Outbreak of invasive group A streptococcus: investigations using agar settle plates detect perineal shedding from a healthcare worker.

BACKGROUND: Outbreaks of group A streptococcus (GAS) infections may occur in healthcare settings. Transmission to patients is sometimes linked to colonized healthcare workers (HCWs) and/or a contaminated environment. AIM: To describe the investigation and control of an outbreak of healthcare-associated GAS on an elderly care medical ward, over six months. METHODS: Four patients developed septicaemia due to GAS infection without a clinically obvious site of infection. The outbreak team undertook an investigation involving a retrospective review of GAS cases, prospective case finding, HCW screening and environmental sampling using both swabs and settle plates. Immediate control measures included source isolation and additional cleaning of the ward environment with a chlorine disinfectant and hydrogen peroxide. FINDINGS: Prospective patient screening identified one additional patient with throat GAS carriage. Settle plate positivity for GAS was strongly associated with the presence of one individual HCW on the ward, who was subsequently found to have GAS perineal carriage. Contamination of a fabric-upholstered chair in an office adjacent to the ward, used by the HCW, was also detected. In total, three asymptomatic HCWs had throat GAS carriage and one HCW had both perineal and throat carriage. All isolates were typed as emm 28. CONCLUSION: This is the first outbreak report demonstrating the use of settle plates in a GAS outbreak investigation on a medical ward, to identify the likely source of the outbreak. Based on this report we recommend that both throat and perineal sites should be sampled if HCW screening is undertaken during an outbreak of GAS. Fabric, soft furnishings should be excluded from clinical areas as well as any adjacent offices because pathogenic bacteria such as GAS may contaminate this environment.

Surveillance of infection associated with external ventricular drains: proposed methodology and results from a pilot study.

BACKGROUND: The insertion of external ventricular drains (EVDs) is necessary in some neurosurgical patients, but increases the risk of meningitis/ventriculitis. While there are well-recognized risk factors, the proportion of patients who develop meningitis/ventriculitis varies partly due to differences in definitions. A multi-disciplinary working group was established to agree definitions for EVD-associated meningitis/ventriculitis, and a surveillance system was piloted in four centres in the UK and Ireland. METHODS: Definitions were agreed based on those published previously and on clinical and microbiological criteria. An agreed dataset was developed to monitor patients after the insertion of an EVD and until the EVD was removed and the microbial aetiology was recorded. FINDINGS: Four neurosurgical centres participated, with 61-564 patients surveyed in each unit. The vast majority of drains were cranial. Intracranial haemorrhage was the most common indication for the EVD insertion. Between 6% and 35% of EVDs were inserted by consultants rather than junior doctors. The proportion of patients who developed meningitis/ventriculitis varied from 3% to 18% and from 4.8 to 12.7/1000 EVD-days. Coagulase-negative staphylococci were the most common microbial causes. CONCLUSIONS: Routine and ongoing monitoring of patients with an EVD in situ to detect meningitis/ventriculitis presents logistical difficulties, and few units do so. This pilot study suggests that a national system of surveillance with agreed definitions and a methodology to enable unit-to-unit comparisons of EVD meningitis/ventriculitis is both necessary and feasible. This will, in turn, inform quality improvement processes leading to the minimization of infection.

Exploring Staff Clinical Knowledge and Practice with LGBT Residents in Long-Term Care: A Grounded Theory of Cultural Competency and Training Needs.

OBJECTIVES: Existing literature shows that LGBT residents are likely to face suboptimal care in LTC facilities due to prejudice and discriminatory policies. The aim of this project was to assess the LGBT cultural competency of staff working in LTC facilities, identify their current training needs, and develop a framework for understanding LGBT cultural competency among LTC staff and providers. METHODS: This grounded theory study comprised data from focus groups of interdisciplinary staff from three LTC facilities. RESULTS: Results suggested that LTC staff struggle with how to be sensitive to LGBT residents' needs. Tension appeared to exist between wanting to provide an equal standard of care to all LTC residents and fearing they would show "favoritism" or "special treatment," which might be viewed as unprofessional. Participants indicated training could help to address the ambivalence they experience about providing sensitive care to subpopulations of residents who face stigma and oppression. CONCLUSIONS: LTC staff stand to benefit from cultural competency training focused on LGBT residents. Training should be not only informational in nature, but also facilitate greater self-awareness and self-efficacy with respect to providing care to LGBT people.

