Do differences in Panton-Valentine leukocidin production among international methicillin-resistant Staphylococcus aureus clones affect disease presentation and severity?

Panton-Valentine leukocidin (PVL) production by methicillin-resistant Staphylococcus aureus (MRSA) was determined in vitro using the enzyme-linked immunosorbent assay (ELISA), and associations with clinical presentation and bacterial genetic characteristics were examined. PVL production ranged from 0.02 to 4.865 µg/ml and correlated with a multilocus sequence type (MLST) clonal complex associated with specific PVL phage types. A relationship between PVL production and clinical presentation or patient demographics could not be demonstrated.

Temporal association of the development of oropharyngeal microbiota with early life wheeze in a population-based birth cohort.

BACKGROUND: A critical window in infancy has been proposed, during which the microbiota may affect subsequent health. The longitudinal development of the oropharyngeal microbiota is under-studied and may be associated with early-life wheeze. We aimed to investigate the temporal association of the development of the oropharyngeal microbiota with early-life wheeze. METHODS: A population-based birth cohort based in London, UK was followed for 24 months. We collected oropharyngeal swabs at six time-points. Microbiota was determined using sequencing of the V3-V5 region of the 16S rRNA-encoding gene. Medical records were reviewed for the outcome of doctor diagnosed wheeze. We used a time-varying model to investigate the temporal association between the development of microbiota and doctor-diagnosed wheeze. FINDINGS: 159 participants completed the study to 24 months and for 98 there was complete sequencing data at all timepoints and outcome data. Of these, 26 had doctor-diagnosed wheeze. We observed significant increase in the abundance of Neisseria between 9 and 24 months in children who developed wheeze (p = 0∙003), while in those without wheezing there was a significant increment in the abundance of Granulicatella (p = 0∙012) between 9 and 12 months, and of Prevotella (p = 0∙018) after 18 months. INTERPRETATION: A temporal association between the respiratory commensal Granulicatella and also Prevotella with wheeze (negative), and between Neisseria and wheeze (positive) was identified in infants prior to one year of age. This adds to evidence for the proposed role of the microbiota in the development of wheeze. FUND: Research funding from the Winnicott Foundation, Meningitis Now and Micropathology Ltd.

Effect of single-dose ivermectin on Onchocerca volvulus: a systematic review and meta-analysis.

The broad-spectrum antiparasitic drug ivermectin was licensed for use against onchocerciasis in 1987, yet the mechanisms by which it exerts a fast decrease and long-lasting suppression of Onchocerca volvulus microfilaridermia, and inhibition of microfilarial release by female worms remain largely unknown. A better understanding of the effects of ivermectin on O volvulus microfilariae and macrofilariae is crucial to improve our ability to predict the long-term effect of treatment. We did a systematic review of individual and population-based ivermectin trials to investigate the temporal dynamics of the drug's microfilaricidal and embryostatic efficacy after administration of a single, standard dose (150 microg/kg). Meta-analyses on data from 26 microfilarial and 15 macrofilarial studies were linked by a mathematical model describing the dynamics of potentially fertile female parasites to skin microfilariae. The model predicts that after treatment, microfilaridermia would be reduced by half after 24 h, by 85% after 72 h, by 94% after 1 week, and by 98-99% after 1-2 months, the latter also corresponding to the time when the fraction of females harbouring live microfilariae is at its lowest (reduced by around 70% from its original value). Our results provide a baseline microfilarial skin repopulation curve against which to compare studies done after long-term treatment.

Breast Infection: A Review of Diagnosis and Management Practices.

Mastitis is a common condition that predominates during the puerperium. Breast abscesses are less common, however when they do develop, delays in specialist referral may occur due to lack of clear protocols. In secondary care abscesses can be diagnosed by ultrasound scan and in the past the management has been dependent on the receiving surgeon. Management options include aspiration under local anesthetic or more invasive incision and drainage (I&D). Over recent years the availability of bedside/clinic based ultrasound scan has made diagnosis easier and minimally invasive procedures have become the cornerstone of breast abscess management. We review the diagnosis and management of breast infection in the primary and secondary care setting, highlighting the importance of early referral for severe infection/breast abscesses. As a clear guideline on the management of breast infection is lacking, this review provides useful guidance for those who rarely see breast infection to help avoid long-term morbidity.

Deriving a management algorithm for emphysematous pyelonephritis: Can we rely on minimally invasive strategies or should we be opting for earlier nephrectomy?

