Study Design, Setting, and Participants
The study design consisted in a retrospective cohort analyses of prospectively collected data of SABSI episodes in adult patients (at least 18 years old) hospitalized from January 2011 to December 2019 in two tertiary care hospitals in Barcelona, Spain: Bellvitge University Hospital, a 700-bed teaching hospital for adults, and Duran i Reynals Hospital, a 200-bed referral cancer center. Positive blood cultures were reported daily by members of the Microbiology Department. All patients were prospectively followed up by infectious disease specialists during hospital admission and for up to 90 days thereafter.
This study was approved by the Clinical Research Ethics Committee of Bellvitge University Hospital (PR326/21). The informed consent form and information sheet were waived because of the retrospective nature of the study. Patient data were anonymized for the purposes of the analysis. Information that could identify patients was protected according to the national normative approach.
Some parts of the methodologies and analyses used in this study were similar to those published in some of our previous studies, reported elsewhere [17, 18].
Variables and Data Sources
Demographic, epidemiological, clinical, and microbiological data were prospectively collected from patients with SABSI. For each patient, the following data were recorded: age, sex, comorbidities, functional and immunological status, history of contact with healthcare providers or prior antibiotic therapy, implanted foreign bodies or devices, clinical data at the BSI onset (grade of severity of illness at presentation, source of infection, and the presence of septic emboli), diagnostic and therapeutic interventions, antibacterial therapy, and outcomes. Follow-up information for up to 90 days after BSI was obtained by reviewing the patients’ electronic clinical charts, in order to assess the mortality and microbiological failure rates.
All consecutive episodes of SABSI detected during the study period were included in the initial analysis with the objective of minimizing selection bias.
SABSI was defined as at least one positive blood culture obtained from a patient with clinical signs and symptoms of infection (namely fever, chills, malaise, specific signs or symptoms of infection, e.g., phlebitis, cellulitis, septic emboli). The presence of underlying diseases was assessed by the Charlson comorbidity index . BSI acquisition categories were considered in three mutually exclusive classes, community-acquired, nosocomial, and healthcare-related, based on the criteria from Friedman et al. . Sepsis was assessed with the quick Sequential Organ Failure Assessment (qSOFA) score, and was defined as a score of at least 2 points .
The source of infection was defined as the infective focus possibly responsible for the BSI, based on the clinical presentation, physical examination, and complementary results. The sources of infection included eight groups: vascular catheter-related infections; infective endocarditis (according to the modified Duke criteria) ; skin and soft tissue infections; pneumonia; osteoarticular infections (with or without prosthetic devices); urinary tract infections; unknown; and other sources (including abdominal, head and neck, and central nervous system sources). IE was considered for both source of infection and complication of BSI from another source.
Platelet count was assessed at the time of hospitalization and confirmed with a second blood count performed 48–72 h after hospital admission. Previous or concomitant use (for at least 3 months before SABSI) of antiplatelet and anticoagulant drugs was recorded. Echocardiography was performed in all patients except those who presented rapid clearance of bacteremia.
Persistent bacteremia was considered when follow-up blood cultures after more than 2 days of treatment were positive. Cases of positive blood culture after negative follow-up blood cultures were considered recurrent bacteremia. We considered consecutive episodes where bacteremia occurred after the 90-day follow-up and after clear resolution of the previous episode. Source control refers to all the physical procedures used to control a focus of infection, including drainage of liquid/purulent abscesses, debridement of necrotic tissues, removal of indwelling catheters and potentially infected devices, and we considered this achieved if performed within the first 72 h from BSI.
Cardiopathy was defined as the presence of one or more of the following conditions: previous predisposing factor for IE heart conditions such as valvular heart disease and/or presence of cardiac devices. Valvulopathy or valvular heart disease was defined as the presence of previous damage in any cardiac valve. Patients with active cancer (PAC) were defined as those with active solid organ cancer or hematological malignancies, who underwent chemotherapy/radiotherapy and/or hematopoietic stem cell transplant in the previous 3 months or who had metastatic cancer. SABSI and S. aureus IE in PAC were compared with patients without cancer (PWC). Mortality was defined as all-cause death and was evaluated 30 days after bacteremia onset.
Blood cultures were processed in a BD BACTEC™ FX blood culture system (Becton Dickinson, Barcelona, Spain) at the Department of Microbiology of Bellvitge University Hospital. In the first 2 years of the study (2011–2012), S. aureus was identified by latex agglutination tests (Pastorex Staph-plus, Bio-Rad Laboratories, Madrid, Spain) and DNase production (DNase test agar, bioMérieux, Marcy l’Etoile, France). From 2013 onwards, identification was carried out by MALDI-TOF (MALDI Biotyper; Bruker Daltonics, Spain). Antimicrobial susceptibility was determined by microdilution using commercially available panels (MicroScan, Beckman Coulter, Barcelona, Spain) and according to the EUCAST guidelines . To rapidly assess methicillin resistance, following positivity of the blood culture and the confirmation of S. aureus isolation, Xpert® MRSA/SA Blood Culture (Cepheid, Sunnyvale, CA) was used.
To calculate the incidence of SABSI and IE, we divided the number of episodes of SABSI and IE, respectively, by the annual hospital discharges. Categorical variables are presented as numbers of episodes and percentages, and continuous variables as means and standard deviation or medians and interquartile range (IQR). Continuous variables were compared using the Student’s t test or Mann–Whitney U test as appropriate. Fisher exact test or Pearson χ2 test was applied to assess the relationship between categorical variables. All consecutive episodes of SABSI detected during the study period were included in the analysis in order to minimize selection bias.
Multivariate logistic regression analysis was then used to assess factors potentially associated with IE and with 30-day mortality, and included all significant variables identified in the univariate analysis along with the relevant ones according to the literature. The goodness of fit of the model was assessed by the Hosmer–Lemeshow test. Relative risks are expressed as adjusted odds ratios (aORs) and 95% confidence intervals. Statistical significance was established at α = 0.05. All reported p values are two tailed.