Nosocomial acquisition of influenza is associated with significant morbidity and mortality: Results of a prospective observational study.

BACKGROUND: Nosocomial acquisition of influenza is known to occur but the risk after exposure to a known case and the outcomes after acquisition are poorly defined. METHODS: Prospective observational study of patients exposed to influenza from another patient in a multi-site healthcare organisation, with follow-up of 7 days or until discharge, and PCR-confirmation of symptomatic disease. Multivariable analysis was used to investigate association of influenza acquisition with high dependency unit/intensive care unit (HDU/ITU) admission and in-hospital mortality. RESULTS: 23/298 (7.7%) contacts of 11 cases were subsequently symptomatic and tested influenza-positive during follow-up. HDU/ITU admission was significantly higher in these secondary cases (6/23, 26%) compared to flu-negative contacts (20/275, 7.2%; p = 0.002). In-hospital mortality was significantly higher in secondary cases (5/23, 21.7%) compared to flu-negative contacts (11/275, 4%; p < 0.001). In multivariable analysis, age (OR 1.25 95% CI: 1.01-1.54, p = 0.02) and being a secondary case (OR 4.77, 95% CI: 1.63-13.9, p = 0.008) were significantly associated with HDU/ITU admission in contacts. Age (OR 1.00, 95% CI: 0.93-1.00, p = 0.02), being a secondary case after exposure to influenza (OR 3.81, 95% CI 1.09-13.3, p = 0.049) and co-morbidity (OR 1.29 per unit increment in the Charlson score, 95% CI 1.02-1.61, p = 0.03) were significantly associated with in-hospital mortality in contacts. CONCLUSIONS: Nosocomial acquisition of influenza was significantly associated with increased risk of HDU/ITU admission and in-hospital mortality.

A multisite evaluation of antifungal use in critical care: implications for antifungal stewardship.

Background: ICUs are settings of high antifungal consumption. There are few data on prescribing practices in ICUs to guide antifungal stewardship implementation in this setting. Methods: An antifungal therapy (AFT) service evaluation (15 May-19 November 2019) across ICUs at three London hospitals, evaluating consumption, prescribing rationale, post-prescription review, de-escalation and final invasive fungal infection (IFI) diagnostic classification. Results: Overall, 6.4% of ICU admissions (305/4781) received AFT, accounting for 11.41 days of therapy/100 occupied bed days (DOT/100 OBD). The dominant prescribing mode was empirical (41% of consumption), followed by targeted (22%), prophylaxis (18%), pre-emptive (12%) and non-invasive (7%). Echinocandins were the most commonly prescribed drug class (4.59 DOT/100 OBD). In total, 217 patients received AFT for suspected or confirmed IFI; 12%, 10% and 23% were classified as possible, probable or proven IFI, respectively. Hence, in 55%, IFI was unlikely. Proven IFI (n = 50) was mostly invasive candidiasis (92%), of which 48% had been initiated on AFT empirically before yeast identification. Where on-site (1 → 3)-ß-d-glucan (BDG) testing was available (1 day turnaround), in those with suspected but unproven invasive candidiasis, median (IQR) AFT duration was 10 (7-15) days with a positive BDG (≥80 pg/mL) versus 8 (5-9) days with a negative BDG (<80 pg/mL). Post-prescription review occurred in 79% of prescribing episodes (median time to review 1 [0-3] day). Where suspected IFI was not confirmed, 38% episodes were stopped and 4% de-escalated within 5 days. Conclusions: Achieving a better balance between promptly treating IFI patients and avoiding inappropriate antifungal prescribing in the ICU requires timely post-prescription review by specialist multidisciplinary teams and improved, evidence-based-risk prescribing strategies incorporating rapid diagnostics to guide AFT start and stop decisions.

Real-world deployment of lateral flow SARS-CoV-2 antigen detection in the emergency department to provide rapid, accurate and safe diagnosis of COVID-19.

