In this cohort study, nearly one half of the patients with S. gallolyticus subsp. pasteurianus bacteremia presented cirrhosis. This finding was consistent with those of related studies reporting that 15 to 39% of patients had liver diseases or cirrhosis. (8, 14, 15)
Regarding the clinical presentations, this study was consistent with others reporting primary bacteremia as the most common clinical presentation, followed by spontaneous bacterial peritonitis, and infective endocarditis. (8, 14, 15) About 20% of participants were diagnosed with malignancy before the onset of bacteremia. As in other studies, a correlation between gastrointestinal and other organ malignancies with the bacteremia could not be demonstrated. (14) Although colonoscopy was performed in only 10% of patients, which might have underestimated the true prevalence of precancerous colorectal lesions, no new malignancy was observed after two years among 76 participants.
With the proportion of 8.5%, endocarditis was still an uncommon finding, similar to what had been reported in related studies. (8, 14) None of the endocarditis patients had cirrhosis, which was demonstrated to be a significantly protective factor. The different pathophysiology and clinical syndromes between cirrhotic and noncirrhotic patients may be explained by the diversity of the bacterial strain regarding the cell attachment ability. Although no study had determined the difference in host-microbe interaction between the two subspecies, the S. gallolyticus endocarditis strain was shown to have the significant capability to adhere to the endothelial cell lining of the human umbilical vein (HUVEC). (20) The cell surface of the blood group antigen sialyl lewis-X (sLex) normally expressed on human leukocytes enabling the rolling of leukocytes on the endothelium, increases the adhesion ability of S. gallolyticus to endothelial cells (21, 22). In contrast, the main origin of bacteremia among patients with cirrhosis arise from the fecal microbiome, which might have inferior virulence and less adhesion ability to the endothelium. (23)
Because S. gallolyticus subsp. pasteurianus, isolated from two or more different blood cultures, is one of the two major Duke criteria raising the suspicion of endocarditis, echocardiography should be performed.(16, 17) From our findings, because of the lower incidence of endocarditis other than S. bovis, this diagnostic procedure might not be needed in patients with cirrhosis, which will decrease the excessive investigation by one half of patients with the bacteremia.
The mortality rate of the bacteremia was higher than related reports. (8, 14) This observation may be explained by the higher proportion of patients with cirrhosis, which usually had higher complications and mortality rates. (23)
Although some isolates were intermediate or resistant to beta-lactams using disk diffusion tests, all isolates were susceptible after the MIC measurement when E-test method was performed. This error is due to the poor discrimination ability of disc diffusion tests between penicillin-susceptible and penicillin-intermediate streptococcal populations. (24, 25) As a result, MIC measurement should be primarily used to interpret susceptibility results or to confirm resistance in resistant isolates determined by the disk diffusion method.
Although this is the first study to demonstrate a correlation between S. gallolyticus subsp. pasteurianus and infective endocarditis among noncirrhotic patients, it had certain limitations. First, although a large number of participants were enrolled in this study, only 8.5% presented endocarditis, which might have overestimated the true association. This small proportion helps confirm that, unlike S. gallolyticus subsp. gallolyticus, S. gallolyticus subsp. pasteurianus uncommonly causes endocarditis. Second, the ability of species identification using VITEK 2 system to discriminate between the two subspecies of S. gallolyticus is not apparent. Nevertheless, studies comparing the Vitek 2 and sodA sequencing method showed generally acceptable agreement. (26) Finally, due to the retrospective design, factors influencing the physician’s reason for the decision to perform colonoscopy and echocardiography was unidentified, which might have underestimated the prevalence of endocarditis and cancer. However, this bias was minimized by the long-term follow-up.