In the present study, SGSP (74%) was the dominant subspecies of SBSEC that caused bacteremia, followed by SGSG (13%), SL (10%), and SISI (3%). These results were consistent with those of previous studies [7, 19, 20]. Specific diseases have been found to be associated with specific SBSEC species or subspecies. For instance, SGSG bacteremia was found to be associated with infective endocarditis and colorectal cancer [4, 5]. In addition, SGSP and S. infantarius were found to be associated with biliary tract infections and biliary-pancreatic cancer [6,7,8,9]. In the present study, excluding primary bacteremia, infective endocarditis was the most common cause of bacteremia (26%), followed by biliary tract infections (23%). These results were also consistent with those of previous studies [8, 20]. However, there were no significant differences in the frequencies of the source of bacteremia among the SBSEC subspecies.
In the present study, there were no significant differences in the incidence of overall malignancies among each SBSEC subspecies. However, the incidence of overall colorectal cancer in patients with SGSG bacteremia was significantly higher than that in patients with bacteremia due to other SBSEC subspecies including SGSP. The strong correlation between colorectal cancer and SGSG has been well-established [5]. A systematic review and meta-analysis showed that the risk of acquiring colorectal cancer was lower in patients with SGSP than in those with SGSG at an odds ratio of 7.26, and that the incidence of colorectal cancer in patients with SGSP did not exceed the incidence in general asymptomatic individuals [5].
As many patients with SBSEC bacteremia have been identified as elderly with comorbidities [19, 20], it may have been difficult to perform colonoscopies in all the patients. In the present study, the primary bacterial sources in patients with colorectal cancer were infective endocarditis and primary bacteremia, and no patients had biliary tract infections. As the study used a retrospective design and no patients with biliary tract infection underwent colonoscopies, it is uncertain whether these patients had colorectal cancer. However, a previous large-cohort study found that colorectal cancer was less common in patients with biliary tract infections [6]. Therefore, in case of SBSEC bacteremia, patients with biliary tract infections may not require colonoscopies. Nevertheless, further studies are required to determine which patients with SBSEC bacteremia have a lower risk of colorectal cancer.
In previous studies, SGSP was associated with biliary pancreatic cancer [6,7,8]. In the present study, bile duct cancer was detected in three of 29 patients with SGSP bacteremia. Bile duct cancer was not found in patients with bacteremia caused by SBSEC, except in those caused by SGSP. Additionally, although 95% of the patients underwent CT scans, no patient was found to have pancreatic cancer. In each previous study, since the number of patients with biliary-pancreatic cancer and SGSP bacteremia was small [6,7,8], further investigation is required to clarify the association between SGSP bacteremia and biliary-pancreatic cancer.
In the present study, four patients with SL bacteremia were identified. The sources of SL bacteremia were infective endocarditis, biliary tract infections, and primary bacteremia. Since the incidence of SL bacteremia is less common than the incidences of SGSG and SGSP, only a few studies have investigated the clinical characteristics of SL bacteremia [19, 20]. Previous studies have reported infective endocarditis and biliary tract infections as sources of SL bacteremia [19, 20]. The results of the present study were consistent with those of previous studies, suggesting that the clinical presentation of patients with SL bacteremia is similar to that of patients with SGSG and SGSP.
In the present study, SGSP was identified in a pregnant woman with infective endocarditis. A previous study suggested that SGSP was an important pathogen of pregnancy-related infections leading to neonatal meningitis [21].
Further, the MALDI Biotyper was significantly more accurate in identifying SBSEC isolates at the subspecies level compared to the VITEK2. However, there were no significant difference in the rates of correct identification of SBSEC isolates at the species level between the MALDI Biotyper and the VITEK2. The MALDI Biotyper correctly identified all the SGSP isolates at the subspecies level. In 17 SGSP cases (59%), all the bacterial species identified using the MALDI Biotyper with a score > 2 were SGSP. Previous studies have also reported that the MALDI-TOF MS analyses using the MALDI Biotyper identified SGSP accurately [13, 22]. In contrast, the VITEK2 identified 69% of SGSP isolates at the subspecies level correctly. Eighty percent of the SGSG isolates were identified correctly at the subspecies level using the MALDI Biotyper. However, in all the SGSG cases, those with scores ≥ 2.0 obtained using the MALDI Biotyper included SGSP strains. In contrast, the VITEK2 correctly identified all the SGSG isolates with a high probability . The differences in the results of the MALDI Biotyper analysis may have been due to the number of reference strains of SGSP in the current database being greater than that of SGSG (7 strains vs. 4 strains). SL was more correctly identified at the subspecies level with the use of the MALDI Biotyper (75%) than with the VITEK2 (25%). SISI was misidentified with the use of the MALDI Biotyper as S. equinus. The same misidentification pattern was reported previously [13]. Moreover, the comparative evaluation of the two MALDI-TOF systems—MALDI Biotyper and VITEK MS—with the 16S rRNA and 16S–23S intergenic spacer region sequencing being used as the reference method, revealed several inaccuracies in both of the systems [13]. Additionally, the accurate identification with the MALDI-TOF MS was correlated significantly with the reference database for the target species [23]. Therefore, it is necessary to increase the number of reference spectra in the database for a more accurate identification of the SBSEC subspecies. The present study found that in terms of association between the subspecies and disease, colorectal cancer was associated significantly with SGSG bacteremia, while there were no significant differences in the frequencies of the source of bacteremia among the SBSEC isolates. The MALDI-TOF MS and phenotypic identification systems in the present and previous studies [13, 22] identified the SBSEC isolates at the species level accurately, but not at subspecies level. Additionally, it was difficult to identify SBSEC genetically using sequencing target genes such as sodA in clinical microbiological laboratories as a routine practice. Therefore, when SBSEC is detected in blood culture, it may be reasonable for clinicians to perform echocardiographies and colonoscopies to detect infective endocarditis and colorectal cancer in all patients with SBSEC bacteremia.
This study had some limitations. This was a retrospective study with a small sample size. The initial methods for identifying SBSEC differed between the three hospitals. There was an absence of a gold standard for the species identification of streptococci. Sequencing of sodA was performed only as an identification reference in the study. Additionally, in the MALDI-TOF MS analysis, we only analyzed the direct transfer method. Given the retrospective design of this study, 41% and 54% of the patients had undergone colonoscopy and transthoracic echocardiography, respectively, while only 8% underwent transesophageal echocardiography. Therefore, infective endocarditis and colorectal cancer may have been underestimated because not all patients underwent echocardiographies and colonoscopies. However, to the best of our knowledge, this was the largest study that investigated the incidence of SBSEC bacteremia in Japan. Further large-scale, prospective studies are required to clarify the clinical and microbiological characteristics of SBSEC bacteremia.