**3. Microbiology**

The microbiology of IE has also evolved over the years. The growing incidence of difficult-totreat infections, methicillin-resistant Staphylococcus, polymicrobial infections with Gramnegative bacteria, primary or opportunistic fungi, and multidrug-resistant organisms has also increased the difficulties in managing this patient population—and is independently a predictor of worse outcomes and hence is often an indication for urgent surgery [7]. Advances in the ability of microbiology labs to better identify unusual organisms—including genetic material—have allowed for more accurately defining causative agents that otherwise would have been considered "culture negative." Furthermore, as more aggressive approaches to the diagnosis and management of sepsis have resulted in a more assertive approach to insuring appropriate and timely cultures, antibiotics, and a search of an infectious focus, there might be a more accurate and timely diagnosis of extensive bacterial infections [8], while it is unclear whether such an aggressive approach toward "septic" patients has changed the incidence of endocarditis or whether the significant increase in case presentations is more of a function of an overall awareness. Without doubt, as resistance patterns emerge within a community and a patient presents, for many reasons, with more unusual infectious, these patterns are also reflected in the microbiologic picture of endocarditis. In addition, the increase in immune modulating medications has also increased the incidence of fungal infections and very unusual pathogens [9]. Similarly, as patients with adult congenital heart disease and prosthetic material live longer, their overall risk of developing unusual infections that evolve into endocarditis also increases [10, 11].

In addition, as discussed in this text, there is a growing body of literature on concepts such as culture negative endocarditis and noninfectious endocarditis such as marantic or Libman-Sacks endocarditis [12].
