High prevalence of multiple serotypes of pneumococci in patients with pneumonia and their associated risk factors

Abstract

Background: Multiple serotypes of pneumococci have epidemiological and clinical implications, such as the emergence of non-vaccine serotypes and the acquisition of antimicrobial resistance. Prevalence of multiple serotypes of pneumococci in adults and their risk factors are not known.

Methods: We enrolled adult patients from age ≥15 years with radiologically confirmed pneumonia in four hospitals across Japan. Pneumococcal pneumonia was defined with a pneumococcal bacterial density of ≥10⁴/mL in sputum by lytA quantitative PCR, and serotypes were determined. Pneumonias with a single serotype were categorised as single-serotype pneumococcal pneumonia and with two or more serotypes as multiple-serotype pneumococcal pneumonia. Multivariable logistic regression was used to assess the risk factors.

Results: 3470 patients (median age 77 years, IQR 65-85) were enrolled. Pneumococcal pneumonia was identified in 476 (18.3%, n=2605) patients. Multiple serotypes were detected in 42% of them. Risk of having multiple serotypes was low among patients who had received 23-valent pneumococcal polysaccharide vaccine (PPSV23) vaccines (adjusted OR 0.51 (95% CI 0.27 to 0.94)). Proportion of non-PCV7 PPSV23 serotypes in overall distribution of multiple serotypes was 67.4% (n=324/481) compared with 46.4% (n=128/276) in that of single serotypes (p=0.001). Serotypes 5, 9N/9L, 10A, 12/22/46, 17F and 35F were associated with multiple-serotype pneumonia, and serotypes 6A/6B, 23F, 11 and 6C/6D were associated with single-serotype pneumonia. Proportion of more invasive serotypes (serotypes 1, 5, 7F, 8) was significantly higher in multiple-serotype pneumonia (p=0.001).

Conclusions: Multiple serotypes of pneumococci are common in sputum of adult patients with pneumonia. The risk of multiple-serotype pneumococcal pneumonia is lower than that of single-serotype pneumococcal pneumonia among PPSV23-vaccinated patients.

Trial registration number: UMIN000006909.

Keywords: bacterial infection; clinical epidemiology; pneumonia; respiratory infection.

Figure 1

Patient enrolment and identification of pneumococcal pneumonia. Flow chart shows the number of adult patients (≥15 years) from the enrolment to the identification of patients with single-serotype and multiple-serotype pneumococcal pneumonias.

Figure 2

Distribution of pneumonia in adults by age in Japan. Bar diagram shows the distribution of radiologically confirmed adult patients with pneumonia (black bar), single-serotype pneumococcal pneumonia (blue bar) and multiple-serotype pneumococcal pneumonia (green bar) by age group.

Figure 3

Distribution of pneumococcal serotypes. Bar diagram showing the distribution of pneumococcal serotype/serogroups in single-serotype pneumococcal pneumonia (number of serotypes=276) and multiple-serotype pneumococcal pneumonia (number of serotypes=481). Blue bar represents serotype distribution in single-serotype pneumonia, whereas orange, green and purple bars represent serotype distributions of first, second and third dominant serotypes in multiple-serotype pneumonia. PPSV23, 23-valent pneumococcal polysaccharide vaccine.

Figure 4

Bacterial density in single-serotype pneumococcal pneumonia and multiple-serotype pneumococcal pneumonia. Box and whisker plot showing the distribution of bacterial density of serotypes in single-serotype pneumococcal pneumonia and multiple-serotype pneumococcal pneumonia in order of dominance. The total number of serotypes identified was 242 in single-serotype pneumonia and 481 in multiple-serotype pneumonia.

Figure 5

Scatter plot showing the relationship between pneumococcal bacterial density and C-reactive protein in single-serotype pneumococcal pneumonia and multiple-serotype pneumococcal pneumonia. Solid lines represent the linear regression fit across the patients. Spearman’s rank correlation coefficients were 0.205 (p=0.001) and 0.184 (p=0.009) for single-serotype pneumococcal pneumonia and multiple-serotype pneumococcal pneumonia, respectively.