Prospective cohort study of microbial and inflammatory events immediately preceding Escherichia coli recurrent urinary tract infection in women.

BACKGROUND: A prospective cohort study was conducted to characterize the temporal sequence of microbial and inflammatory events immediately preceding Escherichia coli recurrent urinary tract infection (rUTI). METHODS: Women with acute cystitis and a history of UTI within the previous year self-collected periurethral and urine samples daily and recorded measurements of urine leukocyte esterase, symptoms, and sexual intercourse daily for 3 months. rUTI strains were characterized by pulsed-field gel electrophoresis and genomic virulence profiling. Urinary cytokine levels were measured. RESULTS: There were 38 E. coli rUTIs in 29 of 104 women. The prevalence of periurethral rUTI strain carriage increased from 46% to 90% during the 14 days immediately preceding rUTI, with similar increases in same-strain bacteriuria (from 7% to 69%), leukocyte esterase (from 31% to 64%), and symptoms (from 3% to 43%), most notably 2-3 days before rUTI (P<.05 for all comparisons). Intercourse with periurethral carriage of the rUTI strain also increased before rUTI (P=.008). Recurrent UTIs preceded by bacteriuria, pyuria, and symptoms were caused by strains less likely to have P fimbriae than other rUTI strains (P=.002). CONCLUSIONS: Among women with frequent rUTIs, the prevalences of periurethral rUTI strain carriage, bacteriuria, pyuria, and intercourse dramatically increase over the days preceding rUTI. A better understanding of the pathogenesis of rUTI will lead to better prevention strategies.

Antibiotherapy and pathogenesis of uncomplicated UTI: difficult relationships.

In a time when conventional antibiotics are becoming increasingly less effective for treatment of infections, the relationship between bacteria and antimicrobial resistance is becoming more and more complicated. This paper provides a current review of studies reported in the literature pertaining to the antibiotherapy of human urinary tract infections (UTI), in a way that helps the reader direct a bibliographic search and develop an integrated perspective of the subject. Highlights are given to (bio)pathogenesis of uncomplicated cystitis. Features associated with the antibiotherapy of UTI such as development of resistance are presented in the text systematically. This review discusses recent advances in the understanding of how the predominant uropathogen Escherichia coli interacts with its host and leads to infection; so one can understand some of the reasons behind antibiotherapy failures.

Placebo found equivalent to amoxicillin for treatment of acute bronchitis in Nairobi, Kenya: a triple blind, randomised, equivalence trial.

BACKGROUND: Antibiotic treatment is not recommended for acute bronchitis in immunocompetent patients in industrialised countries. Whether these recommendations are relevant to the developing world and to immunocompromised patients is unknown. DESIGN, SETTING AND PARTICIPANTS: Randomised, triple blind, placebo controlled equivalence trial of amoxicillin compared with placebo in 660 adults presenting to two outpatient clinics in Nairobi, Kenya, with acute bronchitis but without evidence of chronic lung disease. MAIN OUTCOME MEASURE: The primary study end point was clinical cure, as defined by a >or=75% reduction in a validated Acute Bronchitis Severity Score by 14 days; analysis was by intention to treat with equivalence defined as

Fluconazole susceptibility of vaginal isolates obtained from women with complicated Candida vaginitis: clinical implications.

Despite considerable evidence of azole resistance in oral candidiasis due to Candida species, little is known about the azole susceptibilities of the genital tract isolates responsible for vaginitis. The fluconazole susceptibilities of vaginal isolates obtained during a multicenter study of 556 women with complicated Candida vaginitis were determined by evaluating two fluconazole treatment regimens. Of 393 baseline isolates of Candida albicans, 377 (96%) were highly susceptible to fluconazole (MICs, <8 microg/ml) and 14 (3.6%) were resistant (MICs, >or=64 microg/ml). Following fluconazole therapy, one case of in vitro resistance developed during 6 weeks of monitoring. In accordance with the NCCLS definition, in vitro fluconazole resistance correlated poorly with the clinical response, although a trend of a higher mycological failure rate was found (41 versus 19.6% on day 14). By using an alternative breakpoint of 1 micro g/ml, based upon the concentrations of fluconazole achievable in vaginal tissue, no significant differences in the clinical and mycological responses were observed when isolates (n = 250) for which MICs were 1 microg/ml, although a trend toward an improved clinical outcome was noted on day 14 (odds ratio, >2.7; 95% confidence interval, 0.91, 8.30). Although clinical failure was uncommon, symptomatic recurrence or mycological relapse almost invariably occurred with highly sensitive strains (MICs, <1.0 microg/ml). In vitro fluconazole resistance developed in 2 of 18 initially susceptible C. glabrata isolates following fluconazole exposure. Susceptibility testing for women with complicated Candida vaginitis appears to be unjustified.