BACKGROUND: Point-of-care (POC) SARS-CoV-2 lateral-flow antigen detection (LFD) testing in the emergency department (ED) could inform rapid infection control decisions but requirements for safe deployment have not been fully defined. METHODS: Review of LFD test results, laboratory and POC-RT-PCR results and ED-performance metrics during a two-week high SARS-CoV-2 prevalence period followed by several months of falling prevalence. AIM: Determine whether LFD testing can be safely deployed in ED to provide an effective universal SARS-CoV-2 testing capability. FINDINGS: 93% (345/371) of COVID-19 patients left ED with a virological diagnosis during the 2-week universal LFD evaluation period compared to 77% with targeted POC-RT-PCR deployment alone, on background of approximately one-third having an NHS Track and Trace RT-PCR test-result at presentation. LFD sensitivity and specificity was 70.7% and 99.1% respectively providing a PPV of 97.7% and NPV of 86.4% with disease prevalence of 34.7%. ED discharge-delays (breaches) attributable to COVID-19 fell to 33/3532 (0.94%) compared with the preceding POC-RT-PCR period (107/4114 (2.6%); p=<0.0001). Importantly, LFD testing identified 1 or 2 clinically-unsuspected COVID-19 patients/day. Three clinically-confirmed LFD false positive patients were appropriately triaged based on LFD action-card flowchart, and only 5 of 95 false-negative LFD results were inappropriately admitted to non-COVID-19 areas where no onward-transmission was identified. LFD testing was restricted to asymptomatic patients when disease prevalence fell below 5% and detected 1-3 cases/week. CONCLUSION: Universal SARS-CoV-2 LFD testing can be safely and effectively deployed in ED alongside POC-RT-PCR testing during periods of high and low disease prevalence.

Acquisition of MDR-GNB in hospital settings: a systematic review and meta-analysis focusing on ESBL-E.

INTRODUCTION: Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) and other multi-drug-resistant Gram-negative bacteria (MDR-GNB) have disseminated globally since their discovery in the late 20th century. Various infection prevention and control measures are in place to prevent nosocomial transmission of these organisms, but their efficacy remains disputed. New literature has emerged in recent years providing further evidence which can be used to formulate effective strategies to tackle this issue in the future. METHODS: A systematic review was performed to characterize the prevalence of colonization of multi-drug-resistant organisms and subsequent acquisition of these organisms within hospital settings. A meta-analysis was performed to characterize the prevalence and acquisition of ESBL-E in Europe and North America. RESULTS: Twenty-eight studies fulfilled the inclusion criteria. Escherichia coli formed the main burden of MDR-GNB colonization worldwide. Patient-to-patient transmission of ESBL-E was found to be rare, but increased transmissibility of Klebsiella pneumoniae was described over E. coli. Within European and North American healthcare settings, a meta-analysis of eight studies identified a pooled prevalence of ESBL-E on admission to hospital of 7.91% and an acquisition rate of 3.73%. DISCUSSION: Low prevalence at the point of hospital admission and insufficient evidence of patient-to-patient transmission suggests that infection prevention and control measures such as universal surveillance screening and single-room isolation are unlikely to be practical or effective interventions in reducing the overall burden of ESBL-E in hospitals, in line with current European guidelines. Instead, it is argued that efforts should be placed on controlling the spread of these organisms and other MDR-GNB in the community, predominantly long-term care facilities.

Individual- and community-level risk factors for ESBL Enterobacteriaceae colonization identified by universal admission screening in London.