The dual-acting chemotherapeutic agent Alchemix induces cell death independently of ATM and p53.

Topoisomerase inhibitors are in common use as chemotherapeutic agents although they can display reduced efficacy in chemotherapy-resistant tumours, which have inactivated DNA damage response (DDR) genes, such as ATM and TP53. Here, we characterise the cellular response to the dual-acting agent, Alchemix (ALX), which is a modified anthraquinone that functions as a topoisomerase inhibitor as well as an alkylating agent. We show that ALX induces a robust DDR at nano-molar concentrations and this is mediated primarily through ATR- and DNA-PK- but not ATM-dependent pathways, despite DNA double strand breaks being generated after prolonged exposure to the drug. Interestingly, exposure of epithelial tumour cell lines to ALX in vitro resulted in potent activation of the G2/M checkpoint, which after a prolonged arrest, was bypassed allowing cells to progress into mitosis where they ultimately died by mitotic catastrophe. We also observed effective killing of lymphoid tumour cell lines in vitro following exposure to ALX, although, in contrast, this tended to occur via activation of a p53-independent apoptotic pathway. Lastly, we validate the effectiveness of ALX as a chemotherapeutic agent in vivo by demonstrating its ability to cause a significant reduction in tumour cell growth, irrespective of TP53 status, using a mouse leukaemia xenograft model. Taken together, these data demonstrate that ALX, through its dual action as an alkylating agent and topoisomerase inhibitor, represents a novel anti-cancer agent that could be potentially used clinically to treat refractory or relapsed tumours, particularly those harbouring mutations in DDR genes.

BET inhibition as a single or combined therapeutic approach in primary paediatric B-precursor acute lymphoblastic leukaemia.

Paediatric B-precursor ALL is a highly curable disease, however, treatment resistance in some patients and the long-term toxic effects of current therapies pose the need for more targeted therapeutic approaches. We addressed the cytotoxic effect of JQ1, a highly selective inhibitor against the transcriptional regulators, bromodomain and extra-terminal (BET) family of proteins, in paediatric ALL. We showed a potent in vitro cytotoxic response of a panel of primary ALL to JQ1, independent of their prognostic features but dependent on high MYC expression and coupled with transcriptional downregulation of multiple pro-survival pathways. In agreement with earlier studies, JQ1 induced cell cycle arrest. Here we show that BET inhibition also reduced c-Myc protein stability and suppressed progression of DNA replication forks in ALL cells. Consistent with c-Myc depletion and downregulation of pro-survival pathways JQ1 sensitised primary ALL samples to the classic ALL therapeutic agent dexamethasone. Finally, we demonstrated that JQ1 reduces ALL growth in ALL xenograft models, both as a single agent and in combination with dexamethasone. We conclude that targeting BET proteins should be considered as a new therapeutic strategy for the treatment of paediatric ALL and particularly those cases that exhibit suboptimal responses to standard treatment.

Genomic analysis of extra-intestinal pathogenic Escherichia coli urosepsis.

Urosepsis is a bacteraemia infection caused by an organism previously causing an infection in the urinary tract of a patient, a diagnosis which has been classically confirmed by culture of the same species of bacteria from both blood and urine samples. Given the new insights afforded by sequencing technologies into the complicated population structures of infectious agents affecting humans, we sought to investigate urosepsis by comparing the genome sequences of blood and urine isolates of Escherichia coli from five patients with urosepsis. The results confirm the classical urosepsis hypothesis in four of the five cases, but also show the complex nature of extra-intestinal E. coli infection in the fifth case, where three distinct strains caused two distinct infections. Additionally, we show there is little to no variation in the bacterial genome as it progressed from urine to blood, and also present a minimal set of virulence genes required for bacteraemia in E. coli based on gene association. These suggest that most E. coli have the genetic propensity to cause bacteraemia.

