Hepatitis B Virus (HBV) Replication During Tenofovir Therapy Is Frequent in Human Immunodeficiency Virus/HBV Coinfection.

In the Swiss HIV Cohort Study, 61 of 222 (27%) HIV-suppressed persons with chronic hepatitis B virus (HBV) infection had HBV replication after 2 years on tenofovir, of whom 77% were suppressed thereafter. Self-reported adherence to therapy and HBV viral load at tenofovir initiation were predictors of persistent replication.

Validation of sTREM-1 and IL-6 based algorithms for outcome prediction of COVID-19.

BACKGROUND: A prospective observational cohort study of COVID-19 patients in a single Emergency Department (ED) showed that sTREM-1- and IL-6-based algorithms were highly predictive of adverse outcome (Van Singer et al. J Allergy Clin Immunol 2021). We aim to validate the performance of these algorithms at ED presentation. METHODS: This multicentric prospective observational study of PCR-confirmed COVID-19 adult patients was conducted in the ED of three Swiss hospitals. Data of the three centers were retrospectively completed and merged. We determined the predictive accuracy of the sTREM-1-based algorithm for 30-day intubation/mortality. We also determined the performance of the IL-6-based algorithm using data from one center for 30-day oxygen requirement. RESULTS: 373 patients were included in the validation cohort, 139 (37%) in Lausanne, 93 (25%) in St.Gallen and 141 (38%) in EOC. Overall, 18% (93/373) patients died or were intubated by day 30. In Lausanne, 66% (92/139) patients required oxygen by day 30. The predictive accuracy of sTREM-1 and IL-6 were similar compared to the derivation cohort. The sTREM-1-based algorithm confirmed excellent sensitivity (90% versus 100% in the derivation cohort) and negative predictive value (94% versus 100%) for 30-day intubation/mortality. The IL-6-based algorithm performance was acceptable with a sensitivity of 85% versus 98% in the derivation cohort and a negative predictive value of 60% versus 92%. CONCLUSION: The sTREM-1 algorithm demonstrated good reproducibility. A prospective randomized controlled trial, comparing outcomes with and without the algorithm, is necessary to assess its safety and impact on hospital and ICU admission rates. The IL-6 algorithm showed acceptable validity in a single center and need additional validation before widespread implementation.

Epidemiology and outcomes of bone and joint infections in solid organ transplant recipients.

Bone and joint infection (BJI) epidemiology and outcomes in solid organ transplant recipients (SOTr) remain largely unknown. We aim to describe BJI in a multi-center cohort of SOTr (Swiss Transplant Cohort Study). All consecutive SOTr with BJI (01.05.2008-31.12.2019) were included. A nested case-control study to identify risk factors for BJI was performed. Among 4482 patients, 61 SOTr with 82 BJI were included, at an incidence of 1.4% (95% CI 1.1-1.7), higher in heart and kidney-pancreas SOTr (Gray's test p < .01). Although BJI were predominately late events (median of 18.5 months post-SOT), most infections occurred during the first year post-transplant in thoracic SOTr. Diabetic foot osteomyelitis was the most frequent infection (38/82, 46.3%), followed by non-vertebral osteomyelitis (26/82, 31.7%). Pathogens included Gram-positive cocci (70/131, 53.4%), Gram-negative bacilli (34/131, 26.0%), and fungi (9/131, 6.9%). BJI predictors included male gender (OR 2.94, 95% CI 1.26-6.89) and diabetes (OR 2.97, 95% CI 1.34-6.56). Treatment failure was observed in 25.9% (21/81) patients and 1-year mortality post-BJI diagnosis was 14.8% (9/61). BJI remain a rare event in SOTr, associated with subtle clinical presentations, high morbidity and relapses, requiring additional studies in the future.

Decrease of condom use in heterosexual couples and its impact on pregnancy rates: the Swiss HIV Cohort Study (SHCS).

