Streptococcal endocarditis: a meta-analysis of species dependant risk

Streptococcal infective endocarditis (IE) is a devastating disease. In international guidance, the risk of IE from streptococci is considered the same regardless of species (excluding Streptococcus pyogenes and Streptococcus pneumoniae). However, the idea of homogenous risk has been recently questioned. We aimed to evaluate the risk of IE across streptococcal species through meta-analysis of other published works and our own local data.

We first conducted a scoping review for publications that reported cases of streptococcal bacteraemia differentiated by species and estimated the risk of IE between 1994 and October 2024. Then we supplemented this data with our own laboratory data from four large hospitals. We meta-analysed the risk of IE. Two sensitivity analyses were performed to deal with one manuscript which excluded cultures considered as contaminants: first, by excluding that publication, and second by adjusting for blood culture contamination using our local estimated contamination rates.

Four studies met inclusion criteria comprising a total of 14,183 isolates with 1028 endocarditis cases (7.25% absolute risk of IE). The highest risk species were: Streptococcus mutans: 47% (95% CI 38-56%), Streptococcus cristatus: 41% (95% CI 21-62%), Streptococcus gordonii: 37% (95% CI 30-44%), Streptococcus sanguinis 33% (95% CI 28-39%), and Streptococcus gallolyticus: 31% (95% CI 27-36%). Combined, these species accounted for only 8.4% of bacteraemias but 38.6% of IE. The most common IE pathogen overall was Streptococcus mitis/oralis (23.6% of IE, 8% of bacteraemias) but these infections themselves only carried an IE risk of 12% (95% CI 11-13%). There was strong evidence of heterogeneity detected in S. mitis/oralis (I² 87%; Cochran's Q: 30 p: <0.001) and S. gallolyticus (I² 90%; Q: 29 p: <0.001).

The 'small five' streptococci: S. mutans, S. cristatus, S. gordonii, S. gallolyticus, and S. sanguinis account for only 8% of all streptococcal bloodstream infections but nearly 40% of all streptococcal IE with a risk of IE in individual infections as high as ∼50%. The risk of S. mitis/oralis appears heterogeneous, may depend on species or subspecies, and requires further study.

FH was funded by the NIHR Clinical Lectureship Scheme. TL has salary support from Fonds de Recherche Québec - Santé. PW is funded by a Medical Research Council grant MR/T005408/1.