IMPORTANCE Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia is associated with mortality of more than 20%. Combining standard therapy with a β-lactam antibiotic has been associated with reduced mortality, although adequately powered randomized clinical trials of this intervention have not been conducted. OBJECTIVE To determine whether combining an antistaphylococcal β-lactam with standard therapy is more effective than standard therapy alone in patients with MRSA bacteremia. DESIGN, SETTING, AND PARTICIPANTS Open-label, randomized clinical trial conducted at 27 hospital sites in 4 countries from August 2015 to July 2018 among 352 hospitalized adults with MRSA bacteremia. Follow-up was complete on October 23, 2018.INTERVENTIONS Participants were randomized to standard therapy (intravenous vancomycin or daptomycin) plus an antistaphylococcal β-lactam (intravenous flucloxacillin, cloxacillin, or cefazolin) (n = 174) or standard therapy alone (n = 178). Total duration of therapy was determined by treating clinicians and the β-lactam was administered for 7 days. MAIN OUTCOMES AND MEASURESThe primary end point was a 90-day composite of mortality, persistent bacteremia at day 5, microbiological relapse, and microbiological treatment failure. Secondary outcomes included mortality at days 14, 42, and 90; persistent bacteremia at days 2 and 5; acute kidney injury (AKI); microbiological relapse; microbiological treatment failure; and duration of intravenous antibiotics. RESULTSThe data and safety monitoring board recommended early termination of the study prior to enrollment of 440 patients because of safety. Among 352 patients randomized (mean age, 62.2 [SD, 17.7] years; 121 women [34.4%]), 345 (98%) completed the trial. The primary end point was met by 59 (35%) with combination therapy and 68 (39%) with standard therapy (absolute difference, −4.2%; 95% CI, −14.3% to 6.0%). Seven of 9 prespecified secondary end points showed no significant difference. For the combination therapy vs standard therapy groups, all-cause 90-day mortality occurred in 35 (21%) vs 28 (16%) (difference, 4.5%; 95% CI, −3.7% to 12.7%); persistent bacteremia at day 5 was observed in 19 of 166 (11%) vs 35 of 172 (20%) (difference, −8.9%; 95% CI, −16.6% to −1.2%); and, excluding patients receiving dialysis at baseline, AKI occurred in 34 of 145 (23%) vs 9 of 145 (6%) (difference, 17.2%; 95% CI, 9.3%-25.2%).CONCLUSIONS AND RELEVANCE Among patients with MRSA bacteremia, addition of an antistaphylococcal β-lactam to standard antibiotic therapy with vancomycin or daptomycin did not result in significant improvement in the primary composite end point of mortality, persistent bacteremia, relapse, or treatment failure. Early trial termination for safety concerns and the possibility that the study was underpowered to detect clinically important differences in favor of the intervention should be considered when interpreting the findings.

The resurgence of West Nile virus (WNV) in North America and Europe in recent years has raised the concerns of local authorities and highlighted that mosquito-borne disease is not restricted to tropical regions of the world. WNV is maintained in enzootic cycles involving, primarily, Culex spp. mosquitoes and avian hosts, with epizootic spread to mammals, including horses and humans. Human infection results in symptomatic illness in approximately one-fifth of cases and neuroinvasive disease in less than 1% of infected persons. The most consistently recognized risk factor for neuroinvasive disease is older age, although diabetes mellitus, alcohol excess, and a history of cancer may also increase risk. Despite the increasing public health concern, the current WNV treatments are inadequate. Current evidence supporting the use of ribavirin, interferon α, and WNV-specific immunoglobulin are reviewed. Nucleic acid detection has been an important diagnostic development, which is particularly important for the protection of the donated blood supply. While effective WNV vaccines are widely available for horses, no human vaccine has been registered. Uncertainty surrounds the magnitude of future risk posed by WNV, and predictive models are limited by the heterogeneity of environmental, vector, and host factors, even in neighboring regions. However, recent history has demonstrated that for regions where suitable mosquito vectors and reservoir hosts are present, there will be a risk of major epidemics. Given the potential for these outbreaks to include severe neuroinvasive disease, strategies should be implemented to monitor for, and respond to, outbreak risk. While broadscale mosquito control programs will assist in reducing the abundance of mosquito populations and subsequently reduce the risks of disease, for many individuals, the use of topical insect repellents and other personal protective strategies will remain the first line of defense against infection.

