Evaluating the cost-effectiveness of strategies to prevent vascular access device infections.

The evidence clearly indicates that a care-bundle approach is needed to prevent catheter-related bloodstream infections (CRBSIs). Such an approach includes the need for education, training and adequate staffing, sterile barrier precautions, skin preparation, use of intravenous dressings and antimicrobial prophylaxis. Care bundles advise which aspects must be given priority and what procedures will produce optimum outcomes. All of these activities come at a cost, yet very few studies have investigated the extent to which they are cost-effective. As a result, it is difficult to make evidence-based decisions on the potential cost savings that may be achieved with a care-bundle approach. This article describes the existing health-economic evidence on strategies to prevent CRBSIs and outlines the criteria for future research.

A review of infection control in community healthcare: new challenges but old foes.

The demographics of the healthcare population are changing, with an ever-greater proportion of people being treated outside the traditional hospital setting through community healthcare. This shift in the way that healthcare is delivered raises new concerns over community healthcare-associated infections (HCAIs). A literature search between 2000 and December 2013 was conducted in databases including PubMed, SciVerse ScienceDirect and Google Scholar. National and international guideline and policy documents were searched using Google. Many terms were used in the literature searches, including 'nosocomial', 'healthcare infection', 'community' and 'nursing home'. The rates of HCAI in community healthcare are similar to the rates found in the acute hospital setting, but the types of infection differ, with a greater focus on urinary tract infections (UTIs) in the community and ventilator-associated pneumonias in the hospital setting. Patients who acquire a community HCAI are more likely to exhibit reduced physical condition, have increased levels of morbidity and have higher mortality rates than individuals without infection. Infection control programmes have been developed worldwide to reduce the rates of hospital HCAIs. Such interventions are equally as valid in the community, but how best to implement them and their subsequent impact are much less well understood. The future is clear: HCAIs in the community are going to become an ever-increasing burden and it is critical that our approach to these infections is brought quickly in line with present hospital sector standards.

European perspective and update on the management of nosocomial pneumonia due to methicillin-resistant Staphylococcus aureus after more than 10 years of experience with linezolid.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important cause of antimicrobial-resistant hospital-acquired infections worldwide and remains a public health priority in Europe. Nosocomial pneumonia (NP) involving MRSA often affects patients in intensive care units with substantial morbidity, mortality and associated costs. A guideline-based approach to empirical treatment with an antibacterial agent active against MRSA can improve the outcome of patients with MRSA NP, including those with ventilator-associated pneumonia. New methods may allow more rapid or sensitive diagnosis of NP or microbiological confirmation in patients with MRSA NP, allowing early de-escalation of treatment once the pathogen is known. In Europe, available antibacterial agents for the treatment of MRSA NP include the glycopeptides (vancomycin and teicoplanin) and linezolid (available as an intravenous or oral treatment). Vancomycin has remained a standard of care in many European hospitals; however, there is evidence that it may be a suboptimal therapeutic option in critically ill patients with NP because of concerns about its limited intrapulmonary penetration, increased nephrotoxicity with higher doses, as well as the emergence of resistant strains that may result in increased clinical failure. Linezolid has demonstrated high penetration into the epithelial lining fluid of patients with ventilator-associated pneumonia and shown statistically superior clinical efficacy versus vancomycin in the treatment of MRSA NP in a phase IV, randomized, controlled study. This review focuses on the disease burden and clinical management of MRSA NP, and the use of linezolid after more than 10 years of clinical experience.

The frontal lobe in absence epilepsy: EEG-fMRI findings.

OBJECTIVE: Studies of absence seizures (AS) using EEG with fMRI (EEG-fMRI) show a consistent network with prominent thalamic activation and a variety of cortical changes. Despite evidence suggesting a role of frontal cortex in seizure generation, group studies have not detected consistent AS-related changes in this region. We hypothesized that only a subgroup may show frontal cortical activation. METHOD: We studied 13 subjects with AS during EEG-fMRI to classify the different individual patterns of frontal cortical activation associated with AS. RESULTS: Based upon visual inspection of surface-rendered activation maps we identified 2 subgroups that could be distinguished by the activation in the dorsolateral prefrontal cortex (DLPFC). One group of patients (n = 7) showed a primarily positive signal change (DLPFC-POS), whereas the other group (n = 6) showed a primarily negative signal change (DLFPC-NEG). When the DLPFC-POS group was compared to the DLPFC-NEG group, time-course analysis revealed a larger positive blood oxygenation level-dependent deflection following onset of the AS in cortical and subcortical areas beyond the DLPFC. This suggests a basic biological difference between these groups. CONCLUSION: These observations suggest that there may be at least 2 mechanisms underpinning AS in individuals with absence epilepsy. This may have phenotypic and genetic implications for understanding epilepsy syndromes.

