Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence. Objective: To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength. Evidence Review: This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches. Findings: A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)-only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions. Conclusions and Relevance: In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed.

Real-life experience with IV fosfomycin in Canada: Results from the Canadian LEadership on Antimicrobial Real-life usage (CLEAR) registry.

OBJECTIVES: Data on the use of intravenous (IV) fosfomycin in Canada are limited. Using data captured by the Canadian LEadership on Antimicrobial Real-life usage (CLEAR) registry, we report the use of IV fosfomycin in Canadian patients. METHODS: The CLEAR registry uses the web-based data management program, REDCapTM (https://rcsurvey.radyfhs.umanitoba.ca/surveys/?s=F7JXNDFXEF) to facilitate clinicians' entering of details associated with their clinical experiences using IV fosfomycin. RESULTS: Data were available for 59 patients treated with IV fosfomycin. The most common infections treated were: bacteraemia or sepsis (25.4% of patients), complicated urinary tract infection (20.3%), ventilator-associated bacterial pneumonia (18.6%), and hospital-acquired pneumonia (13.6%). IV fosfomycin was used to treat Gram-negative (88.1%) and Gram-positive (10.2%) infections. The most common pathogens treated were carbapenem-resistant Enterobacterales (44.1%), multidrug-resistant Pseudomonas aeruginosa (18.6%), vancomycin-resistant Enterococcus faecium (5.1%), and methicillin-resistant Staphylococcus aureus (3.4%). IV fosfomycin was primarily used due to resistance to initially prescribed therapies (69.5%), frequently in combination with other agents (86.4%). Microbiological success (eradication/presumed eradication) occurred in 77.4% of patients, and clinical success (clinical cure/improvement) occurred in 62.5%. Overall, 15.3% of patients died because of their infection. Adverse effects were not documented in 73.1% of patients, and no patient discontinued therapy because of an adverse effect. CONCLUSIONS: In Canada, IV fosfomycin is used primarily as directed therapy to treat a variety of severe infections caused by Gram-negative and Gram-positive bacteria. It is primarily used in patients infected with bacteria resistant to other agents and as part of combination therapy. Its use is associated with relatively high microbiological and clinical cure rates, and it has an excellent safety profile.

Real-life experience with ceftolozane/tazobactam in Canada: results from the CLEAR (Canadian LEadership on Antimicrobial Real-life usage) registry.

OBJECTIVES: Ceftolozane/tazobactam is a cephalosporin/ß-lactamase inhibitor combination with activity against Gram-negative bacilli. Here we report the use of ceftolozane/tazobactam in Canada using a national registry. METHODS: The CLEAR registry uses a REDCapTM online survey to capture details associated with clinical use of ceftolozane/tazobactam. RESULTS: Data from 51 patients treated in 2020 with ceftolozane/tazobactam are available. Infections treated included hospital-acquired bacterial pneumonia (37.3% of patients), ventilator-associated bacterial pneumonia (15.7%), bone and joint infection (11.8%), complicated intra-abdominal infection (7.8%) and complicated skin and skin-structure infection (7.8%). Moreover, 17.6% of patients had bacteraemia and 47.1% were in intensive care. Ceftolozane/tazobactam was primarily used as directed therapy for Pseudomonas aeruginosa infections (92.2% of patients). Ceftolozane/tazobactam was used because of resistance to (86.3%), failure of (11.8%) or adverse effects from (2.0%) previously prescribed antimicrobials. Ceftolozane/tazobactam susceptibility testing was performed on isolates from 88.2% of patients. Ceftolozane/tazobactam was used in combination with another antimicrobial active against Gram-negative bacilli in 39.2% of patients [aminoglycosides (15.7%), fluoroquinolones (9.8%) and colistin/polymyxin B (7.8%)]. The dosage regimen was customised in all patients based on creatinine clearance. The treatment duration was primarily >10 days (60.8% of patients), with microbiological success in 60.5% and clinical success in 64.4% of patients. Moreover, 7.8% of patients had adverse effects not requiring drug discontinuation. CONCLUSION: In Canada, ceftolozane/tazobactam is used as directed therapy to treat a variety of severe infections caused by multidrug-resistant P. aeruginosa. It is commonly used in combination with other antimicrobials with relatively high microbiological/clinical cure rates and an excellent safety profile.

