BMC Fam Pract

Background Guidelines that detail preventive measures against Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b, and influenza are published annually in France to decrease the risk of severe infections in immunocompromised patients. We aimed at describing adherence to these guidelines by GPs in the management of their asplenic patients in France between 2013 and 2016. Method We conducted a multicenter retrospective study between January 2013 and December 2016 in three French hospitals: asplenic adults were identified and their GPs were questioned. A descriptive analysis was performed to identify the immunization coverage, type and length of antibiotic prophylaxis, number of infectious episodes, and education of patients. Results 103 patients were finally included in this study: only 57% were adequately vaccinated against Streptococcus pneumoniae or Neisseria meningitidis, 74% against Haemophilus influenzae type b, and 59% against influenza. Only 24% of patients received a combination of all four vaccinations. Two-thirds of patients received prophylactic antibiotics for at least 2 years. Overall, this study found that 50% of splenectomized patients experienced at least one pulmonary or otorhinolaryngological infection, or contracted influenza. Conclusions These data match those reported in other countries, including Australia and the United Kingdom, meaning a still insufficient coverage of preventive measures in asplenic patients. Improved medical data sharing strategies between healthcare professionals, along with educational measures to keep patients and physicians up to date in the prevention of infections after splenectomy would improve health outcomes of asplenic patients

Safe shortening of antibiotic treatment duration for complicated Staphylococcus aureus bacteraemia (SAFE trial): protocol for a randomised, controlled, open-label, non-inferiority trial comparing 4 and 6 weeks of antibiotic treatment

Introduction A major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB.Methods and analysis The SAFE-trial is a multicentre, non-inferiority, open-label, parallel group, randomised controlled trial evaluating 4 versus 6 weeks of antibiotic therapy for complicated SAB. The study is performed in 15 university hospitals and general hospitals in the Netherlands. Eligible patients are adults with methicillin-susceptible SAB with evidence of deep-seated or metastatic infection and/or predictors of complicated SAB. Only patients with a satisfactory clinical response to initial antibiotic treatment are included. Patients with infected prosthetic material or an undrained abscess of 5 cm or more at day 14 of adequate antibiotic treatment are excluded. Primary outcome is success of therapy after 180 days, a combined endpoint of survival without evidence of microbiologically confirmed disease relapse. Assuming a primary endpoint occurrence of 90% in the 6 weeks group, a non-inferiority margin of 7.5% is used. Enrolment of 396 patients in total is required to demonstrate non-inferiority of shorter antibiotic therapy with a power of 80%. Currently, 152 patients are enrolled in the study.Ethics and dissemination This is the first randomised controlled trial evaluating duration of antibiotic therapy for complicated SAB. Non-inferiority of 4 weeks of treatment would allow shortening of treatment duration in selected patients with complicated SAB. This study is approved by the Medical Ethics Committee VUmc (Amsterdam, the Netherlands) and registered under NL8347 (the Netherlands Trial Register). Results of the study will be published in a peer-reviewed journal.Trial registration number NL8347 (the Netherlands Trial Register)

A highly virulent variant of HIV-1 circulating in the Netherlands.

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log <sub>10</sub> increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence