Antimicrobial resistance with Streptococcus pneumoniae in the United States, 1997 98.

From November 1997 to April 1998, 1,601 clinical isolates of Streptococcus pneumoniae were obtained from 34 U.S. medical centers. The overall rate of strains showing resistance to penicillin was 29. 5%, with 17.4% having intermediate resistance. Multidrug resistance, defined as lack of susceptibility to penicillin and at least two other non-ss-lactam classes of antimicrobial drugs, was observed in 16.0% of isolates. Resistance to all 10 ss-lactam drugs examined in this study was directly related to the level of penicillin resistance. Penicillin resistance rates were highest in isolates from middle ear fluid and sinus aspirates of children ambulatory-care settings. Twenty-four of the 34 medical centers in this study had participated in a similar study 3 years before. In 19 of these 24 centers, penicillin resistance rates increased 2.9% to 39.2%. Similar increases were observed with rates of resistance to other antimicrobial drugs

Linear low-dose extrapolation for noncancer health effects is the exception, not the rule

The nature of the exposure-response relationship has a profound influence on risk analyses. Several arguments have been proffered as to why all exposure-response relationships for both cancer and noncarcinogenic end-points should be assumed to be linear at low doses. We focused on three arguments that have been put forth for noncarcinogens. First, the general “additivity-to-background” argument proposes that if an agent enhances an already existing disease-causing process, then even small exposures increase disease incidence in a linear manner. This only holds if it is related to a specific mode of action that has nonuniversal properties—properties that would not be expected for most noncancer effects. Second, the “heterogeneity in the population” argument states that variations in sensitivity among members ofthe target population tend to “flatten out and linearize” the exposure-response curve, but this actually only tends to broaden, not linearize, the dose-response relationship. Third, it has been argued that a review of epidemiological evidence shows linear or no-threshold effects at low exposures in humans, despite nonlinear exposure-response in the experimental dose range in animal testing for similar endpoints. It is more likely that this is attributable to exposure measurement error rather than a true non-threshold association. Assuming that every chemical is toxic at high exposures and linear at low exposures does not comport to modern-day scientific knowledge of biology. There is no compelling evidence-based justification for a general low-exposure linearity; rather, case-specific mechanistic arguments are needed

Advancements in Life Cycle Human Exposure and Toxicity Characterization

BACKGROUND: The Life Cycle Initiative, hosted at the United Nations Environment Programme, selected human toxicity impacts from exposure to chemical substances as an impact category that requires global guidance to overcome current assessment challenges. The initiative leadership established the Human Toxicity Task Force to develop guidance on assessing human exposure and toxicity impacts. Based on input gathered at three workshops addressing the main current scientific challenges and questions, the task force built a roadmap for advancing human toxicity characterization, primarily for use in life cycle impact assessment (LCIA). OBJECTIVES: The present paper aims at reporting on the outcomes of the task force workshops along with interpretation of how these outcomes will impact the practice and reliability of toxicity characterization. The task force thereby focuses on two major issues that emerged from the workshops, namely considering near-field exposures and improving dose-response modeling. DISCUSSION: The task force recommended approaches to improve the assessment of human exposure, including capturing missing exposure settings and human receptor pathways by coupling additional fate and exposure processes in consumer and occupational environments (near field) with existing processes in outdoor environments (far field). To quantify overall aggregate exposure, the task force suggested that environments be coupled using a consistent set of quantified chemical mass fractions transferred among environmental compartments. With respect to dose-response, the task force was concerned about the way LCIA currently characterizes human toxicity effects, and discussed several potential solutions. A specific concern is the use of a (linear) dose-response extrapolation to zero. Another concern addresses the challenge of identifying a metric for human toxicity impacts that is aligned with the spatiotemporal resolution of present LCIA methodology, yet is adequate to indicate health impact potential. CONCLUSIONS: Further research efforts are required based on our proposed set of recommendations for improving the characterization of human exposure and toxicity impacts in LCIA and other comparative assessment frameworks. https://doi.org/10.1289/EHP3871

Toxicity Testing in the 21st Century: Defining New Risk Assessment Approaches Based on Perturbation of Intracellular Toxicity Pathways

