ABSTRACT
OBJECTIVES: To estimate risk factors for AKI and the effect of AKI on mortality in Staphylococcus aureus bacteremia, while taking into account recurrent AKI episodes, competing risks, time-varying variables and time-varying effects. METHODS: We performed an unplanned analysis using data from a multicenter cohort study of patients with SAB. Primary outcome was cumulative incidence of AKI, according to KDIGO definitions. RESULTS: We included 453 patients in this study of whom 194 (43%) patients experienced one or more AKI episodes. Age (HR 1.013, 95% CI 1.001 - 1.024), Charlson comorbidity index (HR 1.07, 95% CI 1.01 - 1.14), prior chronic kidney disease (HR 1.76, 95% CI 1.28 - 2.42), septic shock (HR 3.28, 95% CI 2.31 - 4.66), persistent bacteremia (HR 1.53, 95% CI 1.08 - 2.17) and vancomycin therapy (HR 1.80, 95% CI 1.05 - 3.09) were independently associated with AKI, but flucloxacillin, cefazolin, rifampicin and aminoglycoside therapy were not. After adjustment for confounders and immortal time bias, AKI was associated with an increased risk of 90-day mortality (HR 4.26, 95% CI 2.91 - 6.23). CONCLUSIONS: Incidence of AKI in SAB is high and a substantial proportion of patients develops recurrent episodes of AKI after recovery. AKI is specifically linked to the use of vancomycin and not to anti-staphylococcal penicillins. Clinical outcome of patients with SAB complicated by AKI is worse than previously estimated.
ABSTRACT
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).
Subject(s)
Bacteremia , Staphylococcal Infections , Adult , Humans , Anti-Bacterial Agents , Staphylococcal Infections/drug therapy , Staphylococcal Infections/microbiology , Bacteremia/microbiology , Duration of Therapy , Staphylococcus aureus , Randomized Controlled Trials as Topic , Multicenter Studies as TopicABSTRACT
OBJECTIVES: Standard once-daily dosing of ceftriaxone may not lead to adequate antibiotic exposure in all cases of Staphylococcus aureus bacteraemia (SAB). Therefore, we compared clinical effectiveness of empirical antibiotic treatment with flucloxacillin, cefuroxime and ceftriaxone in adult patients with MSSA bacteraemia. METHODS: We analysed data from the Improved Diagnostic Strategies in Staphylococcus aureus bacteraemia (IDISA) study, a multicentre prospective cohort study of adult patients with MSSA bacteraemia. Duration of bacteraemia and 30 day SAB-related mortality were compared between the three groups using multivariable mixed-effects Cox regression analyses. RESULTS: In total, 268 patients with MSSA bacteraemia were included in the analyses. Median duration of empirical antibiotic therapy was 3 (IQR 2-3) days in the total study population. Median duration of bacteraemia was 1.0 (IQR 1.0-3.0) day in the flucloxacillin, cefuroxime and ceftriaxone groups. In multivariable analyses, neither ceftriaxone nor cefuroxime was associated with increased duration of bacteraemia compared with flucloxacillin (HR 1.08, 95% CI 0.73-1.60 and HR 1.22, 95% CI 0.88-1.71). In multivariable analysis, neither cefuroxime nor ceftriaxone was associated with higher 30 day SAB-related mortality compared with flucloxacillin [subdistribution HR (sHR) 1.37, 95% CI 0.42-4.52 and sHR 1.93, 95% CI 0.67-5.60]. CONCLUSIONS: In this study, we could not demonstrate a difference in duration of bacteraemia and 30 day SAB-related mortality between patients with SAB empirically treated with flucloxacillin, cefuroxime or ceftriaxone. Since sample size was limited, it is possible the study was underpowered to find a clinically relevant effect.
