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Background: Randomised controlled trials (RCTs) investigated analgesics, herbal formulations, delayed prescription of antibiotics, and placebo to prevent overprescription of antibiotics in women with uncomplicated urinary tract infections (uUTI).

Objectives: To estimate the effect of these strategies and to identify symptoms, signs, or other factors that indicate a benefit from these strategies.

Data sources: MEDLINE, EMBASE, Web of Science, LILACS, Cochrane Database of Systematic Reviews and of Controlled Trials, and ClinicalTrials.

Study eligibility criteria, participants and interventions: RCTs investigating any strategies to reduce antibiotics vs. immediate antibiotics in adult women with uUTI in primary care.

Methods: We extracted individual participant data (IPD) if available, otherwise aggregate data (AD). Bayesian random-effects meta-analysis of the AD was used for pairwise comparisons. Candidate moderators and prognostic indicators of treatment effects were investigated using generalised linear mixed models based on IPD.

Results: We analysed IPD of 3524 patients from eight RCTs and AD of 78 patients. Non-antibiotic strategies increased the rates of incomplete recovery (OR 3.0; 95% credible interval (CrI), 1.7–5.5; Bayesian p-value (pB) = 0.0017; τ = 0.6), subsequent antibiotic treatment (OR 3.5; 95% CrI, 2.1–5.8; pB = 0.0003) and pyelonephritis (OR 5.6; 95% CrI, 2.3–13.9; pB = 0.0003). Conversely, they decreased overall antibiotic use by 63%.

Patients positive for urinary erythrocytes and urine culture were at increased risk for incomplete recovery (OR 4.7; 95% CrI, 2.1–10.8; pB = 0.0010), but no difference was apparent where both were negative (OR 0.8; 95% CrI, 0.3–2.0; pB = 0.667). In patients treated using non-antibiotic strategies, urinary erythrocytes and positive urine culture were independent prognostic indicators for subsequent antibiotic treatment and pyelonephritis.

Conclusions: Compared to immediate antibiotics, non-antibiotic strategies reduce overall antibiotic use but result in poorer clinical outcomes. The presence of erythrocytes and tests to confirm bacteria in urine could be used to target antibiotic prescribing.

Recurrent urinary tract infection (rUTI) remains a major problem for many women and therefore the pursuit for genomic and phenotypic traits which could define rUTI has been ongoing. The present study applied a genomic approach to investigate recurrent urinary tract infections by comparative analyses of recurrent and non-recurrent Escherichia coli isolates from general practice. From whole-genome sequencing data, phylogenetic clustering and genomic traits were studied on a collection of isolates which caused recurrent infection compared to non-recurrent isolates. In addition, genomic variation between the 1st and following infection was studied on a subset of the isolates. Evidence of limited adaptation between the recurrent infections based on single nucleotide polymorphism analyses with a range of 0–13 non-synonymous single nucleotide polymorphisms (SNPs) between the paired isolates. This included an overrepresentation of SNPs in metabolism genes. We identified several genes which were more common in rUTI isolates, including nine fimbrial genes, however, not significantly after false-discovery rate. Finally, the results show that recurrent isolates of the present dataset are not distinctive by variation in the core genome, and thus, did not cluster distinct from non-rUTI isolates in a SNP phylogeny.

Introduction: Uncomplicated urinary tract infection (UTI) in women is a common reason to present in general practice and is usually treated with antibiotics to reduce symptom severity and duration. Results of recent clinical trials indicate that non-antibiotic treatment approaches can also be effective. However, it remains unclear which patients would benefit from antibiotic treatment and which can effectively and safely be treated without antibiotics. This systematic review and meta-analysis aims to estimate the effect of treatment strategies to reduce antibiotic use in comparison with immediate antibiotic treatment and to identify prognostic factors and moderators of treatment effects. A further aim is to identify subgroups of patients benefiting from a specific therapy.

Methods and analysis: A systematic literature search will be performed to identify randomised controlled trials which investigated the effect of treatment strategies to reduce antibiotic use in female adults with uncomplicated UTI compared with immediate antibiotic treatment. Therefore, the primary outcome of the meta-analysis is incomplete recovery. Anonymised individual patient data (IPD) will be collected. Aggregate data will be used for pairwise comparisons of treatment strategies using meta-analysis models with random effects accounting for potential between-study heterogeneity. Potential effect moderators will be explored in meta-regressions. For IPD, generalised linear mixed models will be used, which may be adjusted for baseline characteristics. Interactions of baseline variables with treatment effects will be explored. These models will be used to assess direct comparisons of treatment, but might be extended to networks.

Ethics and dissemination: The local institutional review and ethics board judged the project a secondary analysis of existing anonymous data which meet the criteria for waiver of ethics review. Dissemination of the results will be via published scientific papers and presentations. Key messages will be promoted for example, via social media or press releases.