INTRODUCTION: Following the 'Swiss statement' in 2008 it became an option to omit the use of condoms in serodiscordant couples and to conceive naturally. We analysed its impact on condom use and pregnancy events. METHODS: In all, 3023 women (aged 18-49 years) participating in the Swiss HIV Cohort Study were included. Observation time was divided into pre- and post-Swiss statement phases (July 2005-December 2008 and January 2009-December 2019). We used descriptive statistics, Poisson interrupted time series analysis for pregnancy incidence, and logistic regression to identify predictors of live births, spontaneous and induced abortions. RESULTS: Condomless sex in sexually active women increased from 25% in 2005 to 75% in 2019, while pregnancy incidence did not. Women after 2008 experienced higher spontaneous abortion rates (12.1% vs. 17.2%, p = 0.02) while induced abortion and live birth rates did not change significantly. Spontaneous abortions were more common in older women [adjusted odds ratio (aOR) = 1.4, 95% CI: 1.2-1.7, p < 0.001], in women consuming alcohol (aOR = 2.8, 95% CI: 1.9-4.1, p < 0.001) and in those with non-suppressed viral load (aOR = 0.2, 95% CI: 0.1-0.4, p ≤ 0.001). Induced abortions were more likely in women with depression (aOR = 3.4, 95% CI: 1.8-6.3, p < 0.001) and non-suppressed viral load (aOR = 0.3, 95% CI: 0.2-0.7, p = 0.003). CONCLUSIONS: The publication of the Swiss statement resulted in more condomless sex in heterosexual women, but this did not result in a higher incidence of pregnancy. Maternal age and spontaneous abortion rates increased over time, while induced abortion rates were not significantly affected. Women living with HIV in Switzerland have an unmet need regarding family planning counselling.

Post­COVID­19 Syndrome in Outpatients: a Cohort Study.

BACKGROUND: After mild COVID-19, some outpatients experience persistent symptoms. However, data are scarce and prospective studies are urgently needed. OBJECTIVES: To characterize the post-COVID-19 syndrome after mild COVID-19 and identify predictors. PARTICIPANTS: Outpatients with symptoms suggestive of COVID-19 with (1) PCR-confirmed COVID-19 (COVID-positive) or (2) SARS-CoV-2 negative PCR (COVID-negative). DESIGN: Monocentric cohort study with prospective phone interview between more than 3 months to 10 months after initial visit to the emergency department and outpatient clinics. MAIN MEASURES: Data of the initial visits were extracted from the electronic medical file. Predefined persistent symptoms were assessed through a structured phone interview. Associations between long-term symptoms and PCR results, as well as predictors of persistent symptoms among COVID-positive, were evaluated by multivariate logistic regression adjusted for age, gender, smoking, comorbidities, and timing of the survey. KEY RESULTS: The study population consisted of 418 COVID-positive and 89 COVID-negative patients, mostly young adults (median age of 41 versus 36 years in COVID-positive and COVID-negative, respectively; p = 0.020) and healthcare workers (67% versus 82%; p = 0.006). Median time between the initial visit and the phone survey was 150 days in COVID-positive and 242 days in COVID-negative patients. Persistent symptoms were reported by 223 (53%) COVID-positive and 33 (37%) COVID-negative patients (p = 0.006) and proportions were stable among the periods of the phone interviews. Overall, 21% COVID-positive and 15% COVID-negative patients (p = 0.182) attended care for this purpose. Four surveyed symptoms were independently associated with COVID-19: fatigue (adjusted odds ratio 2.14, 95% CI 1.04-4.41), smell/taste disorder (26.5, 3.46-202), dyspnea (2.81, 1.10-7.16), and memory impairment (5.71, 1.53-21.3). Among COVID-positive, female gender (1.67, 1.09-2.56) and overweight/obesity (1.67, 1.10-2.56) were predictors of persistent symptoms. CONCLUSIONS: More than half of COVID-positive outpatients report persistent symptoms up to 10 months after a mild disease. Only 4 of 14 symptoms were associated with COVID-19 status. The symptoms and predictors of the post-COVID-19 syndrome need further characterization as this condition places a significant burden on society.

Clinical sign and biomarker-based algorithm to identify bacterial pneumonia among outpatients with lower respiratory tract infection in Tanzania.

