This was a retrospective multicenter observational study of patients from 55 hospitals, including public and private institutions, in Bogotá, Colombia, that provide health care to about 8 million people. The study was undertaken between January 2012 and January 2019. All patients older than 18 years of age who were diagnosed with IPD were identified and those cases with a fully available clinical history, and positive Spn cultures were included in the study. Patients in whom clinical data were incomplete or other bacteria were isolated (i.e., co-infections) were excluded. The flow chart indicating the selection process is part of the supplemental information in S1 fig. The Translational Science in Infectious Diseases and Critical Care Medicine Research Group from the Universidad de La Sabana developed this study protocol in collaboration with The Public Health Secretary of Bogotá city.
We used the bacterial isolates reported to The Public Health Secretary under a Spn surveillance program. All pneumococcal isolates were confirmed and typed by the National Center of Microbiology (CNM) in a centralized laboratory following the Quellung reaction using polyclonal antisera [21]. This study was approved, and the use of informed consent was waived the Institutional Review Board of the Clinica Universidad de La Sabana (2020_MED-23221). The use of informed consent was waived because this was a retrospective study, without any intervention, and used only a chart review to obtain clinical data. All methods were performed in accordance with the relevant guidelines and local and international regulation.
Study definitions
We used international and well-accepted definitions for each variable and clinical diagnosis. IPD was defined as an infection confirmed by the isolation of Spn from a normally sterile site (e.g., blood, cerebrospinal fluid, and pleural, joint, peritoneal fluid and/or respiratory fluid other than sputum) [22]. CAP was defined according to the American Thoracic Society and Infectious Diseases Society of America (ATS/IDSA) guidelines as an acute infection of the pulmonary parenchyma acquired outside of the hospital setting evidenced by radiological findings (e.g., chest radiograph, computed tomography or pulmonary ultrasound) compatible with alveolar infiltration and characteristic clinical presentation (e.g., acute onset of cough, fever, tachypnea, altered mental status, diaphoresis, etc.) [23]. Pneumococcal meningitis was defined as the identification of Spn in blood cultures and/or CSF in association with the clinical syndrome of meningitis (i.e., fever, headache, meningismus, altered mental status, seizures, confusion or vomiting) According to the IDSA guidelines [24].
To reduce the risk of bias, only confirmed cases of IPD according to international clinical guidelines were included and all the clinical records were evaluated by trained personnel. Additionally, all missing information was not analyzed or inferred, and all clinical charts were reviewed blinded to the isolated pneumococcal serotypes to determine clinical outcomes.
Variables
Data on gender, age, comorbidities, chronic medication, vaccination, physiological admission variables, blood count, bilirubin levels, liver enzymes, arterial blood gases, medical intervention, and antibiotic treatment were recorded for each patient. The initial severity of the disease was assessed using the Sequential Organ Failure Assessment (SOFA), quick Sequential Organ Failure Assesment (qSOFA) [25], and Acute Physiology and Chronic Health Evaluation II (APACHE II) [26]. During hospitalization, ICU admission, need for invasive mechanical ventilation or non-invasive mechanical ventilation, length of hospital and ICU stay were recorded and considered as secondary outcomes. All-cause hospital mortality was the primary outcome.
Data collection
Hospitals sent all isolated Spn strains to a centralized laboratory where each one was characterized. Clinical records were sent to the district health secretary of Bogotá city, and a retrospective review of all medical records was carried out to gather clinical information. Data was recorded onto an electronic case report form (eCRF) hosted in the servers of the health secretary of Bogota and then exported for statistical analysis.
Statistical analysis
For the statistical analysis, descriptive analysis was performed with measures of central tendency and dispersion for the quantitative variables, and frequencies with percentages for the qualitative variables. Numerical data are presented as mean (standard deviation, SD) or median (interquartile ranges, IQR) according to normality distribution. The serotype distribution of Spn was broken down by clinical diagnosis and age. Finally, mortality, ICU admission, need for invasive mechanical ventilation or non-invasive mechanical ventilation, and all-cause hospital mortality were calculated for the group as a whole as well as by diagnosis of IPD. Quantitative variables were contrasted by fisher, and continuos variables were analyzed according to data distribution (i.e., normality) by t-test the Mann Witney. A p < 0,05 was considered statistically significant. All statistical analyses were performed using a statistical package SPSS 25 and Graph Pad Prism for MAC, licensed for the Universidad de La Sabana.