PURPOSE: To analyse the incidence and management of emphysematous pyelonephritis (EPN) in North West London and examine factors that influence immediate and 6-month outcomes with the aim of guiding future management. METHODS: This work analyses EPN cases from the London North West Healthcare NHS Trust from October 2006 to July 2015 (population ≈ 850,000). Diagnosis and stage were confirmed by computed tomography (CT). Demographic, clinical, biochemical and microbiological characteristics were assessed. Treatment modalities were medical management, minimally invasive management (MIM) and surgical. Immediate and 6-month outcomes were analysed. RESULTS: Thirteen cases were identified (f = 8, m = 5) from 5525 CT scans. EPN occurred in patients with diabetes mellitus (n = 11, 84.6%), hypertension (n = 10, 76.9%) or urinary tract calculi (n = 7, 53.85%). Unilateral EPN occurred predominantly (n = 11, 84.6%); 46.1% (n = 6) were class 1 or 2 and 53.8% (n = 7) class 3 or 4. Escherichia coli was most commonly cultured (n = 5, 38.46%). All patients received antibiotics, and ten cases required MIM. Two patients had a delayed nephrectomy, both survived. Mortality was 15.4% (n = 2, grade 1 and 3a), both died acutely post-MIM, neither underwent emergency nephrectomy. At 6 months, eight patients had ongoing renal impairment. No specific poor prognostic factors were identifiable. CONCLUSIONS: Patients with low-grade EPN may also have a high mortality rate. In the two cases who died, earlier consideration for nephrectomy may have been prudent. It may be beneficial to have a low threshold for prompt emergency nephrectomy in severe cases and where MIM treatment has failed. We suggest a management algorithm to guide clinicians and minimise mortality.

Improving the transition from medical student to junior doctor: a one-month course in the final year of medical school.

This article was migrated. The article was marked as recommended. Concern exists that the transition from student to doctor is abrupt and stressful, with new graduates lacking both clinical skills and confidence. This study explores the effect a preparation programme can have on the confidence and skills of final year medical students (FYMSs), prior to commencing their first clinical post. Foundation year one (FY1) doctors were surveyed on challenges they faced when commencing clinical work. Findings were used to design a practical, four-week, eight lecture course, aimed at preparing final year medical students for work. Questionnaires and focus groups were used to establish pre- and post-course concerns. Amongst FY1 doctors (n=105) the predominant concern was the diagnosis and management of unwell patients (66.7%). Medical students expressed similar fears (80.85%). On average each session significantly improved confidence levels by 25.3% (95% CI: 23.27-27.12%, p<0.01). Sessions on prescribing and palliative care showed greatest confidence improvement (31.1% and 29.4% respectively). This programme supports the transition from medical student to practising doctor, and was found to be useful and effective at building student confidence through practical advice from current FY1 doctors to the next generation of junior doctors. It remains unclear as to when (within the year) this course would be most beneficially placed.

Identification of a distinctive phenotype for endocarditis-associated clonal complex 22 MRSA isolates with reduced vancomycin susceptibility.

PURPOSE: We previously identified an association between CC22 meticillin-resistant Staphylococcus aureus (MRSA) bloodstream infection isolates with an elevated vancomycin MIC (V-MIC) in the susceptible range (1.5-2 mg l-1) and endocarditis. This study explores whether these isolates have a specific phenotype consistent with the clinical findings. METHODOLOGY: CC22 and CC30 MRSA isolates with high (1.5-2 mg l-1) and low (≤0.5 mg l-1) V-MICs were tested for fibrinogen and fibronectin binding, virulence in a Galleria mellonella caterpillar model, phenol soluble modulin production and accessory gene regulator (agr) expression. RESULTS: CC22 high V-MIC, but not CC30 high V-MIC isolates, showed sustained fibrinogen binding through a stationary growth phase and increased PSM production, specifically PSMα1, compared with respective low V-MIC isolates. Expression was lower in both CC22 and CC30 high V-MIC isolates compared with respective low V-MIC isolates, although there was no associated reduction in virulence in the caterpillar model. CONCLUSIONS: The identification of a distinct phenotype for CC22 high V-MIC isolates supports the hypothesis that bacterial factors contribute to the mechanism underlying their association with endocarditis. Further study of these isolates could shed light on the molecular mechanism of endocarditis in humans.

Comparative analysis of phenol-soluble modulin production and Galleria mellonella killing by community-associated and healthcare-associated meticillin-resistant Staphylococcusaureus strains.

Community-associated meticillin-resistant Staphylococcus aureus (CA-MRSA) have emerged globally and have been associated with more severe disease than healthcare-associated MRSA (HA-MRSA). The purpose of this study was to determine whether laboratory measures of virulence can distinguish dominant CA-MRSA clones from HA-MRSA clones. We compared the production of phenol-soluble modulins (PSMs) and ability to kill Galleria mellonella caterpillars for a range of CA- and HA-MRSA strains. Twenty-two HA-MRSA strains [ST22-IV (EMRSA-15), ST36-II (EMRSA-16) and ST239-III] and 26 CA-MRSA strains [ST1-IV (PVL+ USA400), ST1-IV (PVL-), ST8-IV (USA300), ST22-IV (PVL+), ST30-IV, ST59-IV and ST80-IV] were analysed. PSM production was measured using and compared using t-tests and ANOVA. A G mellonella (caterpillar) pathogenicity model was performed, and differences were compared using survival analysis and the log-rank test. There was no significant difference in overall PSM production between HA and CA strains (P=0.090), but there was significant variation between clones (P=0.003). G. mellonella caterpillar killing varied significantly by clone (P<0.001), and overall killing was greater for HA compared with CA clones (P=0.007). The increased acute virulence phenotype of CA-MRSA clones in humans is not associated with increased PSM production in vitro or increased killing in an in vivo caterpillar pathogenicity model.