BACKGROUND: Inappropriate antibiotics use in lower respiratory tract infections (LRTI) is a major contributor to resistance. We aimed to design an algorithm based on clinical signs and host biomarkers to identify bacterial community-acquired pneumonia (CAP) among patients with LRTI. METHODS: Participants with LRTI were selected in a prospective cohort of febrile (≥ 38 °C) adults presenting to outpatient clinics in Dar es Salaam. Participants underwent chest X-ray, multiplex PCR for respiratory pathogens, and measurements of 13 biomarkers. We evaluated the predictive accuracy of clinical signs and biomarkers using logistic regression and classification and regression tree analysis. RESULTS: Of 110 patients with LRTI, 17 had bacterial CAP. Procalcitonin (PCT), interleukin-6 (IL-6) and soluble triggering receptor expressed by myeloid cells-1 (sTREM-1) showed an excellent predictive accuracy to identify bacterial CAP (AUROC 0.88, 95%CI 0.78-0.98; 0.84, 0.72-0.99; 0.83, 0.74-0.92, respectively). Combining respiratory rate with PCT or IL-6 significantly improved the model compared to respiratory rate alone (p = 0.006, p = 0.033, respectively). An algorithm with respiratory rate (≥ 32/min) and PCT (≥ 0.25 µg/L) had 94% sensitivity and 82% specificity. CONCLUSIONS: PCT, IL-6 and sTREM-1 had an excellent predictive accuracy in differentiating bacterial CAP from other LRTIs. An algorithm combining respiratory rate and PCT displayed even better performance in this sub-Sahara African setting.

COVID-19 risk stratification algorithms based on sTREM-1 and IL-6 in emergency department.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to surges of patients presenting to emergency departments (EDs) and potentially overwhelming health systems. OBJECTIVE: We sought to assess the predictive accuracy of host biomarkers at clinical presentation to the ED for adverse outcome. METHODS: Prospective observational study of PCR-confirmed COVID-19 patients in the ED of a Swiss hospital. Concentrations of inflammatory and endothelial dysfunction biomarkers were determined at clinical presentation. We evaluated the accuracy of clinical signs and these biomarkers in predicting 30-day intubation/mortality, and oxygen requirement by calculating the area under the receiver-operating characteristic curve and by classification and regression tree analysis. RESULTS: Of 76 included patients with COVID-19, 24 were outpatients or hospitalized without oxygen requirement, 35 hospitalized with oxygen requirement, and 17 intubated/died. We found that soluble triggering receptor expressed on myeloid cells had the best prognostic accuracy for 30-day intubation/mortality (area under the receiver-operating characteristic curve, 0.86; 95% CI, 0.77-0.95) and IL-6 measured at presentation to the ED had the best accuracy for 30-day oxygen requirement (area under the receiver-operating characteristic curve, 0.84; 95% CI, 0.74-0.94). An algorithm based on respiratory rate and sTREM-1 predicted 30-day intubation/mortality with 94% sensitivity and 0.1 negative likelihood ratio. An IL-6-based algorithm had 98% sensitivity and 0.04 negative likelihood ratio for 30-day oxygen requirement. CONCLUSIONS: sTREM-1 and IL-6 concentrations in COVID-19 in the ED have good predictive accuracy for intubation/mortality and oxygen requirement. sTREM-1- and IL-6-based algorithms are highly sensitive to identify patients with adverse outcome and could serve as early triage tools.

[Biomarker-guided antibiotics prescription for lower respiratory tract infections in primary care : CRP or PCT ?] / Prescription des antibiotiques guidée par les biomarqueurs en médecine de famille : CRP ou PCT ?

Lower respiratory tract infections are a frequent cause of excessive antibiotic prescription. The use of CRP and PCT has been evaluated by recent trials as a mean to assist antibiotic prescription. These studies suggest a safe reduction of antibiotic usage when prescription is guided by biomarkers. There is at the moment no evidence benefiting one of the biomarkers over the other, but a recent Swiss trial could suggest an added benefit for PCT. For now, PCT is less available, more expensive and not reimbursed. Democratization of its use, and/or clear thresholds for the use of CRP are additional ways that could participate to reduce excessive antibiotic prescription in primary care.

