Impact of adherence to individual quality-of-care indicators on the prognosis of bloodstream infection due to Staphylococcus aureus: a prospective observational multicentre cohort.

OBJECTIVES: To analyse the adherence and impact of quality-of-care indicators (QCIs) in the management of Staphylococcus aureus bloodstream infection in a prospective and multicentre cohort. METHODS: Analysis of the prospective, multicentre international S. Aureus Collaboration cohort of S. Aureus bloodstream infection cases observed between January 2013 and April 2015. Multivariable analysis was performed to evaluate the impact of adherence to QCIs on 90-day mortality. RESULTS: A total of 1784 cases were included. Overall, 90-day mortality was 29.9% and mean follow-up period was 118 days. Adherence was 67% (n = 1180/1762) for follow-up blood cultures, 31% (n = 416/1342) for early focus control, 77.6% (n = 546/704) for performance of echocardiography, 75.5% (n = 1348/1784) for adequacy of targeted antimicrobial therapy, 88.6% (n = 851/960) for adequacy of treatment duration in non-complicated bloodstream infections and 61.2% (n = 366/598) in complicated bloodstream infections. Full bundle adherence was 18.4% (n = 328/1784). After controlling for immortal time bias and potential confounders, focus control (adjusted hazard ratio = 0.76; 95% CI, 0.59-0.99; p 0.038) and adequate targeted antimicrobial therapy (adjusted hazard ratio = 0.75; 95% CI, 0.61-0.91; p 0.004) were associated with low 90-day mortality. DISCUSSION: Adherence to QCIs in S. Aureus bloodstream infection did not reach expected rates. Apart from the benefits of application as a bundle, focus control and adequate targeted therapy were independently associated with low mortality.

Impact of neutropenia on clinical manifestations and outcome of Staphylococcus aureus bloodstream infection: a propensity score-based overlap weight analysis in two large, prospectively evaluated cohorts.

OBJECTIVES: This study aimed to investigate whether neutropenia influenced mortality and long-term outcomes of Staphylococcus aureus bloodstream (SAB) infection. METHODS: Data from two prospective, multicentre cohort studies (INSTINCT and ISAC) conducted at 20 tertiary care hospitals in six countries between 2006 and 2015 were analyzed. Neutropenic and severely neutropenic patients (defined by proxy of total white blood cell count <1000/µl and <500/µl, respectively, at onset of SAB infection) were compared with a control group using a propensity score model and overlapping weights to adjust for baseline characteristics. Overall survival and time to SAB infection-related late complications (SAB infection recurrence, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed with Cox regression and competing risk analyses, respectively. RESULTS: Of the 3187 included patients, 102 were neutropenic and 70 severely neutropenic at the time of SAB infection onset. Applying overlap weights yielded two groups of 83 neutropenic and 220 nonneutropenic patients, respectively. The baseline characteristics of these groups were exactly balanced. In the Cox regression analysis, we observed no significant difference in survival between the two groups (death during follow up: 36.1% in neutropenic vs. 30.6% in nonneutropenic patients; hazard ratio (HR): 1.21; 95% CI, 0.79-1.83). This finding remained unchanged when we considered severely neutropenic patients (HR: 1.08; 95% CI, 0.60-1.94). A competing risk analysis showed a cause-specific HR of 0.39 (95% CI, 0.11-1.39) for SAB infection-related late complications in neutropenic patients. DISCUSSION: Neutropenia was not associated with a higher survival rate during follow up. The lower rate of SAB infection-related late complications in neutropenic patients should be validated in other cohorts.

Impact of Immunosuppressive Agents on Clinical Manifestations and Outcome of Staphylococcus aureus Bloodstream Infection: A Propensity Score-Matched Analysis in 2 Large, Prospectively Evaluated Cohorts.

BACKGROUND: Staphylococcus aureus bloodstream infection (SAB) is a common, life-threatening infection. The impact of immunosuppressive agents on the outcome of patients with SAB is incompletely understood. METHODS: Data from 2 large prospective, international, multicenter cohort studies (Invasive Staphylococcus aureus Infections Cohort [INSTINCT] and International Staphylococcus aureus Collaboration [ISAC]) between 2006 and 2015 were analyzed. Patients receiving immunosuppressive agents were identified and a 1:1 propensity score-matched analysis was performed to adjust for baseline characteristics of patients. Overall survival and time to SAB-related late complications (SAB relapse, infective endocarditis, osteomyelitis, or other deep-seated manifestations) were analyzed by Cox regression and competing risk analyses, respectively. This approach was then repeated for specific immunosuppressive agents (corticosteroid monotherapy and immunosuppressive agents other than steroids [IMOTS]). RESULTS: Of 3188 analyzed patients, 309 were receiving immunosuppressive treatment according to our definitions and were matched to 309 nonimmunosuppressed patients. After propensity score matching, baseline characteristics were well balanced. In the Cox regression analysis, we observed no significant difference in survival between the 2 groups (death during follow-up: 105/309 [33.9%] immunosuppressed vs 94/309 [30.4%] nonimmunosuppressed; hazard ratio [HR], 1.20 [95% confidence interval {CI}, .84-1.71]). Competing risk analysis showed a cause-specific HR of 1.81 (95% CI, .85-3.87) for SAB-related late complications in patients receiving immunosuppressive agents. The cause-specific HR was higher in patients taking IMOTS (3.69 [95% CI, 1.41-9.68]). CONCLUSIONS: Immunosuppressive agents were not associated with an overall higher mortality. The risk for SAB-related late complications in patients receiving specific immunosuppressive agents such as IMOTS warrants further investigations.

