Clinical and bacteriological outcome of different doses and duration of pivmecillinam compared with placebo therapy of uncomplicated lower urinary tract infection in women: the LUTIW project.

OBJECTIVE: To analyse associations between symptoms and bacteriuria in uncomplicated lower urinary tract infection in women (LUTIW) and to evaluate outcome of therapy with three different regimens of pivmecillinam or placebo. DESIGN: Prospective, multicentre, randomized, double-blind, and placebo-controlled therapy study. Symptoms registered at inclusion, during therapy and at follow-up visits after 8-10 and 35-49 days. Significant bacteriuria defined according to current European guidelines. SETTING: A total of 18 primary healthcare centres in northern Sweden. Subjects. Women aged 18 years and above with symptoms of urgency, dysuria, supra pubic or loin pain. Main outcome measures. Symptoms and bacteriuria at inclusion and course of symptoms, bacteriuria, and their combinations during and post-therapy. RESULTS: At inclusion, no associations or significant differences were found between symptom scores and bacteriuria, bacterial counts, or species. The 884 patients (77%) with significant bacteriuria were followed up. All pivmecillinam therapies were superior to placebo (p < 0.001). From day six until first follow-up, the mean values of all symptoms were higher and the bacteriological cure was lower at first follow-up in the three days (84%) compared with the seven days regimens (93-94%, p < 0.001). At final follow-up clinical cure was similar in all pivmecillinam regimens (65-72%) as was bacteriological cure (83-89%). Pivmecillinam had few low to mild adverse reactions, comparable to placebo. CONCLUSIONS: Symptoms are not conclusive for diagnosis of LUTIW. Pivmecillinam therapies are superior to placebo and seven days regimens are more efficient than three days. Pivmecillinam 200 mg x 2 x 7 days is recommended as a first-line therapy for LUTIW.

Pulsed-field gel electrophoresis typing of Escherichia coli strains from samples collected before and after pivmecillinam or placebo treatment of uncomplicated community-acquired urinary tract infection in women.

The primary infecting Escherichia coli strains from 156 women with community-acquired uncomplicated urinary tract infection (UTI) randomized to pivmecillinam or placebo and the E. coli strains causing UTI at two follow-up visits were typed using pulsed-field gel electrophoresis (PFGE). In the pivmecillinam treatment group PFGE showed that among patients having a negative urine culture at the first follow-up 77% (46/60) had a relapse with the primary infecting E. coli strain and 23% (14/60) had reinfection with a new E. coli strain at the second follow-up. Among patients having E. coli at the first follow-up PFGE showed that 80% (32/40) had persistence with the primary infecting E. coli strain, 15% (6/40) had reinfection with a new E. coli strain, and 5% (2/40) had different E. coli strains at the two follow-up visits (one had reinfection followed by relapse, and the other had persistence followed by reinfection). In the placebo group the majority had E. coli at the first follow-up. PFGE showed that among these patients 96% (50/52) had persistence with the primary infecting E. coli strain and 4% (2/50) had different E. coli strains at the two follow-up visits (both had persistence followed by reinfection). The finding that the majority of UTIs at follow-up are caused by the primary infecting E. coli strain supports the theory of a vaginal and rectal reservoir but could also support the recent discovery that E. coli strains are able to persist in the bladder epithelium despite appropriate antibiotic treatment, constituting a reservoir for recurrent UTI.

The natural course of uncomplicated lower urinary tract infection in women illustrated by a randomized placebo controlled study.

This prospective, multicentre, randomized, double-blind and placebo controlled study was performed to describe the natural course of uncomplicated lower urinary tract infection (UTI). A total of 1143 women 18 y and above, consulting at 18 primary health care centres in northern Sweden for symptoms suggestive of UTI were included. The symptoms urgency, dysuria, suprapubic pain and loin pain were registered, and urine cultures performed at inclusion and follow-up visits 8-10 d and 5-7 weeks later. Associations between all symptoms and bacteriuria or bacterial counts were unpredictable. Eradication of symptoms and bacteriuria and combinations of them were studied in 288 patients placebo treated for 7 d, of whom 39% dropped out after the first follow-up visit. The spontaneous cure rate of symptoms was 28% after the first week, and 37% had neither symptoms nor bacteriuria after 5-7 weeks. Considering the high dropout rate after the first follow-up visit, the spontaneous cure rate of symptoms and bacteriuria was calculated to 24% at the end of study. We conclude that patient near-laboratory tests are required to establish the diagnosis of lower UTI, and the guidelines for diagnosis of UTI need to be revised.