**9.1 Infective endocarditis (IE)**

It was in 1899, that the first report of infective endocarditis due to enterococci was published. The authors were MacCallum and Hastings who provided a detailed report of a case of acute endocarditis in a 37-year-old patient, caused by an organism they called Micrococcus zymogenes, probably the present *E. faecalis*. This bacterium was repeatedly isolated from the patient's blood until his death due to cardiac failure. The authors described that this bacterium was "very hardy and tenacious of life", which is true of enterococcus. They also showed that this particular isolate was haemolytic [8].

If we start with the risk factors for enterococcal infective endocarditis, only a few studies have addressed this. One study done in Denmark found that men were more prone, with prosthetic valve being a significant risk factor and most were community acquired and not related to hospital infection. They went on to say that for all cases of enterococcal bacteremia, it would be worthwhile to do echocardiography to rule out IE, especially in the presence of valve abnormality [16]. Another risk factor commonly encountered in cases of enterococcal IE in patients with valve abnormality is history of colorectal or urogenital disease or surgery [17]. A few case reports have been published describing enterococcal IE after colonoscopy and proctosigmoidoscopy [18]. In women, the ovaries may be a significant source. In a study done in our centre, we encountered a case of recurrent enterococcal endocarditis in a woman that could be resolved only after removal of an ovarian cyst. We also found that 12% of the valvular endocarditis was due to enterococci. Other than *E. faecalis*, *E. gallinarum* was also isolated from IE and was a challenge in treatment as it is intrinsically resistant to Vancomycin [19]. As described in the description of virulence factors, biofilm formation has been described to be a mode of pathogenesis in IE. IE requires a host factor, a thrombus, however enterococci can form micro-colonies on tissue surfaces without the host factor and this may lead to biofilm formation in a susceptible host with turbulent flow. In vitro models studied have not yet been correlated with in vivo studies in animals, and this is still a matter of hypothesis with no definite proof [20]. Treating IE due to enterococci involves getting an accurate identification up to species level, correct susceptibility data with minimum inhibitory concentrations for all antibiotics, including, Ampicillin, Vancomycin (if resistant to Ampicillin) and the aminoglycosides. Aminoglycosides have to be used as synergistic agents, only when they are not having high level antibiotic resistance (HLAR) [5]. The AHA/ IDSA guidelines recommend 6 weeks of treatment if symptoms have been present for more than 3 months [19]. However, there is a raging controversy on the duration of aminoglycoside therapy that may be detrimental to the kidney and the new mode of treatment called a double beta-lactam regimen that adds Ceftriaxone to Ampicillin in spite of the fact that enterococci are intrinsically resistant to all third generation cephalosporins. Readers may refer to recent guidelines issued from time to time by the American Heart Association (AHA). Streptomycin is suggested as an alternative to Gentamicin in cases of High level aminoglycoside resistance(HLAR) to Gentamicin [21].

#### **9.2 Urinary tract infections**

The close proximity of the gut flora to the urethra make *E. faecalis* and *E. faecium* causative organisms of urinary tract infections. Community acquired *E. faecalis* UTI is best treated with Ampicillin and there is no need for any combination. When catheter care is inadequate in a healthcare facility, *E. faecalis* colonises the catheter and this leads to CA-UTI when catheterisation is prolonged. Ascending infection generally causes only cystitis. This can be treated with Nitrofurantoin alone. If there is associated bacteremia, Ampicillin or Fosfomycin may be used for treatment. Fosfomycin can be reserved for Vancomycin resistant enterococci [22].

Enterococci cause a minority of community acquired UTI, 15–30% of catheter associated UTI and is the third common cause of hospital acquired UTI. Enterococci are seen to colonise the cells in the kidney and do not persist in the bladder. They have a tendency to persist inside macrophages in the kidney. Urothelial cells are also seen to have intracellular enterococci. All the above-mentioned constant cell bound virulence factors like Ace and Esp are important in the pathogenesis and persistence of enterococci in the urinary tract. In case of CA-UTI, enterococci can persist in the catheter forming a biofilm. However, CA-UTI due to gram positive bacteria including enterococci cause less inflammatory reaction as seen in a wet film of the urine. This may be the effect of immune evasion due to the biofilm formation.

Enterococci are also encountered in asymptomatic bacteriuria (ABU), like enterococci isolated during routine screening of urine in asymptomatic antenatals, at a healthcare facility. A review article on this subject found that such enterococci are actually protective against symptomatic bacteriuria in the future [23]. Treatment of ABU is recommended only in pregnancy and as part of pre-operative evaluation and decolonisation. ABU treatment is associated with higher incidence of multi drug resistant UTI [24].

Treatment: Ampicillin is the treatment of choice for strains that are sensitive. Ampicillin concentrates in the bladder and patients with strains that are resistant too can be treated with Ampicillin, as demonstrated in a study by Shah et al. Here they showed that Ampicillin can be used for treatment even if Vancomycin resistant strain is isolated. In their study 87.5% of patients on catheter with VRE responded to treatment with Ampicillin alone [25]. Another agent that holds hope in the face of VRE is Nitrofurantoin [26].

#### **9.3 Skin and soft tissue infections**

Enterococcus species are ubiquitous among the SSTIs due to trauma, surgical site infections (SSI), vascular ulcers and device associated infections. NHSN has released the SSI rates pathogen wise for the years 2015–2017 (**Figure 1**) [27].

Among SSTIs that are admitted in hospitals, a study from New Delhi, India, reports that out of 11,524 pus and tissue samples, 86 *Enterococcus* spp. were isolated. Of these, *E. faecium* (48/86, 56%) was the most common, followed by *E. faecalis* (34/86, 40%) and 4 (4%) of *Enterococcus casseliflavus*. Of these 8% were Vancomycin resistant. All VREs had history of prior hospitalisation and antibiotics use, however all were treated successfully with Linezolid or Quinupristin/Dalfopristin monotherapy [28].

In most studies, Vancomycin resistance is reported to be increasing and associated with hospitalisation, though one study reported community acquired Vancomycin resistant strains too [29, 30]. This increase has been variously

*Enterococcal Infections: Recent Nomenclature and Emerging Trends DOI: http://dx.doi.org/10.5772/intechopen.104792*

#### **Figure 1.**

*Enterococcus faecalis isolation rates in SSI in different surgical specialties as per CDC-NHSN 2015–2017 SSI data.*

attributed to prior antibiotic treatment and nosocomial spread due to poor hand hygiene and environmental cleaning practices.