Fluoroquinolones in the treatment of acute uncomplicated urinary tract infections in adult women.

Urinary tract infections (UTIs) are among the most commonly encountered bacterial infections. Acute uncomplicated UTIs in adults include episodes of cystitis and pyelonephritis. The main uropathogens causing uncomplicated UTIs have, in the past, been fairly predictable and they have generally been susceptible to several commonly used oral antimicrobials. There has been a trend, however, towards increasing antimicrobial resistance among uropathogens over the past few years, especially to beta-lactams and trimethoprim-sulfamethoxazole (TMP-SMX). The current standard of therapy for the empiric treatment of acute uncomplicated cystitis is TMP-SMX for 3 days. Since the prevalence of resistance to TMP-SMX among uropathogens is increasing, however, fluoroquinolones, with their low side effect profile, convenient pharmacokinetics and effectiveness, are increasingly being used first-line for the management of cystitis. Treatment of acute pyelonephritis is less controversial and fluoroquinolones are recommended as first-line agents in the empiric treatment of community-acquired pyelonephritis. Of concern, the increased use of fluoroquinolones for the treatment of UTIs and other infectious processes has resulted in an increasing prevalence of fluoroquinolone-resistant uropathogens worldwide. In light of these changing resistance patterns, prudent use of fluoroquinolones for the treatment of UTIs is warranted.

Treatment of complicated Candida vaginitis: comparison of single and sequential doses of fluconazole.

OBJECTIVE: An attempt was made to validate recent recommendations that women with complicated Candida vaginitis (severe or recurrent, non-albicans Candida spp or abnormal host) require longer-duration antifungal therapy to achieve clinical cure and mycologic eradication. STUDY DESIGN: A prospective, multicenter, randomized, double-blind study was performed comparing a single dose of 150 mg of fluconazole with 2 sequential 150-mg doses of fluconazole given 3 days apart. RESULTS: Five hundred fifty-six women with severe or recurrent Candida vaginitis were enrolled, and 398 had at least one postbaseline evaluation (intent to treat) and of these 309 were fully evaluable (efficacy-valid). At baseline, 92% of vaginal isolates were Candida albicans. The 2-dose fluconazole regimen achieved significantly higher clinical cure rates in women with severe vaginitis when evaluated on day 14 (P =.015) and higher clinical and mycologic responses persisted at day 35. Women with recurrent but not severe vaginitis did not benefit clinically short term by the additional fluconazole dose. Multivariate logistic regression analysis showed that being infected with non-albicans Candida predicted significantly reduced clinical and mycologic response regardless of duration of therapy. Fluconazole therapy was well tolerated and free of serious adverse effects. CONCLUSION: Treatment of Candida vaginitis requires individualization, and women with severe Candida vaginitis achieve superior clinical and mycologic eradication with a 2-dose fluconazole regimen.

Patient-initiated treatment of uncomplicated recurrent urinary tract infections in young women.

BACKGROUND: Recurrent urinary tract infections (UTIs) are a common outpatient problem, resulting in frequent office visits and often requiring the use of prophylactic antimicrobial agents. Patient-initiated treatment of recurrent UTIs may decrease antimicrobial use and improve patient convenience. OBJECTIVE: To determine the safety and feasibility of patient-initiated treatment of recurrent UTIs. DESIGN: Uncontrolled, prospective clinical trial. SETTING: University-based primary health care clinic. PARTICIPANTS: Women at least 18 years of age with a history of recurrent UTIs and no recent pregnancy, hypertension, diabetes, or renal disease. INTERVENTION: After self-diagnosing UTI on the basis of symptoms, participating women initiated therapy with ofloxacin or levofloxacin. MEASUREMENTS: Accuracy of self-diagnosis determined by evidence of a definite (culture-positive) or probable (sterile pyuria and no alternative diagnosis) UTI on pretherapy urinalysis and culture. Women with a self-diagnosis of UTI that was not microbiologically confirmed were evaluated for alternative diagnoses. Post-therapy interviews and urine cultures were used to assess clinical and microbiological cure rates, adverse events, and patient satisfaction. RESULTS: 88 of 172 women self-diagnosed a total of 172 UTIs. Laboratory evaluation showed a uropathogen in 144 cases (84%), sterile pyuria in 19 cases (11%), and no pyuria or bacteriuria in 9 cases (5%). Clinical and microbiological cures occurred in 92% and 96%, respectively, of culture-confirmed episodes. No serious adverse events occurred. CONCLUSION: Adherent women can accurately self-diagnose and self-treat recurrent UTIs.

Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract infections.

Community-acquired urinary tract infections (UTIs) are among the most common bacterial infections in women. Therapy for these infections is usually begun before results of microbiological tests are known. Furthermore, in women with acute uncomplicated cystitis, empirical therapy without a pretherapy urine culture is often used. The rationale for this approach is based on the highly predictable spectrum of etiologic agents causing UTI and their antimicrobial resistance patterns. However, antimicrobial resistance among uropathogens causing community-acquired UTIs, both cystitis and pyelonephritis, is increasing. Most important has been the increasing resistance to trimethoprim-sulfamethoxazole (TMP-SMX), the current drug of choice for treatment of acute uncomplicated cystitis in women. What implications do these trends have for treatment of community-acquired UTIs? Preliminary data suggest that clinical cure rates may be lower among women with uncomplicated cystitis treated with TMP-SMX when the infecting pathogen is resistant to TMP-SMX. Women with pyelonephritis also have less bacterial eradication and lower clinical cure rates when treated with TMP-SMX for an infection that is resistant to the drug. Therefore, in the outpatient setting, identifying risk factors for TMP-SMX resistance and knowing the prevalence of TMP-SMX resistance in the local community are important steps in choosing an appropriate therapeutic agent. When choosing a treatment regimen, physicians should consider such factors as in vitro susceptibility, adverse effects, cost-effectiveness, and selection of resistant strains. Using a management strategy that takes these variables into account is essential for maintaining the safety and efficacy of treatment for acute UTI.

Recurrent urinary tract infection in women.

Recurrent urinary tract infections (UTI) are common among young healthy women even though they generally have anatomically and physiologically normal urinary tracts. Women with recurrent UTI have an increased susceptibility to vaginal colonization with uropathogens, which is due to a greater propensity for uropathogenic coliforms to adhere to uroepithelial cells. Risk factors for recurrent UTI include sexual intercourse, use of spermicidal products, having a first UTI at an early age, and having a maternal history of UTIs. Inherited factors may be important in some women with recurrent UTI. Many factors thought to predispose to recurrent UTI in women, such as pre- and post-coital voiding patterns, frequency of urination, wiping patterns, and douching have not been proven to be risk factors for UTI. In contrast to the predominantly behavioral risk factors for young women, mechanical and/or physiological factors that affect bladder emptying are most strongly associated with recurrent UTI in healthy postmenopausal women. The management of recurrent UTI is the same as that for sporadic UTI except that the likelihood of infection with an antibiotic resistant uropathogen is higher in women who have received recent antimicrobials. Strategies to prevent recurrent UTI in young women should include education about the association of recurrent UTI with frequency of sexual intercourse and the usage of spermicide-containing products. Continuous or post-coital prophylaxis with low-dose antimicrobials or intermittent self-treatment with antimicrobials have all been demonstrated to be effective in managing recurrent uncomplicated UTIs in women. Estrogen use is very effective in preventing recurrent UTI in post-menopausal women. Exciting new approaches to prevent recurrent UTI include the use of probiotics and vaccines. Further understanding of the pathogenesis of UTI will lead to more effective and safer methods to prevent these frequent infections.

Urinary tract infection in adults: research priorities and strategies.

Waning interest in urinary tract infection (UTI) research has limited clinical advances during the past two decades. Although care has improved for some specific UTI syndromes, there is limited evidence for most of the decisions made each day in the management of these infections. Additional clinical research is necessary to improve UTI prevention and care strategies.

Effects of vaginal intercourse with and without a condom on vaginal flora and vaginal epithelium.

