Pneumococcal Serotypes Associated with Community-Acquired Pneumonia Hospitalizations in Adults in Spain, 2016-2020: The CAPA Study.

Newer higher valency pneumococcal conjugate vaccines (PCVs) have the potential to reduce the adult community-acquired pneumonia (CAP) burden. We describe the evolution and distribution of adult community-acquired pneumonia (CAP) serotypes in Spain, focusing on serotypes contained in the 20-valent PCV (PCV20). This was a prospective, observational study of chest X-ray (CXR)-confirmed CAP in immunocompetent adults hospitalized in one of four Spanish hospitals between November 2016 and November 2020. Pneumococci were isolated from cultures and detected in urine using BinaxNow® and Pfizer serotype-specific urinary antigen tests UAD1 and UAD2. We included 1948 adults hospitalized with CXR-CAP. The median age was 69.0 years (IQR: 24 years). At least one comorbidity was present in 84.8% (n = 1653) of patients. At admission, 76.1% of patients had complicated pneumonia. Pneumococcus was identified in 34.9% (n = 680) of study participants. The PCV20 vaccine-type CAP occurred in 23.9% (n = 465) of all patients, 68.4% (n = 465) of patients with pneumococcal CAP, and 82.2% (83/101) of patients who had pneumococcus identified by culture. Serotypes 8 (n = 153; 7.9% of all CAP) and 3 (n = 152; 7.8% of all CAP) were the most frequently identified. Pneumococcus is a common cause of hospitalized CAP among Spanish adults and serotypes contained in PCV20 caused the majority of pneumococcal CAP.

The Evolution and Distribution of Pneumococcal Serotypes in Adults Hospitalized With Community-Acquired Pneumonia in Spain Using a Serotype-Specific Urinary Antigen Detection Test: The CAPA Study, 2011-2018.

BACKGROUND: Spain introduced the 13-valent pneumococcal conjugate vaccine (PCV13) in the childhood National Immunization Program in 2015-2016 with coverage of 3 doses of 94.8% in 2018. We assessed the evolution of all pneumococcal, PCV13 vaccine type (VT), and experimental PCV20-VT (PCV13 + serotypes 8, 10A, 11A, 12F, 15B, 22F, 33F) hospitalized community-acquired pneumonia (CAP) in adults in Spain from 2011-2018. METHODS: A prospective observational study of immunocompetent adults (≥18 years) admitted to 4 Spanish hospitals with chest X-ray-confirmed CAP between November 2011 and November 2018. Microbiological confirmation was obtained using the Pfizer serotype-specific urinary antigen detection tests (UAD1/UAD2), BinaxNow test for urine, and conventional cultures of blood, pleural fluid, and high-quality sputum. RESULTS: Of 3107 adults hospitalized with CAP, 1943 were ≥65 years. Underlying conditions were present in 87% (n = 2704) of the participants. Among all patients, 895 (28.8%) had pneumococcal CAP and 439 (14.1%) had PCV13-VT CAP, decreasing from 17.9% (n = 77) to 13.2% (n = 68) from 2011-2012 to 2017-2018 (P = .049). PCV20-VT CAP occurred in 243 (23.8%) of those included in 2016-2018. The most identified serotypes were 3 and 8. Serotype 3 accounted for 6.9% (n = 215) of CAP cases, remaining stable during the study period, and was associated with disease severity. CONCLUSIONS: PCV13-VT caused a substantial proportion of CAP in Spanish immunocompetent adults 8 years after introduction of childhood PCV13 immunization. Improving direct PCV13 coverage of targeted adult populations could further reduce PCV13-VT burden, a benefit that could be increased further if PCV20 is licensed and implemented.

CAPPRIC Study-Characterization of Community-Acquired Pneumonia in Spanish Adults Managed in Primary Care Settings.

The real burden of community-acquired pneumonia (CAP) in non-hospitalized patients is largely unknown. This is a 3-year prospective, observational study of ambulatory CAP in adults, conducted in 24 Spanish primary care centers between 2016-2019. Sociodemographic and clinical variables of patients with radiographically confirmed CAP were collected. Pneumococcal etiology was assessed using the Binax Now® test. Patients were followed up for 10 ± 3 days. A total of 456 CAP patients were included in the study. Mean age was 56.6 (±17.5) years, 53.5% were female, and 53.9% had ≥1 comorbidity. Average incidence of CAP was 1.2-3.5 cases per 1000 persons per year. Eighteen patients (3.9%) were classified as pneumococcal CAP. Cough was present in 88.1% of patients at diagnosis and fever in 70.8%. Increased pulmonary density (63.3%) and alveolar infiltrates with air bronchogram (16.6%) were the most common radiographic findings. After 14.6 ± 6.0 days (95% CI = 13.9-15.3), 65.4% of patients had recovered. Hospitalization rate was 2.8%. The most frequently prescribed antibiotics were quinolones (58.7%) and ß-lactams (31.1%). In conclusion, one-third of CAP patients did not fully recover after two weeks of empiric antibiotic therapy and 2.8% required hospitalization, highlighting the significant burden associated with non-hospitalized CAP in Spain.

