1. Introduction

In this chapter we will analyze the physiopathological changes involved in the inflammatory response of the septic process in infective endocarditis [IE] that culminate with cellular damage and the generation of organic failures; morphological changes, cellular biology, biochemistry, immunology, and genetic vulnerability, which together are called "pathobiology," are the substrate of clinical manifestations of this serious disease, which requires a multidisciplinary group of experts

(cardiologists, infectologists, surgeons, intensivists) to optimize therapeutic approach. IE is defined as a severe multisystem disease, which results from an infection, often bacterial, that initially affects the endocardial surface of the heart [1]. The epidemiological pattern has changed over time [2–4]. The incidence has increased in recent years to 5–10 cases per 100,000 inhabitants [2], due to the fact of a greater number of predisposing factors such as the use of permanent cardiovascular devices, invasion with intravenous catheters in critical care units, and hemodialysis treatments, in addition to having greater accessibility to diagnostic tools. From the etiological point of view, Staphylococcus aureus (S. aureus) is predominant as a causal germ [5, 6]. The clinical course of a patient with IE depends on the inflammatory response, since it is variable; it also depends on the germ and the response of the patient to infection with varying degrees of hemodynamic and metabolic compromise [7–9]. We emphasize the current trend of the search for organic failures associated to the septic processes for their identification and stratification and therapeutic approach [10]. Given the characteristics of the disease, IE has a high mortality that goes from 20 to 30% in the reported series [2, 11]; it is noteworthy that the evolution toward septic shock has been documented in 30% [12], considering this complication as an independent variable of poor prognosis [13].

#### 2. Epidemiology of infective endocarditis

The pathogenesis and the prognosis of IE can be simply described in a general way as the interaction between the host and the germ; however, these factors are not independent and are very importantly linked both in the susceptibility characteristics of the host (advanced age, higher prevalence of comorbid conditions, and exposure to health care) to survive or not to an infectious state, as of the characteristics of the germ involved. To reduce the incidence of IE and improve its outcome, epidemiological studies can provide valuable information on contemporary and modifiable risks to modify their morbidity and mortality [14].

The incidence of hospital discharge diagnoses for drug dependence combined with IE increased more than twelvefold from 0.2 to 2.7 per 100,000 persons per year over this 6-year period. Correspondingly, hospital costs for these patients increased eighteenfold, from \$1.1 million in 2010 to \$22.2 million in 2015 [15].

In another study also conducted in the USA, using a national sample of hospitalized patients from 1998 to 2009 with focus on IE showed an increase in the use of intracardiac devices from 13.3 to 18.9%. In cases with pathogens identified, S. aureus was the most common, increasing from 37.6% in 1998 to 49.3% in 2009, 53.3% of which were methicillin-resistant Staphylococcus aureus (MRSA) [16]. The above can give us an idea of the economic and assistance impact of treating patients with severe sepsis such as IE. It is an infection inside the organ that is responsible for distributing blood to practically the whole organism.

The evolution of an inflammatory process plus infection frequently occurs with clinical manifestations unspecified such as fever or hypothermia, tachycardia, tachypnea, or abnormal white blood cell count, progressing to septic shock and acute organ failure [17].

Epidemiological data of more than five decades tell us that S. aureus is the most important causal agent of IE [4]; so in the development of systemic inflammation that is generated by the host-germ interaction, we will consider the S. aureus as the best example of IE due to its virulence and an emergent property that we know as resistance to antibiotics, sophisticated defense mechanisms, and the ability to cause apoptosis in cells when it is alive inside the cell. The interaction of S. aureus-host allows us to develop in a substantive way, on one hand, the importance of the

virulence of the germ and, on the other, the defense mechanisms of the host, showing how the inflammation is generated and amplified to offer a step to oxidative stress. It is important to mention that other agents can cause IE such as streptococci and fungi.