Healthcare‐acquired infections (HAI) impact on patient care and have cost implications for the Australian healthcare system. The management of HAI is exacerbated by rising rates of antimicrobial resistance (AMR). Health‐care workers and a contaminated hospital environment are increasingly implicated in the transmission and persistence of multi‐resistant organisms (MRO), as well as other pathogens, such as Clostridium difficile. This has resulted in a timely focus on a range of HAI prevention actions. Core components include antimicrobial stewardship, to reduce overuse and ensure evidence‐based antimicrobial use; infection prevention strategies, to control MRO – particularly methicillin‐resistant Staphylococcus aureus (MRSA), vancomycin‐resistant Enterococcus spp. (VRE) and, more recently, multi‐resistant Gram‐negative bacteria; enhanced institutional investment in hand hygiene; hospital cleaning and disinfection; and the development of prescribing guidelines and standards of care. AMR surveillance and comparisons of prescribing are useful feedback activities once effectively communicated to end users. Successful implementation of these strategies requires cultural shifts at local hospital level and, to tackle the serious threat posed by AMR, greater co‐ordination at a national level. HAI prevention needs to be multi‐modal, requires broad healthcare collaboration, and the strong support and accountability of all medical staff.

Summary Background 80% of individuals with cancer will require a surgical procedure, yet little comparative data exist on early outcomes in low-income and middle-income countries (LMICs). We compared postoperative outcomes in breast, colorectal, and gastric cancer surgery in hospitals worldwide, focusing on the effect of disease stage and complications on postoperative mortality. Methods This was a multicentre, international prospective cohort study of consecutive adult patients undergoing surgery for primary breast, colorectal, or gastric cancer requiring a skin incision done under general or neuraxial anaesthesia. The primary outcome was death or major complication within 30 days of surgery. Multilevel logistic regression determined relationships within three-level nested models of patients within hospitals and countries. Hospital-level infrastructure effects were explored with three-way mediation analyses. This study was registered with ClinicalTrials.gov , NCT03471494 . Findings Between April 1, 2018, and Jan 31, 2019, we enrolled 15 958 patients from 428 hospitals in 82 countries (high income 9106 patients, 31 countries; upper-middle income 2721 patients, 23 countries; or lower-middle income 4131 patients, 28 countries). Patients in LMICs presented with more advanced disease compared with patients in high-income countries. 30-day mortality was higher for gastric cancer in low-income or lower-middle-income countries (adjusted odds ratio 3·72, 95% CI 1·70–8·16) and for colorectal cancer in low-income or lower-middle-income countries (4·59, 2·39–8·80) and upper-middle-income countries (2·06, 1·11–3·83). No difference in 30-day mortality was seen in breast cancer. The proportion of patients who died after a major complication was greatest in low-income or lower-middle-income countries (6·15, 3·26–11·59) and upper-middle-income countries (3·89, 2·08–7·29). Postoperative death after complications was partly explained by patient factors (60%) and partly by hospital or country (40%). The absence of consistently available postoperative care facilities was associated with seven to 10 more deaths per 100 major complications in LMICs. Cancer stage alone explained little of the early variation in mortality or postoperative complications. Interpretation Higher levels of mortality after cancer surgery in LMICs was not fully explained by later presentation of disease. The capacity to rescue patients from surgical complications is a tangible opportunity for meaningful intervention. Early death after cancer surgery might be reduced by policies focusing on strengthening perioperative care systems to detect and intervene in common complications. Funding National Institute for Health Research Global Health Research Unit.

Prospective memory performance is sensitive to regular and even moderate ecstasy use. Importantly, ecstasy users experience generalized difficulties with prospective memory, suggesting that these deficits are likely to have important implications for day-to-day functioning.

