**2. Microbiology**

According to current evidence, IE among IDUs presents a large spectrum of microbial pathogens (**Table 1**) [26–31].

Pathogens as *Pseudomonas aeruginosa*, other gram-negative microorganisms, fungi, enterococci, streptococci, and polymicrobial infections occur less frequently [16]. Importantly, other pathogens noted in IDUs are oral bacteria such as *Prevotella intermedia*, *Haemophilus parainfluenzae*, *S. constellatus*, and *E. corrodens*  [32–36].

The most common etiology of right-sided IE in IDUs is *Staphylococcus aureus (S. aureus)* in about 75% [1, 4, 6, 37–39] followed by streptococci, Gram-negative bacilli, and fungi [40]. In fact, published data supports the involvement of *S. aureus* among IDUs in 40–74% cases of IE [38, 41, 42]. *S. aureus* is the most common cause of tricuspid valve endocarditis regardless of associated risk factors in IDUs [1, 4, 16, 18, 43].

The incidence of negative blood cultures is reported as 2.5–31% and is associated with delayed diagnosis and treatment [44], with large vegetations [45], and with highest morbidity and mortality [16, 45, 46].

Regarding HIV, a prevalence of HIV as high as 60% among IDUs has been reported by centers from Europe and the USA [11, 40]. HIV is more common among IDUs with right-sided IE than left-sided IE [47].

 *Polymicrobial endocarditis* is characteristically for IDUs [48] and may involve microorganisms such as *Bartonella* spp., *Candida* spp., or *Tropheryma whipplei* [49]. The presence of *E. corrodens* should aware the likelihood of polymicrobial IE with embolic complications and relapses. In fact, there is a synergism between streptococci and *E. corrodens* [50–52].


#### **Table 1.**

*Spectrum of microbial pathogens may constitute comorbidity in IDUs [26–31].* 