Pharmacokinetics of Tobramycin Administered at the Beginning of Intermittent Hemodialysis Session (ESRD Study).

BACKGROUND AND OBJECTIVES: There is a renewed interest in the successful use of aminoglycosides due to increasing resistance in gram-negative infections. Few studies to date have examined the pharmacokinetics (PK) of intradialytic infusions of tobramycin. This study sought to characterize the pharmacokinetic profile of intradialytically administered tobramycin in infected patients receiving chronic intermittent hemodialysis and to determine whether it is possible to achieve favorable PK targets. DESIGN SETTING PARTICIPANTS AND MEASUREMENTS: In this prospective pharmacokinetic study, a single dose (5 mg/kg) of tobramycin was administered intradialytically to 11 noncritically ill patients undergoing chronic intermittent hemodialysis. Blood samples were collected at selected time to determine tobramycin serum concentrations. The PK analysis was performed using Phoenix™ NLME. The efficacy exposure outcome for nonsevere gram-negative infections sensitive to tobramycin with a minimum inhibitory concentration ≤1 were maximum concentration (Cmax ≥ 10 mg/L) and area under the curve (AUC24 h > 30 mg⋅h/L). For toxicity, the goal was to identify plasma trough concentrations <2 mg/L. RESULTS: Tobramycin disposition was best described by a one-compartment model using a total clearance composed of the systemic clearance and a transitory hemodialysis clearance. Tobramycin mean (SD) Cmax, trough levels, and AUC24h were 13.1 (1.3) mg/L, 1.32 (0.47) mg/L, and 61 (23) mg⋅h/L, respectively. Monte Carlo simulation run with 1000 virtual patients showed that a 5 mg/kg dose of tobramycin administered intradialytically can outperformed the usual low-dose postdialysis dosing (80% meeting all targets versus <1%, respectively). CONCLUSIONS: A single high dose of tobramycin can achieve favorable PK outcome when administered using intradialytic infusions in hemodialysis patients. This practical dosing regimen may represent an effective and safer alternative to the usual dosing in the treatment of nonsevere gram-negative infections.

CONTEXTE ET OBJECTIFS: La résistance croissante des infections à Gram négatif suscite un regain d'intérêt pour l'utilisation efficace des aminoglycosides. À ce jour, peu d'études ont examiné la pharmacocinétique (PK) des infusions intradialytiques de tobramycine. La présente étude a tenté de caractériser le profil pharmacocinétique de la tobramycine administrée par infusion intradialytique chez des patients malades recevant des traitements intermittents d'hémodialyse de façon chronique. L'étude visait également à déterminer s'il est possible d'atteindre des objectifs de pharmacocinétique favorables. MÉTHODOLOGIE: Pour cette étude de pharmacocinétique prospective, une dose unique (5 mg/kg) de tobramycine a été administrée par infusion intradialytique à onze patients suivant des traitements d'hémodialyse intermittente de façon chronique ne nécessitant pas une admission aux soins intensifs. Des échantillons de sang ont été prélevés à des moments précis afin de mesurer les concentrations sériques de tobramycine. L'analyse de la PK a été effectuée à l'aide du PhoenixMC NLME. Les issues d'exposition d'efficacité avec une concentration minimale inhibitrice inférieure ou égale à 1 pour les infections à Gram négatifs non graves sensibles à la tobramycine étaient la concentration maximum (Cmax: ≥10 mg/L) et la surface sous la courbe (SSC24h: >30 mg⋅h/L). Quant à la toxicité, l'objectif était l'observation de concentrations plasmatiques inférieures à 2 mg/L. RÉSULTATS: La disponibilité de la tobramycine a été mieux décrite par un modèle à un compartiment utilisant une clairance totale composée de la clairance systémique et de la clairance transitoire de l'hémodialyse. La Cmax moyenne, la concentration minimale et la SSC24h de la tobramycine (écart-type) s'établissaient respectivement à 13,1 (1,3) mg/L, à 1,32 (0,47) mg/L et à 61 (23) mg⋅h/L. Une simulation de Monte Carlo réalisée avec 1 000 patients virtuels a montré qu'une dose unique de 5 mg/kg de tobramycine administrée par infusion intradialytique surpasse la faible dose normalement administrée après la dialyse (80 % des objectifs atteints pour la dose unique contre moins de 1 %, respectivement). CONCLUSIONS: Une dose unique élevée de tobramycine permet d'atteindre des paramètres pharmacocinétiques favorables si elle est administrée par infusion intradialytique chez les patients hémodialysés. Ce schéma posologique peut représenter une solution de remplacement efficace et plus sûre au dosage normalement administré pour le traitement des infections à Gram négatifs non graves.