Effects of a single episode of intercourse on vaginal flora and epithelium were examined in subjects randomly assigned to groups that used no condom or lubricated nonspermicide condoms. Subjects were evaluated at visits before (1 month and 1-2 days) and after (8-12 h, 2-3 days, and 6-8 days) an index episode of sexual intercourse. The 22 subjects who used no condoms had significantly more Escherichia coli and a high concentration (> or =10(5) cfu/mL) of E. coli in the vagina (both, P<.001) and urine (all <10(5) cfu/mL; P=.004) at visit 3 than at visits 1 and 2. The 20 subjects who used condoms had a trend toward more vaginal E. coli (P=.06) and a significant increase in other enteric gram-negative rods (P=.001) after intercourse. Intercourse was not associated with gross, colposcopic, or histologic vaginal epithelial abnormalities.

Antimicrobial resistance: a plan of action for community practice.

Antibiotic resistance was once confined primarily to hospitals but is becoming increasingly prevalent in family practice settings, making daily therapeutic decisions more challenging. Recent reports of pediatric deaths and illnesses in communities in the United States have raised concerns about the implications and future of antibiotic resistance. Because 20 percent to 50 percent of antibiotic prescriptions in community settings are believed to be unnecessary, primary care physicians must adjust their prescribing behaviors to ensure that the crisis does not worsen. Clinicians should not accommodate patient demands for unnecessary antibiotics and should take steps to educate patients about the prudent use of these drugs. Prescriptions for targeted-spectrum antibiotics, when appropriate, can help preserve the normal susceptible flora. Antimicrobials intended for the treatment of bacterial infections should not be used to manage viral illnesses. Local resistance trends may be used to guide prescribing decisions.

Thalidomide in low intermittent doses does not prevent recurrence of human immunodeficiency virus-associated aphthous ulcers.

A multicenter, double-blind, randomized, placebo-controlled study was conducted to determine the safety and efficacy of thalidomide in reduced, intermittent doses for preventing recurrences of oral and esophageal aphthous ulcers in patients with human immunodeficiency virus (HIV) infection. Forty-nine HIV-infected patients whose ulcers previously had healed as a result of thalidomide therapy were randomly assigned to receive either 100 mg of oral thalidomide or placebo 3 times per week for 6 months. Ulcers recurred in 14 (61%) of 23 thalidomide-randomized patients, compared with 11 (42%) of 26 placebo-randomized patients, with no significant difference in the median time to recurrence of ulcers (P=.221). There were no changes in plasma levels of HIV RNA, tumor necrosis factor (TNF)-alpha, and soluble TNF receptor II at the time of ulcer recurrence. Adverse events among patients treated with thalidomide included neutropenia (5 patients), rash (5 patients), and peripheral sensory neuropathy (3 patients). Thalidomide in lower intermittent doses is ineffective at preventing recurrence of aphthous ulcers in HIV-infected persons.

Effects of oral contraceptive pill use on vaginal flora and vaginal epithelium.

The objective of this study was to examine the effect of oral contraceptive (OC) use on vaginal discharge, epithelium, and flora. Thirty women who planned to use OC for contraception were evaluated before and 2 months after the start of OC use. At both visits, genital symptoms and exposures were assessed by questionnaire; vaginal signs were assessed by speculum examination and colposcopy; vaginal microflora was evaluated by quantitative culture; and a vaginal biopsy was obtained for histopathologic evaluation. Variables were compared between the initial visit and after 2 months of OC use. It was found that OC use did not change the gross, colposcopic, or histologic appearance of the vaginal epithelium or characteristics of vaginal or cervical discharge. Vaginal flora essentially remained unchanged after 2 months of OC use, except that a small decrease occurred in the number of subjects with > or =10(5) colony forming units/mL of H(2)O(2) producing Lactobacillus from 16 at baseline to 9 (p = 0.04) and in the total number of subjects with Ureaplasma urealyticum from 17 at baseline to 10 of 29 (p = 0.04). The results indicate minimal effect of OC use on the vaginal epithelium and vaginal and cervical discharge, and a small effect on vaginal flora.

Epithelial cell layer thickness and immune cell populations in the normal human vagina at different stages of the menstrual cycle.

