Suchergebnisse

The accessory gene regulator (agr) locus of Staphylococcus aureus is a quorum-sensing virulence regulator. Although there are many studies concerning the effect of dysfunctional agr on the outcomes of S. aureus infection, there is no systematic review to date. We systematically searched for clinical studies reporting outcomes of invasive S. aureus infections and the proportion of dysfunctional agr among their causative strains, and we performed a meta-analysis to obtain estimates of the odds of outcomes of invasive S. aureus infection with dysfunctional versus functional agr. Of 289 articles identified by our research strategy, 20 studies were meta-analysed for crude analysis of the impact of dysfunctional agr on outcomes of invasive S. aureus infection. Dysfunctional agr was generally associated with unfavourable outcomes (OR 1.32, 95% CI 1.05–1.66), and the impact of dysfunctional agr on outcome was more prominent in invasive methicillin-resistant S. aureus (MRSA) infections (OR 1.54, CI 1.20–1.97). Nine studies were meta-analysed for the impact of dysfunctional agr on the 30-day mortality of invasive S. aureus infection. Invasive MRSA infection with dysfunctional agr exhibited higher 30-day mortality (OR 1.40, CI 1.03–1.90) than that with functional agr. On the other hand, invasive MSSA infection with dysfunctional agr exhibited lower 30-day mortality (OR 0.51, CI 0.27–0.95). In the post hoc subgroup analysis by the site of MRSA infection, dysfunctional agr was associated with higher 30-day mortality in MRSA pneumonia (OR 2.48, CI 1.17–5.25). The effect of dysfunctional agr on the outcome of invasive S. aureus infection may vary depending on various conditions, such as oxacillin susceptibility and the site of infection. Dysfunctional agr was generally associated with unfavourable clinical outcomes and its effect was prominent in MRSA and pneumonia. Dysfunctional agr may be applicable for outcome prediction in cases of invasive MRSA infection with hardly eradicable foci such as pneumonia. ; This work was supported by a National Research Foundation of Korea (NRF) Grant funded by the Korean Government (MSIP) (NRF-2018R1A1A1A05079369).

SAFO study group and the Spanish Network for Research in Infectious Diseases (REIPI). ; [Introduction] Methicillin-susceptible Staphylococcus aureus (MSSA) bacteraemia is a frequent condition, with high mortality rates. There is a growing interest in identifying new therapeutic regimens able to reduce therapeutic failure and mortality observed with the standard of care of beta-lactam monotherapy. In vitro and small-scale studies have found synergy between cloxacillin and fosfomycin against S. aureus. Our aim is to test the hypothesis that cloxacillin plus fosfomycin achieves higher treatment success than cloxacillin alone in patients with MSSA bacteraemia. ; [Methods] We will perform a superiority, randomised, open-label, phase IV–III, two-armed parallel group (1:1) clinical trial at 20 Spanish tertiary hospitals. Adults (≥18 years) with isolation of MSSA from at least one blood culture ≤72 hours before inclusion with evidence of infection, will be randomly allocated to receive either cloxacillin 2 g/4-hour intravenous plus fosfomycin 3 g/6-hour intravenous or cloxacillin 2 g/4-hour intravenous alone for 7 days. After the first week, sequential treatment and total duration of antibiotic therapy will be determined according to clinical criteria by the attending physician. Primary endpoints: (1) Treatment success at day 7, a composite endpoint comprising all the following criteria: patient alive, stable or with improved quick-Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA at day 7. (2) Treatment success at test of cure (TOC) visit: patient alive and no isolation of MSSA in blood culture or at another sterile site from day 8 until TOC (12 weeks after randomisation). We assume a rate of treatment success of 74% in the cloxacillin group. Accepting alpha risk of 0.05 and beta risk of 0.2 in a two-sided test, 183 subjects will be required in each of the control and experimental groups to obtain statistically significant difference of 12% (considered clinically significant). ; [Ethics and dissemination] Ethical approval has been obtained from the Ethics Committee of Bellvitge University Hospital (AC069/18) and from the Spanish Medicines and Healthcare Product Regulatory Agency (AEMPS, AC069/18), and is valid for all participating centres under existing Spanish legislation. The results will be presented at international meetings and will be made available to patients and funders. ; [Trial registration number] The protocol has been approved by AEMPS with the Trial Registration Number EudraCT 2018-001207-37. ClinicalTrials.gov Identifier: NCT03959345; Pre-results. ; The SAFO trial is supported by a competitive grant awarded by the Fondo de Investigaciones Sanitarias at the Spanish government's National Institute of Health Research, Instituto de Salud Carlos III (ISCIII), (FIS PI17/01116). This study was supported by Plan Nacional de I+D+i 2017–2021 and Instituto de Salud Carlos III, Subdirección General de Redes y Centros de Investigación Cooperativa, Ministerio de Economía, Industria y Competitividad, Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005). ; Peer reviewed