Pneumococcal Community-Acquired Pneumonia Requiring Hospitalization Among Adults in Colombia (Pneumo-CAP Colombia)

This study aims to learn more about pneumococcal community-acquired pneumonia (CAP) caused by Streptococcus pneumoniae among adults hospitalized in 11 hospitals in the Sabana Centro region of Colombia. The study will describe the characteristics of adults with CAP, estimate pneumococcal CAP prevalence in the area, and examine the specific serotypes of S. pneumoniae causing this infection. This research is essential for understanding which microorganism is the most prevalent cause of CAP in the region, whether pneumococcal vaccines included in governmental vaccination programs protect adults, which specific pneumococcal serotypes are circulating, and which available vaccine will best protect people against pneumococcal CAP.

The study will be conducted at 11 hospitals in the Sabana Centro region and will collect data over 2 years. The study will gather detailed information on each patient's condition, including symptoms, medical history, and outcomes such as death or the need for intensive care.

This prospective, multicenter surveillance study aims to provide a detailed understanding of pneumococcal community-acquired pneumonia (CAP), a leading cause of hospitalization and mortality, in adults in the Sabana Centro region of Colombia. Pneumococcal CAP, caused by the bacterium Streptococcus pneumoniae, remains a significant global health burden despite widespread vaccination programs. The study will investigate the incidence, prevalence, and serotype distribution of pneumococcal CAP, with a particular focus on strains included in the 15-valent pneumococcal conjugate vaccine (PCV15).

The study's objectives will help inform future vaccine development, public health policies, and the clinical management of pneumococcal infections in adult populations, particularly in low- and middle-income countries (LMICs), where vaccine coverage and disease burden remain concerns.

Study Goals and Objectives:

The study has four primary objectives:

1. To describe the demographic and clinical characteristics of adults ≥18 years hospitalized with pneumococcal CAP in the Sabana Centro region, including both bacteremic and non-bacteremic cases of the infection.

2. To determine the prevalence of pneumococcal CAP among patients requiring hospitalization for CAP in the Sabana Centro region of Colombia.

3. To determine the prevalence of pneumococcal serotypes included in the PCV15 vaccine in hospitalized adults with pneumococcal CAP, including both bacteremic and non-bacteremic cases.

4. To estimate the incidence of pneumococcal CAP that requires hospitalization and the contribution of PCV15 serotypes to the disease burden in the region.

   The study will also explore secondary objectives, including the association between pneumococcal positivity and severe clinical outcomes like ICU admission, mechanical ventilation, vasopressor use, and mortality.

   Study Design:

   This is a prospective, observational, multicenter study with active surveillance. The research will take place at 11 hospitals across the Sabana Centro region, including both public and private institutions. The study will collect data over two years, with a recruitment period of one year and a follow-up period of up to three months post-discharge.

   Inclusion and Exclusion Criteria:

   Inclusion Criteria:

   -1. Age ≥ 18 years old.

   -2. Hospitalized at one of the hospitals of Sabana Centro Region, including both in-patient and observation status stay.

   -3.Clinical signs and/or symptoms of an acute respiratory illness, as defined by ≥ 1 of the following:

   -New or worsening shortness of breath in the past 7 days

   -New or worsening cough in the past 7 days

   -New or worsening sputum production in the past 7 days

   -New or worsening chest pain in the past 7 days

   -Tachypnea to respiratory rate ≥ 22 breaths/min, not known to be chronic

   -Hypoxia to SpO2 ≤ 92% not known to be chronic

   -Initiation of invasive or non-invasive mechanical ventilation.

   -4. Clinical signs and/or symptoms of an acute infection, as defined by ≥ 1 of the following:

   -Body temperature ≥ 38º C (100.4º F) or ≤ 35.5º C (95.9º F)

   -Reported fever, chills, or feeling feverish at home without explicit documentation of a fever within the past 7 days

   -White blood cell count > 10.7 or < 3.9 thousand cells/mcL-C-reactive protein > 10 mg/L

   • Altered mental status
   • 5. Radiologic evidence of pneumonia interpreted by a radiologist, defined as ≥ 1 of the following findings on chest x-ray (CXR), computed tomography (CT), or lung ultrasound completed within 48 hours before or after hospital admission:
   • Pulmonary infiltrate not known to be chronic
   • Pulmonary opacity is not known to be chronic (including ground-glass opacities on CT)
   • Pulmonary consolidation is not known to be

   Exclusion Criteria:

   -1. Enrollment in this study within the past 90 days.

   -2. Development of pneumonia (as defined in the inclusion criteria) more than 48 hours after hospital admission (pneumonia developed 48 hours after admission will be considered hospital-acquired pneumonia).

   -3. Inability to obtain consent from patient or surrogate for this study within 48 hours of hospital admission (including time at a transferring hospital before admission at a study hospital).

   -4. Inability or unwillingness of the patient to provide any of the samples (Blood, Urine, and Sputum) within 48 hours of hospital admission (including time at a transferring hospital before admission at a study hospital).

