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The Scotian Slope in the North Atlantic Ocean extends for ∼ 500 km along the coast of Nova Scotia, Canada. Its surface sediments host microbial communities, which respond to complex geochemical drivers that not only include communication with the overlying water column, but also potential advection from deeper basinal fluids. Archaea are fundamental components of these communities, and their lipids act as important historical indicators of environmental geochemical change and microbial interactions within marine sediments. This study evaluates the spatial abundance and diversity of archaeal lipids preserved in shallow Scotian Slope sediments to better understand processes. Seventy-four sediment samples from 32 gravity and piston cores, reaching a maximum of 9 m below seafloor (m b.s.f.) were collected during three survey cruises. In total, 14 archaeal lipid classes comprising 42 unique compounds were detected. The lipid distributions reflect a high contribution of anaerobic methanotrophic (ANME) archaeal groups, such as ANME-1 to -3. Hierarchical cluster analysis and principal components analysis were used to show varying contributions of four lipid classes that included distinct assemblages of intact polar lipids (IPLs), core lipids (CLs), and their degradation products (CL-DPs). IPL to CL and CL to CL-DP turnover rates were estimated for the various lipid classes. Four stratigraphically distinct archaeal lipidomes were observed. The first, reflects a unique community influenced by a nearby cold seep. Three additional ambient sediment lipidomes were detected with overlapping depth intervals. These lipidomes contained varying abundances of IPL, CL, and CL-DPs, which likely mark geochemically controlled, microbial community variations that are further accompanied by a systematic increase to the stockpile of diagenetically altered lipids. The ambient sediment lipidomes appear to be highly spatially conserved across the latitudinal extent of the study area marking a resolvable shallow sediment lipostratigraphy that occupies a sediment stratigraphy that spans ∼ 27 000±4000 years of basin evolution for the Scotian Slope.

In this trial involving 387 patients with Staphylococcus aureus bacteremia, ceftobiprole, a cephalosporin active against methicillin-sensitive and -resistant S. aureus , was noninferior to daptomycin.

Significance Human populations are both extremely cooperative and highly structured. Mathematical models have shown that fixed network interaction structures can lead to cooperation under certain conditions, by allowing cooperators to cluster together. Here, we provide empirical evidence of this phenomenon. We explore how different fixed social network structures can promote cooperation using economic game experiments. We find that people cooperate at high stable levels, as long as the benefits created by cooperation are larger than the number of neighbors in the network. This empirical result is consistent with a rule predicted by mathematical models of evolution. Our findings show the important role social networks can play in human cooperation and provide guidance for promoting cooperative behavior. The evolution of cooperation in network-structured populations has been a major focus of theoretical work in recent years. When players are embedded in fixed networks, cooperators are more likely to interact with, and benefit from, other cooperators. In theory, this clustering can foster cooperation on fixed networks under certain circumstances. Laboratory experiments with humans, however, have thus far found no evidence that fixed network structure actually promotes cooperation. Here, we provide such evidence and help to explain why others failed to find it. First, we show that static networks can lead to a stable high level of cooperation, outperforming well-mixed populations. We then systematically vary the benefit that cooperating provides to one’s neighbors relative to the cost required to cooperate ( b / c ), as well as the average number of neighbors in the network ( k ). When b / c > k , we observe high and stable levels of cooperation. Conversely, when b / c ≤ k or players are randomly shuffled, cooperation decays. Our results are consistent with a quantitative evolutionary game theoretic prediction for when cooperation should succeed on networks and, for the first time to our knowledge, provide an experimental demonstration of the power of static network structure for stabilizing human cooperation.

Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance. Pediatric community-acquired pneumonia (CAP) is often treated with 10 days of antibiotics. Shorter treatment strategies may be effective and lead to less resistance. The impact of duration of treatment on the respiratory microbiome is unknown. Data are from children ( n  = 171), ages 6 to 71 months, enrolled in the SCOUT-CAP trial (NCT02891915). Children with CAP were randomized to a short (5 days) versus standard (10 days) beta-lactam treatment strategy. Throat swabs were collected at enrollment and the end of the study and used for shotgun metagenomic sequencing. The number of beta-lactam and multidrug efflux resistance genes per prokaryotic cell (RGPC) was significantly lower in children receiving the short compared to standard treatment strategy at the end of the study (Wilcoxon rank sum test, P  < 0.05 for each). Wilcoxon effect sizes were small for beta-lactam ( r : 0.15; 95% confidence interval [CI], 0.01 to 0.29) and medium for multidrug efflux RGPC ( r : 0.23; 95% CI, 0.09 to 0.37). Analyses comparing the resistome at the beginning and end of the trial indicated that in contrast to the standard strategy group, the resistome significantly differed in children receiving the short course strategy. Relative abundances of commensals such as Neisseria subflava were higher in children receiving the standard strategy, and Prevotella species and Veillonella parvula were higher in children receiving the short course strategy. We conclude that children receiving 5 days of beta-lactam therapy for CAP had a significantly lower abundance of antibiotic resistance determinants than those receiving standard 10-day treatment. These data provide an additional rationale for reductions in antibiotic use when feasible. IMPORTANCE Antibiotic resistance is a major threat to public health. Treatment strategies involving shorter antibiotic courses have been proposed as a strategy to lower the potential for antibiotic resistance. We examined relationships between the duration of antibiotic treatment and its impact on resistance genes and bacteria in the respiratory microbiome using data from a randomized controlled trial of beta-lactam therapy for pediatric pneumonia. The randomized design provides reliable evidence of the effectiveness of interventions and minimizes the potential for confounding. Children receiving 5 days of therapy for pneumonia had a lower prevalence of two different types of resistance genes than did those receiving the 10-day treatment. Our data also suggest that children receiving longer durations of therapy have a greater abundance of antibiotic resistance genes for a longer period of time than do children receiving shorter durations of therapy. These data provide an additional rationale for reductions in antibiotic use.

The combination of rituximab and lenalidomide achieved results that were similar to those of rituximab plus chemotherapy in the treatment of previously untreated patients with advanced follicular lymphoma.

Background. The causes of persistent bacteremia (PB) due to methicillin-resistant Staphylococcus aureus (MRSA) are poorly understood. This investigation examined potential associations between PB with key clinical features and several in vitro bacterial genotypic and phenotypic characteristics, in isolates from 1 institution. Methods. Pulsed-field gel electrophoresis (PFGE) relatedness, thrombin-induced platelet microbicidal protein (tPMP)-susceptibility phenotype, accessory gene regulator (agr) genotype and functionality (via δ-lysin production), and autolysis phenotypes were assessed in MRSA isolates from the bloodstream of 21 prospectively identified patients with PB (blood cultures positive after ⩾7 days of therapy) and of 18 patients with resolving bacteremia (RB) (sterile blood cultures within the first 2–4 days of therapy) due to MRSA. Results. The 2 groups had comparable baseline characteristics but differed in their clinical courses (e.g., endocarditis was more frequent in patients with PB than in those with RB [43% vs. 0%, respectively; P = .0016]); isolates from patients with PB exhibited higher rates of (1) survival in vitro after exposure to tPMP (22.4 ± 14.8% vs. 11.6 ± 6.5%, respectively; P = .005); (2) defective δ-lysin production (71.4% vs. 38.9%, respectively; P = .057); (3) non-agr genotype II profile (100% vs. 77.8%, respectively; P = .037); and (4) overrepresentation of a specific PFGE genotype (85.7% vs. 44.4%, respectively; P = .015). Conclusions. Isolates from patients with PB differed from those in patients with RB, in several in vitro characteristics. Further studies will be necessary to define how these factors might affect clinical outcome.

Background. Because of its ease of dosing, vancomycin is commonly used to treat methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia in patients undergoing long-term hemodialysis. Clinical outcomes resulting from such a therapeutic strategy have not been well defined. Methods. We prospectively identified patients undergoing long-term hemodialysis who received a diagnosis of MSSA bacteremia. Clinical outcomes were grouped according to the predominant antibiotic received during their therapy (vancomycin or a first-generation cephalosporin [cefazolin]). Treatment failure (defined as death or recurrent infection) was determined at 12 weeks after the initial positive blood culture results. A multivariable analysis was used to adjust for confounders. Results. During an 84-month period, 123 hemodialysis-dependent patients with MSSA bacteremia were identified. Patients receiving vancomycin (n = 77) tended to be younger (51 vs. 57 years; P = .06) and had a lower rates of metastatic complications at presentation (11.7% vs. 36.7%; P = .001) than did those receiving cefazolin (n = 46). The 2 groups were similar with regard to Acute Physiology and Chronic Health Evaluation II scores, comorbidities, source of infection, type of hemodialysis access, and access removal rates. Treatment failure was more common among patients receiving vancomycin (31.2% vs. 13%; P = .02). In the multivariable analysis, factors independently associated with treatment failure included vancomycin use (odds ratio, 3.53; 95% confidence interval, 1.15–13.45) and retention of the hemodialysis access (odds ratio, 4.99; 95% confidence interval, 1.89–13.76). Conclusions. Hemodialysis-dependent patients with MSSA bacteremia treated with vancomycin are at a higher risk of experiencing treatment failure than are those receiving cefazolin. In the absence of patient specific circumstances (e.g., allergy to β-lactams), vancomycin should not be continued beyond empirical therapy for hemodialysis-dependent patients with MSSA bacteremia.

