Genomic analysis uncovers a phenotypically diverse but genetically homogeneous Escherichia coli ST131 clone circulating in unrelated urinary tract infections.

OBJECTIVES: To determine variation at the genome level in Escherichia coli ST131 clinical isolates previously shown to be phenotypically diverse. METHODS: The genomes of 10 ST131 isolates extensively characterized in previous studies were sequenced using combinations of Illumina and 454 sequencing technology. Whole-genome comparisons and phylogenetic comparisons were then performed across the strain set and with other closely related extraintestinal pathogenic E. coli (ExPEC) strain types. RESULTS: E. coli ST131 is overrepresented in a collection of clinical isolates, and there is large phenotypic variation amongst isolates. In contrast, genome sequencing of a selection of non-related clinical isolates shows almost no genetic variation between ST131 strains, and E. coli ST131 shows evidence of a genetically monomorphic pathogen showing a similar evolutionary trend to hypervirulent Clostridium difficile. CONCLUSIONS: A dominant circulating clone of E. coli ST131 has been identified in unrelated clinical urine samples in the UK. The clone splits into two distinct subgroups on the basis of antimicrobial resistance levels and carriage of extended-spectrum ß-lactamase plasmids. This provides the most comprehensive snapshot to date of the true molecular epidemiology of ST131 clinical isolates.

Molecular epidemiology of extraintestinal pathogenic Escherichia coli isolates from a regional cohort of elderly patients highlights the prevalence of ST131 strains with increased antimicrobial resistance in both community and hospital care settings.

OBJECTIVES: To assess the molecular epidemiology and prevalence of antibiotic resistance in Escherichia coli causing urinary tract infections of elderly patients from community and hospital settings. Also, to determine whether the possession of antibiotic resistance and virulence-associated genes can be linked to patient location or the clonal group of the organisms in question. METHODS: E. coli were isolated from the urine samples of elderly patients from the Nottingham area, and subjected to antibiotic susceptibility testing, virulence gene detection by PCR and multilocus sequence typing. RESULTS: No correlation was observed between community- or hospital-derived strains with regard to antibiotic resistance levels or virulence gene profiles. E. coli ST131 (where ST stands for sequence type) was the predominant ST found in both hospital and community samples, and demonstrated high levels of antibiotic resistance to the test panel, but did not possess a significantly larger array of virulence genes or a specific gene profile compared with other STs. CONCLUSIONS: The level of antibiotic resistance or virulence gene possession in uropathogenic E. coli is not directly associated with the healthcare setting of the patient, but there is a variation in antibiotic resistance and virulence gene possession depending on clonal group. ST131 is highly virulent and demonstrates high levels of antibiotic resistance, but its virulence does not appear to be attributable to the possession of a specific virulence-associated gene set or the possession of any virulence-associated gene in significantly higher levels than in any other ST.

Increased human pathogenic potential of Escherichia coli from polymicrobial urinary tract infections in comparison to isolates from monomicrobial culture samples.

The current diagnostic standard procedure outlined by the Health Protection Agency for urinary tract infections (UTIs) in clinical laboratories does not report bacteria isolated from samples containing three or more different bacterial species. As a result many UTIs go unreported and untreated, particularly in elderly patients, where polymicrobial UTI samples are especially prevalent. This study reports the presence of the major uropathogenic species in mixed culture urine samples from elderly patients, and of resistance to front-line antibiotics, with potentially increased levels of resistance to ciprofloxacin and trimethoprim. Most importantly, the study highlights that Escherichia coli present in polymicrobial UTI samples are statistically more invasive (P<0.001) in in vitro epithelial cell infection assays than those isolated from monomicrobial culture samples. In summary, the results of this study suggest that the current diagnostic standard procedure for polymicrobial UTI samples needs to be reassessed, and that E. coli present in polymicrobial UTI samples may pose an increased risk to human health.

Bacterial septic arthritis in adults.

Symptoms and signs of septic arthritis are an important medical emergency, with high morbidity and mortality. We review the changing epidemiology of septic arthritis of native joints in adults, encompassing the increasing frequency of the disorder and its evolving antibiotic resistance. We discuss various risk factors for development of septic arthritis and examine host factors (tumour necrosis factor alpha, interleukins 1 and 10) and bacterial proteins, toxins, and enzymes reported to be important determinants of pathogenesis in mouse models. Diagnosis of disease is largely clinical, guided by investigations and the opinion of skilled clinicians. We emphasise the need for timely medical and surgical intervention-most importantly, through diagnostic aspiration of relevant joints, choice of suitable antibiotic, and appropriate supportive measures. Management is growing in complexity with the advent of novel and antibiotic-resistant causative microorganisms and within the current climate of increased immunosuppression. Findings from animal models and patients are shedding light on disease pathogenesis and the possibility of novel adjunctive treatments, including systemic corticosteroids, cytokines and anticytokines, and bisphosphonates.

