**5. Treatment of CNE**

60] are the most widely reported. Commercial tests that detect fungal wall antigens such as galactomannan [2, 61, 62] and β-1,3-D-glucan [62] can show good sensitivity and specificity in diagnosis of fungal CNE. Jinno et al. [56] reported negative urine *Histoplasma* antigen results in their patient with *H. capsulatum* CNE, with diagnosis based on valvular pathology and tissue

Our understanding of the etiology of CNE and our ability to offer more targeted treatment to patients with CNE have been dramatically affected by the large number of novel diagnostic tests now available to add to our investigative armamentarium. The following discussion will focus on methods that allow diagnosis without removal of infected valves or cardiac devices (prosthetic valves, endovascular grafts, pacemaker and defibrillator leads, ventricular assist devices, etc.) versus methods that require removal of tissue or a device for diagnostic and

Imaging using positron emission tomography (PET) scanning has been utilized to diagnose a case of *T. whipplei* endocarditis [63]. The infected prosthetic valve was subsequently removed providing material for PCR-based methods to confirm the diagnosis, but the impetus to remove the valve came from the PET scan. Four-dimensional cardiac MRI was used to better define valvular damage and diagnose aortic valve endocarditis in a case of *C. bur‐ netti* CNE in a patient with exposure to domesticated buffalos and positive serologies [64]. PCR combined with electrospray ionization mass spectrometry (PCR/ESI-MS) methods have been applied to detect pathogens in blood cultures in patients already receiving antibiotics and made a diagnosis in 41 out of 410 cases, although not specifically in persons with CNE [65]. Broad range PCR on blood culture specimens has also been utilized [2]. Serum galactomannan and β-1,3-D-glucan have already been mentioned as serum diagnos-

Methodologies to increase numbers of planktonic organisms that can be cultured from devices have been devised, using sonication of the devices [66, 67]. Metagenomic analysis of the results of next generation sequencing has been used to diagnose *A. defectiva* CNE [68]. A universal PCR/sequencing test has been applied to diagnose CNE on blood and valvular tissue [69]. Immunofluorescent antibody detection, Western blot analysis and real time-PCR of 16s RNA have been used to diagnose CNE due to *Bartonella* spp. [38]. PCR/ESI-MS has been uti-

culture.

**4. Diagnostic methods**

108 Contemporary Challenges in Endocarditis

therapeutic reasons.

**4.1. Non-invasive methods**

tic tests for fungal CNE [2, 61, 62].

lized on valve tissue to diagnose CNE [70, 71].

**4.2. Invasive methods**

There are some distinct differences in the management of infective endocarditis according to the United States [1] versus European guidelines [72] updated in 2015. These are reviewed in Tattevin et al. [73]. However, in regard to treatment of the following etiologic agents of CNE, there is good agreement in general.
