Age-Dependent Serotype-Associated Case-Fatality Rate in Invasive Pneumococcal Disease in the Autonomous Community of Madrid between 2007 and 2020

Abstract

The aim of this study was to investigate the serotype-associated fatality rate in cases of invasive pneumococcal disease (IPD) in the Spanish region of Madrid between 2007 and 2020. Serotyping was performed by Pneumotest Latex and the Quellung reaction using commercial antisera. Case-fatality rate was estimated as the ratio between the number of deaths at hospital discharge and the number of cases attributable to each serotype. To evaluate the association measures, the odds ratios with a 95% confidence interval were calculated. Twenty five pneumococcal serotypes were associated to mortality and comprised 87.8% of the total number of isolates characterized. Serotypes 8, 3, 19A, 1, 7F, 22F, 12F, and 11A were the most prevalent (≥3% each). Serotypes 31, 11A, and 19F were significantly associated to high case-fatality rates (>20% each). The lower significantly associated case-fatality rate (<10% each) was found in serotypes 5, 1, 12B, 7F, 12F, 8, 33, and 10A. The serotypes with higher mortality levels (≥0.04 per 100,000 population) were 11A (fatality 24.0%), 3 (fatality 18.7%), 19A (fatality 12.5%), and 8 (fatality 7.2%). Serotype 3 was worrisome because it is associated with important fatality levels combined with very high incidence and mortality rates. Serotype 11A also showed a high fatality with marked incidence and mortality levels. Some few frequent serotypes as 31, 19F, and 15A despite its high fatality had low levels of mortality. By contrast other serotypes as 8 showing low fatality had high mortality ranges because it shows a wide extended distribution. Finally, common serotypes, such as 1 and 5, presented small mortality length, due to their low case-fatality rates.

Effect of pneumococcal conjugate vaccines and SARS-CoV-2 on antimicrobial resistance and the emergence of Streptococcus pneumoniae serotypes with reduced susceptibility in Spain, 2004–20: a national surveillance study

“… 15 Hence, the profound potential of this serotype to produce infection might explain why serotype 11A was the serotype with the second highest fatality rate in a lethality study. 28 Another non-PCV13 serotype that has emerged is serotype 24F. This serotype is also alarming, because it displays resistance to penicillin and erythromycin, and its prevalence in the paediatric and adult population is increasing in various countries.…”

Evolution of Antimicrobial Susceptibility to Penicillin in Invasive Strains of Streptococcus pneumoniae during 2007–2021 in Madrid, Spain

“…This genotype of serotype 11A is associated with high levels of antibiotic resistance, shows a greater ability to form biofilms and avoids very efficiently the host immune response [34]. In a recent study conducted by our group, this prevalent serotype was detected with the second highest fatality rate [36] and has shown an increase in penicillin resistance in the last years. Indeed, the pandemic of SARS-CoV-2 has increased the resistance levels of circulating strains of serotype 11A in Spain, with an increase in MIC90 to penicillin from 2mg/L during 2016-2019 to 4mg/L in 2020 [26].…”

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“…The fact that this serotype was less frequent among older adults may be associated with this antimicrobial susceptibility pattern, as antimicrobial-resistant pneumococci appear more frequently in older patients with comorbidities [11]. Previous studies have linked the presence of serotype 8 to highly invasive disease and moderate CFR [15]. If Spain implements PCV20 among older adults and young children, the degree to which serotype 8 is reduced will depend on serotype-specific efficacy against disease and carriage, as well as vaccine uptake, and will require ongoing monitoring of IPD and CAP, including non-bacteraemic CAP.…”

“…The 20-valent PCV (PCV20) is the highest valency PCV currently licensed by the European Medicines Agency (EMA) for the prevention of invasive disease and pneumonia caused by Streptococcus pneumoniae in individuals 18 years of age and older [12]. PCV20 includes PCV13 serotypes plus seven additional serotypes (8, 10A, 11A, 12F, 15B, 22F, 33F) [12] that have been commonly associated with invasive pneumococcal disease (IPD) [2,13] and linked to antibiotic resistance or greater disease severity [14][15][16][17].…”