Les infections respiratoires basses sont une cause fréquente de prescription inappropriée d'antibiotiques en médecine de famille. L'utilisation de la CRP et de la procalcitonine (PCT) a été évaluée par plusieurs études comme moyen de guider la prescription d'antibiotiques. Ces études suggèrent une diminution sûre de la prescription lorsque l'utilisation est guidée par des biomarqueurs. Il n'y a pour l'instant pas d'évidence en faveur d'une supériorité d'un biomarqueur mais une étude suisse pourrait suggérer un effet additionnel de la PCT. Pour l'instant, elle est moins facilement accessible, plus chère et non remboursée. La démocratisation de son utilisation et/ou la définition de seuils clairs pour l'utilisation de la CRP pourraient aider à diminuer la prescription excessive d'antibiotiques en ambulatoire.

[Antibiotics use for common ENT infections]. / Antibiothérapies lors d'infections courantes de la sphère ORL.

Upper respiratory tract infections are among the most common reasons for medical consultation and the single most frequent cause of antibiotics use in ambulatory care medicine in Switzerland. In this article, we propose an update on the indications, choice and modalities for antibiotic use in frequent ENT infections, highlighting the Swiss Society for Infectious Diseases guidelines which are freely available on the internet and updated on a regular basis.

Les infections des voies respiratoires supérieures sont l'un des motifs les plus fréquents de consultation et la première cause de consommation d'antibiotiques en médecine ambulatoire en Suisse. Dans cet article, nous proposons de faire le point sur les indications à initier une antibiothérapie pour des infections courantes de la sphère ORL ainsi que sur le choix des molécules, leur posologie et la durée, en mettant en avant les recomman dations de la Société suisse d'infectiologie qui sont disponibles en libre accès sur internet et régulièrement mises à jour.

[Multidisciplinary approach to fracture-related infection]. / Prise en charge multidisciplinaire des infections de fracture.

Fracture-related infection is a feared complication of trauma surgery with potentially major repercussions on quality of life and healthcare systems. Its management is based on two pillars: a radical surgical debridement along with a targeted long-term antibiotic therapy based on multiple deep tissue samples obtained during the chosen surgical procedure. Multidisciplinary management and early diagnosis are essential for treatment success. The implementation of a standardized definition for fracture-related infections since 2018 has allowed the optimization and streamlining of management algorithms and their validation in the literature. This article provides a comprehensive and in-depth review of recent advances in the diagnosis and management of fracture-related infections.

L'infection de fracture est une complication redoutée en traumatologie avec des répercussions importantes sur la qualité de vie des patients et le système de santé. Sa prise en charge repose sur deux piliers : un débridement chirurgical radical associé à une antibiothérapie ciblée de longue durée basée sur des prélèvements profonds multiples peropératoires. Une prise en charge multidisciplinaire ainsi qu'un diagnostic précoce sont essentiels pour le succès du traitement. Depuis 2018, une définition a permis d'optimiser et de standardiser la prise en charge des infections de fracture et de valider plusieurs critères diagnostiques. Cet article offre une vue d'ensemble et approfondie des avancées récentes dans le diagnostic et la prise en charge des infections de fracture.

Lung Ultrasonography for Risk Stratification in Patients with Coronavirus Disease 2019 (COVID-19): A Prospective Observational Cohort Study.

BACKGROUND: Lung ultrasonography (LUS) is a promising pragmatic risk-stratification tool in coronavirus disease 2019 (COVID-19). This study describes and compares LUS characteristics between patients with different clinical outcomes. METHODS: Prospective observational study of polymerase chain reaction-confirmed adults with COVID-19 with symptoms of lower respiratory tract infection in the emergency department (ED) of Lausanne University Hospital. A trained physician recorded LUS images using a standardized protocol. Two experts reviewed images blinded to patient outcome. We describe and compare early LUS findings (≤24 hours of ED presentation) between patient groups based on their 7-day outcome (1) outpatients, (2) hospitalized, and (3) intubated/dead. Normalized LUS score was used to discriminate between groups. RESULTS: Between 6 March and 3 April 2020, we included 80 patients (17 outpatients, 42 hospitalized, and 21 intubated/dead). Seventy-three patients (91%) had abnormal LUS (70% outpatients, 95% hospitalized, and 100% intubated/dead; P = .003). The proportion of involved zones was lower in outpatients compared with other groups (median [IQR], 30% [0-40%], 44% [31-70%], 70% [50-88%]; P < .001). Predominant abnormal patterns were bilateral and there was multifocal spread thickening of the pleura with pleural line irregularities (70%), confluent B lines (60%), and pathologic B lines (50%). Posterior inferior zones were more often affected. Median normalized LUS score had a good level of discrimination between outpatients and others with area under the ROC of .80 (95% CI, .68-.92). CONCLUSIONS: Systematic LUS has potential as a reliable, cheap, and easy-to-use triage tool for the early risk stratification in patients with COVID-19 presenting to EDs.

