**3. Genetic factors and antibiotic resistance in VRE**

The genes Van A, Van B, Van C, Van D and Van E are responsible for vancomycin resistance in Enterococci. Van M has been identified which is also an important vancomycin resistant determinant among different *E. faecium* lineages in hospitals in Shanghai, China [15]. Each Van operon has different ecological origin, Van A has originated from soil organisms, van B, Van G and Van D from gut microbiota [16]. Vancomycin resistance in Enterococci is of two types (a) Intrinsic resistance—Enterococci spp. like *E. gallinarum* and *E. casseliflavus* show an inherent low level resistance to Vancomycin. They have Van C genes that produce Vancomycin minimum inhibitory concentration (2–32 μg/ml) [17] A hospital wide outbreak of vancomycin resistant *E. gallinarum* has been reported in Colombia showing that uncommon species of Enterococci are capable of spreading in the hospital environment and producing nosocomial infections [18]. The second type is (b) acquired resistance—Enterococci species acquire resistance genes and become resistant to vancomycin. This is seen in *E. faecium* and *E. faecalis* and to some extent in *E. raffinosus*, *E. avium*, *E. durance* and other enterococcal species. The most common isolated Enterococci species which is VRE in hospital settings is *E. faecium*. It has been seen that *E. faecium* produces high vancomycin minimum inhibitory concentration (64–1000 μg/ml) [19]. There has been a significant increase in VRE prevalence. The emergence and rapid spread of VRE has led to the use of new antibiotics like linezolid, daptomycin and tigecycline. Linezolid is a oxazolidinone antibiotic. An oxazolidinone resistance gene optr A has been identified in *E. faecalis* and *E. faecium* isolates of human and animal origin [20] .Linezolid resistance is still less prevalent reported as 1.1 and 1.8% in *E. faecium* and *E. faecalis* isolates from 19 US hospitals [21]. Daptomycin resistance is more prevalent in *E. faecium* than *E. faecalis* isolates. Around 3.9 and 0.2% of *E. faecium* and *E. faecalis* isolates have been reported in various hospital settings [22]. Tigecycline is a semisynthetic derivative of tetracycline. Tigecycline resistance in *E. faecium* and *E. faecalis* is rare and reported as 0.3%. It is being used to treat bacteremia caused by MDR enterococci. The increased use of antibiotics in hospitals is causing gut dysbiosis and enterococci possess surviving ability take over the niche in the gastrointestinal tract and this could be the primary source of enterococcal infections [23].

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*Enterococci: An Important Nosocomial Pathogen DOI: http://dx.doi.org/10.5772/intechopen.90550*

**4. Lineages of nosocomial Enterococci**

coexist with commensal enterococci in humans [29].

**5. Nosocomial infections by VRE**

**6. Urinary tract infection (UTI)**

The ability of *E. faecium* to exchange mobile genetic elements carrying antimicrobial resistance genes and virulence determinants has resulted in hospital adapted clones [24]. Esp was the first adaptive element found in hospital strains of *E. faecium*. The *E. faecium* esp. gene has been linked to biofilm formation, UTI and endocarditis [24]. New determinants have been now linked to hospital isolates of *E. faecium*. A genomic analysis study of *E. faecium* hospital strains identified gain and loss of gene clusters in clinical and non-clinical isolates of *E. faecium* [25]. Genomic studies of nosocomial *E. faecium* infection have confirmed the transmission of *E. faecium* Clad A115. Recently it has been seen a significant presence of hospital associated VRE fm lineages in the wastewater and need of controlling healthcare associated dissemination of VRE fm [26]. However studies on *E. faecalis* ecotypes have shown no appearance of distinct *E. faecalis* strains over a significant period of time. Virulence factors like antibiotic resistance and virulence genes, esp., capsule polysaccharide genes and genes determining gelatinase, aggregation factor, cytolysin and ace are identified in *E. faecalis* isolates [27]. The non-emergence of distinct ecotypes of *E. faecalis* and multiplicity of closely related ecotypes is not seen in *E. faecalis* as compared to *E. faecium*. A genomic analysis of 168 *E. faecalis* hospital isolates showed no genes and non-synonymous single nucleotide polymorphisms in the three lineages of hospital strains [28]. A recent study has also demonstrated that the acquisition of mobile genetic elements in *E. faecalis* V583, makes it unable to

Nosocomial infections by Enterococci are Urinary tract infection, endocarditis, bacteremia, catheter related infections, wound infections, intra- abdominal and

Enterococci cause both uncomplicated and complicated health care associated UTI. *E. faecalis*. Vancomycin resistant *E. faecalis* and vancomycin resistant *E. faecium* have been mainly implicated in Enterococcal UTI. VRE is fast becoming a major cause of health care associated UTI. The treatment of UTI involves the use of broad spectrum antibiotics which is a major cause of resistant strains to vancomycin (VRE). The complications range from uncomplicated cystitis, pyelonephritis, perinephric abscess, and prostatitis. These organisms are responsible for nosocomial infection of urinary tract particularly in intensive care units (ICU). Enterococci have been particularly reported in catheter associated urinary tract infections, CAUTI (28.4%). Enterococci species are capable of producing biofilms, which are a population of cells attached irreversibly on various biotic and abiotic surfaces. CAUTI are associated with multispecies biofilms. Biofilms are difficult to remove and result in many chronic infections. Bacteria in biofilms colonize medical devices such as catheters, pacemakers, prosthetic heart valves and orthopedic appliances [30]. These multispecies biofilms have synergistic or antagonistic effects of interspecies interaction. Many studies have shown the association of biofilm producing enterococci and urinary catheter [31, 32]. Enterococci biofilms which are formed on catheter in CAUTI are resistant to immune clearance, urination

pelvic infections and recently even oral infections have been reported.

*Pathogenic Bacteria*

prevalent in intensive care units of hospitals. These infections are particularly high in presence of underlying health factors like diabetes, liver transplantation, neutropenia, diabetes mellitus and renal dysfunction. Recently it has also been seen that VRE bloodstream infections have higher mortality rates as compared to vancomycin susceptible Enterococci (VSE) [6, 7]. Data from countries like Germany shows an increase of VRE from less than 5% in 2001 to 14.5% in 2013 mainly vancomycin resistant *E. faecium* [8]. In Europe of all the nosocomial infections reported 9.6% were of Enterococci [9]. In USA 3% of the nosocomial infections are due to VRE [10]. VRE nosocomial infections cause greater number of invasive treatment resulting in extended stay in hospital and cost [11]. Hospitals in some countries have now established VRE screening in high risk areas and isolation of patients to prevent spread of the resistant pathogen [12]. A study has shown the prevalence of VRE colonization in patients who had history of previous administration of antibiotics for more than 2 weeks were 10 times more likely of getting VRE colonization [13]. Other studies have also reported similar findings which show antibiotic exposure can cause colonization of VRE in hospital settings because of their resistance to commonly used antibiotics, virulence factors and ability to acquire genes [14].

The genes Van A, Van B, Van C, Van D and Van E are responsible for vancomycin

resistance in Enterococci. Van M has been identified which is also an important vancomycin resistant determinant among different *E. faecium* lineages in hospitals in Shanghai, China [15]. Each Van operon has different ecological origin, Van A has originated from soil organisms, van B, Van G and Van D from gut microbiota [16]. Vancomycin resistance in Enterococci is of two types (a) Intrinsic resistance—Enterococci spp. like *E. gallinarum* and *E. casseliflavus* show an inherent low level resistance to Vancomycin. They have Van C genes that produce Vancomycin minimum inhibitory concentration (2–32 μg/ml) [17] A hospital wide outbreak of vancomycin resistant *E. gallinarum* has been reported in Colombia showing that uncommon species of Enterococci are capable of spreading in the hospital environment and producing nosocomial infections [18]. The second type is (b) acquired resistance—Enterococci species acquire resistance genes and become resistant to vancomycin. This is seen in *E. faecium* and *E. faecalis* and to some extent in *E. raffinosus*, *E. avium*, *E. durance* and other enterococcal species. The most common isolated Enterococci species which is VRE in hospital settings is *E. faecium*. It has been seen that *E. faecium* produces high vancomycin minimum inhibitory concentration (64–1000 μg/ml) [19]. There has been a significant increase in VRE prevalence. The emergence and rapid spread of VRE has led to the use of new antibiotics like linezolid, daptomycin and tigecycline. Linezolid is a oxazolidinone antibiotic. An oxazolidinone resistance gene optr A has been identified in *E. faecalis* and *E. faecium* isolates of human and animal origin [20] .Linezolid resistance is still less prevalent reported as 1.1 and 1.8% in *E. faecium* and *E. faecalis* isolates from 19 US hospitals [21]. Daptomycin resistance is more prevalent in *E. faecium* than *E. faecalis* isolates. Around 3.9 and 0.2% of *E. faecium* and *E. faecalis* isolates have been reported in various hospital settings [22]. Tigecycline is a semisynthetic derivative of tetracycline. Tigecycline resistance in *E. faecium* and *E. faecalis* is rare and reported as 0.3%. It is being used to treat bacteremia caused by MDR enterococci. The increased use of antibiotics in hospitals is causing gut dysbiosis and enterococci possess surviving ability take over the niche in the gastrointestinal tract and this

**3. Genetic factors and antibiotic resistance in VRE**

could be the primary source of enterococcal infections [23].

**84**