OBJECTIVES: We evaluated risk factors for gastrointestinal carriage of Enterobacteriaceae which produce extended-spectrum ß-lactamases (ESBL-E), including individual-level variables such as antibiotic use and foreign travel, and community-level variables such as housing and deprivation. METHODS: In an observational study in 2015, all patients admitted to a London hospital group were approached to be screened for ESBL-E carriage using rectal swabs for 4 months. Patients completed a risk factor questionnaire. Those with a residential postcode in the local catchment area were linked to a database containing community-level risk factor data. Risk factors for ESBL-E carriage were determined by binary logistic regression. RESULTS: Of 4006 patients, 360 (9.0%) carried ESBL-E. Escherichia coli was the most common organism (77.8%), and CTX-M-type ESBLs were the most common genes (57.9% CTX-M-15 and 20.7% CTX-M-9). In multivariable analysis, risk factors for phenotypic ESBL-E among the 1633 patients with a residential postcode within the local catchment area were: travel to Asia (OR 4.4, CI 2.5-7.6) or Africa (OR 2.4, CI 1.2-4.8) in the 12 months prior to admission, two or more courses of antibiotics in the 6 months prior to admission (OR 2.0, CI 1.3-3.0), and residence in a district with a higher-than-average prevalence of overcrowded households (OR 1.5, CI 1.05-2.2). . CONCLUSIONS: Both individual and community variables were associated with ESBL-E carriage at hospital admission. The novel observation that household overcrowding is associated with ESBL-E carriage requires confirmation, but raises the possibility that targeted interventions in the community could help prevent transmission of antibiotic-resistant Gram-negative bacteria.

Intensive care unit (ICU)-acquired bacteraemia and ICU mortality and discharge: addressing time-varying confounding using appropriate methodology.

BACKGROUND: Studies often ignore time-varying confounding or may use inappropriate methodology to adjust for time-varying confounding. AIM: To estimate the effect of intensive care unit (ICU)-acquired bacteraemia on ICU mortality and discharge using appropriate methodology. METHODS: Marginal structural models with inverse probability weighting were used to estimate the ICU mortality and discharge associated with ICU-acquired bacteraemia among patients who stayed more than two days at the general ICU of a London teaching hospital and remained bacteraemia-free during those first two days. For comparison, the same associations were evaluated with (i) a conventional Cox model, adjusting only for baseline confounders and (ii) a Cox model adjusting for baseline and time-varying confounders. FINDINGS: Using the marginal structural model with inverse probability weighting, bacteraemia was associated with an increase in ICU mortality (cause-specific hazard ratio (CSHR): 1.29; 95% confidence interval (CI): 1.02-1.63) and a decrease in discharge (CSHR: 0.52; 95% CI: 0.45-0.60). By 60 days, among patients still in the ICU after two days and without prior bacteraemia, 8.0% of ICU deaths could be prevented by preventing all ICU-acquired bacteraemia cases. The conventional Cox model adjusting for time-varying confounders gave substantially different results [for ICU mortality, CSHR: 1.08 (95% CI: 0.88-1.32); for discharge, CSHR: 0.68 (95% CI: 0.60-0.77)]. CONCLUSION: In this study, even after adjusting for the timing of acquiring bacteraemia and time-varying confounding using inverse probability weighting for marginal structural models, ICU-acquired bacteraemia was associated with a decreased daily ICU discharge risk and an increased risk of ICU mortality.

Does appropriate empiric antibiotic therapy modify intensive care unit-acquired Enterobacteriaceae bacteraemia mortality and discharge?

BACKGROUND: Conflicting results have been found regarding outcomes of intensive care unit (ICU)-acquired Enterobacteriaceae bacteraemia and the potentially modifying effect of appropriate empiric antibiotic therapy. AIM: To evaluate these associations while adjusting for potential time-varying confounding using methods from the causal inference literature. METHODS: Patients who stayed more than two days in two general ICUs in England between 2002 and 2006 were included in this cohort study. Marginal structural models with inverse probability weighting were used to estimate the mortality and discharge associated with Enterobacteriaceae bacteraemia and the impact of appropriate empiric antibiotic therapy on these outcomes. FINDINGS: Among 3411 ICU admissions, 195 (5.7%) ICU-acquired Enterobacteriaceae bacteraemia cases occurred. Enterobacteriaceae bacteraemia was associated with an increased daily risk of ICU death [cause-specific hazard ratio (HR): 1.48; 95% confidence interval (CI): 1.10-1.99] and a reduced daily risk of ICU discharge (HR: 0.66; 95% CI: 0.54-0.80). Appropriate empiric antibiotic therapy did not significantly modify ICU mortality (HR: 1.08; 95% CI: 0.59-1.97) or discharge (HR: 0.91; 95% CI: 0.63-1.32). CONCLUSION: ICU-acquired Enterobacteriaceae bacteraemia was associated with an increased daily risk of ICU mortality. Furthermore, the daily discharge rate was also lower after acquiring infection, even when adjusting for time-varying confounding using appropriate methodology. No evidence was found for a beneficial modifying effect of appropriate empiric antibiotic therapy on ICU mortality and discharge.