[Diagnosis and management of chronic osteomyelitis of long bones in adults]. / Diagnostic et prise en charge de l'ostéomyélite chronique des os longs chez l'adulte.

Chronic osteomyelitis is an inflammatory process of the bone caused by an infectious agent. This condition leads to altered bone vascularization and thus to bone destruction and formation of necrotic bone fragments (sequestrum). The treatment of chronic osteomyelitis is primarily based on surgical management, which includes debridement of the sequestrum and sampling of bone tissue for microbiological analysis in order to initiate a targeted antibiotic therapy. A multidisciplinary approach is essential, involving expertise in orthopedic surgery, musculoskeletal imaging and nuclear medicine, infectious diseases, as well as plastic or vascular surgery for complex cases with soft tissue and/or vascular defects.

L'ostéomyélite chronique est un processus inflammatoire osseux causé par un agent infectieux. Cette pathologie provoque une altération de la vascularisation intraosseuse et périostée donnant lieu à des fragments d'os nécrotiques (séquestres). Le traitement de l'ostéomyélite chronique repose sur une prise en charge chirurgicale permettant de débrider les séquestres et de réaliser des prélèvements osseux pour des analyses microbiologiques afin d'instaurer une antibiothérapie ciblée sur l'agent pathogène. Une approche multidisciplinaire doit impliquer une expertise en chirurgie orthopédique, en imagerie musculosquelettique et médecine nucléaire, en maladies infectieuses, ainsi qu'en chirurgie plastique ou vasculaire pour les cas avec perte des tissus mous ou défaut de vascularisation.

Prognostic Accuracy of Soluble Triggering Receptor Expressed on Myeloid Cells (sTREM-1)-based Algorithms in Febrile Adults Presenting to Tanzanian Outpatient Clinics.

BACKGROUND: The inability to identify individuals with acute fever at risk of death is a barrier to effective triage and management of severe infections, especially in low-resource settings. Since endothelial and immune activation contribute to the pathogenesis of various distinct life-threatening infections, we hypothesized that measuring mediators of these pathways at clinical presentation would identify febrile adults at risk of death. METHODS: Plasma concentrations of markers of endothelial (angiopoetin-1/2, soluble fms-like tyrosine kinase-1, soluble vascular cell adhesion molecule-1, soluble intercellular adhesion molecule-1) and immune (soluble triggering receptor expressed on myeloid cells [sTREM-1], interleukin-6, interleukin-8, chitinase-3-like protein-1, soluble tumor necrosis factor receptor-1, procalcitonin [PCT], C-reactive protein [CRP]) activation pathways were determined in consecutive adults with acute fever (≥38°C) at presentation to outpatient clinics in Dar es Salaam, Tanzania. We evaluated the accuracy of these mediators in predicting all-cause mortality and examined whether markers could improve the prognostic accuracy of clinical scoring systems, including the quick sequential organ failure assessment (qSOFA) and Glasgow coma scale (GCS). RESULTS: Of 507 febrile adults, 32 died (6.3%) within 28 days of presentation. We found that sTREM-1 was the best prognostic marker for 28-day mortality (area under the receiver operating characteristic [AUROC] 0.87, 95% confidence interval [CI] 0.81-0.92) and was significantly better than CRP (P < .0001) and PCT (P = .0001). The prognostic accuracy of qSOFA and the GCS were significantly enhanced when sTREM-1 was added (0.80 [95% CI 0.76-0.83] to 0.91 [95% CI 0.88-0.94; P < .05] and 0.72 [95% CI 0.63-0.80] to 0.94 [95% CI 0.91-0.97; P < .05], respectively). CONCLUSIONS: Measuring sTREM-1 at clinical presentation can identify febrile individuals at risk of all-cause febrile mortality. Adding severity markers such as sTREM-1 to simple clinical scores could improve the recognition and triage of patients with life-threatening infections in resource-limited settings.