Background Telavancin, a novel lipoglycopeptide, exerts concentration-dependent, rapid bactericidal activity on account of its multiple mechanisms of action. Telavancin is highly active against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate, and vancomycin-resistant strains. Methods We conducted a randomized, double-blind, controlled, phase-2 clinical trial. Patients ⩾18 years of age with a diagnosis of complicated skin and soft-tissue infection caused by suspected or confirmed gram-positive organisms were randomized to receive either intravenously administered telavancin once daily or standard therapy (antistaphylococcal penicillin 4 times daily or vancomycin twice daily). Results For the study, 167 patients were randomized and received at least 1 dose of study medication. Success rates were similar in all analysis populations at the test-of-cure evaluation. Of patients with S. aureus infection at baseline (n = 102), 80% of the telavancin group were cured and 77% of the standard therapy group were cured. For patients with MRSA infection at baseline (n = 48), cure rates were 82% for the telavancin group and 69% for the standard therapy group. Microbiologic eradication in patients with MRSA infection was 84% for the telavancin group versus 74% for the standard therapy group. MIC90 values were lower for telavancin in all tested strains of S. aureus (⩽0.25 ug/mL) compared with the MIC90 values for vancomycin and oxacillin. Similar proportions of patients discontinued therapy for adverse events in both treatment groups (∼5%). Fewer serious adverse events were reported in the telavancin group (4 events) than were for the standard therapy group (9). Conclusion Clinical and microbiological results of this study support the further development of telavancin, especially for treatment of infection due to MRSA.

Although cardiac devices have been found to reduce symptoms and mortality rates in appropriate patient populations, the implications of certain important risks, such as infection, are incompletely understood. The purpose of this study was to use a large population-based database to define the population that is at risk for cardiac device infections, determine the prevalence of device infections, and study changes in the rates of cardiac device implantation and infection in the past decade. Patients with cardiac device implantations and infections were identified with claims files from the Health Care Finance Administration for Medicare beneficiaries from January 1, 1990, through December 31, 1999. Rates of implantation of cardiac devices were determined. Time trend analyses were performed to determine the significance of the observed change in rates. Cardiac device implantation rates increased from 3.26 implantations per 1000 beneficiaries in 1990 to 4.64 implantations per 1000 beneficiaries in 1999, which represents an increase of 42% in 10 years ( P for trend <.001). Cardiac device infections showed a larger increase, from 0.94 device infections per 1000 beneficiaries in 1990 to 2.11 device infections per 1000 beneficiaries in 1999, which represents an increase of 124% during the study period ( P for trend <.001). During the previous decade, there was a significant increase in both cardiac device implantations and infections in elderly patients, although the increase in the rates of device infections was substantially higher. Additional studies are needed to better understand the relationship and timing between cardiac device implantation and infection.

Background. Telavancin is an investigational, rapidly bactericidal lipoglycopeptide with a multifunctional mechanism of action. Methods. We conducted 2 parallel, randomized, double-blind, active-control, phase 3 studies with a prespecified pooled analysis design. Patients aged ⩾18 years who had complicated skin and skin-structure infections caused by suspected or confirmed gram-positive organisms were randomized to receive either telavancin (10 mg/kg intravenously every 24 h) or vancomycin (1 g intravenously every 12 h). Results. A total of 1867 patients were randomized and received ⩾1 dose of study medication. In the clinically evaluable population, at 7–14 days after receipt of the last antibiotic dose, success was achieved in 88% and 87% of patients who received telavancin and vancomycin, respectively (95% confidence interval for the difference, −2.1 to 4.6). Methicillin-resistant Staphylococcus aureus was isolated at baseline from samples from 579 clinically evaluable patients. Among these patients with methicillin-resistant S. aureus infection, cure rates were 91% among patients who received telavancin and 86% among patients who received vancomycin (95% confidence interval for the difference, −1.1 to 9.3). Microbiologic eradication among patients infected with methicillin-resistant S. aureus was 90% in the telavancin treatment group and 85% in the vancomycin treatment group (95% confidence interval for the difference, −0.9 to 9.8). Therapy was discontinued because of adverse events in 8% and 6% of patients who received telavancin and vancomycin, respectively. Except for mild taste disturbance, nausea, vomiting, and serum creatinine concentration elevation in the telavancin treatment group and pruritus in the vancomycin treatment group, adverse events were similar between groups with regard to type and severity. Conclusions. Telavancin given once daily is at least as effective as vancomycin for the treatment of patients with complicated skin and skin-structure infections, including those infected with methicillin-resistant S. aureus.