The recent US Food and Drug Administration approval of pivmecillinam-an oral prodrug of the amidinopenicillin antibiotic mecillinam-presents a valuable opportunity to address the need for new treatments for uncomplicated urinary tract infection (uUTI). We report findings of a systematic literature review of the safety profile of pivmecillinam/mecillinam based on more than 40 years' experience, mainly in Europe and Canada, to describe its tolerability profile and identify any important safety signals. In total, 110 eligible publications were identified describing use of pivmecillinam/mecillinam as monotherapy or in combination, for treatment of uUTI or other infectious conditions.
View Article and Find Full Text PDFPrimary care antimicrobial stewardship programs have limited success in reducing antibiotic use, prompting the search for new strategies. Convincing general practitioners to resist antibiotic prescription amid uncertainty or patient demands usually poses a significant challenge. Despite common practice, standard durations for common infections lack support from clinical studies.
View Article and Find Full Text PDFObjectives: We aimed to identify specific anaerobic bacteria causing bacteraemia and a subsequent diagnosis of colorectal cancer.
Methods: A nationwide population-based cohort study, which included all episodes of defined specific anaerobic bacteraemia from 2010 (5,534,738 inhabitants) through 2020 (5,822,763 inhabitants) and all cases of colorectal cancer diagnosed from 2010 through 2021 in Denmark. We calculated the incidence and risk of colorectal cancer after bacteraemia with specific anaerobic bacteria using Escherichia coli bacteraemia as reference.
Background: The aminoglycoside apramycin has been proposed as a drug candidate for the treatment of critical Gram-negative systemic infections. However, the potential of apramycin in the treatment of drug-resistant bloodstream infections (BSIs) has not yet been assessed.
Methods: The resistance gene annotations of 40 888 blood-culture isolates were analysed.
Background: Population-based studies have shown an increased risk of dementia after infections, but weaker links were reported for autoimmune diseases. Evidence is scarce for whether the links may be modified by the dementia or exposure subtype.
Objective: We aimed to investigate the association between infections and/or autoimmune diseases and rates of major types of dementias in the short- and long terms.
The antimicrobial agent nitrofurantoin is becoming increasingly important for treatment of urinary tract infections (UTIs) due to widespread occurrence of multidrug-resistant Escherichia coli. Despite many years of use, little data on nitrofurantoin pharmacokinetics (PK) or -dynamics (PD) exist. The objective of this study was to (i) evaluate the pharmacokinetics of nitrofurantoin in a mouse model and (ii) use that data to design an in vivo dose fractionation study in an experimental model of UTI with E.
View Article and Find Full Text PDFExpert Rev Anti Infect Ther
June 2024
Herein, we report the hit-to-lead identification of a drug-like pleuromutilin conjugate , based on a triaromatic hit reported in 2020. The lead arose as the clear candidate from a hit-optimization campaign in which Gram-positive antibacterial activity, solubility, and P-gp affinity were optimized. Conjugate was extensively evaluated for its ADMET performance which, apart from solubility, was overall on par with lefamulin.
View Article and Find Full Text PDFExpert Rev Anti Infect Ther
November 2023
Introduction: Urinary tract infections (UTIs) are associated with 25-40% of antibiotics consumed in primary care and are, therefore, driving antibiotic resistance. The worldwide increase in antibiotic resistance especially in Escherichia coli has complicated the treatment choices for UTIs and absence of effective oral antibiotics may lead to increasing need for more effective treatments.
Areas Covered: In this review we focus on the importance of the correct diagnosis of UTI as based on proof of urinary pathogens in the urine and discuss diagnostic measures including microscopy, dipstick, and culture.
Importance: Systemic inflammation has been suggested to explain reported associations between infections and dementia. Associations between autoimmune diseases and dementia also suggest a role for peripheral systemic inflammation.
Objective: To investigate the associations of infections and autoimmune diseases with subsequent dementia incidence and to explore potential shared signals presented by the immune system in the 2 conditions.
This study aimed to investigate the role played by pets as reservoirs of strains causing human urinary tract infections (UTIs) in household contacts. Among 119 patients with community-acquired UTIs, we recruited 19 patients who lived with a dog or a cat. Fecal swabs from the household pet(s) were screened by antimicrobial selective culture to detect displaying the resistance profile of the human strain causing UTI.