Increase in the Risk of Respiratory Disorders in Adults and Children Related to Crop-Growing in Niger.

Background and Objective. Environmental factors are an increasing concern for respiratory health in developing countries. The objective of this study was to investigate whether Nigerien people living in cultivated areas have more respiratory symptoms than those living in pastoral areas. Method. A cross-sectional study was conducted in 2013 in two populations during the rainy season when land is cultivated. Environmental factors including pesticide use and respiratory symptoms were collected in adults and children during face-to-face interviews. Multivariate analysis between exposures and symptoms was performed in children and in adults separately. Results. The study included 471 adults and 229 children. Overall, none of the households reported the use of pesticides for agricultural purposes. However, 87.2% reported the use of insecticides at home. Multivariate analysis showed that people living in agricultural areas compared to those in pastoral areas had an increased risk of respiratory symptoms in adults (wheezing, dyspnea, sudden shortness of breath, and cough without fever) and in children (cough without fever). The use of insecticides showed no effect on respiratory symptoms after adjustment. Conclusion. This first epidemiological study on the environment and respiratory health conducted in Niger demonstrates a significant relationship between respiratory manifestations and the agricultural characteristics of the living area. However only the effect of insecticides in the home on respiratory health was observed.

Environmental exposure to pesticides and respiratory health.

Respiratory effects of environmental exposure to pesticides are debated. Here we aimed to review epidemiological studies published up until 2013, using the PubMed database. 20 studies dealing with respiratory health and non-occupational pesticide exposure were identified, 14 carried out on children and six on adults. In four out of nine studies in children with biological measurements, mothers' dichlorodiphenyldichloroethylene (DDE) blood levels during pregnancy were associated with asthma and wheezing in young children. An association was also found between permethrin in indoor air during pregnancy and wheezing in children. A significant association between asthma and DDE measured in children's blood (aged 7-10 years) was observed in one study. However, in three studies, no association was found between asthma or respiratory infections in children and pesticide levels in breast milk and/or infant blood. Lastly, in three out of four studies where post-natal pesticide exposure of children was assessed by parental questionnaire an association with respiratory symptoms was found. Results of the fewer studies on pesticide environmental exposure and respiratory health of adults were much less conclusive: indeed, the associations observed were weak and often not significant. In conclusion, further studies are needed to confirm whether there is a respiratory risk associated with environmental exposure to pesticides.

Occupational exposure to pesticides and respiratory health.