Audit of treatment of Staphylococcus aureus bacteraemia.

Staphylococcus aureus bacteraemia remains a significant cause of morbidity and mortality. National guidelines recommend that a minimum of 14 days of antibiotics should be used to treat uncomplicated bacteraemia. Five hospitals in the East Midlands region conducted a retrospective audit to assess compliance to these guidelines before and after the introduction of extra text to laboratory reports of S. aureus bacteraemia advising clinicians on the minimum length of treatment. Introduction of this extra text resulted in an increase in compliance with the national recommendation from 44% to 60%. This increase in compliance was noted in both methicillin-sensitive S. aureus (45% versus 58%) and methicillin-resistant S. aureus (42% versus 62%) bacteraemia. This audit demonstrated a simple and effective intervention that has improved the treatment of this potentially life-threatening condition.

Oral versus i.v. antibiotics for community-acquired pneumonia in children: a cost-minimisation analysis.

Community-acquired pneumonia represents a high financial burden to healthcare providers. This manuscript seeks to estimate and compare the costs of treating children hospitalised with community-acquired pneumonia, with oral and intravenous antibiotics, thus determining which treatment is cost minimising. A cost-minimisation analysis was undertaken alongside a randomised controlled non-blinded equivalence trial. 232 children (from eight paediatric centres in England) diagnosed with pneumonia, who required admission to hospital, were randomised to receive oral amoxicillin or i.v. benzyl penicillin. The analysis considered the cost to the health service, patients and society, from pre-admission until the child was fully recovered. Oral amoxicillin and i.v. benzyl penicillin have equivalent efficacy. Children treated with i.v. antibiotics were found to have significantly longer in-patient stays (3.12 versus 1.93 days; p<0.001). i.v. treatment was found to be more expensive than oral treatment ( pound1,256 versus pound769; difference pound488; 95% CI: pound233- pound750), such that treatment of community-acquired pneumonia with oral amoxicillin would result in savings of between pound473 and pound518 per child (euro545 and euro596 per child) admitted. The findings demonstrate that oral amoxicillin is a cost-effective treatment for the majority of children admitted to hospital with pneumonia.

Defunctioning stomas in patients with locally advanced rectal cancer prior to preoperative chemoradiotherapy.

OBJECTIVE: A literature search did not produce any evidence-based objective criteria to determine which patients with locally advanced rectal cancer would benefit from a defunctioning stoma prior to neoadjuvant chemoradiotherapy. Our criteria for formation of a defunctioning stoma are: faecal incontinence and inability to cannulate the tumour at colonoscopy. The aim of this study was to examine whether these current criteria are appropriate. METHOD: Forty-nine consecutive locally advanced rectal cancer patients treated from February 2003 to November 2006 were identified from our colorectal database. All received long-course chemoradiotherapy (Bossett regimen) and definitive surgery was performed 6-8 weeks later. RESULTS: Of the 49 patients, 31 presented with diarrhoea and two with faecal incontinence; nine patients were defunctioned by trephine stoma prior to treatment [cannulation impossible at colonoscopy (n = 8); faecal incontinence (n = 1)]. One patient with faecal incontinence refused early defunctioning stoma. Median hospital stay was 12 days (interquartile range: 7-30), and complications included pneumonia (n = 1) and peristomal cellulitis (n = 2). Of the 40 patients who went directly to neoadjuvant chemoradiotherapy, two subsequently required a defunctioning stoma for severe diarrhoeal symptoms during therapy. Eight patients had worsening diarrhoeal symptoms but tolerated treatment. Three patients, who had stoma formation, did not proceed to definitive surgery following neoadjuvant therapy: poor operative fitness (n = 2) and disease progression (n = 1). CONCLUSION: Stenosis causing inability to cannulate the tumour at colonoscopy and faecal incontinence were the only objective indications for an early defunctioning stoma. Worsening diarrhoea during therapy (unless severe) did not appear to be a good indication for a defunctioning stoma.

