**3. Diagnosis**

 History and classic Oslerian manifestations (persistent bacteremia or fungemia, active valvulitis, immunological vascular phenomena, and peripheral emboli) help with a straightforward diagnosis in IE [1]. Typical clinical manifestations of IE comprise fever, positive blood cultures, and valvular vegetations on echocardiography [53]. IE should be suspected in the presence of fever and embolic phenomena [16]. Persistent fever and bacteremia are common manifestations of tricuspid valve IE [16].

Clinical manifestations are usually limited in the early IE of IDUs, right-sided endocarditis and *S. aureus* [1]. Right-sided IE mainly present fever, cough, hemoptysis, dyspnea caused by pulmonary emboli, anemia, and no systemic emboli [23]. Characteristically, right-sided IE does not develop immunological vascular phenomena (splinter hemorrhages, Roth spots, and glomerulonephritis) and the peripheral emboli [1]. Right-sided IE can be associated with septic pulmonary emboli [1]. In fact, pulmonary embolism is often present in right-sided IE and pacemaker wires IE [16].

Usually, the association of clinical findings, positive blood cultures, and positive echocardiography set up the diagnosis [23]. However, these typical clinical manifestations of IE are often absent among IDUs, especially in those infected with *S. aureus* and HACEK (*Haemophilus species*, *Actinobacillus actinomycetemcomitans*, *Cardiobacterium hominis*, *Eikenella corrodens*, *Kingella kingae*) [54]. Common complications of right-sided IE are valvular regurgitations, cardiac abscess, and septic pulmonary emboli [55].

Relapse and reinfection are two types of recurrence [16]. Basically, recurrence within 6 months of same IE produced by same microorganisms is termed *relapse* [55]. Reinfection or recurrent IE refers to the *recurrence* of same IE with same microorganisms after 6 months from initial episode [53]. Recurrent IE has higher frequency in IDUs with increased valve replacement [16] with a reported incidence as 41% [56].

 The landmark lesion of IE is the *vegetation* (**Figure 1**) [57]. In this context, IDUs population with vegetations >20 mm may present higher embolic risk [58] and higher mortality as well [25, 58, 59].

 The cornerstone of imaging diagnosing for infective endocarditis is echocardiography [16]. Transthoracic echocardiography (TTE) and/or transesophageal echocardiography (TOE) are vital in the diagnosis of any IE [16]. TTE is the first line recommendation either for native valve endocarditis or for prosthetic valve endocarditis. In case of suspected native valve endocarditis, TTE has a sensitivity of 50–90% and a specificity of 90% [60]. For IE with vegetation, TTE has a moderate sensitivity (75%) and high specificity (>90%) [61]. For suspected prosthetic valve endocarditis, TTE has a reduced sensitivity of 40–70%. However, TTE comes up with significant information regarding ventricular size and function, and "hemodynamic severity of valve lesions" [60]. Major criteria in the diagnosis of IE are represented by three echocardiographic features: vegetation, abscess or pseudoaneurysm, and prosthetic valve with new dehiscence [16]. Moreover, TTE provides useful information in the diagnosis of anterior prosthetic aortic valve abscesses, which are difficult to be seen on TEE [60].

 TOE is recommended when TTE is nondiagnostic or positive, suspected complications, or in presence of intracardiac device leads [60]. In case of native valve endocarditis, TOE has a sensitivity of 90–100% and a specificity of 90% for revealing vegetations. As such, TOE is highly superior to TOE regarding the detection

#### **Figure 1.**

*Macroscopy and microscopy of the involved tricuspid valve and vegetation. (a) Yellow arrowhead: the large vegetation, blue arrowhead: rupture main chordae tendineae. (b) Blue arrowheads: multiple verrucous nodular vegetation on the atrial surface of leaflet. (c) Resected tricuspid valve. Blue arrowheads: multiple small vegetations, yellow arrowhead: rupture main chordae tendineae. (d) Microscopy of the vegetation adhered to the leaflet, magnification 4×, hematoxylin and Eosin stain. (e) Enlarged square area in (e) showing inflammatory cell infiltration and fibrin-platelet thrombi, magnification 20×, hematoxylin and Eosin stain. NOTE: every figure specifies this sentence beginning: From Bai et al. [57]. It is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.* 

of abscesses, perforations, and fistulae [60]. TOE has higher sensibility in the detection of pulmonary vegetations [62]. When clinical manifestations sustain IE with negative or unclear TTE, TOE has high sensitivity (>90%) and may reveal: (1) vegetations; (2) paravalvular or intracardiac abscess, (3) new valvular regurgitations, and (4) prosthetic valve dehiscence (**Figure 2**) [57, 63, 64].

Currently, 3D TOE provides useful information about the morphology and size of vegetation, evaluation of perivalvular extension, dehiscence of prosthetic valve, and valve perforation [65].