OBJECTIVE: The aim of our study was to examine vaginal tissue during 3 phases of the menstrual cycle for the number of cell layers and epithelial immune cells. STUDY DESIGN: Vaginal biopsies were performed during 3 phases of the normal menstrual cycle (menstrual, days 1-5; preovulatory, days 7-12; and postovulatory, days 19-24) in 74 subjects. A subset of women had vaginal tissues stained with specific monoclonal antibody markers for Langerhans cells (CD1a), macrophages (KP1), T and B lymphocytes (CD4, CD8, CD21) and neutrophils (CD15). The number of cell layers and the number of immune cells in the vaginal tissue biopsy specimen were determined by a single observer who was blinded to clinical data. RESULTS: At 3 phases of the normal menstrual cycle, the mean number of epithelial cell layers underwent a small but statistically significant decrease from 27.8 +/- 0.7 on days 1-5 and 28.1 +/- 0.6 on days 7-12 to 26.0 +/- 0.7 on days 19-24 of the cycle (P =.01). Nonovulating women had a reduced mean epithelial cell layer count on days 7-12 (23.7 +/- 1. 4) compared with the epithelial cell layer count in ovulating women (28.8 +/- 0.7; P =.005). No significant changes were observed in the mean number per high-power field of Langerhans cells, macrophages, CD4 or CD8 lymphocytes, and neutrophil cell populations during the 3 phases of the cycle. B lymphocytes were not observed in the vaginal tissues. CONCLUSION: A small but statistically significant reduction in the number of vaginal epithelial cells was observed over the menstrual cycle. This reduction is not likely to be clinically significant. Immune cell populations in the vaginal tissues appeared stable throughout the menstrual cycle.

Pathogenesis of urinary tract infections: an update.

The pathogenesis of uncomplicated urinary tract infection (UTI) is complex and influenced by many host biological and behavioural factors and by properties of the infecting uropathogens. Most uncomplicated UTIs in women are not associated with underlying functional or anatomical abnormalities of the urinary tract, whereas sexual intercourse, spermicide use, a history of recurrent UTI and recent antimicrobial chemotherapy are important risk factors. A maternal history of UTI and young age at first UTI, as well as sexual intercourse and spermicide use, are risk factors for recurrent UTI in young women. In some young healthy women, especially those with 'low UTI risk' behaviour, features of pelvic anatomy appear to be associated with UTI risk. In postmenopausal women, anatomical and functional characteristics of the genitourinary tract are more strongly associated with UTI risk than in younger women. A genetic predisposition to recurrent UTI is suggested by the association of recurrent UTI in certain age groups with the ABH blood group non-secretor phenotype, a maternal history of UTI and early age at onset of UTI. Virulence determinants of uropathogens are much more important in the normal host than in the host who has a functional or anatomical abnormality of the genitourinary tract.

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.

Retroviral rebound syndrome after cessation of suppressive antiretroviral therapy in three patients with chronic HIV infection.

BACKGROUND: Although viral rebound follows cessation of suppressive antiretroviral therapy in chronic HIV infection, a viremic clinical syndrome has not been described. OBJECTIVE: To describe a retroviral syndrome associated with cessation of effective antiretroviral therapy in chronic HIV infection. DESIGN: Case reports. SETTING: Outpatient HIV specialty clinics in Seattle, Washington, and Boston, Massachusetts. PATIENTS: Three patients with chronic HIV infection who discontinued suppressive antiretroviral therapy. MEASUREMENTS: Clinical course, plasma HIV RNA levels, and CD4 cell counts before, during, and after cessation of antiretroviral therapy. RESULTS: Within 6 weeks after stopping antiretroviral therapy, each patient experienced a clinical illness that resembled a primary HIV syndrome. This coincided with a marked increase in HIV RNA level and, in two of three patients, a decrease in CD4 cell count. After antiretroviral therapy was restarted, each patient's symptoms rapidly resolved in association with resuppression of HIV RNA and increase in CD4 cell count or percentage. CONCLUSION: A retroviral rebound syndrome similar to that seen in primary HIV syndrome can occur in patients with chronic HIV infection after cessation of suppressive antiretroviral therapy.

Risk factors for recurrent urinary tract infection in young women.

To define host factors associated with an increased risk of recurrent urinary tract infection (RUTI), a case-control study was conducted in 2 populations: university women and health maintenance organization enrollees. Case patients were 229 women 18-30 years old with RUTIs; control subjects were 253 randomly selected women with no RUTI history. In a multivariate model, independent risk factors for RUTI included recent 1-month intercourse frequency (odds ratio [OR], 5.8; 95% confidence interval [CI], 3.1-10.6 for 4-8 episodes), 12-month spermicide use (OR, 1.8; 95% CI, 1.1-2.9), and new sex partner during the past year (OR, 1.9; 95% CI, 1.2-3.2). Two newly identified risk factors were age at first urinary tract infection (UTI)