Efficacy and acceptability of rectal and perineal sampling for identifying gastrointestinal colonization with extended spectrum ß-lactamase Enterobacteriaceae.

OBJECTIVES: We evaluated 'pre-laboratory' factors associated with the detection of extended spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) colonization including anatomical site, and staff and patient factors. METHODS: All admissions to a large London hospital over 3 months were approached to provide rectal and perineal swabs, which were cultured for ESBL-E using chromogenic media. ESBL-E detection rates for patient- or staff-collected rectal or perineal swabs were compared using McNemar tests. Binary logistic regression was used to explore factors associated with patients declining to provide a rectal swab. The impact of simplifying the verbal study description to patients to improve the participation rate was evaluated. RESULTS: Carriage of ESBL-E was significantly higher in rectal swabs than perineal swabs (7.8% of 4006 versus 3.8% of 4006, p <0.001), whether collected by staff or patients; 31.9% of 869 patients did not provide a rectal swab before the change in study description compared with 7.6% of 3690 patients afterwards (p <0.001). In multivariable analysis, factors associated with patients declining to provide a rectal swab were younger age (OR 0.99, 95% CI 0.99-1.00), female gender (OR 1.26, 95% CI 1.04-1.52), transfers from other hospitals (OR 1.77, 95% CI 1.07-2.93) or an unknown admission route (OR 1.61, 95% CI 1.09-2.37), being admitted before the change in study description (OR 0.39, 95% CI 0.31-0.48), and the staff member who consented the patient (p <0.001); ethnicity was not a significant factor. CONCLUSIONS: Rectal swabs are recommended for the detection of ESBL-E colonization. Staff and patient factors influence whether patients participate in prevalence studies, which may skew their findings.

Gram-negative bacteraemia; a multi-centre prospective evaluation of empiric antibiotic therapy and outcome in English acute hospitals.

Increasing antibiotic resistance makes choosing antibiotics for suspected Gram-negative infection challenging. This study set out to identify key determinants of mortality among patients with Gram-negative bacteraemia, focusing particularly on the importance of appropriate empiric antibiotic treatment. We conducted a prospective observational study of 679 unselected adults with Gram-negative bacteraemia at ten acute english hospitals between October 2013 and March 2014. Appropriate empiric antibiotic treatment was defined as intravenous treatment on the day of blood culture collection with an antibiotic to which the cultured organism was sensitive in vitro. Mortality analyses were adjusted for patient demographics, co-morbidities and illness severity. The majority of bacteraemias were community-onset (70%); most were caused by Escherichia coli (65%), Klebsiella spp. (15%) or Pseudomonas spp. (7%). Main foci of infection were urinary tract (51%), abdomen/biliary tract (20%) and lower respiratory tract (14%). The main antibiotics used were co-amoxiclav (32%) and piperacillin-tazobactam (30%) with 34% receiving combination therapy (predominantly aminoglycosides). Empiric treatment was inappropriate in 34%. All-cause mortality was 8% at 7 days and 15% at 30 days. Independent predictors of mortality (p <0.05) included older age, greater burden of co-morbid disease, severity of illness at presentation and inflammatory response. Inappropriate empiric antibiotic therapy was not associated with mortality at either time-point (adjusted OR 0.82; 95% CI 0.35-1.94 and adjusted OR 0.92; 95% CI 0.50-1.66, respectively). Although our study does not exclude an impact of empiric antibiotic choice on survival in Gram-negative bacteraemia, outcome is determined primarily by patient and disease factors.