Diagnostic Performance of Conventional and Ultrasensitive Rapid Diagnostic Tests for Malaria in Febrile Outpatients in Tanzania.

BACKGROUND: A novel ultrasensitive malaria rapid diagnostic test (us-RDT) has been developed for improved active Plasmodium falciparum infection detection. The usefulness of this us-RDT in clinical diagnosis and fever management has not been evaluated. METHODS: Diagnostic performance of us-RDT was compared retrospectively to that of conventional RDT (co-RDT) in 3000 children and 515 adults presenting with fever to Tanzanian outpatient clinics. The parasite density was measured by an ultrasensitive qPCR (us-qPCR), and the HRP2 concentration was measured by an enzyme-linked immunosorbent assay. RESULTS: us-RDT identified few additional P. falciparum-positive patients as compared to co-RDT (276 vs 265 parasite-positive patients detected), with only a marginally greater sensitivity (75% vs 73%), using us-qPCR as the gold standard (357 parasite-positive patients detected). The specificity of both RDTs was >99%. Five of 11 additional patients testing positive by us-RDT had negative results by us-qPCR. The HRP2 concentration was above the limit of detection for co-RDT (>3653 pg of HRP2 per mL of blood) in almost all infections (99% [236 of 239]) with a parasite density >100 parasites per µL of blood. At parasite densities <100 parasites/µL, the HRP2 concentration was above the limits of detection of us-RDT (>793 pg/mL) and co-RDT in 29 (25%) and 24 (20%) of 118 patients, respectively. CONCLUSION: There is neither an advantage nor a risk of using us-RDT, rather than co-RDT, for clinical malaria diagnosis. In febrile patients, only a small proportion of infections are characterized by a parasite density or an HRP2 concentration in the range where use of us-RDT would confer a meaningful advantage over co-RDT.

[Side effects of selected antibiotics, not to be missed†!] / Effets indésirables à ne pas manquer de certains antibiotiques.

Antibiotics are among the most frequently used drugs in outpatients. Their side effects can lead to emergency room visits, hospital admissions and considerable economic costs. In this article, we will discuss some often-overlooked side effects of selected antibiotics used in outpatients. Adverse events such as hematological toxicity of linezolid, neurotoxicity of metronidazole, nitrofurantoin pulmonary toxicity or even risk of aortic aneurysm from fluoroquinolones require cautious use and an individualized assessment of the risk-benefit.

Les antibiotiques sont parmi les médicaments les plus fréquemment utilisés en ambulatoire. Leurs effets indésirables (EI) peuvent conduire à des consultations aux urgences, à des admissions à l'hôpital et à des coûts économiques considérables. Dans cet article, nous allons discuter des EI souvent méconnus de certains antibiotiques utilisés en ambulatoire, tels que l'hématotoxicité du linézolide, la neurotoxicité du métronidazole, la toxicité pulmonaire de la nitrofurantoïne ou le risque d'anévrisme de l'aorte des fluoroquinolones. Les antibiotiques nécessitent une utilisation précautionneuse et une évaluation individualisée du rapport bénéfice-risque.

[Infectious diseases†: «â€ less is more†¼]. / Infectiologie: «less is more ¼.

Among carefully selected patients, an early oral antibiotic switch is safe and efficient in severe bacterial infections. New data are available on dual antibiotherapy in severe Staphylococcus aureus infections. Neisseria gonorrhoeae strains resistant to ceftriaxone emerge, highlighting the necessity to develop new therapeutic strategies. Alongshan virus is a new tick-borne virus discovered in China. Ebola continues to rage in Democratic Republic of Congo, while Europe and Switzerland face measles outbreaks. North american guidelines for the diagnosis and management of Influenza have been updated, shortly before the FDA approval of baloxavir marboxil, a new antiviral treatment for Influenza infections.

