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BMC Infectious Diseases Dec 2014Although uncomplicated cystitis is often self-limiting, most such patients will be prescribed antibiotic treatment. We are investigating whether treatment of cystitis... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Although uncomplicated cystitis is often self-limiting, most such patients will be prescribed antibiotic treatment. We are investigating whether treatment of cystitis with an NSAID is as effective as an antibiotic in achieving symptomatic resolution.
METHODS/DESIGN
This is a randomized, controlled, double blind trial following the principles of Good Clinical Practice. Women between the ages of 18 to 60 presenting with symptoms of uncomplicated cystitis are screened for eligibility. 500 women from four sites in Norway, Sweden and Denmark are allocated to treatment with 600 mg ibuprofen three times a day or 200 mg mecillinam three times a day for three days. Allocation is conducted using block randomization. The primary outcome is the number of patients who feel cured by day four as recorded in a diary. Adverse events will be handled and reported in accordance with Good Clinical Practice.
DISCUSSION
If treatment of uncomplicated cystitis with ibuprofen is as effective as mecillinam for symptom relief, we can potentially reduce the use of antibiotics on a global scale.
TRIAL REGISTRATION
EudraCTnr: 2012-002776-14. ClinicalTrials.gov: NCT01849926.
Topics: Adolescent; Adult; Amdinocillin; Anti-Bacterial Agents; Anti-Inflammatory Agents, Non-Steroidal; Clinical Protocols; Cystitis; Double-Blind Method; Drug Administration Schedule; Female; Humans; Ibuprofen; Middle Aged; Treatment Outcome; Young Adult
PubMed: 25516016
DOI: 10.1186/s12879-014-0693-y -
BMC Infectious Diseases Dec 2016Uncomplicated lower urinary tract infections (LUTI) are very common, and presumably around 200,000 female patients are treated for this annually in Denmark. The current... (Randomized Controlled Trial)
Randomized Controlled Trial
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 .
Topics: Adolescent; Adult; Aged; Amdinocillin Pivoxil; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Denmark; Double-Blind Method; Drug Administration Schedule; Female; Humans; Middle Aged; Prospective Studies; Urinary Tract Infections; Young Adult
PubMed: 27905884
DOI: 10.1186/s12879-016-2022-0 -
Scandinavian Journal of Primary Health... Mar 2020
Topics: Adolescent; Adult; Amdinocillin Pivoxil; Anti-Bacterial Agents; Denmark; Escherichia coli; Humans; Male; Middle Aged; Nitrofurantoin; Prescriptions; Retrospective Studies; Trimethoprim; Urinary Tract Infections; Young Adult
PubMed: 31997687
DOI: 10.1080/02813432.2020.1718301 -
PLoS Genetics Jul 2017Bacterial cells are typically surrounded by an net-like macromolecule called the cell wall constructed from the heteropolymer peptidoglycan (PG). Biogenesis of this...
Bacterial cells are typically surrounded by an net-like macromolecule called the cell wall constructed from the heteropolymer peptidoglycan (PG). Biogenesis of this matrix is the target of penicillin and related beta-lactams. These drugs inhibit the transpeptidase activity of PG synthases called penicillin-binding proteins (PBPs), preventing the crosslinking of nascent wall material into the existing network. The beta-lactam mecillinam specifically targets the PBP2 enzyme in the cell elongation machinery of Escherichia coli. Low-throughput selections for mecillinam resistance have historically been useful in defining mechanisms involved in cell wall biogenesis and the killing activity of beta-lactam antibiotics. Here, we used transposon-sequencing (Tn-Seq) as a high-throughput method to identify nearly all mecillinam resistance loci in the E. coli genome, providing a comprehensive resource for uncovering new mechanisms underlying PG assembly and drug resistance. Induction of the stringent response or the Rcs envelope stress response has been previously implicated in mecillinam resistance. We therefore also performed the Tn-Seq analysis in mutants defective for these responses in addition to wild-type cells. Thus, the utility of the dataset was greatly enhanced by determining the stress response dependence of each resistance locus in the resistome. Reasoning that stress response-independent resistance loci are those most likely to identify direct modulators of cell wall biogenesis, we focused our downstream analysis on this subset of the resistome. Characterization of one of these alleles led to the surprising discovery that the overproduction of endopeptidase enzymes that cleave crosslinks in the cell wall promotes mecillinam resistance by stimulating PG synthesis by a subset of PBPs. Our analysis of this activation mechanism suggests that, contrary to the prevailing view in the field, PG synthases and PG cleaving enzymes need not function in multi-enzyme complexes to expand the cell wall matrix.
Topics: Amdinocillin; Cell Wall; Drug Resistance, Bacterial; Endopeptidases; Escherichia coli; Escherichia coli Proteins; Gene Expression Regulation, Bacterial; Genome, Bacterial; Penicillin-Binding Proteins; Peptidoglycan
PubMed: 28749938
DOI: 10.1371/journal.pgen.1006934