Expression of CD11c and EMR2 on neutrophils: potential diagnostic biomarkers for sepsis and systemic inflammation.

There is a need for cellular biomarkers to differentiate patients with sepsis from those with the non-infectious systemic inflammatory response syndrome (SIRS). In this double-blind study we determined whether the expression of known (CD11a/b/c, CD62L) and putative adhesion molecules [CD64, CD97 and epidermal growth factor (EGF)-like molecule containing mucin-like hormone receptor (EMR2)] on blood neutrophils could serve as useful biomarkers of infection and of non-infectious SIRS in critically ill patients. We studied 103 patients with SIRS, 83 of whom had sepsis, and 50 healthy normal subjects, using flow cytometry to characterize neutrophils phenotypically in whole blood samples. Patients with SIRS had an increased prevalence of neutrophils expressing CD11c, CD64 and EMR2 in comparison with healthy subjects (P < 0.001), but normal expression of CD11a, CD11b, CD62L and CD97. An increase in the percentage of neutrophils bearing CD11c was associated with sepsis, EMR2 with SIRS and CD64 with sepsis and SIRS. Neutrophils expressing CD11c had the highest sensitivity (81%) and specificity (80%) for the detection of sepsis, and there was an association between the percentage of neutrophils expressing EMR2 and the extent of organ failure (P < 0.05). Contrary to other reports, we did not observe an abnormal expression of CD11b or CD62L on neutrophils from patients with SIRS, and suggest that this discrepancy is due to differences in cell processing protocols. We propose that blood neutrophils expressing CD11c and EMR2 be considered as potential biomarkers for sepsis and SIRS, respectively.

Surface-attached cells, biofilms and biocide susceptibility: implications for hospital cleaning and disinfection.

Microbes tend to attach to available surfaces and readily form biofilms, which is problematic in healthcare settings. Biofilms are traditionally associated with wet or damp surfaces such as indwelling medical devices and tubing on medical equipment. However, microbes can survive for extended periods in a desiccated state on dry hospital surfaces, and biofilms have recently been discovered on dry hospital surfaces. Microbes attached to surfaces and in biofilms are less susceptible to biocides, antibiotics and physical stress. Thus, surface attachment and/or biofilm formation may explain how vegetative bacteria can survive on surfaces for weeks to months (or more), interfere with attempts to recover microbes through environmental sampling, and provide a mixed bacterial population for the horizontal transfer of resistance genes. The capacity of existing detergent formulations and disinfectants to disrupt biofilms may have an important and previously unrecognized role in determining their effectiveness in the field, which should be reflected in testing standards. There is a need for further research to elucidate the nature and physiology of microbes on dry hospital surfaces, specifically the prevalence and composition of biofilms. This will inform new approaches to hospital cleaning and disinfection, including novel surfaces that reduce microbial attachment and improve microbial detachment, and methods to augment the activity of biocides against surface-attached microbes such as bacteriophages and antimicrobial peptides. Future strategies to address environmental contamination on hospital surfaces should consider the presence of microbes attached to surfaces, including biofilms.

Implications of targeted versus universal admission screening for meticillin-resistant Staphylococcus aureus carriage in a London hospital.

Universal admission screening for meticillin-resistant Staphylococcus aureus (MRSA) has been performed in England since 2010. We evaluated the predictive performance of a regression model derived from the first year of universal screening for detecting MRSA at hospital admission. If we had used our previous targeted screening policy, 75% fewer patients (21,699 per year) would have been screened. However, this would have identified only ~55% of all MRSA carriers, 65% of healthcare-associated MRSA strains, and 40% of community-associated strains. Failing to identify ~45% of patients (262 per year) carrying MRSA at hospital admission may have implications for MRSA control.