Universal screening for meticillin-resistant Staphylococcus aureus in acute care: risk factors and outcome from a multicentre study.

BACKGROUND: A Health Technology Assessment (HTA) model on effectiveness of meticillin-resistant Staphylococcus aureus (MRSA) screening in Scotland suggested that universal screening using chromogenic agar was the preferred option in terms of effectiveness and cost. AIM: To test the model's validity through a one-year pilot-study. METHOD: A large one-year prospective cohort study of MRSA screening was carried out in six acute hospitals in NHS Scotland, incorporating 81,438 admissions. Outcomes (MRSA colonization and infection rates) were subjected to multivariable analyses, and trends before and after implementation of screening were compared. FINDINGS: The initial colonization prevalence of 5.5% decreased to 3.5% by month 12 of the study (P < 0.0001). Colonization was associated with the number of admissions per patient, specialty of admission, age, and source of admission (home, other hospital or care home). Around 2% of all admissions with no prior history of MRSA infection or colonization tested positive. Those who were screen positive on admission and not previously known positive were 12 times more likely than those who screened negative to develop infection, increasing to 18 times if they were both screen positive and previously known positive. MRSA infections (7.5 per 1000 inpatient-days overall) also reduced significantly over the study year (P = 0.0209). CONCLUSION: The risk factors identified for colonization and infection indicate that a universal clinical risk assessment may have a role in MRSA screening.

A retrospective cohort study into acquisition of MRSA and associated risk factors after implementation of universal screening in Scottish hospitals.

OBJECTIVE: To estimate the proportion of patients who acquire methicillin-resistant Staphylococcus aureus (MRSA) while in hospital and to identify risk factors associated with acquisition of MRSA. DESIGN: Retrospective cohort study. PATIENTS: Adult patients discharged from 36 general specialty wards of 2 Scottish hospitals that had implemented universal screening for MRSA on admission. METHODS: Patients were screened for MRSA on discharge from hospital by using multisite body swabs that were tested by culture. Discharge screening results were linked to admission screening results. Genotyping was undertaken to identify newly acquired MRSA in MRSA-positive patients on admission. RESULTS: Of the 5,155 patients screened for MRSA on discharge, 2.9% (95% confidence interval [CI], 2.43-3.34) were found to be positive. In the subcohort screened on both admission and discharge (n = 2,724), 1.3% of all patients acquired MRSA while in hospital (incidence rate, 2.1/1,000 hospital bed-days in this cohort [95% CI, 1.5-2.9]), while 1.3% remained MRSA positive throughout hospital stay. Three risk factors for acquisition of MRSA were identified: age above 64 years, self-reported renal failure, and self-reported presence of open wounds. On a population level, the prevalence of MRSA colonization did not differ between admission and discharge. CONCLUSIONS: Cross-transmission of MRSA takes place in Scottish hospitals that have implemented universal screening for MRSA. This study reinforces the importance of infection prevention and control measures to prevent MRSA cross-transmission in hospitals; universal screening for MRSA on admission will in itself not be sufficient to reduce the number of MRSA colonizations and subsequent MRSA infections.

The core network in absence epilepsy. Differences in cortical and thalamic BOLD response.

