High-Resolution Analysis by Whole-Genome Sequencing of an International Lineage (Sequence Type 111) of Pseudomonas aeruginosa Associated with Metallo-Carbapenemases in the United Kingdom.

Whole-genome sequencing (WGS) was carried out on 87 isolates of sequence type 111 (ST-111) of Pseudomonas aeruginosa collected between 2005 and 2014 from 65 patients and 12 environmental isolates from 24 hospital laboratories across the United Kingdom on an Illumina HiSeq instrument. Most isolates (73) carried VIM-2, but others carried IMP-1 or IMP-13 (5) or NDM-1 (1); one isolate had VIM-2 and IMP-18, and 7 carried no metallo-beta-lactamase (MBL) gene. Single nucleotide polymorphism analysis divided the isolates into distinct clusters; the NDM-1 isolate was an outlier, and the IMP isolates and 6/7 MBL-negative isolates clustered separately from the main set of 73 VIM-2 isolates. Within the VIM-2 set, there were at least 3 distinct clusters, including a tightly clustered set of isolates from 3 hospital laboratories consistent with an outbreak from a single introduction that was quickly brought under control and a much broader set dominated by isolates from a long-running outbreak in a London hospital likely seeded from an environmental source, requiring different control measures; isolates from 7 other hospital laboratories in London and southeast England were also included. Bayesian evolutionary analysis indicated that all the isolates shared a common ancestor dating back ∼50 years (1960s), with the main VIM-2 set separating approximately 20 to 30 years ago. Accessory gene profiling revealed blocks of genes associated with particular clusters, with some having high similarity (≥95%) to bacteriophage genes. WGS of widely found international lineages such as ST-111 provides the necessary resolution to inform epidemiological investigations and intervention policies.

Diagnosis of Clostridium difficile infection by toxin detection kits: a systematic review.

Clostridium difficile can be a fatal hospital-acquired infection and its prevalence has increased. Accurate diagnosis of C difficile is essential for patient management, infection control, and for defining its epidemiology. We did a systematic review of commonly used commercial assays for detection of C difficile toxin (CDT) A and B in stool samples. By comparison of detection of CDT in cell culture with or without selective culture for C difficile, the median sensitivities and specificities (IQR) were as follows: Meridian Premier 0.95 (0.86-0.97) and 0.97 (0.95-0.98), TechLab Tox A/B II 0.83 (0.82-0.85) and 0.99 (0.98-1.00), TechLab Tox A/B Quik Chek 0.84 (0.81-0.87) and 1.00 (0.99-1.00), Remel Xpect 0.82 (0.75-0.89) and 0.96 (0.95-0.98), Meridian Immunocard 0.90 (0.84-0.92) and 0.99 (0.98-1.00), and BioMérieux VIDAS 0.76 and 0.93. If the prevalence of CDT A and B in stool samples is relatively low (<10%), the positive predictive value of these assays is unacceptably low (eg, <50% in some circumstances) and will vary depending on the assay and number of samples tested. This low positive predictive value impinges on clinical management, outbreaks, and makes epidemiological data unreliable. To improve diagnosis, we suggest a two-stage testing strategy for C difficile toxin with an initial highly sensitive rapid screening test to identify positive samples that are then confirmed by a reference method.

Epidemiology of invasive pneumococcal disease in Kumasi, Ghana.

There are few data on the epidemiology of invasive pneumococcal disease in Africa. We undertook a prospective study of these infections in Kumasi, Ghana, collecting clinical data on all patients with laboratory-confirmed pneumococcal meningitis, pneumonia or systemic sepsis associated with bacteraemia. A total of 140 cases were identified in the period from January 2002 to April 2005. The disease was most prevalent among patients <5 years of age and immediately following the peak of the harmattan wind. The majority of patients were treated with a combination of antibiotics, in part reflecting concerns regarding antibiotic resistance. Mortality was high (47%), with no evidence of an improved prognosis compared with earlier studies in the region. Although most isolates of pneumococci were resistant to tetracyclines and co-trimoxazole, there was no high-level resistance to penicillin and only 12% of isolates showed intermediate level resistance. Serotype 1 was the most common serotype (36%), whilst intermediate-level penicillin resistance was associated with serotype 14. Theoretical coverage by existing 7-, 9-, 11- and 23-valent vaccines was 26%, 63%, 64% and 76%, respectively. Vaccination may improve control of pneumococcal disease in Ghana, although modified vaccine formulations are required for local use.

What were the risk factors and trends in antimicrobial resistance for enteric fever in London 2005-2012?

Purpose. A study was undertaken to determine the risk factors and trends in antimicrobial resistance for enteric fever.Methodology. Demographic, antimicrobial susceptibility, typing and epidemiological data were examined for 2005-2012 in patients with enteric fever in London. Single and multivariable logistic regression was used to determine the risk factors associated with antibiotic resistance.Results. 453 cases with Salmonella enterica subsp. enterica serovar Paratyphi A, 17 with S. Paratyphi B and 611 with S. enterica subsp. enterica serovar Typhi were examined. For travellers, 335 (88 %) of S. Paratyphi A isolates were resistant to ciprofloxacin, but resistance to other antimicrobials was low. Almost 80 % (395) of the S. Typhi isolates were resistant to ciprofloxacin, 131 (26 %) to ampicillin, 131 (27 %) to chloramphenicol, 137 (28 %) to trimethoprim and 171 (28 %) to sulphonamide. None of the isolates were resistant to cephalosporins.A trend analysis for S. Typhi isolates showed no significant change in resistance to ampicillin, chloramphenicol, sulphonamide and trimethoprim or for multidrug resistance (P=0.38). Overall resistance to ciprofloxacin increased for S. Paratyphi A (P=0.018) and for S. Typhi (P<0.001) but fell for S. Typhi in 2011-2012. Resistance profiles were reflected by specific phage types and countries visited by the travellers.Conclusions. The proportion of S. Typhi strains resistant to ampicillin, chloramphenicol and cotrimoxazole remained steady for the period 2005-2012. There was a significant increase in a trend for resistance to ciprofloxacin which increased until 2010, followed by a fall in 2011-2012. S. Paratyphi resistance to ciprofloxacin increased until 2012. Specific phage types were associated with resistance to specific antimicrobials and travel abroad.