L'excellente efficacité d'un relais oral précoce lors du traitement d'infections sévères semble se confirmer lorsque les patients sont soigneusement sélectionnés. De nouvelles données sont disponibles concernant l'utilité d'une double antibiothérapie lors d'infections sévères à Staphylococcus aureus. La résistance aux antibiotiques progresse avec l'émergence de souches de Neisseria gonorrhoeae résistant à la ceftriaxone. Un nouveau virus transmis par les tiques a été isolé en Chine. Depuis août 2018, Ebola continue de faire rage en République Démocratique du Congo, alors que la rougeole sévit en Suisse et en Europe. Les recommandations nord-américaines pour la prise en charge de la grippe saisonnière ont été mises à jour, peu avant la mise sur le marché du baloxavir marboxil, un nouvel antiviral efficace contre le virus Influenza.

Procalcitonin and lung ultrasonography point-of-care testing to decide on antibiotic prescription in patients with lower respiratory tract infection in primary care: protocol of a pragmatic cluster randomized trial.

BACKGROUND: A minority of patients presenting with lower respiratory tract infection (LRTI) to their general practitioner (GP) have community-acquired pneumonia (CAP) and require antibiotic therapy. Identifying them is challenging, because of overlapping symptomatology and low diagnostic performance of chest X-ray. Procalcitonin (PCT) can be safely used to decide on antibiotic prescription in patients with LRTI. Lung ultrasound (LUS) is effective in detecting lung consolidation in pneumonia and might compensate for the lack of specificity of PCT. We hypothesize that combining PCT and LUS, available as point-of care tests (POCT), might reduce antibiotic prescription in LRTIs without impacting patient safety in the primary care setting. METHODS: This is a three-arm pragmatic cluster randomized controlled clinical trial. GPs are randomized either to PCT and LUS-guided antibiotic therapy or to PCT only-guided therapy or to usual care. Consecutive adult patients with an acute cough due to a respiratory infection will be screened and included if they present a clinical pneumonia as defined by European guidelines. Exclusion criteria are previous antibiotics for the current episode, working diagnosis of sinusitis, severe underlying lung disease, severe immunosuppression, hospital admission, pregnancy, inability to provide informed consent and unavailability of the GP. Patients will fill in a 28 day-symptom diary and will be contacted by phone on days 7 and 28. The primary outcome is the proportion of patients prescribed any antibiotic up to day 28. Secondary outcomes include clinical failure by day 7 (death, admission to hospital, absence of amelioration or worsening of relevant symptoms) and by day 28, duration of restricted daily activities, episode duration as defined by symptom score, number of medical visits, number of days with side effects due to antibiotics and a composite outcome combining death, admission to hospital and complications due to LRTI by day 28. An evaluation of the cost-effectiveness and of processes in the clinic using a mixed qualitative and quantitative approach will also be conducted. DISCUSSION: Our intervention targets only patients with clinically suspected CAP who have a higher pretest probability of definite pneumonia. The intervention will not substitute clinical assessment but completes it by introducing new easy-to-perform tests. TRIAL REGISTRATION: The study was registered on the 19th of June 2017 on the clinicaltrials.gov registry using reference number; NCT03191071 .

Efficacy and safety of continuous infusions with elastomeric pumps for outpatient parenteral antimicrobial therapy (OPAT): an observational study.

Objectives: This study aimed to evaluate the efficacy and safety of continuous antimicrobial infusion using elastomeric pumps in an outpatient setting, while simultaneously documenting circulating antibiotic concentration exposure achieved with this mode of administration. Methods: Clinical outcomes, adverse events and antibiotic plasma concentrations were recorded for all patients treated by continuous infusion with elastomeric pumps at the outpatient parenteral antimicrobial therapy (OPAT) unit of the University Hospital of Lausanne between December 2013 and January 2017. The study was registered under ClinicalTrials.gov identifier NCT03221140. Results: One hundred and fifty outpatients were treated by continuous intravenous infusions using flucloxacillin (70 patients), cefepime (36), vancomycin (32) and piperacillin/tazobactam (12). The calculated free fractions of each antibiotic were above the epidemiological cut-off values for resistance (ECOFF) of the treated microorganisms in 92% of measurements. Cure was achieved in 143 patients (95%) 3 months after the end of treatment. Four patients needed unexpected readmission and three had a relapse. In none of the patients with unsuccessful treatment was the ratio of free antibiotic plasma concentration/ECOFF <1. Sixteen patients (11%) had an adverse event, none of them being of severity grade 4 or 5. Conclusions: Continuous infusions of flucloxacillin, cefepime, vancomycin and piperacillin/tazobactam using elastomeric pumps seem to be an effective and safe approach to treat outpatients. The number of treatment successes was very high and adverse events occurred at a similar rate as reported by other OPAT centres. The measured antibiotic plasma concentrations confirmed adequate drug concentration exposure for the vast majority of patients.