OBJECTIVES: We used EEG-fMRI to study epileptiform activity in a cohort of untreated children with typical absence seizures (AS). Our aim was to identify cortical and subcortical regions involved in spike and wave events and to explore the timing of activity in these regions. METHODS: Eleven children with AS confirmed on video-EEG underwent EEG-fMRI. An event-related analysis of epileptiform activity was performed. Regions of interest (ROIs), identified in the event-related analysis, were used to study the time course of the blood oxygen level-dependent (BOLD) signal prior to and immediately following events of interest in these ROIs. RESULTS: Group analysis confirmed positive BOLD in the thalamus and negative BOLD in the lateral and mesial parietal lobe, caudate nuclei, and additionally the brainstem reticular formation. The event-related time course differed between the thalamus, the parietal cortex, and the pons and caudate nuclei. In the subcortical structures, BOLD signal change occurred at, or immediately after, electrographic onset. Importantly, in the parietal cortex, but not in other cortical regions, there was a subtle BOLD signal increase for 10 seconds prior to the onset of epileptiform activity. CONCLUSIONS: In children with typical AS, we have confirmed a core network of structures involved in generalized epileptiform activity that includes the reticular structures of the brainstem. Furthermore, we have identified changes in parietal BOLD signal which precede the onset of epileptiform activity, suggesting the parietal cortex has a role in the initiation of epileptiform activity.

Universal screening for meticillin-resistant Staphylococcus aureus: interim results from the NHS Scotland pathfinder project.

Following recommendations from a Health Technology Assessment (HTA), a prospective cohort study of meticillin-resistant Staphylococcus aureus (MRSA) screening of all admissions (N=29 690) to six acute hospitals in three regions in Scotland indicated that 7.5% of patients were colonised on admission to hospital. Factors associated with colonisation included re-admission, specialty of admission (highest in nephrology, care of the elderly, dermatology and vascular surgery), increasing age, and the source of admission (care home or other hospital). Three percent of all those who were identified as colonised developed hospital-associated MRSA infection, compared with only 0.1% of those not colonised. Specialties with a high rate of colonisation on admission also had higher rates of MRSA infection. Very few patients refused screening (11 patients, 0.03%) or had treatment deferred (14 patients, 0.05%). Several organisational issues were identified, including difficulties in achieving complete uptake of screening (88%) or decolonisation (41%); the latter was largely due to short duration of stay and turnaround time for test results. Patient movement resulted in a decision to decolonise all positive patients rather than just those in high risk specialties as proposed by the HTA. Issues also included a lack of isolation facilities to manage patients with MRSA. The study raises significant concerns about the contribution of decolonisation to reducing risks in hospital due to short duration of stay, and reinforces the central role of infection control precautions. Further study is required before the HTA model can be re-run and conclusions redrawn on the cost and clinical effectiveness of universal MRSA screening.

The neural architecture of discourse compression.

Re-telling a story is thought to produce a progressive refinement in the mental representation of the discourse. A neuroanatomical substrate for this compression effect, however, has yet to be identified. We used a discourse re-listening task and functional magnetic resonance imaging (fMRI) to identify brain regions responsive to repeated discourse in twenty healthy volunteers. We found a striking difference in the pattern of activation associated with the first and subsequent presentations of the same story relative to rest. The first presentation was associated with a highly significant increase in blood oxygen level dependent (BOLD) signal in a bilateral perisylvian distribution, including auditory cortex. Listening to the same story on subsequent occasions revealed a wider network with activation extending into frontal, parietal, and subcortical structures. When the first and final presentations of the same story were directly compared, significant increments in activation were found in the middle frontal gyrus bilaterally, and the right inferior parietal lobule, suggesting that the spread of activation with re-listening reflected an active neural process over and above that required for comprehension of the text. Within the right inferior parietal region the change in BOLD signal was highly correlated with a behavioural index of discourse compression based in re-telling, providing converging evidence for the role of the right inferior parietal region in the representation of discourse. Our findings demonstrate, for the first time, the existence of a neural network underlying discourse compression, showing that parts of this network are common to re-telling and re-listening effects.

Guidelines for the management of hospital-acquired pneumonia in the UK: report of the working party on hospital-acquired pneumonia of the British Society for Antimicrobial Chemotherapy.

These evidence-based guidelines have been produced after a systematic literature review of a range of issues involving prevention, diagnosis and treatment of hospital-acquired pneumonia (HAP). Prevention is structured into sections addressing general issues, equipment, patient procedures and the environment, whereas in treatment, the structure addresses the use of antimicrobials in prevention and treatment, adjunctive therapies and the application of clinical protocols. The sections dealing with diagnosis are presented against the clinical, radiological and microbiological diagnosis of HAP. Recommendations are also made upon the role of invasive sampling and quantitative microbiology of respiratory secretions in directing antibiotic therapy in HAP/ventilator-associated pneumonia.

