**5. Clinical presentation and complications**

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

Okada et al. noted that [5] NVS isolates from endocarditis patients and from normal oral flora

Identification of *Abiotrophia* and *Granulicatella* spp. in blood cultures is extremely difficult. NVS do not grow well in subcultures and may be regarded as contaminant bacteria. Their extreme pleomorphism may lead to misidentification of these bacteria as other bacteria, even fungi [36, 37]. Christensen and Facklam [38] studied 101 NVS isolates and reported that isolates were gram variable and pleomorphic, forms varied from bacilli with spore like swellings to cocci predominantly in pairs and chains when gram stain preparations were made from agar plates. NVS can demonstrate bulbous swelling and filament formation and they can form rough colony morphology on chocolate agar that can be suggestive of other microorgan-

NVS show morphologic variations depending on the pyridoxal concentrations in the growth medium [39]. Due to the difficulties in identification of these bacteria, it is crucial for microbiology staff to be vigilant and be aware of the pleomorphic nature of the NVS to prevent

NVS should be suspected when gram stain shows microbial cells but cultures are negative [2]. Once their nutritional growth requirements are supplemented in media, NVS convert to streptococci-like cells [39] and gram positivity making them easier to identify, although it was also shown that correcting nutritional deficiency may not convert all abnormalities [40]. For *G. elegans*, addition of cysteine to growth media would have the effect of reversal of pleomorphic morphology but addition of pyridoxal HCl does not [29]. The difficulty in identifying these organisms leads to delays in diagnosis and thus timely initiation of appropriate

Contemporary blood culture methods enable *Abiotrophia* and *Granulicatella* spp. to grow routinely, visible colonies of these organisms appear in 48 h on subculture from positive blood

Cargill et al. noted that anaerobic blood culture bottles became positive sooner than aerobic blood cultures bottles; (3.56 h, standard deviation 8.49 h) although they noted that this was

Specific phenotypic characteristics of NVS can be identified by examining their patterns of production of α-galactosidase, β-galactosidase, β-glucosidase, N-acetyl-β-glucosaminidase and β-glucuronidase, and fermentation of trehalose, pullulan, tagatose and sucrose [32, 38]. *A. defectiva* produces α-galactosidase, β-galactosidase and produces acid from trehalose,

culture media supplemented with *Brucella* and chocolate subculture media [3].

sucrose and pullulan. Its acid production from tagatose is variable [38].

isms such as *Streptobacillus moniliformis* or *Erysipelothrix rhusiopathiae* [36].

less virulent than *A. defectiva* and *G. adiacens* [5].

**4. Diagnosis**

44 Advanced Concepts in Endocarditis

misidentification.

antimicrobial treatment [41].

not significant or reliable [31].

both had the ability to cause infective endocarditis.

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 embolization in both immunocompetent and immunocompromised patients.

Mortality rate associated with endocarditis caused by NVS is 17% which is higher than that of viridans streptococci (0–12%) and enterococci (9%) [47].

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

Embolization is a common complication of Abiotrophia endocarditis affecting one-third of patients. Typical peripheral manifestations of endocarditis such as petechia, digital clubbing, Osler nodes are not frequently found [41].

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 by viridans streptococci [4].

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 as positive blood cultures after 7 days of appropriate antibiotic therapy, relapse following a course of therapy with appropriate antibiotics, or a positive valve culture). It is notable that bacteriologic failure was seen despite the sensitivity of the organisms to the antibiotics used in two thirds of the cases. About 31% of the patients required surgery. Mortality rate was 17% which was higher than that of endocarditis caused by enterococci or viridans streptococci [41].

reliable. Microbiological cure is difficult and infective endocarditis caused by these organisms is associated with high rates of treatment failures. Therefore, AHA (American Heart Association) and British Society for Antimicrobial Chemotherapy (BSAC) Infective Endocarditis treatment guideline for *Abiotrophia defectiva* and *Granulicatella* species is very similar to treatment guide-

Endocarditis Caused by *Abiotrophia* and *Granulicatella* Species

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

47

Recommended treatment regimen is Ampicillin (12 g/d in divided doses) or penicillin (18–30 million U/D in divided doses or by continuous infusion) plus gentamicin 3 mg/kg/d in 2–3

For those patients who are intolerant to penicillin, Vancomycin alone without the use of gentamicin can be given for therapy. This is in contrast to enterococcal endocarditis treatment

