**2.7. Infective endocarditis in children**

**PATHOGEN EARLY PVE\* (%)**

Adapted from Wang et al. [53]. \*

42 Contemporary Challenges in Endocarditis

**Table 2.** Causative organisms for early and late PVE.

surpasses greatly that of the pacemaker [79–81].

**2.5. Ventricular-assist devices infection**

**2.4. Cardiovascular-implantable electronic devices infection**

valve endocarditis.

*Staphylococcus aureus* **36 18** *Coagulase‐negative Staphylococci* **17 20** *Enterococcus* **8 13** *Viridans streptococci* **2 10** *Streptococcus bovis* **2 7** HACEK **0 2** Fungi **9 3** Other **6 14** Culture negative **17 12**

*N* **= 53**

HACEK: *Hemophilus, Aggregatibacter spp., Cardiobacterium hominis, Eikenella corrodens, Kingella kingae*. PVE: Prosthetic

The most commonly used cardiovascular-implantable electronic device (CIED) are permanent pacemaker, cardiac resynchronization therapy, and implantable cardioverter-defibrillator. Most of these are implanted using transvenous leads. This practice had dramatically reduced the risk of infection associated with the procedure. Nevertheless, complication by infection remains a problem that can lead to significant morbidity, mortality, and elevated costs [73– 75]. Reports of CIED infection vary according to different series and range from 0.13 to 19.9% [76–78]. In a 16-year survey of Nationwide Inpatient Sample (NIS) from 1993 to 2008, the rate of CIED implantation increased 4.7% annually. The incidence of CIED infection remained stable until 2004, but increased almost twice in a 4-year period (2004–2008) from 1.53 to 2.41%, respectively [75]. The rate of infection associated with implantable cardioverter-defibrillator

Patients who receive ventricular-assist devices (VADs) usually have various comorbidities, including a state of immune compromise. The risk of infection varies depending on the duration of VAD support [82]. Higher rates of infection are observed in the destination therapy group compared with the group where VAD is used as a bridge to transplantation [82]. Hravnak reported that registry patients with implant duration longer than 60 days were twice as likely to develop infection than those patients supported for less than 30 days [83]. The reported rates of infection in patients with VAD range from 13 to 80% and depend on multiple factors, including comorbidities, type of device implanted, and duration of VAD support [84]. Infection of VAD can present as three different syndromes: driveline infection (most frequent)

Early refers to IE within 2 months and late after 2 months, according to Wang et al.

**LATE PVE\* (%)** *N* **= 331**

> As in adults, trends in children IE are related to the evolution of care in the sick child, particularly children born with congenital heart disease. The incidence of children IE provides limited data, mostly based on inpatient admission which could not represent accurately the general population. In a report between 1933 and 1972, the incidence was 0.22–0.55 cases per 1000 pediatric hospital admissions [91]. A retrospective review between 1972 and 1982 found an incidence of 1/1280 pediatric admissions [92]. Later, in a multicenter study, the incidence of IE slightly decreased, ranging from 0.005 to 0.12 cases per 1000 pediatric admissions [93]. In other report including 47,518 patients, from 1998 to 2010, congenital heart disease was found as the major underlying condition associated to IE in children in high-income countries, with a cumulative incidence of 6.1 per 1000 children [94]. The distribution of IE between boys and girls is balanced in contrast with series in adults in whom men have a higher tendency to suffer the condition [94, 95]. Rheumatic fever is rare in developed countries, nevertheless is commonly found in low-income countries. In the presurgical era, the proportion of IE in children with rheumatic heart disease ranged from 30 to 50% [96]. A single center report covering seven decades found that IE occurred in 31% of rheumatic heart disease patients in presurgical era, compared to era 3 (1992–2004) with only 1.1% of patients having the condition [97]. Approximately 50% of cases of pediatric IE complicating congenital heart disease have had previous cardiac surgery, especially palliative shunts of complex cardiac repair [98]. Risk of postoperative IE in children depends greatly on the type of surgery; for example, a study from Oregon found a relatively low incidence of IE after tetralogy of Fallot repair (1.3%), ventricular septal repair (2.7%), atrial septal repair (2.8%), and aortic coarctation repair (3.5%). Nevertheless, a high incidence of IE was found in aortic stenosis (valve replacement) with a cumulative incidence at 25 years of 13.3% [99]. The rate of IE in structurally normal hearts is lower than those with a predisposing condition (22 vs. 78%), respectively [100]. A major risk factor to develop IE in an anatomically normal heart is an indwelling vascular catheter [101].