Effect of synbiotic therapy on the incidence of ventilator associated pneumonia in critically ill patients: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: To investigate the effect of enteral Synbiotic 2000 FORTE (a mixture of lactic acid bacteria and fibre) on the incidence of ventilator associated pneumonia (VAP) in critically ill patients. DESIGN: Prospective, randomised, double blind, placebo controlled trial. SETTING: Tertiary referral centre, general Adult Intensive Care Unit (ICU). PATIENTS AND PARTICIPANTS: 259 enterally fed patients requiring mechanical ventilation for 48 h or more were enrolled. INTERVENTION: All patients were enterally fed as per a standard protocol and randomly assigned to receive either synbiotic 2000 FORTE (twice a day) or a cellulose-based placebo for a maximum of 28 days. MEASUREMENTS AND RESULTS: Treatment group (n = 130) was well matched with placebo group (n = 129) for age (mean 49.5 and 50 years, respectively) and APACHE II score (median 17 for both). Oropharyngeal microbial flora and colonisation rates were unaffected by synbiotics. The overall incidence of VAP was lower than anticipated (11.2%) and no statistical difference was demonstrated between groups receiving synbiotic and placebo in the incidence of VAP (9 and 13%, P = 0.42), VAP rate per 1,000 ventilator days (13 and 14.6, P = 0.91) or hospital mortality (27 and 33%, P = 0.39), respectively. CONCLUSIONS: Enteral administration of Synbiotic 2000 FORTE has no statistically significant impact on the incidence of VAP in critically ill patients.

Comparison of oral amoxicillin and intravenous benzyl penicillin for community acquired pneumonia in children (PIVOT trial): a multicentre pragmatic randomised controlled equivalence trial.

OBJECTIVE: To ascertain whether therapeutic equivalence exists for the treatment of paediatric community acquired pneumonia by the oral and intravenous (IV) routes. METHODS: A multicentre pragmatic randomised controlled non-blinded equivalence trial was undertaken in eight paediatric centres in England (district general and tertiary hospitals). Equivalence was defined as no more than a 20% difference between treatments of the proportion meeting the primary outcome measure at any time. 246 children who required admission to hospital and had fever, respiratory symptoms or signs and radiologically confirmed pneumonia were included in the study. Exclusion criteria were wheeze, oxygen saturations <85% in air, shock requiring >20 ml/kg fluid resuscitation, immunodeficiency, pleural effusion at presentation requiring drainage, chronic lung condition (excluding asthma), penicillin allergy and age <6 months. The patients were randomised to receive oral amoxicillin for 7 days (n = 126) or IV benzyl penicillin (n = 120). Children in the IV group were changed to oral amoxicillin after a median of six IV doses and received 7 days of antibiotics in total. The predefined primary outcome measure was time for the temperature to be <38 degrees C for 24 continuous hours and oxygen requirement to cease. Secondary outcomes were time in hospital, complications, duration of oxygen requirement and time to resolution of illness. RESULTS: Oral amoxicillin and IV benzyl penicillin were shown to be equivalent. Median time for temperature to settle was 1.3 days in both groups (p<0.001 for equivalence). Three children in the oral group were changed to IV antibiotics and seven children in the IV group were changed to different IV antibiotics. Median time to complete resolution of symptoms was 9 days in both groups. CONCLUSION: Oral amoxicillin is effective for most children admitted to hospital with pneumonia (all but those with the most severe disease who were excluded from this study). Prior to this study, the British Thoracic Society guidelines on childhood pneumonia could not draw on evidence to address this issue. This will spare children and their families the trauma and pain of cannulation, and children will spend less time in hospital.

Guideline for the management of the hot swollen joint in adults with a particular focus on septic arthritis.

The British Society for Rheumatology (BSR) Standards, Guidelines and Audit Working Group, in conjunction with the British Society for Antimicrobial Chemotherapy, British Orthopaedic Association, Royal College of General Practitioners and British Health Professionals in Rheumatology, has produced an evidence-based guideline for the management of the hot swollen joint with particular focus on the septic joint. The aim of the guideline is to help accurate diagnosis and appropriate treatment when a joint is hot because of sepsis, while also ensuring that other causes such as crystal arthritis are recognized and not over-treated.