Serotypes and genotypes of S. pneumoniae isolates from adult invasive disease in Spain: A 5-year prospective surveillance after pediatric PCV13 licensure. The ODIN study.

Serotypes/genotypes causing invasive pneumococcal disease (IPD) in adults are determined by vaccination strategies. The aim of this study was to assess the epidemiology of IPD in adults (≥18 years) after PCV13 introduction for children: serotypes, clonal complexes, antibiotic non-susceptibility and clinical presentations. We performed a prospective, clinical surveillance of hospitalized culture-confirmed IPDs in adults in nine Spanish hospitals (August 2010-June 2015). A total of 1087 culture-confirmed IPD episodes were included, of which 772 (71.0%) had bacteremic pneumonia (401 complicated/371 uncomplicated pneumonia), 122 (11.2%) meningitis, 102 (9.4%) non-focal bacteremia, 34 (3.1%) peritonitis and 57 (5.3%) others. The most common serotypes were: 3 (12.7%), 19A (8.5%), 8 (7.7%), 7F (6.3%), 1 (4.2%), 6C (4.2%), 11A (4.2%), 22F (4.2%) and 14 (4.0%). Vaccine types (PCV13 + 6C) caused 49.8% of IPD episodes, with a significant decrease over the 5-year period, and significant decreases in serotypes 6C and 7F. The most common genotypes were: CC180 (8.4%), CC191 (6.0%), and CC53 (5.0%). Vaccine types caused 53.9% (414/768) pneumonia episodes and 58.9% (235/399) complicated pneumonia, 53.4% IPD in adults <50 years (143/268), and 54.7% IPD in immunocompetent patients (337/616). Overall non-susceptibility was 25.9% to penicillin (1.1% for parenteral criteria), 24.9% to erythromycin and 2.7% to levofloxacin. CONCLUSIONS: Although the percentage of vaccine-types causing IPDs in adults significantly decreased, it remained high. Associations of vaccine types with pneumonia (with complicated pneumonia for specific serotypes), and immunocompetent patients point to the burden of IPD caused by PCV13 serotypes.

The burden of PCV13 serotypes in hospitalized pneumococcal pneumonia in Spain using a novel urinary antigen detection test. CAPA study.

BACKGROUND: Streptococcus pneumoniae serotypes distribution in community-acquired pneumonia (CAP) requiring hospitalization in adults after introduction of PCV13 in children is not well known. Our aim was to evaluate the distribution of serotypes in pneumococcal pneumonia according to risk factors and comorbidity conditions after the introduction of PCV13 in children in 2010. METHODS: A prospective study from 2011 to 2014 was performed in immunocompetent adults hospitalized with CAP in 3 Spanish hospitals. Microbiological confirmation was obtained using a serotype specific urinary antigen detection test (UAD test), Binax Now and conventional cultures. RESULTS: 1258 adults were enrolled and pneumococcal pneumonia (invasive disease in 17.7%) was confirmed in 368 (29.3%) and 17.6% of the any-cause CAP were caused by PVC13 serotypes (3.5% PCV7 serotypes). Around 60% of pneumococcal CAP were caused by PCV13 serotypes (74.6% in invasive episodes vs 57.4% in non-invasive ones). The most prevalent serotypes in invasive disease were 1, 3, 7F, 19A and 14. No significant differences were observed in the distribution of PCV13 serotypes across the study periods. Regarding comorbidity, the rate of PCV13 serotypes was similar among them, and it was slightly higher in those with no underlying conditions. CONCLUSIONS: Serotypes included in PCV13 caused a significant proportion of CAP in adults with underlying conditions and in healthy adults, with no significant changes in cases due to PCV7 or PCV13 from 2011 to 2014, suggesting an insufficient indirect protection from childhood vaccination. Strategies for implementing pneumococcal vaccination of adults are encouraged to reduce the incidence of pneumococcal episodes.

Invasive Disease vs Urinary Antigen-Confirmed Pneumococcal Community-Acquired Pneumonia.

