Risk factors for antimicrobial resistance in patients with Escherichia coli bacteraemia related to urinary tract infection.

Introduction: NHS Lothian policy has recently changed to avoid first-line use of trimethoprim for uncomplicated urinary tract infections (UTI) in patients with risk factors for trimethoprim resistance, in line with national guidance. This study aimed to identify risk factors for antimicrobial resistance in Escherichia coli bacteraemia related to UTI. Methods: A retrospective cohort study of 687 patients with E. coli bacteraemia related to UTI in NHS Lothian from 01/02/18 to 29/02/20 was undertaken. Demographics and comorbidities were collected from electronic patient records. Community prescribing and microbiology data were collected from the prescribing information system and Apex. Univariate and multivariate analysis was undertaken using RStudio to analyse trimethoprim, gentamicin and multi-drug resistance (MDR). Results: Trimethoprim resistance was present in 282/687(41%) of blood culture isolates. MDR was present in 278/687(40.5%) isolates. Previous urinary trimethoprim resistant E. coli was a significant risk factor for both trimethoprim resistance (OR 9.44, 95%CI 5.83-15.9) and MDR (OR 4.81, 95%CI 3.17-7.43) on multivariate modelling. Trimethoprim prescription (OR 2.10, 95% CI 1.33-3.34) and the number of community antibiotic courses (OR 1.19, 95%CI 1.06-1.35) were additional risk factors for trimethoprim resistance. Multiple independent risk factors were also identified for trimethoprim resistance, MDR and gentamicin resistance. Discussion: This study showed a high prevalence of trimethoprim resistance and MDR in patients with E. coli bacteraemia related to UTI. This supports the withdrawal of trimethoprim from first-line treatment of UTIs in patients with risk factors for trimethoprim resistance. It has also identified risk factors for MDR in E. coli bacteraemia.

Evaluation of the molecular detection of ciprofloxacin resistance in Neisseria gonorrhoeae by the ResistancePlus GC assay (SpeeDx).

There is growing concern due to the emergence of multidrug resistance in Neisseria gonorrhoeae. A rapid molecular test which guides and provides antimicrobial susceptibility knowledge prior to start of treatment is needed. This study evaluated the clinical performance of the ResistancePlus GC assay compared to in-house PCR and antimicrobial susceptibility results for ciprofloxacin resistance. Samples were selected from a range of sites with corresponding cultures isolated from the same patient episode. The ResistancePlus GC assay displayed high sensitivity for N. gonorrhoeae detection (98.5%) and gyrA detection (97.1%). There was high agreement (98.9%) between the ResistancePlus GC assay and culture phenotype. Mixed population testing showed that the assay was able to detect resistance in a sample containing a minority variant of 27% resistant. The ResistancePlus GC assay performed well and could be used to provide a clinically relevant indication of ciprofloxacin susceptibility for the treatment of gonorrhoea.

A case of cutaneous toxigenic Corynebacterium ulcerans likely acquired from a domestic dog.

INTRODUCTION: Corynebacterium ulcerans can produce diphtheria toxin and although still rare, is now the predominant cause of toxigenic diphtheria infection in the UK, making this organism of great clinical and public health importance. Here we describe a cutaneous case, likely secondary to domestic animal contact. CASE PRESENTATION: A 60-year-old female presented with a slow-healing finger-burn wound. A skin swab cultured Corynebacterium ulcerans, which was confirmed to be toxin producing. She resided with her partner and two dogs, one of which had a chronic skin lesion. Her most recent diphtheria vaccine was in 2009. Four close contacts were identified, two of whom were healthcare professionals, and nose and throat swabs were obtained. The patient was treated with clarithromycin (14 day course), diphtheria vaccine and excluded from work until completion of antibiotics and negative clearance swabs. Contacts were given erythromycin (7 day course), vaccinated and healthcare worker contacts excluded from work until swab negative. A veterinary practitioner swabbed the throats and a skin lesion of their dogs. One contact (partner of patient) and all dog swabs were positive. Partial allelic profiles from MLST supported an epidemiological link. The dogs were treated with antibiotics and antimicrobial skin wash. Repeat swabs for the index case, contact and both dogs were negative following treatment. CONCLUSION: This was a rare case of cutaneous diphtheria secondary to Corynebacterium ulcerans with domestic animals the most likely source, although human-to-human contact could not be excluded, with important human and animal public health implications.

Fgf receptor 3 activation promotes selective growth and expansion of occipitotemporal cortex.

BACKGROUND: Fibroblast growth factors (Fgfs) are important regulators of cerebral cortex development. Fgf2, Fgf8 and Fgf17 promote growth and specification of rostromedial (frontoparietal) cortical areas. Recently, the function of Fgf15 in antagonizing Fgf8 in the rostral signaling center was also reported. However, regulation of caudal area formation by Fgf signaling remains unknown. RESULTS: In mutant mice with constitutive activation of Fgf receptor 3 (Fgfr3) in the forebrain, surface area of the caudolateral cortex was markedly expanded at early postnatal stage, while rostromedial surface area remained normal. Cortical thickness was also increased in caudal regions. The expression domain and levels of Fgf8, as well as overall patterning, were unchanged. In contrast, the changes in caudolateral surface area were associated with accelerated cell cycle in early stages of neurogenesis without an alteration of cell cycle exit. Moreover, a marked overproduction of intermediate neuronal progenitors was observed in later stages, indicating prolongation of neurogenesis. CONCLUSION: Activation of Fgfr3 selectively promotes growth of caudolateral (occipitotemporal) cortex. These observations support the 'radial unit' and 'radial amplification' hypotheses and may explain premature sulcation of the occipitotemporal cortex in thanatophoric dysplasia, a human FGFR3 disorder. Together with previous work, this study suggests that formation of rostral and caudal areas are differentially regulated by Fgf signaling in the cerebral cortex.