#### **2.8. Infective endocarditis in adults**

An important condition related to IE in the elderly is the congenital bicuspid aortic valve. In a prospective multicenter study, it was present in 16% of cases of native valve endocarditis [102]. Degenerative cardiac lesions assume an important role in the development of IE without underlying valve disease. In one study, degenerative lesions were present in 50% of patients with native valve IE older than 60 years [103]. Calcified mitral annulus is a common finding in elderly women but rarely complicate with IE (3.8%) [104]. Even not a classical condition related to IE, idiopathic hypertrophic subaortic stenosis may represent up to 5% of incidence of the infection [105]. And there is a higher mortality rate correlation if a murmur is present (up to 36% of patients with hypertrophic aortic stenosis and IE) [105]. Another condition associated with IE is the mitral prolapse syndrome. In different series, the range of IE in those patients with mitral valve prolapse can go from 11 to 23% [106, 107]. In another study, 8.6% of patients with mitral valve prolapse who were monitored prospectively for 9–22 years developed IE [108]. This syndrome must be suspected in patients with mid-systolic click with or without a late systolic murmur. This condition is not uncommon and has been found in 0.5– 20% of otherwise healthy people, especially young women. It has become apparent that a significant proportion of patients with mitral valve prolapse have an anthropometrically distinct habitus, suggesting that this condition is only an element of a generalized developmental syndrome [109]. It may be useful to have in mind these characteristics to help identify patients with a high risk of developing IE. Having valvular redundancy and thickened leaflets may increase the risk of IE [103]. The combination of mitral valve prolapse and men older than 45 years also may increase the risk of IE [110]. In a detailed case-control study, 25% of patients with IE had mitral valve prolapse; the odds ratio (8.2 of 95% confidence interval, 2.4–28.4) indicated a substantially higher risk for IE in patients with mitral valve prolapse than for those without it [111]. Another study found that mitral valve prolapse IE presented with more subtle symptoms, less mortality, and responded better to antimicrobial therapy than other types of left-sided IE, even though recognition of the infection was delayed [112].

#### **2.9. Infective endocarditis in drug abusers**

All estimations of IE incidence in drug abusers are hindered because there are no enough data reporting the exact number of victims of illicit drug-abuse epidemic. Reports from the United States present an incidence of IE in intravenous drug abusers that range from 2 to 5% per year [113] or 1.5–2 cases per 1000 years of IV drug abuse with men more commonly affected [114]. Although congenital cardiac disease and right-sided heart instrumentation are associated with IE, IV drug abusers retain the majority of cases. Intravenous drug users and those with HIV primarily consist of relatively young adults [115]. Acute infection accounts for approximately 60% of hospital admissions among drug abusers and IE is responsible of 5–15% of these episodes [116]. The presence of IE in a drug addict is difficult to predict, especially from history and physical examination findings alone [117, 118]. More than 60% of IV drug abusers with IE do not have an underlying preexisting valvular disease [119]. Although cocaine use by an intravenous drug abuser should raise the suspicion of IE infection [120], the most credible predictors of IE in febrile intravenous drug users are visualization of vegetations by echocardiography and the presence of embolic phenomena [118]. Up to 13% of cases of IV drug abusers with febrile episodes have an echocardiographically demonstrated IE [118]. Although leftsided native valve endocarditis may be present in this group of patients, the tricuspid valve is more commonly affected in intravenous drug users [121, 122]. Only two-third of patients with proven IE diagnostic presented with heart murmurs on admission [116]. The frequency of valvular involvement is tricuspid alone or in combination with other valves, 52.2%; aortic alone, 18.5%; mitral alone 10.8%; and mitral and aortic combined, 12.5% [123]. Most of these patients are young (20–40 years old), and men are more commonly affected than women with a ratio of 4:1–6:1. Approximately 66% of the patients have extravalvular compromise which may help in the diagnosis [124–126]. Although there are studies reporting infection rate reductions (such as HIV, hepatitis, or abscess) with the implementation of a needle-exchange program [127, 128], to date, there are no conclusive evidence showing reduction in IE among this special group.