This article aims to review the available literature regarding the link between occupational exposure to pesticides and respiratory symptoms or diseases. Identification of epidemiological studies was performed using PubMed. 41 articles were included, 36 regarding agricultural workers and five regarding industry workers. Among the 15 cross-sectional studies focusing on respiratory symptoms and agricultural pesticide exposure, 12 found significant associations with chronic cough, wheeze, dyspnoea, breathlessness or chest tightness. All four studies on asthma found a relationship with occupational exposure, as did all three studies on chronic bronchitis. The four studies that performed spirometry reported impaired respiratory function linked to pesticide exposure, suggestive of either obstructive or restrictive syndrome according to the chemical class of pesticide. 12 papers reported results from cohort studies. Three out of nine found a significant relationship with increased risk of wheeze, five out of nine with asthma and three out of three with chronic bronchitis. In workers employed in pesticide production, elevated risks of chronic obstructive pulmonary disease (two studies out of three) and impaired respiratory function suggestive of an obstructive syndrome (two studies out of two) were reported. In conclusion, this article suggests that occupational exposure to pesticides is associated with an increased risk of respiratory symptoms, asthma and chronic bronchitis, but the causal relationship is still under debate.

Balance control interferes with the tracing performance of a pattern with mirror-reversed vision in older persons.

When tracing a template with mirror-reversed vision (or distorted vision), the sensory information arising from the movement does not match the expected sensory consequences. In such situations, participants have to learn a new visuomotor mapping in order to trace the template with an accuracy and speed approaching that observed when tracing with direct vision. There are several suggestions that such visuomotor learning requires lowering the gain of the proprioceptive inputs. Generally, subjects learn this task in a seated condition offering a stable postural platform. Adapting to the new visuomotor relationship in a standing condition could add complexity and even hinder sensorimotor adaptation because balance control and processing of additional information typically interfere with each other. To examine this possibility, older individuals and young adults (on average, 70 and 22 years of age, respectively) were assigned to groups that trained to trace a shape with mirror-reversed vision in a seated or a standing condition for two sessions. For a third session, the seated groups (young and elderly) transferred to the standing condition while the standing groups continued to perform the tracing task while standing. This procedure allowed comparing the tracing performance of all groups (with the same amount of practice) in a standing condition. The standing groups also did a fourth session in a seated condition. Results show that older participants initially exposed to the standing condition were much slower to trace the template than all other groups (including the older group that performed the tracing task while seated). This slowness did not result from a baseline general slowness but from a genuine interference between balance control and the visuomotor conflict resulting from tracing the pattern with mirror-reversed vision. Besides, the Standing-Old participants that transferred to a seated condition in the fourth session immediately improved their tracing by reducing the total displacement covered by the pen to trace the template. Interestingly, the results did not support a transfer-appropriate practice hypothesis which suggests that training in a standing condition (at the third session) should have benefited the performance of those individuals who initially learned to trace the mirror pattern in a standing condition. This has important clinical implications: training at adapting to new sensory contexts or environmental conditions in conditions that do not challenge balance control could be necessary if one desires to attenuate the detrimental consequences on the postural or motor performances brought up by the interference between maintaining balance and the sensory reweighing processes.

Lower-Limb Power cannot be Estimated Accurately from Vertical Jump Tests.

The countermovement jump test is often adopted to monitor lower-limb power of an individual. Despite several studies on the validity of this test, there is still a need to determine the minimal difference needed to be confident that a difference in power between two individuals is present or that a true change in the performance of an individual has occurred. In this study, power was measured from ground reaction forces and compared to that obtained from predictive equations for two groups of subjects (67 trained and 20 highly trained individuals). The height of each jump was determined with kinematic techniques. The main outcome is a large discrepancy between power calculated from ground reaction forces and that calculated from predictive equations. For the trained group, the R-square value between power and predicted power was 0.53 and the minimal difference to consider that two individuals were different was 821.7 W. For the highly trained individuals, a much larger R-square value was obtained (0.94). Despite this, the minimal difference to consider that two individuals were different was still large (689.3 W). The large minimal differences obtained raise serious concerns about using countermovement jumps for appraisal and monitoring of lower-limb power of an individual.