Multiplex molecular testing for management of infectious gastroenteritis in a hospital setting: a comparative diagnostic and clinical utility study.

Laboratory diagnosis and clinical management of inpatients with diarrhoea is complex and time consuming. Tests are often requested sequentially and undertaken in different laboratories. This causes prolonged unnecessary presumptive isolation of patients, because most cases are non-infectious. A molecular multiplex test (Luminex(®) Gastrointestinal Pathogen Panel (GPP)) was compared with conventional testing over 8 months to determine diagnostic accuracy, turnaround times, laboratory costs, use of isolation facilities and user acceptability. A total of 262 (12%) patients had a pathogen detected by conventional methods compared with 483 (22.1%) by GPP. Most additional cases were detected in patients developing symptoms in the first 4 days of admission. Additional cases were detected because of presumed improved diagnostic sensitivity but also because clinicians had not requested the correct pathogen. Turnaround time (41.8 h) was faster than bacterial culture (66.5 h) and parasite investigation (66.5 h) but slower than conventional testing for Clostridium difficile (17.3 h) and viruses (27 h). The test could allow simplified requesting by clinicians and a consolidated laboratory workflow, reducing the overall number of specimens received by the laboratory. A total of 154 isolation days were saved at an estimated cost of £30 800. Consumables and labour were estimated at £150 641 compared with £63 431 for conventional testing. Multiplex molecular testing using a panel of targets allowed enhanced detection and a consolidated laboratory workflow. This is likely to be of greater benefit to cases that present within the first 4 days of hospital admission.

Development and validation of a risk model for identification of non-neutropenic, critically ill adult patients at high risk of invasive Candida infection: the Fungal Infection Risk Evaluation (FIRE) Study.

BACKGROUND: There is increasing evidence that invasive fungal disease (IFD) is more likely to occur in non-neutropenic patients in critical care units. A number of randomised controlled trials (RCTs) have evaluated antifungal prophylaxis in non-neutropenic, critically ill patients, demonstrating a reduction in the risk of proven IFD and suggesting a reduction in mortality. It is necessary to establish a method to identify and target antifungal prophylaxis at those patients at highest risk of IFD, who stand to benefit most from any antifungal prophylaxis strategy. OBJECTIVES: To develop and validate risk models to identify non-neutropenic, critically ill adult patients at high risk of invasive Candida infection, who would benefit from antifungal prophylaxis, and to assess the cost-effectiveness of targeting antifungal prophylaxis to high-risk patients based on these models. DESIGN: Systematic review, prospective data collection, statistical modelling, economic decision modelling and value of information analysis. SETTING: Ninety-six UK adult general critical care units. PARTICIPANTS: Consecutive admissions to participating critical care units. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Invasive fungal disease, defined as a blood culture or sample from a normally sterile site showing yeast/mould cells in a microbiological or histopathological report. For statistical and economic modelling, the primary outcome was invasive Candida infection, defined as IFD-positive for Candida species. RESULTS: Systematic review: Thirteen articles exploring risk factors, risk models or clinical decision rules for IFD in critically ill adult patients were identified. Risk factors reported to be significantly associated with IFD were included in the final data set for the prospective data collection. DATA COLLECTION: Data were collected on 60,778 admissions between July 2009 and March 2011. Overall, 383 patients (0.6%) were admitted with or developed IFD. The majority of IFD patients (94%) were positive for Candida species. The most common site of infection was blood (55%). The incidence of IFD identified in unit was 4.7 cases per 1000 admissions, and for unit-acquired IFD was 3.2 cases per 1000 admissions. Statistical modelling: Risk models were developed at admission to the critical care unit, 24 hours and the end of calendar day 3. The risk model at admission had fair discrimination (c-index 0.705). Discrimination improved at 24 hours (c-index 0.823) and this was maintained at the end of calendar day 3 (c-index 0.835). There was a drop in model performance in the validation sample. Economic decision model: Irrespective of risk threshold, incremental quality-adjusted life-years of prophylaxis strategies compared with current practice were positive but small compared with the incremental costs. Incremental net benefits of each prophylaxis strategy compared with current practice were all negative. Cost-effectiveness acceptability curves showed that current practice was the strategy most likely to be cost-effective. Across all parameters in the decision model, results indicated that the value of further research for the whole population of interest might be high relative to the research costs. CONCLUSIONS: The results of the Fungal Infection Risk Evaluation (FIRE) Study, derived from a highly representative sample of adult general critical care units across the UK, indicated a low incidence of IFD among non-neutropenic, critically ill adult patients. IFD was associated with substantially higher mortality, more intensive organ support and longer length of stay. Risk modelling produced simple risk models that provided acceptable discrimination for identifying patients at 'high risk' of invasive Candida infection. Results of the economic model suggested that the current most cost-effective treatment strategy for prophylactic use of systemic antifungal agents among non-neutropenic, critically ill adult patients admitted to NHS adult general critical care units is a strategy of no risk assessment and no antifungal prophylaxis. FUNDING: Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.