*Infective Endocarditis in Intravenous Drug Users: Surgical Treatment DOI: http://dx.doi.org/10.5772/intechopen.84708* 

#### **Figure 2.**

*Transesophageal echocardiography images of the patient before surgery. (a) Tricuspid regurgitation, Yellow arrowhead: wide and reversed blood flow signals at TV site. (b) A large vegetation formation. Yellow arrowhead: a large vegetation adheres to anterior leaflet of TV. (c) Suspicious multiple vegetations on 3D echo image. Yellow arrowheads: multiple verrucous abnormal nodular projections on the leaflet surface. RA right atrium, RV right ventricle, LA left atrium, LV left ventricle, TV tricuspid valve. NOTE: every figure specifies this sentence beginning: From Bai et al. [57]. It is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.* 

 Other imaging techniques such as magnetic resonance imaging (MRI), multislice computed tomography (MSCT), and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) are also valuable for the diagnosis of IE [16]. MSCT, MRI, and cardiac CT can provide greater information when compared with TEE regarding either paravalvular anatomy or complications (e.g. mycotic aneurysms, paravalvular abscesses) with lesser prosthetic valve artifacts [60]. Currently, using CT imaging in the diagnosis of paravalvular lesions is a major criterion in the 2015 ESC guidelines on IE [16].

Modified Duke criteria (2000) for diagnostic classification are well-known [64] and reviewed by 2015 ESC Guidelines for the management of infective endocarditis [16]. Only that, these modified Duke criteria have poorer diagnostic precision in the early diagnosis of IE from IDUs, which present fewer typical clinical manifestations [16]. The addition of imagistic techniques cardiac/whole-body CT scan, cerebral MRI, 18F-FDG PET/CT, and radiolabelled leucocyte SPECT/CT may increase accuracy of the modified Duke criteria in IDUs. To sum up, these modified Duke criteria are useful, but they do not substitute the decision of a multidisciplinary team or of the "Endocarditis Team" that is defined later [16].

### **4. Treatment**

 The initial treatment of IE is empirical in majority of cases [1]. Consistent with published data, the main effective treatment is medical therapy, whilst surgery is a choice in smaller cases [16]. So that, medical treatment in right-sided IE of IDUs is usually effective with good prognosis up to 80% cases [16, 23, 66].

*S. aureus* is the most frequent cause of IE in IDUs; as a result, medical treatment should cover this pathogen [16]. Short courses of antimicrobial therapy in rightsided IE with *S. aureus* in IDUs assure high cure rates (>85%) [1].

A short course (2 weeks) with oxacillin or cloxacillin is mainly sufficient [16]. Initial therapy comprises penicillinase-resistant penicillins, vancomycin, or daptomycin in combination with gentamicin [16]. Short course (2 weeks) with oxacillin or cloxacillin is mainly efficient for isolated tricuspid IE with good compliance to therapy, vegetation <20 mm, MSSA, without empyema or other metastatic sites of infection, without prosthetic valve or left-sided IE, without cardiac/extracardiac complications and without severe immunosuppression (<200CD4 cells/μL) with/ without AIDS. Anti-pseudomonas agent should be added in pentazocine addict [59]. Antifungal therapy for Candida spp. is added when an IDU utilizes brown heroin combined with lemon juice [67].

 A traditional approach for the treatment of right-sided IE is the regimen formed from gentamicin with nafcillin or oxacillin. Another approach of IDUs with rightsided *S. aureus* IE and no other complications (e.g. aortic or mitral valve involvement, extra pulmonary infections or meningitis, renal failure, MRSA infection) is the antimicrobial coverage with short-course (2 weeks) of beta-lactam plus aminoglycoside that may be greatly successful [1]. Current guidelines still suggest the use of gentamicin, but some available data suggest that it might be unnecessary [68].

 Moreover, daptomycin monotherapy is approved for the therapy of *S. aureus*  bacteremia or right-sided *S. aureus* IE [69]. If laboratory evaluation shows opiate withdrawal, 10–20 mg of long-acting methadone can be prescribed until the regular doses are established [70].

 To sum up, it is problematic to treat IE in IDUs because of the frequent exposures to virulent microorganisms; poor compliance with treatment; illegal drug use or withdrawal manifestations during hospitalization; opioid maintenance therapy; and early self-discharge or long hospitalization [70, 71]. Regardless of correct antimicrobial therapy, IDUs develop *relapsing IE* [56, 72, 73].

#### **5. Surgery**

Surgery is not a contraindication for IDUs with IE [4]. However, surgery indications are complex and are based on the clinical manifestations, associated risk factors (e.g. age, microorganisms, size of vegetation, perivalvular infection, embolism,

#### *Infective Endocarditis in Intravenous Drug Users: Surgical Treatment DOI: http://dx.doi.org/10.5772/intechopen.84708*

heart failure, and other associated comorbidities) and the expertise of surgery team [1]. A multidisciplinary team or the "Endocarditis team" with knowledge in cardiology, infectious diseases, microbiologists, imaging, neurologists, neurosurgeons, and cardiothoracic surgery should provide decisions regarding the indication and timing of surgery [1]. Cardiac surgery in IDUs with IE aims to remove infection with hemodynamics stabilization hemodynamic may be suggested for IDUs [74].

In terms of surgery, right-sided IE has better outcomes than left-sided IE [1]. General approach of IDUs with right-sided IE is medical therapy and to delay as much as possible the use of valve prostheses [1].

Surgical treatment indications for right-sided IE are following [1, 16, 28, 75]:

