increase in the time of the next recurrence in patients with either first or recurrent genital herpes. Topical acyclovir appears effective in shortening some of the clinical manifestations of genital HSV infections.

Perineal Anatomy and Urine-Voiding Characteristics of Young Women with and without Recurrent Urinary Tract Infections

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A randomized, double-blind, comparative trial comparing high- and standard-dose oral acyclovir for first-episode genital herpes infections.

Orally administered acyclovir ameliorates the clinical course and decreases the duration of viral shedding in patients with first-episode genital herpes infections. We investigated in a randomized, double-blind, comparative trial whether a higher (4 g) than standard (1 g) daily dose of oral acyclovir results in greater clinical benefit and influences the time to first recurrence. A total of 139 patients with first-episode genital herpes were randomized to receive orally 4 or 1 g of acyclovir daily. A total of 52 subjects were excluded from the efficacy analysis because most had recurrent disease. Of 87 eligible subjects, 28 (32%) had primary herpes simplex virus type 1 (HSV-1) infections, 48 (55%) had primary HSV-2 infections, and 11 (13%) had nonprimary HSV-2 infections. We did not find any statistically significant differences in the duration of symptoms or viral shedding between the two dose groups, nor did the median time to first recurrence differ between the two groups. Initiation of therapy with either dose within the first 3 days of the appearance of symptoms shortened the duration of the first episode. Adverse gastrointestinal effects developed in 8% of subjects receiving the higher dose, whereas no adverse reactions were observed among those receiving the standard dose (P = 0.10). We conclude that, in comparison with standard therapy, higher-dose oral acyclovir does not result in additional clinical benefit or modify the time to first recurrence. The present study may have implications for the development and efficacy of congeners of acyclovir which provide higher levels in blood than the standard dose of acyclovir.