Indicators of bacterial infection in patients with acute exacerbation of chronic bronchitis for application in clinical trials of antibacterial drugs.

OBJECTIVES: This study examined the accuracy of: (a) patient symptoms; (b) microscopic examination of sputum purulence (>25 WBCs and <10 epithelial cells) and (c) microscopic examination of morphological bacterial cell types, in identifying bacterial infection in patients with an acute exacerbation of chronic bronchitis (AECB) for entry to clinical trials. METHODS: Subjects had a worsening of at least two symptoms from: dyspnoea, sputum volume, and sputum purulence (Anthonisen Type 1 or 2 exacerbation). Sputum samples were collected from all subjects. RESULTS: A total of 97 sputum samples were evaluated. Overall, 58 (60%) subjects were culture-positive; 22 of 29 (76%) subjects with Type 2 exacerbation had a bacterial pathogen isolated compared with 36 of 68 (53%) Type 1 subjects. This difference was not statistically significant. Microscopically purulent samples were found to be significantly more likely to be culture-positive than non-purulent samples. However, the sensitivity (60%) and specificity (67%); and the positive predictive value (73%) and negative predictive value (53%) observed, means that this is not an ideal predictive test for clinical trials. A semi-quantitative approach to Gram staining was identified as a potential indicator of bacterial infection. Sputum specimens with one bacterial cell type present at >10 cells per field, or more than one cell type present with at least one type at a concentration of >25 cells per field, had a high proportion (91%) of culture-positive specimens. CONCLUSIONS: Symptoms alone are a poor indicator of bacterial infection. A semi-quantitative examination of a Gram-stained sputum preparation was the best indicator of bacterial infection. This finding may have relevance in the design of clinical trials of antibacterial drugs in AECB.

Hospital-acquired pneumonia guidelines in Europe: a review of their status and future development.

Hospital-acquired pneumonia (HAP) is the most common healthcare-acquired infection contributing to death. Effective management requires accurate diagnosis, administration of a suitable antibiotic regimen early in infection and implementation of prevention strategies. In recent years, there has been a rapid increase in the number of country-specific HAP guidelines in Europe, which vary in their formulation, coverage of different disease aspects and overall recommendations. Development of comprehensive pan-European HAP guidelines would rationalize the conflicting proposals, provide a useful resource and limit guideline proliferation. However, careful consideration needs to be given to the principles of guideline development to ensure that the output is rigorous, broadly applicable and facilitates update as new data becomes available. The use of an evidence-based approach to HAP guideline development is optimal, but is compromised by limitations in the supporting data. The implementation of a formalized evidence grading system is key to introducing consistency into the guideline development process. Pan-European guidelines should provide recommendations on core aspects of HAP common to all treatment settings and locations, and reflect the differing perspectives of the countries involved. Given the different antibiotic susceptibility profiles across Europe, such guidelines should provide general treatment recommendations suitable for local adaptation. The development of such guidelines represents an ideal time to identify priorities for European research, by addressing controversies and identifying previously unconsidered aspects of HAP. Establishing a pan-European consensus on core processes of care should be viewed as an impetus for change to improve clinical practices and should include a suitable implementation strategy.

The place of guidelines in hospital-acquired pneumonia.

The recent increase in hospital-acquired infections (HAIs) has meant that hospital-acquired pneumonia (HAP) has come under the spotlight. HAP is the most common HAI contributing to death and affects about 0.5-1% of all patients admitted to hospital. HAP significantly increases health complications and extends the length of time patients stay in hospital by up to 13 days on average, thus impacting significantly on hospital resources. The British Society of Antimicrobial Chemotherapy Hospital-Acquired Pneumonia guidelines were published on the society's website last year and represent one of only two sets of evidence-based HAP guidelines in the world which deal with the trio of prevention, diagnosis and treatment. This paper reviews the evolution and status of HAP guidelines, drawing attention to recent developments, differences in approach and outcomes and further areas of work. There are clear indications that the implementation of evidence-based guidelines will reduce HAP and improve patient outcomes.

