**1. Introduction**

Culture-negative endocarditis (CNE) is one of the most challenging infectious diseases clinical syndromes both diagnostically and therapeutically. The prevalence of CNE varies widely in various modern series: it is estimated that on average, in 20% (range 5–71%) of echocardiographically evident endocarditis, both native and prosthetic valve, blood cultures do not yield a specific pathogen [1–7]. The morbidity but not necessarily mortality associated with CNE is higher than in instances where a specific pathogen is found, primarily due to the increased burden of diagnostic testing, delays in administration of antibiotics and the

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

extended use of broad spectrum anti-microbial agents [8]. This chapter will review the epidemiology and likely microbiology of CNE, as well as enhanced diagnostic methods and treatment recommendations.

A useful definition of CNE has been put forth by Tattevin et al. [9] wherein one can think of this entity as (1) true bacterial endocarditis with blood cultures sterilized by previous receipt of antimicrobials; (2) CNE caused by fastidious or unusual organisms such as the bacteria known as the "HACEK" group, nutritionally deficient *Streptococci, Pasturella* spp., *Helicobacter* spp., Mycobacteria and fungal organisms and (3) "true" CNE involving intracellular organisms that are detectable via serology or polymerase chain reaction (PCR) of valvular tissue, e.g. *Bartonella quintana, Coxiella burnetti* and *Tropheryma whipplei*. In addition, there are noninfectious causes of endocarditis, e.g. murantic that will not be covered in this chapter.
