**3. Pathophysiology**

*Abiotrophia* consists of *Abiotrophia defectiva* and genus *Granulicatella* consists of *Granulicatella adiacens*, *Granulicatella elegans*, *Granulicatella balaenopterae* and *Granulicatella para-adiacens*.

NVS are members of the normal flora of human pharynx, human urogenital and intestinal

Infective endocarditis caused by NVS is rare, causing approximately 2% of all cases of infective endocarditis [3]. Over 125 cases of infective endocarditis caused by *Abiotrophia* and *Granulicatella* spp. have been reported to date. It is estimated that approximately 5–6% of all cases of streptococcal endocarditis are caused by NVS [4]. Due to the fastidious nature of these organisms and difficulties in diagnosis, it is possible that endocarditis caused by NVS may be under-recognized. NVS are among the organisms causing culture negative endocarditis. The main reservoir of infective endocarditis inducing NVS is oral cavity as in the case of other viridans streptococci [5]. Although endocarditis and bacteremia are the most common infections associated by *Abiotrophia* and *Granulicatella* spp., the literature for infections caused by *Abiotrophia* and *Granulicatella* spp. has been growing with new sites of infections being reported as our aware-

Ophthalmological infections have been encountered, ranging from keratitis to endophthalmitis [6]. NVS are known to cause corneal ulcers [7], vitreous infections [8] and infectious crystalline keratopathy [9]. Orthopedic infections, including prosthesis infection, septic arthritis, discitis and sacroiliitis have been reported [10–12]. Synovial biopsy sample from a patient with culture negative endocarditis also yielded NVS [13]. NVS are also associated with central nervous system infections; more commonly brain abscesses but rarely meningitis [14], subarachnoid hemorrhage [15] and intracranial aneurysms [3] have been reported. CNS infections have been commonly linked to embolic phenomena, neurosurgical instrumentation and immunosuppression [10, 16]. NVS have been isolated from patients with otitis media [1], otitis externa [2], sinusitis [17], parapneumonic effusion [18], cirrhosis [19], peritonitis [20], pancreatic abscess [21], bacteremia associated with postpartum or postabortal sepsis [19], tuboovarian abscess [22], breast implant associated infection [23], wound infections, and vaginal discharge [24]. Endarteritis caused by *A. defectiva* involving the main pulmonary artery in a

Nutritionally variant streptococci were first described by Frenkel and Hirsch in 1961 from blood cultures of cases of subacute bacterial endocarditis and from otitis media. These cell wall deficient, L form 'streptococci' were noted to grow in satellite colonies around other bacteria requiring substances secreted by other bacteria for growth [1]. 'Abiotrophia' means life nutrition deficiency, referring to the need of specific nutrients in media for growth of these bacteria [26]. They are catalase-negative, oxidase-negative, facultative anaerobic gram positive bacteria [27]. They often form white-gray, non-hemolytic colonies. These organisms hardly grow in culture media that streptococci ordinarily grow, such as sheep blood agar. They require supplementation of L-cysteine or pyridoxal HCl. In the absence of these supplements, NVS can also grow forming satellite colonies adjacent to streaks of helper bacteria such as *Staphylococcus aureus* or *Staphylococcus epidermidis*.

ness of these bacteria heightens and our diagnostic capabilities improve.

patient with asymptomatic patent ductus arteriosus has been reported [25].

tracts [2].

42 Advanced Concepts in Endocarditis

**2. Microbiology**

Bacterial attachment to damaged heart valves is the key factor in infective endocarditis. Intact vascular endothelium can resist the development of endocarditis [33]. Experimental animal models showed that when catheter induced endocardial damage is produced; these endocardial lesions can be infected by direct inoculation of bacteria or by intravenous inoculation [34]. Pathophysiology of infective endocarditis typically would start with endothelial cell denudation, followed by exposure of underlying extracellular matrix (ECM) and finally binding of fibrin and platelets [33]. Extracellular matrix proteins are exposed during damage to the cardiac endothelium providing potential sites of attachment for virulent organisms [35] *Granulicatella* and *Abiotrophia* spp. have the ability to bind to fibronectin and other extracellular matrix proteins. The ability to bind to extracellular matrix proteins appears to correlate with the degree of infectivity of NVS [5].