BACKGROUND: The burden of pneumococcal disease is measured only through patients with invasive pneumococcal disease. The urinary antigen test (UAT) for pneumococcus has exhibited high sensitivity and specificity. We aimed to compare the pneumococcal pneumonias diagnosed as invasive disease with pneumococcal pneumonias defined by UAT results. METHODS: A prospective observational study of consecutive nonimmunosuppressed patients with community-acquired pneumonia was performed from January 2000 to December 2014. Patients were stratified into two groups: invasive pneumococcal pneumonia (IPP) defined as a positive blood culture or pleural fluid culture result and noninvasive pneumococcal pneumonia (NIPP) defined as a positive UAT result with negative blood or pleural fluid culture result. RESULTS: We analyzed 779 patients (15%) of 5,132, where 361 (46%) had IPP and 418 (54%) had NIPP. Compared with the patients with IPP, those with NIPP presented more frequent chronic pulmonary disease and received previous antibiotics more frequently. Patients with IPP presented more severe community-acquired pneumonia, higher levels of inflammatory markers, and worse oxygenation at admission; more pulmonary complications; greater extrapulmonary complications; longer time to clinical stability; and longer length of hospital stay compared with the NIPP group. Age, chronic liver disease, mechanical ventilation, and acute renal failure were independent risk factors for 30-day crude mortality. Neither IPP nor NIPP was an independent risk factor for 30-day mortality. CONCLUSIONS: A high percentage of confirmed pneumococcal pneumonia is diagnosed by UAT. Despite differences in clinical characteristics and outcomes, IPP is not an independent risk factor for 30-day mortality compared with NIPP, reinforcing the importance of NIPP for pneumococcal pneumonia.

Retrospective epidemiological study for the characterization of community- acquired pneumonia and pneumococcal pneumonia in adults in a well-defined area of Badalona (Barcelona, Spain).

BACKGROUND: Community-acquired pneumonia (CAP) has large impact on direct healthcare costs, especially those derived from hospitalization. This study determines impact, clinical characteristics, outcome and economic consequences of CAP in the adult (≥18 years) population attended in 6 primary-care centers and 2 hospitals in Badalona (Spain) over a two-year period. METHODS: Medical records were identified by codes from the International Classification of Diseases in databases (January 1st 2008-December 31st 2009). RESULTS: A total of 581 patients with CAP (55.6% males, mean age 57.5 years) were identified. Prevalence: 0.64% (95% CI: 0.5%-0.7%); annual incidence: 3.0 cases/1,000 inhabitants (95% CI: 0.2-0.5). Up to 241 (41.5%) required hospitalization. Hospital admission was associated (p<0.002) with liver disease (OR=5.9), stroke (OR=3.6), dementia (OR=3.5), COPD (OR=2.9), diabetes mellitus (OR=1.9) and age (OR=1.1 per year). Length of stay (4.4±0.3 days) was associated with PSI score (ß=0.195), in turn associated with age (r=0.827) and Charlson index (r=0.497). Microbiological tests were performed in all inpatients but only in 35% outpatients. Among patients with microbiological tests, results were positive in 51.7%, and among them, S pneumoniae was identified in 57.5% cases. Time to recovery was 29.9±17.2 days. Up to 7.5% inpatients presented complications, 0.8% required ICU admission and 19.1% readmission. Inhospital mortality rate was 2.5%. Adjusted mean total cost was €2,332.4/inpatient and €698.6/outpatient (p<0.001). Patients with pneumococcal CAP (n=107) showed higher comorbidity and hospitalization (76.6%), higher PSI score, larger time to recovery and higher overall costs among inpatients. CONCLUSIONS: Strategies preventing CAP, thus reducing hospital admissions could likely produce substantial costs savings in addition to the reduction of CAP burden.

Changes in bone turnover markers after calcium-enriched milk supplementation in healthy postmenopausal women: a randomized, double-blind, prospective clinical trial.

OBJECTIVE: To assess the effect of calcium, phosphorus, lactose, and vitamin D fortified skimmed milk on biomarkers of bone turnover in healthy postmenopausal women. DESIGN: The design was of a prospective, double-blind, randomized, 6 months study. Eighty postmenopausal women (aged 49-71 y) were allocated in two groups receiving 750 mL/day of a fortified skimmed milk containing 1,200 mg of calcium and 5.7 microg of vitamin D (group A) or 900 mg of calcium and 5.7 microg of vitamin D (group B). Ultrasound bone mass measurements and biochemical markers of bone formation, serum bone-specific alkaline phosphatase (AP), and carboxi-terminal propeptide of type I procollagen (PICP) and of bone resorption, urinary excretion of pyridinoline (Pyr), deoxypyridinoline (D-Pyr), and urinary type I collagen cross-linked N-telopeptide (NTx) were performed at baseline and after 10 weeks and 6 months of follow-up. RESULTS: PICP levels showed a significant reduction during the study, but no differences were observed between groups (-18.47 +/- 11.4 group A vs -14.42 +/- 12.5 group B). Pyr levels decreased in group A (P < 0.001), whereas no changes were detected in group B. At the end of the study, a significant difference (P < 0.01) was detected between groups in Pyr (-23.66 +/- 5.7 group Avs 3.465 +/- 7.1 group B) and D-Pyr (-16.64 +/- 1.6 group Avs 2.955 +/- 2.1 group B). At the 6th month, serum 25OH vitamin D increased in group A and decreased in group B (P = 0.007). Additionally, no differences were observed between groups in bone mass and in the other bone markers. Body weight was unchanged for group A, whereas a significant increase was observed in group B. CONCLUSIONS: The daily intake of 750 mL of enriched skimmed milk containing 1,200 mg of calcium appears to be a useful, safe, and acceptable measure to calcium supplementation in healthy elderly postmenopausal women.