Defining persistent Staphylococcus aureus bacteraemia: secondary analysis of a prospective cohort study.

BACKGROUND: Staphylococcus aureus persistent bacteraemia is only vaguely defined and the effect of different durations of bacteraemia on mortality is not well established. Our primary aim was to analyse mortality according to duration of bacteraemia and to derive a clinically relevant definition for persistent bacteraemia. METHODS: We did a secondary analysis of a prospective observational cohort study at 17 European centres (nine in the UK, six in Spain, and two in Germany), with recruitment between Jan 1, 2013, and April 30, 2015. Adult patients who were consecutively hospitalised with monomicrobial S aureus bacteraemia were included. Patients were excluded if no follow-up blood culture was taken, if the first follow-up blood-culture was after 7 days, or if active antibiotic therapy was started more than 3 days after first blood culture. The primary outcome was 90-day mortality. Univariable and time-dependent multivariable Cox regression analysis were used to assess predictors of mortality. Duration of bacteraemia was defined as bacteraemic days under active antibiotic therapy counting the first day as day 1. FINDINGS: Of 1588 individuals assessed for eligibility, 987 were included (median age 65 years [IQR 51-75]; 625 [63%] male). Death within 90 days occurred in 273 (28%) patients. Patients with more than 1 day of bacteraemia (315 [32%]) had higher Charlson comorbidity index and sequential organ failure assessment scores and a longer interval from first symptom to first blood culture. Crude 90-day mortality increased from 22% (148 of 672) with 1 day of bacteraemia, to 39% (85 of 218) with 2-4 days, 43% (30 of 69) with 5-7 days, and 36% (10 of 28) with more than 7 days of bacteraemia. Metastatic infections developed in 39 (6%) of 672 patients with 1 day of bacteraemia versus 40 (13%) of 315 patients if bacteraemia lasted for at least 2 days. The second day of bacteraemia had the highest HR and earliest cutoff significantly associated with mortality (adjusted hazard ratio 1·93, 95% CI 1·51-2·46; p<0·0001). INTERPRETATION: We suggest redefining the cutoff duration for persistent bacteraemia as 2 days or more despite active antibiotic therapy. Our results favour follow-up blood cultures after 24 h for early identification of all patients with increased risk of death and metastatic infection. FUNDING: None.

Survival following Staphylococcus aureus bloodstream infection: A prospective multinational cohort study assessing the impact of place of care.

BACKGROUND: Staphylococcus aureus bloodstream infection (SAB) is a common, life-threatening infection with a high mortality. Survival can be improved by implementing quality of care bundles in hospitals. We previously observed marked differences in mortality between hospitals and now assessed whether mortality could serve as a valid and easy to implement quality of care outcome measure. METHODS: We conducted a prospective observational study between January 2013 and April 2015 on consecutive, adult patients with SAB from 11 tertiary care centers in Germany, South Korea, Spain, Taiwan, and the United Kingdom. Factors associated with mortality at 90 days were analyzed by Cox proportional hazards regression and flexible parametric models. RESULTS: 1851 patients with a median age of 66 years (64% male) were analyzed. Crude 90-day mortality differed significantly between hospitals (range 23-39%). Significant variation between centers was observed for methicillin-resistant S. aureus, community-acquisition, infective foci, as well as measures of comorbidities, and severity of disease. In multivariable analysis, factors independently associated with mortality at 90 days were age, nosocomial acquisition, unknown infective focus, pneumonia, Charlson comorbidity index, SOFA score, and study center. The risk of death varied over time differently for each infective focus. Crude mortality differed markedly from adjusted mortality. DISCUSSION: We observed significant differences in adjusted mortality between hospitals, suggesting differences in quality of care. However, mortality is strongly influenced by patient mix and thus, crude mortality is not a suitable quality indicator.