A case of endocarditis due to Granulicatella adiacens Granulicatella (Abiotrophia) adiacens is a bacterium implicated in endocarditis. Its isolation is dif®cult, and its role could be underestimated due to the fact that some cases of culture-negative endocarditis could be brought about by this microorganism. We present a case of endocarditis due to G. adiacens. CASE STUDY A 57-year-old man had severe mitral regurgitation caused by a myxomatous valve. Four and seven months before the onset of endocarditis symptoms, the patient underwent dental manipulation with antibiotic prophylaxis and minor surgery for a hyperkeratotic skin lesion. Three months prior to hospitalization, he presented to hospital with prolonged fever >38 8C associated with chills. He received three courses of therapy with amoxicillin 750 mg every 8 h (seven to ten days each course), and this was followed by transitory improvement. His symptoms reappeared a few days after the completion of antibiotic treatment. One month after the onset of fever, two months prior to hospitalization, he presented with vertigo, balance dif®culty, and chills of 24-h duration. On admission, his temperature was 37.4 8C. A holosystolic murmur of III/IV intensity was heard at the cardiac apex, with radiation to the axilla. The remainder of the physical examination, including optic fundi, was normal. Full blood count, serum biochemistry, coagulation studies, rheumatoid factor, antinuclear antibody, immunoglobulins, complement and urine analysis were within normal limits. C-reactive protein was 1.38 mg/d (0±0.38). EKG showed left anterior fascicular block and left ventricular hypertrophy. Chest X-ray was normal. Transthoracic echocardiography showed no vegetations or other ®ndings suggesting endocarditis. Brain magnetic resonance imaging disclosed lacunar lesions affecting the white matter of both frontal lobes, suggesting ischemic lesions. With this clinical picture and microbiological ®ndings (two positive blood culture series), a diagnosis of endocarditis was made following the Duke criteria . Treatment was initiated with ampicillin 2 g every 4 h for four weeks and gentamicin 80 mg/kg every 8 h for
two weeks. Two series of blood cultures with a total of ®ve blood samples were drawn within 24 h. Cultures were processed with the BACTEC 9240 system (Becton Dickinson Sparks, MD, USA). Bacterial growth was detected within 24 h. Microscopic staining revealed Gram-variable diplococci. Subculture on chocolate agar and incubation in 10% CO2 provided weak growth in the ®rst 24 h. The growth became more obvious after 48 h. The colonies were minute and showed a-hemolysis. Oxidase and catalase were negative. API rapid ID 32 SREPT (BioMeÂrieux, Lyon, France) was performed, and Abiotrophia adjacens identi®cation was obtained with the 00000101120 biotype. The pyrrolidonyl arylamidase (PYR) production test was positive, as were the acidi®cation of saccharose, maltose, and tagatose. Complementary tests, such as growth in BACTEC enriched media with 0.01 g of pyridoxal/L, and satellitism in blood agar using Staphylococcus aureus, were positive. In vitro susceptibility testing using a disk diffusion method in chocolate agar and incubation in 10% CO2 revealed susceptibility to ampicillin, cefalotin, cefoxitin, cefotaxime, cipro¯oxacin, co-trimoxazole, imipenem, rifampin, vancomycin, and teicoplanin, and resistance to gentamicin, amikacin, clindamycin, and cloxacillin. Repeat blood cultures 48 h after initiation of treatment were negative. The patient clinically improved. There was no evidence of relapse one month after his discharge from the hospital. DISCUSSION The genus Granulicatella has three species: G. adiacens, G. elegans, and G. balaenopterae; these were previously included in the genus Abiotrophia. All of them are classi®ed as nutritionally variant streptococci (NVS) . These microorganisms not only form part of normal ¯ora, but also cause infections such as pancreatic abscess, conjunctivitis, endophthalmitis, infectious keratopathy, otitis, and postpartum sepsis. The isolation of Granulicatella spp. is dif®cult. Media with pyridoxal (active vitamin B6) are needed. Pyridoxal is responsible for coenzymatic transformation of Lalanine into D-alanine, which is necessary for peptidoglycan production [3,4]. In our case, the bacterium was isolated only on chocolate agar, which contains a little pyridoxal from red cell hemolysis. The requirement for growth supple-