Dengue fever in Dar es Salaam, Tanzania: clinical features and outcome in populations of black and non-black racial category.

BACKGROUND: Although the incidence of dengue across Africa is high, severe dengue is reported infrequently. We describe the clinical features and the outcome of dengue according to raceduring an outbreak in Dar es Salaam, Tanzania that occurred in both native and expatriate populations. METHODS: Adults with confirmed dengue (NS1 and/or IgM on rapid diagnostic test and/or PCR positive) were included between December 2013 and July 2014 in outpatient clinics. Seven-day outcome was assessed by a visit or a call. Association between black race and clinical presentation, including warning signs, was assessed by logistic regression adjusted for age, malaria coinfection, secondary dengue and duration of symptoms at inclusion. The independent association between demographic and comorbidities characteristics of the patients and severe dengue was evaluated by multivariate logistic regression that included potential confounders. RESULTS: After exclusion of 3 patients of mixed race, 431 patients with dengue (serotype 2, genotype Cosmopolitan) were included: 241 of black and 190 of non-black race. Black patients were younger (median age 30 versus 41 years; p < 0.001) and attended care after a slightly longer duration of symptoms (median of 2.9 versus 2.7 days; p = 0.01). Malaria coinfection was not significantly different between black (5%) and non-black (1.6%) patients (p = 0.06). The same proportion of patients in both group had secondary dengue (13 and 14%; p = 0.78). Among warning signs, only mucosal bleed was associated with race, black race being protective (adjusted OR 0.44; 95% CI 0.21-0.92). Overall, 20 patients (4.7%) presented with severe dengue. Non-black race (adjusted OR 3.9; 95% CI 1.3-12) and previously known diabetes (adjusted OR 43; 95% CI 5.2-361) were independently associated with severe dengue. CONCLUSIONS: Although all patients were infected with the same dengue virus genotype, black race was independently protective against a severe course of dengue, suggesting the presence of protective genetic or environmental host factors among people of African ancestry. The milder clinical presentation of dengue in black patients might partly explain why dengue outbreaks are under-reported in Africa and often mistaken for malaria. These results highlight the need to introduce point-of-care tests, beside the one for malaria, to detect outbreaks and orientate diagnosis. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT01947075 , retrospectively registered on the 13 of September 2014.

[Travelers' exposure to HIV and HIV-infected travelers]. / Le voyageur face au VIH et le voyageur vivant avec le VIH.

In Switzerland, 20 % of the population travel to the tropics every year and many have unprotected sexual practices during their stay. A third of newly diagnosed HIV infections among Swiss citizens are acquired abroad. Travel clinics are probably important partners in the fight against sexually transmitted infections and HIV. People living with HIV often travel to the tropics but rarely attend a travel clinic before leaving. Travels are a risk factor of HIV viral rebound and antiretroviral treatment failure, particularly in sub-Saharan African patients. Pre-travel counselling should be part of a usual follow-up medical consultation with a focus on treatment adherence.

En Suisse, 20 % de la population voyage sous les tropiques chaque année et de nombreuses personnes ont un comportement sexuel à risque durant leur voyage. Un tiers des nouvelles infections VIH diagnostiquées chez des Suisses sont acquises à l'étranger. Les centres de conseils prévoyage ont donc certainement un rôle à jouer dans la prévention des infections sexuellement transmissibles et particulièrement du VIH. Les gens vivant avec le VIH se rendent fréquemment sous les tropiques et ne consultent que rarement une structure spécialisée dans les voyages. Le voyage est un facteur de risque d'échec du traitement antirétroviral, principalement chez les personnes d'Afrique subsaharienne. Des questions concernant un voyage futur devraient donc faire partie intégrante d'une consultation infectiologique de suivi, avec un accent sur l'importance de l'adhésion au traitement.