Low prevalence of meticillin-resistant Staphylococcus aureus carriage at hospital admission: implications for risk-factor-based vs universal screening.

BACKGROUND: There is debate over the optimal policy for detecting meticillin-resistant Staphylococcus aureus (MRSA) colonization at hospital admission. The emergence of community-associated (CA)-MRSA may compromise targeted screening strategies based on risk factors for healthcare-associated (HA)-MRSA. AIM: To determine the prevalence of MRSA colonization at admission, and the genotype and molecular epidemiology of the strains involved. METHODS: A 12-month observational study was performed at a 1200-bed London tertiary referral hospital from 1 April 2008 to 1 March 2009. All available MRSA isolates were genotyped by spa and staphylococcal cassette chromosome mec (SCCmec) typing. FINDINGS: The overall MRSA colonization rate was 2.0% of 28,892 admissions (range 6.6% in critical care to 0.8% in obstetrics/gynaecology/neonatology). The overall frequency of previously unknown carriage of MRSA on admission was 1.4%. Most colonizing strains were epidemic HA-MRSA-15 and -16. However, heterogeneous CA strains accounted for 18% of recovered isolates, including 37.5% of MRSA from accident and emergency and 23.1% of MRSA from surgery. The CA-MRSA strain types had significantly different epidemiological associations from the HA-MRSA strains, so risk factors used for the identification of HA-MRSA may not detect CA-MRSA reliably. CONCLUSION: The low rate of HA-MRSA in the UK increases the relative proportion due to CA-MRSA, for which conventional risk-factor-based screening strategies may be less effective. Cost-benefit analyses of universal MRSA admission screening will need to take account of this new epidemiology.

Effect of systemic antibiotics and topical chlorhexidine on meticillin-resistant Staphylococcus aureus carriage in intensive care unit patients.

Antibiotics and antiseptics have the potential to influence carriage and transmission of meticillin-resistant Staphylococcus aureus (MRSA), although effects are likely to be complex, particularly in a setting where multiple agents are used. Here admission and weekly MRSA screens and daily antibiotic and antiseptic prescribing data from 544 MRSA carriers on an intensive care unit (ICU) are used to determine the effect of these agents on short-term within-host MRSA carriage dynamics. Longitudinal data were analysed using Markov models allowing patients to move between two states: MRSA positive (detectable MRSA carriage) and MRSA negative (no detectable carriage). The effect of concurrent systemic antibiotic and topical chlorhexidine (CHX) on movement between these states was assessed. CHX targeted to MRSA screen carriage sites increased transition from culture positive to negative and there was also weaker evidence that it decreased subsequent transition from negative back to positive. In contrast, there was only weak and inconsistent evidence that any antibiotic influenced transition in either direction. For example, whereas univariate analysis found quinolones to be strongly associated with both increased risk of losing and then reacquiring MRSA carriage over time intervals of one day, no effect was seen with weekly models. Similar studies are required to determine the generalisability of these findings.