Management of septic arthritis: a systematic review.

OBJECTIVE: To evaluate the existing evidence on the diagnosis and management of septic arthritis in native joints. DESIGN: Systematic review. DATA SOURCES: Cochrane Library, Medline, Embase, National Electronic Library for Health, reference lists, national experts. REVIEW METHODS: Systematic review of the literature with evaluation of the methodological quality of the selected papers using defined criteria set out by the Clinical Effectiveness and Evaluation Unit of the Royal College of Physicians. RESULTS: 3291 citations were initially identified. Of these, 189 full text articles were identified for potential selection. Following review of these full text articles, 80 articles were found to fulfil the inclusion criteria and were included in the final list. Conclusions were drawn on the diagnosis, investigation and management of septic arthritis. DISCUSSION: Little good quality evidence exists to guide the diagnosis and management of septic arthritis. Overall, no investigation is more reliable in the diagnosis of septic arthritis than the opinion of an experienced doctor. Aspiration and culture of synovial fluid is crucial to the diagnosis, but measurement of cell count is unhelpful. Antibiotics are clearly required for a prolonged period, but there are no data to indicate by which route or for how long. Key unanswered questions remain surrounding the medical and surgical management of the infected joint.

Management of septic arthritis: a systematic review.

OBJECTIVE: To evaluate the existing evidence on the diagnosis and management of septic arthritis in native joints. DESIGN: Systematic review. DATA SOURCES: Cochrane Library, Medline, Embase, National Electronic Library for Health, reference lists, national experts. REVIEW METHODS: Systematic review of the literature with evaluation of the methodological quality of the selected papers using defined criteria set out by the Clinical Effectiveness and Evaluation Unit of the Royal College of Physicians. RESULTS: 3291 citations were initially identified. Of these, 189 full text articles were identified for potential selection. Following review of these full text articles, 80 articles were found to fulfil the inclusion criteria and were included in the final list. CONCLUSIONS: were drawn on the diagnosis, investigation and management of septic arthritis. DISCUSSION: Little good quality evidence exists to guide the diagnosis and management of septic arthritis. Overall, no investigation is more reliable in the diagnosis of septic arthritis than the opinion of an experienced doctor. Aspiration and culture of synovial fluid is crucial to the diagnosis, but measurement of cell count is unhelpful. Antibiotics are clearly required for a prolonged period, but there are no data to indicate by which route or for how long. Key unanswered questions remain surrounding the medical and surgical management of the infected joint.

Evaluation of the sensitivity of a rapid polymerase chain reaction for detection of group B streptococcus.

The objective of this study was to compare detection of group B streptococcal (GBS) carriage using 'real-time' polymerase chain reaction (PCR) and microbiological standard culture. The study design was a test accuracy study comparing a novel molecular technique against the standard microbiological cultural technique in normal pregnant women. The setting and population consisted of 143 pregnant women with pre-labour rupture of the membranes, recruited from two large teaching hospitals in the UK. The study examined the efficacy of a polymerase chain reaction (PCR) assay for screening pregnant women who presented with term rupture of the membranes. Low vaginal specimens were obtained from the women. The specimens were tested for GBS by conventional culture and with a GBS-specific real-time PCR assay. The main outcome measure was the sensitivity and specificity of the PCR assay with 95% confidence intervals (CI) compared with the standard culture. The length of time to obtain a result was also reported for both methods. Among the 143 women, the results of the culture were positive (at least one colony) for GBS in 20 women (14%). The PCR assay detected GBS carriage in 10 women (7%). As compared with the culture method, the sensitivity and specificity of the PCR assay were 45% and 99%, respectively. The positive and negative predictive values of the PCR assay were 90% and 92%, respectively. The length of time required to obtain results for the majority of women (94%) was <2.5 h for the PCR assay and at least 24 h for culture. While a rapid result (within 3 h) of carriage of GBS can be obtained by the PCR assay, at present, it cannot replace conventional culture without further optimisation of the DNA extraction method. The sensitivity may further be improved by testing both low vaginal and rectal specimens.