   -5. Non-pneumonia illness completely explains the patient's acute symptoms. Alternative non-pneumonia illnesses could include pulmonary embolism, acute heart failure, lung cancer, and pulmonary hemorrhage.

   o- Key Outcomes and Data Collection:

   The study will track multiple outcomes, including:

   o- Incidence of pneumococcal CAP (overall, and by specific serotypes included in PCV15).

   o- Prevalence of pneumococcal serotypes, particularly those contained in PCV15.

   o- Clinical outcomes such as:

   o Mortality (hospital mortality and 3-month post-discharge mortality)

   o ICU admission

   o Need for invasive mechanical ventilation

   o Use of vasopressors

   o Duration of hospital and ICU stay

   o- Quality of life measures using the EQ-5D-5L and mMRC scales, assessed at baseline, 1 month, and 3 months post-discharge.

   o- Laboratory Tests and Procedures:

   The study will use a combination of diagnostic methods to detect S. pneumoniae and characterize the pneumococcal strains involved, including:

   o Urine antigen tests.

   o Blood cultures.

   • Sputum cultures.
   • Real-time PCR for molecular detection of S. pneumoniae in blood and sputum samples.

   In addition, the study will collect data on the antimicrobial resistance patterns of the isolated pneumococcal strains, evaluating resistance to penicillins, macrolides, and other antibiotic classes.

   o-Data Management and Analysis: All data will be collected electronically through the RedCap platform, a secure, web-based system. The data will be analyzed using descriptive statistics for demographic and clinical characteristics, as well as incidence and prevalence rates of pneumococcal CAP. Multivariate regression models will be used to assess associations between pneumococcal infection and clinical outcomes, while adjusting for potential confounders such as age, sex, comorbidities, and vaccination status.

   o- Follow-Up: Patients will be followed up by phone at 1 and 3 months post-discharge to evaluate long-term outcomes, including survival, functional recovery, and quality of life. This follow-up is crucial for understanding the long-term burden of pneumococcal CAP and the potential impact of vaccination.

   o- Study Timeline and Sample Size: The study is expected to run for 2 years. The study will include all eligible patients hospitalized during this time, and the number of qualifying cases observed will determine the sample size.

   o- Ethical Considerations and Confidentiality: The study will be conducted in accordance with ethical guidelines for human research and will obtain approval from institutional review boards (IRBs) at all participating hospitals. Informed consent will be obtained from all patients (or their legal representatives) before enrollment. All patient data will be kept confidential, and participants will be identified only by a study-specific ID.

   o- Study Significance and Expected Impact: This study is the first of its kind in Colombia to comprehensively evaluate the incidence, prevalence, and clinical outcomes of pneumococcal CAP in adults. The findings will provide crucial data on the pneumococcal serotypes circulating in the region, informing vaccine policy and the potential introduction of new pneumococcal vaccines, such as PCV15, into the Colombian adult population. The study also aims to address the significant knowledge gap in the epidemiology of pneumococcal infections in LMICs, where data on adult pneumococcal CAP is limited.

Inclusion Criteria:

• (1) Age ≥ 18 years old.
• (2) Hospitalized at one of the hospitals of Sabana Centro Region, including both in-patient and observation status stay.
• (3) Clinical signs and/or symptoms of an acute respiratory illness, as defined by ≥ 1 of the
• following:
• -New or worsening shortness of breath in the past 7 days
• -New or worsening cough in the past 7 days
• -New or worsening sputum production in the past 7 days
• -New or worsening chest pain in the past 7 days
• -Tachypnea to respiratory rate ≥ 22 breaths/min, not known to be chronic
• -Hypoxia to SpO2 ≤ 92% not known to be chronic
• -Initiation of invasive or non-invasive mechanical ventilation
• (4) Clinical signs and/or symptoms of an acute infection, as defined by ≥ 1 of the following:
• -Body temperature ≥ 38º C (100.4º F) or ≤ 35.5º C (95.9º F)
• -Reported fever, chills, or feeling feverish at home without explicit documentation of a fever within the past 7 days
• -White blood cell count > 10.7 or < 3.9 thousand cells/mcL-C-reactive protein > 10 mg/L
• -Altered mental status
• (5) Radiologic evidence of pneumonia interpreted by a radiologist, defined as ≥ 1 of the following findings on chest x-ray (CXR), computed tomography (CT), or lung ultrasound completed within 48 hours before or after hospital admission:
• -Pulmonary infiltrate not known to be chronic
• -Pulmonary opacity is not known to be chronic (including ground-glass opacities on CT)
• -Pulmonary consolidation is not known to be

Exclusion Criteria:

• (1) Enrollment in this study within the past 90 days.
• (2) Development of pneumonia (as defined in the inclusion criteria) more than 48 hours after hospital admission (pneumonia developed 48 hours after admission will be considered hospital-acquired pneumonia).
• (3) Inability to obtain consent from patient or surrogate for this study within 48 hours of hospital admission (including time at a transferring hospital before admission at a study hospital).
• (4) Inability or unwillingness of the patient to provide any of the samples (Blood, Urine, and Sputum) within 48 hours of hospital admission (including time at a transferring hospital before admission at a study hospital).
• (5) Non-pneumonia illness completely explains the patient's acute symptoms. Alternative non-pneumonia illnesses could include pulmonary embolism, acute heart failure, lung cancer, and pulmonary hemorrhage.

The study population will consist of adults aged 18 years or older hospitalized with community-acquired pneumonia (CAP) in the Sabana Centro region of Colombia. This region includes 11 municipalities around Bogotá and represents a diverse socio-economic and demographic population with a well-organized healthcare system.

The decision regarding the sharing of individual participant data has not yet been finalized. IPD availability will depend on ethical approvals, institutional policies, and data-governance requirements across participating sites.