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ments is also revealed by the phenomenon of satellitism. This is a form of microbial commensalism in which the growth of Granulicatella spp. is dependent on the nutrients released by other bacteria. Colonies are 0.2±0.5 mm in diameter, and do not usually show hemolysis. However, some strains, as in our case, show a-hemolysis. G. adiacens and A. defectiva appear to have higher degree of infectivity, and this has been attributed to their capacity to bind to the cardiac valvular tissue. Other species such as G. elegans and A. paradiacens are less virulent, and this could be due to their poor binding to extracellular matrix proteins . Pre-existing valvular pathology is, as in our case, frequent. Nevertheless, classic endocarditis signs such as digital clubbing, petechiae and Osler nodes are rare. The most common valves affected are the aortic valve and the mitral valve. Twodimensional transthoracic echocardiography may be helpful, with detectable vegetations being observed in about 64% of cases with this method . Long-term combination therapy with penicillin and an aminoglycoside is usually recommended. Vancomycin is an effective alternative against resistant strains. In vitro, these bacteria display susceptibility to amoxicillin, ceftriaxone, meropenem, rifampin, o¯oxacin, levo¯oxacin, vancomycin, and quinupristin±dalfopristin . In spite of in vitro results, treatment failure is observed in about 41% of cases, and almost 27% require prosthetic valve replacement, especially due to congestive heart failure or major systemic emboli . In summary, Granulicatella spp. should be considered in cases of endocarditis, particularly when routine blood cultures are initially negative. Media containing 0.001% pyridoxal, such as enriched BACTEC media, are essential for its isolation. Gram stain, weak growth in chocolate agar and
a positive PYR test could be helpful for its de®nitive identi®cation. A. Perkins, S. Osorio, M. Serrano, M. C. del Ray, C. SarriaÂ, D. Domingo and M. LoÂpez-Brea Department of Microbiology, Hospital Universitario de La Princesa, Diego de Leon, 62 Madrid 28006, Spain Tel: 91 520 23 17 Fax: 91 520 24 03 E-mail: [email protected]
REFERENCES 1. Vivancos R, Barakat S, Alvarez J et al. Diagnostic criteria of infective endocarditis: from Von Reyn to Duke. Transthoracic and transesophageal echography. Rev Esp Cardiol 1998; 51(suppl): 29±39. 2. Collins MD, Lawson PA. The genus Abiotrophia (Kawamura et al.) is not monophyletic: proposal of Granulicatella gen. nov., Granulicatella adiacens comb. nov., Granulicatella elegans comb. nov., and Granulicatella balaenopterae comb. nov. Int J Syst Evol Microbiol 2000; 50: 365±9. 3. Ruoff KL. Nutritionally variant streptococci. Clin Microbiol Rev 1991; 4: 184±90. 4. Ruoff KL. Update on nutritionally variant streptococci (Streptococcus defectivus and Streptococcus adjacens). Clin Microbiol News 1990; 12: 97±104. 5. Okada Y, Kitada K, Takagaki M, Ito HO, Inoue M. Endocardiac infectivity and binding to extracellular matrix proteins of oral flora Abiotrophia species. FEMS Inmunol Med Microbiol 2000; 27: 257±61. 6. Steckelberg JM, Murphy JG, Ballard D et al. Emboli in infective endocarditis: the prognostic value of echocardiography. Ann Intern Med 1991; 114: 635±40. 7. Trohy MJ, Procop GW, Washington JA. Antimicrobial susceptibility of Abiotrophia adjacens and Abiotrophia defectiva. Diagn Microbiol Infect Dis 2000; 38: 189±91. 8. Brouqui P, Raoult D. Endocarditis due to rare and fastidious bacteria. Clin Microbiol Rev 2001; 14: 177±207.
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