Novel H1N1 influenza and Panton-Valentine leukocidin Staphylococcus aureus necrotizing pneumonia.

The association between seasonal influenza and staphylococcal pneumonia has long been recognized (Chickering and Park, 1919; Roberts et al, 2008), and both meticillin-resistant Staphylococcus aureus and Panton-Valentine leukocidin S. aureus have been associated with seasonal influenza pandemics (Roberts et al, 2008; Kearns et al, 2009; Murray et al, 2010).

Growth and morphology control of carbon nanotubes at the apexes of pyramidal silicon tips.

We describe the development of catalysed chemical vapour deposition (cCVD) growth schemes suitable for the production of carbon nanotube atomic force microscopy (CNT-AFM) probes. Growth and sample processing conditions are utilized that both incorporate safety in the process, e.g. the use of ethanol (EtOH) vapour as a carbon feedstock and hydrogen at only 4% (flow proportion), and simplicity, e.g. no catalyst patterning is required. Cobalt is employed as the growth catalyst and thin films of aluminium on silicon as the substrate material. Purpose-fabricated silicon substrates containing large numbers of tip structures are used as models of AFM probes. This enables growth to be carried out on many tips at once, facilitating a thorough investigation of the effect of different growth schemes on yields. cCVD growth schemes are chosen which produce stabilizing high density networks of carbon nanotubes on the sidewalls of the pyramidal tips to aid in anchoring the apex protruding carbon nanotube(s) in place. This results in long-lasting AFM imaging tips. We demonstrate that through rational tailoring of cCVD conditions it is possible to tune the growth conditions such that CNTs which protrude straight from tip apexes can be obtained at yields of greater than or equal to 78%. Application of suitable growth schemes to CNT growth on commercially available AFM probes resulted in CNT-AFM probes which were found to be extremely useful for extended lifetime metrological profiling of complex structures.

Intravascular catheter infections.

Formerly an under-appreciated iatrogenic infection, catheter-related bloodstream infections (CRBSIs) are now the focus of considerable preventive strategies. Although robust clinical definitions remain elusive due to the difficulty in identifying the focus of infection in hospitalised patients, surveillance definitions are proving useful to monitor and compare institutional rates of CRBSI and to target infection control resources. New catheter-sparing diagnostic techniques have been developed, that are probably most applicable to assessment of infection in stable ambulatory patients with single long-term tunnelled catheters rather than acutely unwell hospitalised patients. There is an impressive body of evidence that can be used to support implementation, surveillance and audit of basic infection control practices that should help institutions reduce CRBSI rates. The introduction of preventive antimicrobial strategies at the catheter site has been recommended by international guidelines, yet there remains justifiable concern about long-term selection of resistant organisms. This has not been adequately addressed in current studies. Economic analyses require data on the clinical effect of CRBSIs to adequately assess the benefit; such data are scarce, owing to the difficulty in assessing the contribution from comorbidities, with consequential conflicting results. Overall, institutions can justifiably first assess the benefit of a sustained programme of re-enforcing basic infection control practice on CRBSI before assessing whether the introduction of additional preventive antimicrobial strategies are likely to have any benefit.

Neutrophils in development of multiple organ failure in sepsis.

Multiple organ failure is a major threat to the survival of patients with sepsis and systemic inflammation. In the UK and in the USA, mortality rates are currently comparable with and projected to exceed those from myocardial infarction. The immune system combats microbial infections but, in severe sepsis, its untoward activity seems to contribute to organ dysfunction. In this Review we propose that an inappropriate activation and positioning of neutrophils within the microvasculature contributes to the pathological manifestations of multiple organ failure. We further suggest that targeting neutrophils and their interactions with blood vessel walls could be a worthwhile therapeutic strategy for sepsis.