The duration of treatment for *Abiotrophia* or *Granulicatella* endocarditis needs to be determined by consultation with an infectious disease expert. As a general guidance, AHA recommenda-

The treatment duration is 4 weeks for native valve endocarditis with symptoms or illness ≤3 months. 6 week therapy is recommended for patients with symptoms >3 months. For prosthetic valve or other prosthetic cardiac material infections, minimum 6 weeks of antibiotic

Historically, in animal models it was shown that Penicillin alone was inferior to Penicillin plus aminoglycoside or Vancomycin alone for the treatment of infective endocarditis caused by NVS [57, 58]. it was shown that penicillin plus low dose (0.32 mg/kg) vs. high dose (1.05 mg/kg) gen-

There is encouraging data to suggest that shortened courses of aminoglycosides in the treatment regimens (median 15 days) may result is similar clinical outcomes in treatment of enterococcal endocarditis. However this particular issue requires further study and it is not yet known how this would apply to treatment of infective endocarditis caused by *Abiotrophia* 

Given the growing concerns over antibiotic resistance among NVS, poor treatment outcomes and high rates of treatment failures it is important to look into data for susceptibilities of a broad range of antibiotics. There is however limited data available regarding the antibiotic susceptibilities of *Granulicatella* and *Abiotrophias* spp. due to the rare nature of the infections, the specific nutritional growth requirements and difficulties in standardization of testing methodologies.

NVS have the highest in vitro penicillin resistance compared to any other streptococci. The rate of penicillin resistance among NVS appears to be rising over the years. While an earlier study by Cooksey and Swenson in 1979 [59] and Gephart and Washington in 1982 [60] showed no isolates had a penicillin MIC >1 μg/ml, subsequent studies showed significantly increasing penicillin resistance; Bosley and Facklam in 1990 [61] noted 9% rate of resistance

tions for treatment durations for enterococcal endocarditis are as follows:

lines for enterococcal endocarditis [33, 56].

where Vancomycin is combined with gentamicin [33].

tamicin treatment results were virtually identical [57].

divided doses).

therapy is recommended [33].

*defectiva* or *Granulicatella* species. [49].

**7. Penicillin**

Similarly a more recent review of 29 cases of solely *Granulicatella* endocarditis by Adam et al. showed very high rates of complications and adverse outcomes. Incidence of heart failure was 30%, embolism was seen in 30% of patients and perivalvular abscess was seen in 11%. The mortality rate was 17%. The average vegetation size was 16 mm (31). They found that aortic (44%) and the mitral (38%) valves were the most commonly effected and multivalvular involvement was (13%) [50].

Large vegetation sizes are associated with increased risk of systemic embolism in infective endocarditis. Case studies reveal large vegetation sizes with infective endocarditis caused by NVS (greater than 10 mm in 7 out of 8 cases reviewed by Lin et al., and average vegetation size of 16 mm in a case series of 29 patients by Adam et al.) [50]. These findings correlate with the high rates of systemic embolism seen in endocarditis caused by NVS.

Endocarditis caused by NVS is associated with high rates of infectious intracranial cerebral aneurysms although the exact incidence is unknown. Having a low threshold for obtaining imaging of the CNS is reasonable even for patients with vague complaints such as severe localized headaches or mild confusion [3]. Many infectious intracranial cerebral aneurysms resolve by antibiotic treatment with reductions in size in the first 1–2 weeks. The risk of rupture decreases with time on antibiotic therapy [3].

Endocarditis caused by NVS is associated with 13% of aortic valve damage and 11% of mitral valve damage. If not recognized on a timely basis, these patients may present with congestive heart failure as the first presenting manifestation of the infection [51]. Congestive heart failure is a potential complication of valvular destruction which can necessitate heart valve replacement surgery.

Aorto-RV fistula is a rare complication of *A. defectiva* endocarditis that requires early surgical intervention for closure [52]. Development of hemophagocytic lymphohistiocytosis was reported in a previously healthy patient with *A. defectiva* endocarditis [53].

Endocarditis caused by NVS has rarely been reported in children. According to a review of 13 pediatric cases in children, 69% had underlying heart disease [54]. Similar to adult patients, endocarditis caused by NVS in pediatric populations also appears to be associated with high complication rates including severe valvular damage, surgical valve replacement and systemic embolization [54, 55].