Bronchitis-like symptoms and proximity air pollution in French elderly.

BACKGROUND: Our aim was to explore the association between respiratory health and proximity air quality in elderly. METHODS: The prevalence of respiratory conditions was linked in 2104 individuals aged > or =65 years recruited in Bordeaux (3C Study) to home address concentrations of NO2, CO, SO2, fine particles (PM(10)), VOCs and benzene, estimated through a dispersion model combining data on background air pollution, traffic characteristics, and conditions of topographical and meteorological dispersion of air pollutants. RESULTS: Mean [minimum; maximum] values of the annual concentrations (microg/m(3)) of proximity air pollutants were respectively: 28 [18; 72.2] for NO2, 420 [350; 1337] for CO, 7.5[5; 13.7] for SO2, 23.1 [19; 51] for PM(10), 8.1 [0.01; 116.6] for VOCs and 1.8 [1.5; 6.9] for benzene. Using a binary logistic regression model, PM(10) were significantly associated with usual cough (Odds-Ratio=1.33 (95% confidence interval: 1.00-1.77) for exposed compared to non-exposed) and SO(2) with usual cough (1.55 (1.16-2.08)) and phlegm (1.45 (1.04-2.01)). We found a 10% and a 23% increase in usual cough for a 10microg/m(3) increment in PM(10) and a 1microg/m(3) increment in SO2 respectively, and a 23% increase in usual phlegm for a 1microg/m(3) increase in SO2. A sensitivity analysis showed similar results when considering 3-year proximity pollution. A more pronounced effect of SO2 and PM(10) on usual cough and phlegm was observed in woman. CONCLUSIONS: Our assessment of exposure to proximity air pollution has shown an increased prevalence of bronchitis-like symptoms in elderly living in areas polluted by SO2 and PM(10).

Tobacco addiction and HIV infection: toward the implementation of cessation programs. ANRS CO3 Aquitaine Cohort.

In treated HIV-infected patients, mortality is now dominated by non-AIDS-related causes in which tobacco smoking is a predominant risk factor. The implementation of tobacco smoking cessation programs is therefore warranted to increase survival but should consider the specificities of this population to be successful. All outpatients consulting in May to June 2004 within the ANRS CO3 Aquitaine Cohort of HIV-infected patients were asked to complete a self-administered questionnaire including questions about tobacco and other drugs consumption, the Fagerström Test for Nicotine Dependence (FTND), a visual scale to estimate motivation to stop smoking and the Center for Epidemiologic Studies Depression (CESD) scale. Among 509 patients included, mean age was 44 years, 74% were men, 19% were infected through injection drug use, and 257 (51%) were regular smokers (at least one cigarette per day). Among them, 60% had a medium or strong nicotine dependence (FTND = 5), 40% were motivated to quit smoking and 70% had already tried at least once. An FTND of 5 or more was more frequently reported in the 146 smokers (62%) with depressive symptoms compared to other smokers (70% versus 48%). Fifty-five regular smokers (23%) were codependent on cannabis and 31 (12%) to alcohol. Overall, only 35 (14%) regular smokers were motivated, non-codependent, without depressive symptoms, and could be proposed a standard tobacco cessation program. Depressive symptoms were highly prevalent in this representative population of HIV-infected patients. To be successful, smoking cessation interventions should be specifically built to take into account depression and codependencies in addition to nicotine dependence and motivation.

Effects of particulate air pollution on systolic blood pressure: A population-based approach.

