**3. Microbiology of CNE**

The microbiology of CNE is varied and depends on host and environmental factors that predispose to one type of pathogen versus another [1]. As per the classification of Tattevin et al. [9], the microbiologic discussion will follow this paradigm.

#### **3.1. CNE due to pre-treatment of typical bacterial endocarditis**

According to one of the largest surveys of infective endocarditis recently performed, in the last decade, 29.7% of IE were due to *S. aureus*, 17.6% were due to oral *Streptococci*, 10% were due to coagulase-negative *Staphylococci* and 10% were due to *Enterococci*. Approximately, 16% of IE cases were thus due to Gram-negative bacteria, fungi and mycobacteria that could be cultured from blood. Because the presentation of infective endocarditis can be non-specific and is often associated with clinical sepsis, patients receive empiric broad spectrum antibacterials before sufficient numbers of blood cultures can be obtained. In one contemporary survey, antibiotics were used before blood cultures 74% of the time, with many patients coming from outside hospitals before a diagnosis of endocarditis was established [4]. The distribution of bacterial etiologies in these cases should represent what is seen generally when blood cultures are obtained prior to initiation of antibiotics. PCR of valve tissue in the cases where pretreatment occurred showed a predominance of *Streptococcus oralis* (54%), *Streptococcus aureus* (7.7%) and *Streptococcus gallolyticus* (formerly known as *Streptococcus bo‐ vis*) 5.1%. This likely reflects the ability of these organisms to attach to endovascular epithelium and be detectable by PCR methods.