An extended genotyping framework for Salmonella enterica serovar Typhi, the cause of human typhoid.

The population of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, exhibits limited DNA sequence variation, which complicates efforts to rationally discriminate individual isolates. Here we utilize data from whole-genome sequences (WGS) of nearly 2,000 isolates sourced from over 60 countries to generate a robust genotyping scheme that is phylogenetically informative and compatible with a range of assays. These data show that, with the exception of the rapidly disseminating H58 subclade (now designated genotype 4.3.1), the global S. Typhi population is highly structured and includes dozens of subclades that display geographical restriction. The genotyping approach presented here can be used to interrogate local S. Typhi populations and help identify recent introductions of S. Typhi into new or previously endemic locations, providing information on their likely geographical source. This approach can be used to classify clinical isolates and provides a universal framework for further experimental investigations.

Mapping public engagement with research in a UK University.

Notwithstanding that 'public engagement' is conceptualised differently internationally and in different academic disciplines, higher education institutions largely accept the importance of public engagement with research. However, there is limited evidence on how researchers conceptualise engagement, their views on what constitutes engagement and the communities they would (or would not) like to engage with. This paper presents the results of a survey of researchers in the Open University that sought to gather data to fill these gaps. This research was part of an action research project designed to embed engagement in the routine practices of researchers at all levels. The findings indicate that researchers have a relatively narrow view of public engagement with research and the communities with which they interact. It also identified that very few strategically evaluate their public engagement activities. We conclude by discussing some of the interventions we have introduced with the aim of broadening and deepening future researcher engagement.

East London experience with enteric fever 2007-2012.

PURPOSE: The clinical presentation and epidemiology for patients with enteric fever at two hospitals in East London during 2007-2012 is described with the aim to identify preventive opportunities and to reduce the cost of treatment. METHODS: A retrospective analysis of case notes from patients admitted with enteric fever during 2007 to 2012 with a microbiologically confirmed diagnosis was undertaken. Details on clinical presentation, travel history, demographic data, laboratory parameters, treatment, patient outcome and vaccination status were collected. RESULTS: Clinical case notes were available for 98/129 (76%) patients including 69 Salmonella enterica serovar Typhi (S. Typhi) and 29 Salmonella enterica serovar Paratyphi (S. Paratyphi). Thirty-four patients (35%) were discharged from emergency medicine without a diagnosis of enteric fever and then readmitted after positive blood cultures. Seventy-one of the 98 patients (72%) were UK residents who had travelled abroad, 23 (23%) were foreign visitors/new entrants to the UK and four (4%) had not travelled abroad. Enteric fever was not considered in the initial differential diagnosis for 48/98 (49%) cases. The median length of hospital stay was 7 days (range 0-57 days). The total cost of bed days for managing enteric fever was £454,000 in the two hospitals (mean £75,666/year). Median time to clinical resolution was five days (range 1-20). Seven of 98 (7%) patients were readmitted with relapsed or continued infection. Six of the 71 (8%) patients had received typhoid vaccination, 34 (48%) patients had not received vaccination, and for 31 cases (44%) vaccination status was unknown. CONCLUSIONS: Further interventions regarding education and vaccination of travellers and recognition of the condition by emergency medicine clinicians in travellers to South Asia is required.

Trends in antibiotic susceptibility of enteric fever isolates in East London.

BACKGROUND: The study sought evidence for changes in the proportions of antibiotic resistant strains among isolates of Salmonella enterica serovar Typhi (S. typhi) and Salmonella enterica serovar Paratyphi (S. paratyphi) between 2005 and 2012. METHODS: Blood culture isolates of S. typhi and S. paratyphi from patients attending Newham and The Royal London Hospitals were included in the study. The organisms were cultured on selective media and identified by Maldi-ToF, API 20E and serology. Minimum inhibitory concentrations (MICs) of augmentin, chloramphenicol, co-trimoxazole, ceftriaxone, ciprofloxacin and azithromycin were determined by E tests for 194 isolates. RESULTS: Median MICs of ciprofloxacin and ceftriaxone were stable at 0.5 mg/L and 0.125 mg/L, respectively. Chloramphenicol, azithromycin, co-trimoxazole and augmentin median MICs were 4 mg/L, 8 mg/L, 0.064 mg/L and 0.5 mg/L, respectively. MIC90 values were lower than the resistant breakpoint for ceftriaxone, azithromycin and augmentin, but were >256 mg/L for chloramphenicol, 32 mg/L for co-trimoxazole and 1 mg/L for ciprofloxacin. CONCLUSIONS: Antibiotic resistance remained stable for enteric fever isolates between 2005 and 2012. The isolates remained susceptible to augmentin, ceftriaxone and azithromycin over this period, but the MIC90 was greater than the resistant breakpoint for chloramphenicol, cotrimoxazole and ciprofloxacin. The implications for clinical practice are that isolates of S. typhi and S. paratyphi from East London remain sensitive to ceftriaxone and azithromycin.