Given the hypothesis that particulate air pollution is associated with systolic blood pressure, the effect of daily concentrations of air pollution on blood pressure was assessed in 2612 elderly subjects in the urban area of Bordeaux, France. Blood pressure was measured by a digital monitor. Particle concentrations (PM10) were obtained from the AIRAQ association that operates a local monitoring network of the air quality. To represent the ambient urban air pollution, stations had to be sufficiently correlated (i.e., correlation >0.70) and to have sufficiently similar mean levels of pollution. Linear regression was used to model the association between concentrations of particles (PM10) and systolic blood pressure. We observed associations between the fifth lag hour and systolic blood pressure for an increase of 10 microg/m3 of PM10 (beta = -1.12, 95% confidence interval: [-1.90; -0.30]). Despite contradictory results, fine particles must be considered nowadays as a major component of atmospheric air pollution in which everything must be put into practice in terms of public health actions in order to protect the general population and particularly the elderly group.

Do subject characteristics modify the effects of particulate air pollution on daily mortality among the elderly?

OBJECTIVE: Studies have reported associations between mortality and air pollution, but questions subsist on the identification of susceptible subgroups in the population. We studied individual characteristics that modify the relationship between particulate air pollution and mortality among elderly. METHOD: We examined 527 nonaccidental deaths (197 cardiorespiratory deaths) among the 1469 subjects from the Personnes Agees QUID cohort in Bordeaux between 1988 and 1997. Air pollution was measured as black smoke by urban monitoring background stations. We used a case crossover approach and calculated odds ratio by conditional logistic regression models. RESULTS: We observed associations between the third lag day and cardiorespiratory mortality for an increase of 10 microg/m3 of black smoke (odds ratio = 1.30, 95% confidence interval: 1.01-1.68). CONCLUSIONS: Our results provide insight into factors possibly conferring susceptibility to the acute effect of urban air pollution.

Difference in the relation between daily mortality and air pollution among elderly and all-ages populations in southwestern France.

Numerous time series studies around the world have reported an association between mortality and particulate air pollution. We investigated the distribution over time of effect of air pollution on short-term mortality among subjects aged 65 years and older and of all ages in Bordeaux, France. Statistical analysis was based on generalized additive models using either loess or penalized spline smoothing. Our study found a significant positive association between air pollution and all nonaccidental mortality and specific mortality in both group of population (all ages and elderly) with a greater effect among the elderly, particularly for respiratory mortality. For this case, we observed a greater effect according to distributed lag models (0-5 days) among the elderly, with an estimated increase of 9.2% in the daily number of deaths for 10 microg/m(3) of daily black smoke [95% CI, 3.4-15.3]. These results contribute to the efforts made to understand how air pollution promotes adverse health effects and to identify susceptible subgroups.

Long-term air pollution indicator assessment: example of black smoke in Bordeaux, France.

The aim of the second phase of the Pollution Atmosphérique et Affections Respiratoires Chroniques (PAARC) study, started in 1974, was to compare the long-term mortality between populations living in areas with different air pollution levels. In Bordeaux (France), four different areas were concerned by the study. The black smoke measures were realized between 1974 and 1981. After 1981, the stations set specifically for the study were not used any more. The purpose of this study was to estimate the evolution of air pollution in those areas between 1982 and 1997 using the measures of 12 Association de Prévention de la Pollution Atmosphérique (APPA) stations located in Bordeaux city but not in the PAARC areas. The method used was divided in three phases: a correlation study between the stations of the different networks, a selection of the pertinent stations and the setting up of indicators using the arithmetic means method. Monthly means concentrations were estimated from January 1982 to December 1997. Models showed a decrease in black smoke levels whatever the area. The difference in level from one area to another, existing between the areas in 1974, was still with predicted values in 1997, but less important. Black smoke mean concentration for 1982-1997 was, respectively, 16.4 and 16.2 microg/m3, in areas 1 and 2. It was a little bit higher in area 3 with 18.9 microg/m3. Area 4 still has the highest level with 26.3 microg/m3. To conclude, this method enabled to assess different air pollution levels at different times in the four areas of the PAARC study in Bordeaux. Those levels could be used to study the impact of the air pollution on long-term mortality on populations living in the areas considered.