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c Sequence analysis of the internal transcribed spacer (ITS) region was employed as the gold standard method for yeast identification in the China Hospital Invasive Fungal Surveillance Net (CHIF-NET). It has subsequently been found that matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) is potentially a more practical approach for this purpose. In the present study, the performance of the Vitek MS v2.0 system for the identification of yeast isolates collected from patients with invasive fungal infections in the 2011 CHIF-NET was evaluated. A total of 1,243 isolates representing 31 yeast species were analyzed, and the identification results by the Vitek MS v2.0 system were compared to those obtained by ITS sequence analysis. By the Vitek MS v2.0 system, 96.7% (n ‫؍‬ 1,202) of the isolates were correctly assigned to the species level and 0.2% (n ‫؍‬ 2) of the isolates were identified to the genus level, while 2.4% (n ‫؍‬ 30) and 0.7% (n ‫؍‬ 9) of the isolates were unidentified and misidentified, respectively. After retesting of the unidentified and misidentified strains, 97.3% (n ‫؍‬ 1,209) of the isolates were correctly identified to the species level. Based on these results, a testing algorithm that combines the use of the Vitek MS system with selected supplementary ribosomal DNA (rDNA) sequencing was developed and validated for yeast identification purposes. By employing this algorithm, 99.7% (1,240/1,243) of the study isolates were accurately identified with the exception of two isolates of Candida fermentati and one isolate of Cryptococcus gattii. In conclusion, the proposed identification algorithm could be practically implemented in strategic programs of fungal infection surveillance.T he global antifungal surveillance programs have provided important global epidemiology and susceptibility data for invasive yeast infections (1-6). In July 2009, the multicenter nationwide China Hospital Invasive Fungal Surveillance Net (CHIF-NET) study was established, and since then it has provided important information on the epidemiology of fungal diseases in China (7). The importance of confirmatory identification in fungal surveillance programs has been highlighted by reports that the initial identifications by the participating laboratories may be inaccurate, particularly for isolates that are uncommon or have unusual biochemical or phenotypic profiles (7,8). Currently, sequencing-based methods are recognized as the gold standard for identifying yeast species (9). In the 2010 CHIF-NET surveillance study, all 814 isolates were confirmed by internal transcribed spacer (ITS) region sequencing in a central laboratory (7). However, the subsequent expansion of the CHIF-NET program has led to a dramatic increase in the numbers of both the participating laboratories and the referred isolates, precluding the universal application of the high-cost and labor-intensive sequence-based identification methods.Recently, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass...

BackgroundTo describe the clinical epidemiology, environmental surveillance and infection control interventions undertaken in a six-year persistence of bla-IMP-4 metallo-beta-lactamase (MBL) producing Enterobacteriaceae within a separately confined hospital burns unit in a tertiary hospital in Sydney, Australia.MethodsMBL positive clinical and environmental isolates were collected from the Burns Unit, from the first detection of isolates in September 2006 to August 2012. Unit-acquired clinical isolates were included, and patient outcomes analyzed amongst those who acquired clinically significant infections. Environmental isolates were analyzed with regard to relationship to clinical isolates, bacterial species, and persistence despite cleaning efforts.ResultsThirty clinical isolates detected from 23 patients were identified. Clinically significant infection developed in 7 (30%) patients – 2 bacteremias, 2 central venous catheter tip infections without bacteremia, and 3 wound infections. All patients survived at 30 days. Seventy-one environmental isolates were confirmed to be MBL-positive, with 85% sourced from shower facilities or equipment. MBL organisms persisted at these sites despite both usual hospital cleaning, and following targeted environmental disinfection interventions.ConclusionsClear association exists between environmental Burns Unit contamination by MBLs and subsequent patient colonization. Clinical infection occurred in a small proportion of patients colonized by MBLs, and with generally favorable outcomes. Its persistence in the Burns Unit environment, despite concerted infection control measures, pose concern for ongoing clinical transmission.