Relationship between language lateralization and handedness in left-hemispheric partial epilepsy.

OBJECTIVE: To investigate the relationship between language lateralization and handedness in patients with epilepsy and a left-sided seizure focus and in healthy control subjects. METHODS: We recruited a consecutive series of 74 patients and 70 control subjects. Functional MRI, using a noun-verb generation task, was performed to establish the language laterality index (LI). Handedness was quantified using the Edinburgh Handedness Inventory. RESULTS: Patients showed a shift toward atypical language lateralization (0.43 +/- 0.47; controls 0.57 +/- 034; p < or = 0.05) and left-handedness (55 +/- 57; controls 74 +/- 39; p < or = 0.05). The LI and handedness were correlated in patients (r = 0.54; F = 25.9; p < 0.001) but not in control subjects (r = 0.1; F = 0.64; NS). A combination of left-handedness and atypical LI was more frequent in patients (12%) than control subjects (0%; p < or = 0.05). Crossed hemispheric specialization (e.g., right-handedness associated with atypical LI) was equally frequent in patients (20%) and control subjects (16%; NS). CONCLUSION: In epilepsy patients with a left-sided seizure focus, language lateralization is correlated to handedness. The increased frequency of left-handedness and associated atypical language lateralization is most likely related to the left-hemispheric seizure focus, influencing hemispheric specialization for both domains.

Results of two worldwide surveys into physician awareness and perceptions of extended-spectrum beta-lactamases.

An omnibus survey of microbiologists (n = 400) and a survey of participants (n = 49) in the Meropenem Yearly Susceptibility Test Information Collection (MYSTIC) programme were conducted to determine the awareness and prevalence of extended-spectrum beta-lactamases (ESBLs), and the regularity and method of screening. Of the omnibus survey participants, 69% screened regularly for ESBLs, compared with 83% of MYSTIC participants. In both surveys, ESBLs were more common in Klebsiella pneumoniae (73% and 79%, respectively) and Escherichia coli (63% and 81%, respectively) than in other bacteria. The surveys demonstrated that awareness of, and testing for, ESBLs is inconsistent.

Appropriate antimicrobial treatment in nosocomial infections-the clinical challenges.

Resistance to antimicrobial agents is emerging in a wide variety of pathogens, particularly those that cause nosocomial infections. As a consequence of this increasing resistance, morbidity and mortality in nosocomial infections is also increasing. It is therefore critical to treat nosocomial infections appropriately by starting antimicrobial treatment early in the course of infection, using the correct agent, at the most appropriate dose, and for an adequate duration. Indeed, early 'appropriate' antibiotic prescribing has been shown significantly to reduce mortality, length of intensive care unit and hospital stay and overall costs. Early use of the correct antibiotic at the appropriate dose and for an adequate duration are key to initial appropriate antibiotic prescribing. Choosing the right antibiotic depends mainly on the likely pathogen(s) and the expected local susceptibility patterns. Selection of appropriate antimicrobial therapy requires a thorough understanding of the likely microbial cause of the infection, including local susceptibility patterns, as well as the properties of the antimicrobials available for treating these infections, namely spectrum of activity and potency (including activity versus known resistance mechanisms), pharmacokinetic profile and tolerability and safety. This review, based on a series of presentations at the 5th International Conference of the Hospital Infection Society (Edinburgh, 2002) examines the importance of appropriate antimicrobial therapy in nosocomial infections, and provides guidance on how to achieve this.

Investigation into the selection frequency of resistant mutants and the bacterial kill rate by levofloxacin and ciprofloxacin in non-mucoid Pseudomonas aeruginosa isolates from cystic fibrosis patients.

The frequency by which resistant Pseudomonas aeruginosa strains could be selected was compared for two antibiotics, levofloxacin and ciprofloxacin. Seven distinct strains were cultured on plates containing 1x, 2x, 4x and 8x the minimum inhibitory concentration (MIC) of the antibiotic under investigation. Resistant mutants were more readily isolated by growth on culture plates that contained ciprofloxacin, and the resulting MIC of the resistant mutant was also more frequently increased. Time-kill studies on comparable strains where the MIC for both antibiotics had increased by at least fourfold showed no difference between the two agents.