Some groups of NVS are more pathogenic and other groups are less pathogenic. Highly pathogenic *G. adiacens* has high fibronectin binding ability. Highly pathogenic *A. defectiva* strains also have strong ability to bind to fibronectin and other ECM proteins whereas less pathogenic *G. para*-*adiacens* and *G. elegans* strains show low ability to bind to fibronectin and all other ECM proteins [5]. Similarly, among non-NVS streptococci that are commonly associated with infective endocarditis, *S. mutans*, *S. mitis*, *S. sanguis* and *S. fecalis* also have the ability to bind to the extracellular matrix [35].

By binding to the extracellular matrix proteins, bacteria are able to adhere to the damaged endocardium and subsequently producing colonization and infection. ECM binding ability however is not the sole indicator of pathogenicity. Some strains of NVS have high infectivity without significant binding to the ECM proteins suggesting other mechanisms involved in pathogenesis. Other mechanisms of endocardial infectivity of NVS remains to be discovered [5].

As a group, NVS have heterogenous properties of pathogenicity. *A. defectiva* has higher pathogenicity compared to other species of NVS [5]. About 73% of all NVS isolates from patients with bacterial endocarditis are *Abiotrophia defectiva*. *G. para-adiacens* and *G. elegans* strains are less virulent than *A. defectiva* and *G. adiacens* [5].

*G. adiacens* produces β-glucuronidase and produces acid from sucrose and tagatose. *G. elegans* hydrolyses arginine. Its hippurate hydrolysis is variable. It produces acid from sucrose*. G. balaenopterae* hydrolyses arginine and produces acid from trehalose and pullulan. [38]

Endocarditis Caused by *Abiotrophia* and *Granulicatella* Species

http://dx.doi.org/10.5772/intechopen.74252

45

*G. para-adiacens* produces β-glucosidase, does not produce α- or β-galactosidase or arginine

Molecular diagnostic techniques can be used for rapid and accurate diagnosis of NVS in blood or tissue samples. PCR amplification of 16S rRNA and restriction fragment length polymorphism (RFLP) for routine detection of NVS was developed by Ohara-Nemoto et al. in 1997 [42]. For culture negative infective endocarditis, molecular techniques appear to be more sen-

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a fast, reliable and cost-effective technique used to identify microorganisms by utilizing MALDI-TOF MS devices in the clinical microbiology labs [44]. These devices carry the potential to complement or replace the phenotypic identification of various microorganisms including bacteria [44]. MALDI-TOF MS is a rapid and accurate diagnostic tool that has been

In culture negative endocarditis, *Abiotrophia* and *Granulicatella* spp. should be suspected and supplemented media should be performed for the organisms to grow. Once the growth is achieved, PCR amplification of 16S rRNA or MALDI-TOF mass spectrometry can be utilized

Endocarditis caused by NVS typically follows a slow and indolent course. Endocarditis develops as a result of bacteremia. *Abiotrophia* and *Granulicatella* spp. are causes of endocarditis with severe complications such as congestive heart failure, valvular destruction, systemic

Mortality rate associated with endocarditis caused by NVS is 17% which is higher than that of

Underlying valvular disease is commonly seen as a predisposing factor for development of endocarditis. Over 90% of the cases have preexisting heart disease and 10% of patients have prosthetic heart valves [48]. Newer data however, suggest that there is increased involvement

Embolization is a common complication of Abiotrophia endocarditis affecting one-third of patients. Typical peripheral manifestations of endocarditis such as petechia, digital clubbing,

It has been known that infective endocarditis caused by NVS carries a higher risk of embolization, treatment failure and increased mortality as compared to infective endocarditis caused

Stein et al. reviewed 30 published case reports of endocarditis caused by NVS and found that 17% of patients had relapses after antibiotic therapy. Bacteriologic failure rate was 41% (defined

embolization in both immunocompetent and immunocompromised patients.

and does not ferment trehalose, pullulan or tagatose [32].

used to identify and timely diagnose NVS [45].

**5. Clinical presentation and complications**

viridans streptococci (0–12%) and enterococci (9%) [47].

of normal heart valves in the past decade [49].

Osler nodes are not frequently found [41].

by viridans streptococci [4].

for rapid and accurate diagnosis [46].

sitive in resected valvular tissue compared to blood samples [43].

Okada et al. noted that [5] NVS isolates from endocarditis patients and from normal oral flora both had the ability to cause infective endocarditis.