The approaches to quantitatively assessing the health risks of chemical exposure have not changed appreciably in the past 50 to 80 years, the focus remaining on high-dose studies that measure adverse outcomes in homogeneous animal populations. This expensive, low-throughput approach relies on conservative extrapolations to relate animal studies to much lower-dose human exposures and is of questionable relevance to predicting risks to humans at their typical low exposures. It makes little use of a mechanistic understanding of the mode of action by which chemicals perturb biological processes in human cells and tissues. An alternative vision, proposed by the U.S. National Research Council (NRC) report Toxicity Testing in the 21st Century: A Vision and a Strategy, called for moving away from traditional high-dose animal studies to an approach based on perturbation of cellular responses using well-designed in vitro assays. Central to this vision are (a) “toxicity pathways” (the innate cellular pathways that may be perturbed by chemicals) and (b) the determination of chemical concentration ranges where those perturbations are likely to be excessive, thereby leading to adverse health effects if present for a prolonged duration in an intact organism. In this paper we briefly review the original NRC report and responses to that report over the past 3 years, and discuss how the change in testing might be achieved in the U.S. and in the European Union (EU). EU initiatives in developing alternatives to animal testing of cosmetic ingredients have run very much in parallel with the NRC report. Moving from current practice to the NRC vision would require using prototype toxicity pathways to develop case studies showing the new vision in action. In this vein, we also discuss how the proposed strategy for toxicity testing might be applied to the toxicity pathways associated with DNA damage and repair

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Commercial Broth Microdilution Panel Validation and Reproducibility Trials for Garenoxacin (BMS-284756), a Novel Desfluoroquinolone

Results from garenoxacin dry-form broth microdilution MIC panels prepared commercially (Sensititre, TREK Diagnostics) were compared to reference frozen-form MICs to ensure the validity of the longer-shelf-life product. A total of 1,078 organisms from seven major organism groups were used in this trial. All commercial MIC results were within ± one log(2) dilution of reference garenoxacin values, and reproducibility trials produced identical MIC results for 90.5 to 92.1% of garenoxacin MIC comparisons. Control quinolones (ciprofloxacin and gatifloxacin) also performed at a similarly high level of accuracy

Brain Tissue Damage Induced by Multimodal Neuromonitoring In Situ during MRI after Severe Traumatic Brain Injury: Incidence and Clinical Relevance

Both neuromonitoring and early magnetic resonance imaging (MRI) provide crucial information for treatment management and prognosis in patients with severe traumatic brain injury (sTBI). So far, neuromonitoring in situ impedes the routine implementation of MRI due to safety concerns. We aimed to evaluate the brain tissue damage induced by inserted neuromonitoring devices and its clinical relevance. Nineteen patients with sTBI and being exposed to at least one MRI with neuromonitoring in situ and one follow-up MRI after neuromonitoring removal were analyzed. All MRIs were reviewed for specific tissue damage. Three females and sixteen males (aged 20–74 years, mean 42.8 years) with an initial median GCS of 5 (range 3–8) were analyzed. No lesion was observed in six patients (31.6%), whereas another six patients (31.6%) demonstrated a detectable probe trajectory. Probe-related tissue damage was visible in seven patients (36.8%) with the size of the lesion prone to further enlarge with increasing cumulative duration of MRI examinations. Upon interdisciplinary evaluation, the lesions were not considered clinically relevant. Neuromonitoring probes in situ during MRI examinations may cause local brain tissue damage, yet without any clinical implications if placed correctly. Therefore, indications must be strictly based on joint decision from all involved disciplines

In vitro activity of omiganan pentahydrochloride tested against vancomycin-tolerant, -intermediate, and -resistant Staphylococcus aureus

Omiganan, a novel topical cationic peptide active against a broad spectrum of bacteria and yeast, is targeted for the prevention of catheter-associated infections. the spectrum of this agent was evaluated against contemporary methicillin-(oxacillin)-resistant Staphylococcus aureus (MRSA; 109 isolates), including subgroups displaying reduced susceptibility to vancomycin. Strain phenotypes included: vancomycin-tolerant (MBC/MIC ratio, >= 32-fold);vancomycin-intermediate (VISA; MIC values, 4-8 pg/ml); heterogeneous vancomycin-intermediate (hVISA); and vancomycin-resistant (VRSA; MIC values, >= 16 pg/ml) S. aureus. All S. aureus tested were inhibited by <= 64 mu g/ml of omiganan, with MIC50/MTC90 values of 16/32 mu g/ml, respectively. Compared to wild-type S. aureus, MIC90 values were only 2-fold greater for vancomycin-tolerant, hVISA and VISA strains. the VRSA isolates, representing the most resistant strains tested, were inhibited by 16 mu g/ml (mode for all groups). Omiganan demonstrated potent activity against S. aureus, regardless of harbored resistance mechanism. Given the worrisome emergence of S. aureus with reduced susceptibility to vancomycin, the demonstration that omiganan remains equally active against all isolates of this species at a level significantly below the clinical formulation concentration (1% gel; 10,000 mu g/ml) is an important attribute. (C) 2008 Elsevier Inc. All rights reserved.JMI Labs, North Liberty, IA 52317 USAUniversidade Federal de São Paulo, Div Infect Dis, BR-04023900 São Paulo, BrazilUniversidade Federal de São Paulo, Div Infect Dis, BR-04023900 São Paulo, BrazilWeb of Scienc