Abstract: Background: Urinary tract infections (UTIs) are common bacterial infections dominated by lower UTI in women (LUTIW). Symptoms only are insufficient for diagnosis and accordingly, near patient diagnostic tests confidently confirming significant bacteriuria are desirable. The nitrite test (NIT) has low sensitivity, while bacterial and leukocyte counts disjunctively paired in urine sediment microscopy (SED) have high sensitivity. Similar symptomatic cure rates are found post antibiotic vs. placebo therapy in patients with negative cultures. Consequently, prescription on symptoms only implies unnecessary antibiotic therapy. Aims: to evaluate the diagnostic outcomes of NIT, SED and NIT disjunctively paired with SED (NIT+SED) vs. urine culture, with special focus on bladder incubation time (BIT), and to assess if NIT+SED can reduce unnecessary antibiotic therapy. Methods: A diagnostic, primary care, multicentre study including 1070 women with symptoms suggestive of lower UTI. Results: Significant bacteriuria was found in 77%. The BIT highly influenced the diagnostic outcomes and the optimal duration was 4h with sensitivity of 66, 90 and 95% for NIT, SED and NIT+SED, respectively. SED performed only in NIT negative specimens could reduce unnecessary antibiotics by 10% vs. prescription on symptoms only. The number needed to test with SED to reduce one unnecessary antibiotic course was five patients at BIT 4h and six patients at 3h or overall. Conclusion: The BIT highly influences the diagnostic outcomes with the highest accuracy of NIT+SED. Diagnosis of LUTIW with NIT+SED can reduce unnecessary antibiotic therapy and subsequently decrease antimicrobial resistance. Trial registration: The Swedish Medical Product Agency 1995 03 01:151:01783/94.

Pivmecillinam (PIV) is a first-line antimicrobial for treatment of lower urinary tract infection in women (LUTIW). Mecillinam, the active substance of PIV, is bactericidal mainly against gram-negative uropathogens, whereas gram-positive species are considered intrinsically resistant. However, successful treatment of LUTIW caused by Staphylococcus saprophyticus has been reported, but more rarely for other gram-positive species. The aim of this study was to compare clinical and bacteriological outcome of PIV vs placebo treatment among uropathogens with special focus on mecillinam-resistant isolates. We analysed data from a prospective, multicentre, placebo-controlled, primary health care, therapy study performed in Sweden in 1995-1998 that included 1143 women with symptoms suggestive of LUTIW. Urine cultures were collected and symptoms registered at inclusion and at follow-up visits. Overall, the efficacy of PIV was superior to that of placebo. Clinical and bacteriological outcomes of PIV treatment were similar for S. saprophyticus, Escherichia coli as for most other uropathogens irrespective of their susceptibility to mecillinam. However, the occurrence of enterococci increased nearly fivefold shortly post PIV treatment, although with mild symptoms and a high spontaneous eradication. As susceptibility to mecillinam in vitro did not predict bacteriological and clinical outcome of PIV treatment, we suggest that the present breakpoints for mecillinam should be revised.

The epidemiology of urinary tract infection (UTI) in the population of Vännäs (8 000 inhabitants) was studied during one year. The annual incidence increased from 0.5% in the first decade of life to more than 10% in the age group 90-100 years. Male UTI comprised only 13% of the episodes, increased after middle age and contributed 4 0% by > 80 years of age. At 17 PHC centres (PHCCs) a prevalence study (McPHC) of mainly uncomplicated UTI was performed. Most episodes were acutely symptomatic (lower 75%, upper 5%).

Microscopy of wet-stained urinary sediment with a minimum of moderate amount of bacteria and/or 5 leukocytes per high power field (4 00 x) as breakpoint resulted in a desired high sensitivity (97%) and 86% efficacy in acutely symptomatic patients. Diagnosis of bacteriuria using Uricult dipslides yielded acceptable results with an overall efficacy of 88%. Nitrite test and Uriglox showed an unacceptable low mean sensitivity ofR56 and 69%, respectively. A positive nitrite, sediment or Uricult , when used in combination, was optimal in diagnosing UTI with a sensitivity of 98% in acutely symptomatic patients during their office visits.

The average risk of drug resistance was 17% in the Vännäs study. Sensicult satisfactorily predicted drug sensitivity (93%) but not bacterial drug resistance (50%). Using Uricult with classification of bacteriuria by Gram-grouping, lactose and catalase reactions for targeting UTI therapy, according to local guidelines, resulted in a similar low risk (6 %) of prescribing drugs to which the organisms were resistagt as when using Sensicult (7%). This development of the Uricult method is simple and can be recommended for office practice in PHC.

The spectrum of bacteria causing UTI and their drug resistance was more associated with the selection of patients, sex and age than with symptoms. The pattern of drug resistance was little influenced by UTI history and the mean pretherapy resistance for the seven drugs tested in McPHC was low (7%). Drug resistance was increased in failure (mean 24%) but not in early or repeated recurrence. In McPHC therapy resulted in 8% bacteriological failure and 12% early recurrence, irrespective of whether the bacteria were classified as sensitive or resistant in vitro to the drug given. Thus, in order to be of prognostic value for therapy of uncomplicated UTI, high-level breakpoints focusing more on peak urinary drug concentrations need to be studied.

UTI symptoms in McPHC were eradicated in only 2/3 of the bacterio- logically cured episodes and in 1/3 of the failures at control 1-3 days posttherapy showing that symptoms are an unreliable indicator of UTI.

From current literature, it seems unlikely that asymptomatic bacteriuria (ABU) plays a major role in the development of uremia due to chronic pyelonephritis. With the exception of ABU in pregnancy, therapy seems to yield no benefit. Omitting posttherapy bacteriuria controls in patients with symptoms eradicated, at least in women with uncomplicated UTI, would lead to considerable savings both for patients and the health care system.