View Article and Find Full Text PDFArch Dis Child Fetal Neonatal Ed
December 2023
A cross-sectional survey was conducted in eight Ghanaian communities to investigate the extent of intestinal colonization with 3-generation cephalosporin-resistant Enterobacterales. The study collected faecal samples and corresponding lifestyle data from 736 healthy residents to assess the occurrence of cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae, with a focus on genotypes of plasmid-mediated ESBLs, AmpCs, and carbapenemases. The results showed that 371 participants (50.
View Article and Find Full Text PDFBackground: The risk of pyelonephritis following uncomplicated lower urinary tract infection (cystitis) in women has not been studied in well-powered samples. This is likely due to the previous lack of nationwide primary healthcare data. We aimed to examine the risks of pyelonephritis following cystitis in women and explore if antibiotic treatment, cervical cancer, parity, and sociodemographic factors are related to these risks.
View Article and Find Full Text PDFObjectives: Pivmecillinam, the oral version of mecillinam, represents one of the major recommended and used antibiotics for empiric and targeted treatment of urinary tract infections in primary care in Denmark, Norway and Sweden. Mecillinam resistant mutants in Escherichia coli develop easily in vitro, but their fitness cost has been shown to be high.
Methods: We revisited the resistance and consumption data from the monitoring programmes in the three countries and compared pivmecillinam with ciprofloxacin from 2010 to 2020.
Background: Carbapenemase-producing Klebsiella pneumoniae and Escherichia coli have become a significant global health challenge. This has created an urgent need for new treatment modalities. We evaluated the efficacy of mecillinam in combination with either avibactam or ceftazidime/avibactam against carbapenemase-producing clinical isolates.
View Article and Find Full Text PDFObjectives: It is unknown whether invasive procedures are associated with brain abscess.
Methods: Nationwide, population-based, matched case-control study of patients with culture verified brain abscess in Denmark from 1989 to 2016. Exposure was invasive procedures 0-6 months before study inclusion.
Background: It is unknown whether patients diagnosed with brain abscess have an increased risk of psychiatric disorders.
Methods: In this nationwide, population-based matched cohort study from Denmark, we compared the incidence of psychiatric disorders, use of psychiatric hospitals, and receipt of psychiatric medications between patients diagnosed with brain abscess and individuals from the general population, matched on date of birth, sex, and residential area.
Results: We included 435 patients diagnosed with brain abscess and 3909 individuals in the comparison cohort: 61% were male and median age was 54 years.
Objectives: To evaluate the activity of meropenem-amikacin and meropenem-colistin combinations with checkerboard broth microdilution (CKBM) compared with isothermal microcalorimetry (ITMC) assays against a multi-centric collection of multi-drug-resistant Gram-negative clinical isolates; and to compare the fractional inhibitory concentration (FIC) index and time to results of CKBM and ITMC.
Methods: A collection of 333 multi-drug-resistant Gram-negative clinical isolates showing reduced susceptibility to meropenem (121 Klebsiella pneumoniae, 14 Escherichia coli, 130 Pseudomonas aeruginosa and 68 Acinetobacter baumannii) isolated from different centres (Florence, Madrid, Rotterdam and Stockholm) was included in the study. The antimicrobial activity of meropenem-amikacin and meropenem-colistin combinations was evaluated with CKBM and ITMC.
Denmark has experienced an increase in the proportion of invasive vancomycin-resistant Enterococcus faecium (VRE) since 2002 (e.g. <4% in 2015, 7.
View Article and Find Full Text PDFHere, we present a longitudinal shotgun sequencing metagenomics study of 16 healthy, Danish women in the reproductive age. The aim of the study was to investigate whether lactobacilli, orally consumed, had any impact on the vaginal microbiome and its functional potential. The 16 women aged 19-45 years were recruited from Copenhagen, Denmark.
View Article and Find Full Text PDFAntimicrobial susceptibility testing (AST) should be fast and accurate, leading to proper interventions and therapeutic success. Clinical microbiology laboratories rely on phenotypic methods, but the continuous improvement and decrease in the cost of whole-genome sequencing (WGS) technologies make them an attractive alternative. Studies evaluating the performance of WGS-based prediction of antimicrobial resistance (AMR) for selected bacterial species have shown promising results.
View Article and Find Full Text PDFBackground: Cervical cancer is a major cause of mortality and morbidity in women worldwide. This study aimed to estimate the association between common urogenital infections and cervical neoplasia.
Methods: A multi-register national cohort study of 4,120,557 women aged ≥15 years (2002-2018) was conducted.