The efficacy of pivmecillinam: 3 days or 5 days t.i.d against community acquired uncomplicated lower urinary tract infections – a randomized, double-blinded, placebo-controlled clinical trial study protocol

BACKGROUND: Uncomplicated lower urinary tract infections (LUTI) are very common, and presumably around 200,000 female patients are treated for this annually in Denmark. The current Danish national clinical practice guidelines recommend pivmecillinam as a first-line drug (i.e., 400 mg t.i.d. for 3 days). Pivmecillinam is also one of the first-line drugs recommended in the international guidelines for LUTIs (i.e., 400 mg b.i.d. for 5 days). The international recommended duration is based on evidence saying that a 7-day regimen is better than a 3-day regimen. However, no data says that a 5-day regimen is superior to a 3-day regimen. With this study we aim to identify and to compare the efficacy of pivmecillinam 400 mg t.i.d in a 3-day respectively 5-day regimen, against community acquired uncomplicated LUTI, i.e., in women at the age of 18–70 year old. METHOD/DESIGN: The general practitioner will at consultation give a suitable patient the opportunity to participate in the study. If the patient will give her consent, a double-blinded kit (i.e., the antibiotic with/without placebo, questionnaires and self-urinary samples) will be given to the patient. We aim for 161 evaluable patients in each arm. DISCUSSION: Pivmecillinam is an excellent choice against urinary tract infections and we believe this study will fill in the gaps and strengthen the evidence on the treatment against one of the most common infections in our society. Thus, aiming to provide a more rational and ecological beneficial antimicrobial therapy. TRIAL REGISTRATION: EudraCTno.: 2014-001321-32

Growth Rate of <i>Escherichia coli</i> During Human Urinary Tract Infection:Implications for Antibiotic Effect

Escherichia coli is the primary cause of urinary tract infection (UTI), which is one of the most frequent human infections. While much is understood about the virulence factors utilized by uropathogenic E. coli (UPEC), less is known about the bacterial growth dynamics taking place during infection. Bacterial growth is considered essential for successful host colonization and infection, and most antibiotics in clinical use depend on active bacterial growth to exert their effect. However, a means to measure the in situ bacterial growth rate during infection has been lacking. Due to faithful coordination between chromosome replication and cell growth and division in E. coli, chromosome replication provides a quantitative measure of the bacterial growth rate. In this study, we explored the potential for inferring in situ bacterial growth rate from a single urine sample in patients with E. coli bacteriuria by differential genome quantification (ori:ter) performed by quantitative PCR. We found active bacterial growth in almost all samples. However, this occurs with day-to-day and inter-patient variability. Our observations indicate that chromosome replication provides not only a robust measure of bacterial growth rate, but it can also be used as a means to evaluate antibiotic effect

Efficacy of seven and fourteen days of antibiotic treatment in uncomplicated Staphylococcus aureus bacteremia (SAB7):study protocol for a randomized controlled trial

SPIRIT 2013 checklist. (DOC 122 kb

The competence and warmth of Thai students’ attitudes towards varieties of English: the effect of gender and perceptions of L1 diversity

Previous language attitude research indicates that presenting speech forms allows listeners to index information about and attach social meaning to the perceived group(s) of speakers. Despite the volume of research undertaken elsewhere in Asia, there appear to be no in-depth studies investigating Thai nationals’ evaluations of specific varieties of English speech. This large-scale study examines 204 Thai university students’ attitudes towards forms of UK, US, Japanese, Chinese, Thai and Indian English, provided by highly proficient female speakers. The study also examines the extent to which Thai students’ perceptions of linguistic diversity in their L1 and their gender affect their attitudes. Multivariate analysis demonstrated UK, US and Thai English speech was ranked significantly higher than other Asian forms of English, for competence and warmth, attitudinal dimensions consistent with recent findings in social cognition. Further analysis indicated females and those most positive towards L1 variation expressed significantly higher levels of ingroup loyalty towards Thai English speakers. The findings are compared and contrasted with the results of equivalent studies undertaken in other Asian contexts and, given recent cutting-edge research in social cognition confirming the primacy of warmth judgements, calls for language attitude researchers to consider speaker warmth ratings more fully in future studies

Effects of Antibiotics on the Intestinal Microbiota of Mice

Studies on human and mouse gastrointestinal microbiota have correlated the composition of the microbiota to a variety of diseases, as well as proved it vital to prevent colonization with resistant bacteria, a phenomenon known as colonization resistance. Antibiotics dramatically modify the gut community and there are examples of how antibiotic usage lead to colonization with resistant bacteria [e.g., dicloxacillin usage selecting for ESBL-producing E. coli carriage], as shown by Hertz et al. Here, we investigated the impact of five antibiotics [cefotaxime, cefuroxime, dicloxacillin, clindamycin, and ciprofloxacin] on the intestinal microbiota in mice. Five different antibiotics were each given to groups of five mice. The intestinal microbiotas were profiled by use of the IS-pro analysis; a 16S–23S rDNA interspace [IS]-region-based profiling method. For the mice receiving dicloxacillin and clindamycin, we observed dramatic shifts in dominating phyla from day 1 to day 5. Of note, diversity increased, but overall bacterial load decreased. For ciprofloxacin, cefotaxime, and cefuroxime there were few overall changes. We speculate that antibiotics with efficacy against the abundant anaerobes in the gut, particularly Bacteroidetes, can in fact be selected for resistant bacteria, disregarding the spectrum of activity

Uropathogenic Escherichia coli Metabolite-Dependent Quiescence and Persistence May Explain Antibiotic Tolerance during Urinary Tract Infection

In the present study, it is shown that although Escherichia coli CFT073, a human uropathogenic (UPEC) strain, grows in liquid glucose M9 minimal medium, it fails to grow on glucose M9 minimal medium agar plates seeded with ≤106 CFU. The cells on glucose plates appear to be in a “quiescent” state that can be prevented by various combinations of lysine, methionine, and tyrosine. Moreover, the quiescent state is characteristic of ~80% of E. coli phylogenetic group B2 multilocus sequence type 73 strains, as well as 22.5% of randomly selected UPEC strains isolated from community-acquired urinary tract infections in Denmark. In addition, E. coli CFT073 quiescence is not limited to glucose but occurs on agar plates containing a number of other sugars and acetate as sole carbon sources. It is also shown that a number of E. coliCFT073 mini-Tn5 metabolic mutants (gnd, gdhA, pykF, sdhA, and zwf) are nonquiescent on glucose M9 minimal agar plates and that quiescence requires a complete oxidative tricarboxylic acid (TCA) cycle. In addition, evidence is presented that, although E. coli CFT073 quiescence and persistence in the presence of ampicillin are alike in that both require a complete oxidative TCA cycle and each can be prevented by amino acids, E. coli CFT073 quiescence occurs in the presence or absence of a functional rpoS gene, whereas maximal persistence requires a nonfunctional rpoS. Our results suggest that interventions targeting specific central metabolic pathways may mitigate UPEC infections by interfering with quiescence and persistence