The specimen repository of the ICE-Micro multinational consortium provided us with a unique opportunity to examine CNS isolates associated with invasive disease. To our knowledge, this study is the first to fully characterize the species distribution and susceptibility patterns of CNS isolates from patients with definite endocarditis. Sequencing of the rpoB gene served as a robust target for identification to the species level, suggested an absence of clonality in strains causing S. epidermidis endocarditis, and identified high-level rifampin resistance in S. epidermidis isolates.
Historically, investigators have relied on conventional methods for the identification and susceptibility testing of CNS; this may have served as a barrier to the full appreciation of the epidemiology of CNS disease. In fact, previous reviews of CNS endocarditis have discussed the spectrum of disease from the perspective of phenotypic identifications with limited attention to specific species (17
). We found S. epidermidis
as the most common CNS species, an observation corroborated by previous reports on non-endocarditis patients with invasive CNS disease (1
). The rank order of non-S. epidermidis
infections differs in our report from that in others. We report S. lugdunensis
as the second most common pathogen, whereas non-endocarditis studies have observed S. hominis
, S. haemolyticus
, and S. capitis
as the next most commonly encountered CNS pathogens (1
The clinical implications of more accurate identification of CNS by gene sequencing are not fully known. In our study, we observed that the rpoB
gene serves as a reliable indicator of genetic diversity, which may be helpful as an epidemiological tool to distinguish multiple CNS strains. Also, fast identification of two distinct CNS strains may prove useful when interpreting the clinical significance of blood cultures in patients with intracardiac devices. With our limited data set, we did not observe distinct regional variations among clusters of CNS isolates; however, the ability to rapidly identify isolates to the species and subspecies levels may prove valuable for monitoring the dissemination of unusual strains between and within institutions. Only by gene sequencing were we able to identify and now report the first case of S. pasteuri
endocarditis. Additionally, rpoB
gene sequencing affords greater specificity by providing a unique genetic signature for CNS species that may have implications for global surveillance. While multilocus sequence typing schemes have emerged as important tools to assess clonal complexes for S. epidermidis
, the optimal discriminatory loci to serve as the gold standard have not been firmly established (20
). The use of the rpoB
gene shows promise as a marker for unique clones, but its use as a sole epidemiological target warrants further study by multilocus sequence typing.
Accurate isolate identification to the species level is also important for examining susceptibility patterns and alerting clinicians to those species with known increased virulence. Although we did not observe reduced susceptibilities to glycopeptides in S. epidermidis
and S. haemolyticus
, these species reportedly exhibit heterogeneous susceptibility to glycopeptides (4
) and their identification may heighten clinician awareness of therapeutic failures of vancomycin therapy. Similarly, identification of S. lugdunensis
may alter the diagnostic approach because this species is considered to be more susceptible to beta-lactam agents, more virulent, and associated with a higher mortality compared with other CNS species (2
). Finally, we report the first use of the rifampin resistance-determining region of the rpoB
gene to predict rifampin resistance in isolates identified as S. epidermidis
. Given the need for rifampin in patients with CNS prosthetic valve endocarditis, a reliable method to identify locations known to confer rifampin resistance by single-step mutations may be clinically important.
In conclusion, the ICE-Micro consortium enabled us to evaluate a large number of CNS isolates from patients with definite endocarditis from diverse geographic regions with a hierarchy of gene sequence data. From this extensive global repository, we provide novel and valuable information about the genetic diversity of CNS species that cause endocarditis, suggesting that strains causing CNS endocarditis have unique genetic signatures which are found across vast geographic distances. The clinical significance of more accurate identification to the species level remains to be defined, but rpoB sequence analysis may serve as a useful tool for surveillance and may improve our understanding of the host-pathogen relationships in native and prosthetic valve endocarditis.