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  Table of Contents  
Year : 2016  |  Volume : 34  |  Issue : 4  |  Page : 547-550

Infections related to Granulicatella adiacens: Report of two cases and review of literature

1 Department of Medical Microbiology, Microbiology Laboratory, Şrnak State Hospital, Şırnak, Turkey
2 Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey
3 Department of Medical Microbiology , Faculty of Medicine, Hacettepe University, Ankara, Turkey
4 Department of Medical Microbiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey

Date of Submission14-Sep-2016
Date of Acceptance18-Oct-2016
Date of Web Publication8-Dec-2016

Correspondence Address:
S Macin
Department of Medical Microbiology, Microbiology Laboratory, Şrnak State Hospital, Şırnak
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0255-0857.195377

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 ~ Abstract 

Infections due to nutritionally variant streptococci are diagnosed rarely due to difficulties encountered during identification and isolation. Mortality rate in these infections is high therefore appropriate supplemented media and reliable detection systems should be implemented to isolate these fastidious organisms. Here, we describe two cases of Granulicatella adiacens infections. All microbiologic identifications were made with MALDI-TOF Vitek MS (BioMerieux, France), and the results confirmed by 16S ribotyping.

Keywords: Granulicatella adiacens, infection, matrix-assisted laser desorption ionisation – time of flight mass spectrometry

How to cite this article:
Macin S, İnkaya A, Tuncer &, Ünal S, Akyön Y. Infections related to Granulicatella adiacens: Report of two cases and review of literature. Indian J Med Microbiol 2016;34:547-50

How to cite this URL:
Macin S, İnkaya A, Tuncer &, Ünal S, Akyön Y. Infections related to Granulicatella adiacens: Report of two cases and review of literature. Indian J Med Microbiol [serial online] 2016 [cited 2020 Feb 22];34:547-50. Available from:

 ~ Introduction Top

The nutritionally variant streptococci (NVS) are Gram-positive cocci first identified in 1961 from a patient with infective endocarditis (IE). NVS were erroneously classified in viridans streptococci. In 2000, NVS were reclassified into four groups: Abiotrophia defectiva, Granulicatella adiacens, Granulicatella elegans and Granulicatella balaenopterae by 16S rRNA sequencing. Infections due to NVS have a high mortality rate because of therapeutic failures. In a recent survey, mortality rate in NVS infections was found to be 9.0%.[1] This may be because of difficulties in robust and reliable diagnosis of G. adiacens infections.

Granulicatella spp. do not grow on blood or chocolate agars unless pyridoxal (Vitamin B6) is supplied either by placing a pyridoxal disk or by inoculation to Vitamin B6-supplemented culture media. Blood culture media support the growth of this microorganism. Blood cultures that appear positive and show chaining Gram-positive cocci on Gram stain should be considered Granulicatella or Abiotrophia growth. Since these species do not grow on blood or chocolate agars, therefore, samples should be resubcultured with pyridoxal disk. Granulicatella spp. lead to alpha haemolysis on tryptic soy agar supplemented with 5% sheep blood. Granulicatella spp. are catalase-negative, Gram-positive cocci that tend to grow in pairs or chains and display satellites, but they can appear also pleomorphic.

Granulicatella is present in the normal flora of human mouth, genital and intestinal tracts, but rarely they cause disease. G. adiacens has been associated with bacteraemia, vertebral osteomyelitis, pancreatic abscess, otitis media and endovascular, central nervous system, ocular, oral, bone and joint and genitourinary infections.[2]

The clinical significance of G. adiacens is clear therefore robust and rapid identification methods are needed in clinical microbiology laboratories. Granulicatella spp. are usually identified either by biochemically, however, identifications relying on biochemical characteristics might be inaccurate.[3] A variety of molecular techniques has been developed to accelerate the identification of Granulicatella, but the reagents costs are higher than the biochemical testing, and trained personnel is needed.

The development of matrix-assisted laser desorption ionisation – time of flight mass spectrometry (MALDI-TOF MS) technology helps the rapid and accurate diagnosis of the previously difficult bacteria such as Granulicatella.[4] In this report, we aimed to describe the two different cases with G. adiacens infections followed in our unit and to review the reports about G. adiacens infections published from 2000 to date. The review was performed through PubMed using the key terms G. adiacens infections.

 ~ Case Reports Top

Case 1

A 61-year-old male diabetic, osteopetrosis patient with bladder carcinoma applied to our hospital because of mandibular osteomyelitis. His physical examination was normal other than a swelling (10 cm × 10 cm) at the right mandibular arm from where he underwent bone biopsy. Tissue samples were examined histologically and microbiologically as described below. Anaerobic tissue sample was cultivated in thioglycollate medium. Aerobic sample was inoculated on 5% sheep blood agar and chocolate agar. Cultures were incubated at 37°C in CO2. After 24 h incubation, non-haemolytic, smooth colonies grew, and Gram staining demonstrated Gram-positive cocci compatible with G. adiacens. Ceftriaxone plus metronidazole commenced after antibiotic susceptibility results became available. He received ceftriaxone plus metronidazole for 1 month when the treatment switched to oral amoxicillin/clavulanate 1 g BID. His clinical condition was improved significantly.

Case 2

An 18-year-old male patient with T-cell lymphoblastic lymphoma and a previous history of febrile neutropenia underwent an intensive chemotherapy as his disease was refractory to initial regimen (CVAD). After the first course of FLAG-IDA regimen, the patient developed a second febrile neutropenia episode and readmitted. Initial physical examination revealed an induration (2 cm × 2 cm) on his left maxilla and abdominal tenderness. Meropenem plus vancomycin was commenced empirically. On this episode, sepsis due to G. adiacens and invasive pulmonary aspergillosis was diagnosed. Voriconazole was added to the antibiotic regimen. Unfortunately, the patient passed away on the 10th day of febrile neutropenia because of severe septic shock.

 ~ Conclusion Top

G. adiacens may lead different infections including endocarditis, osteomyelitis, arthritis, sepsis, implant, or prosthesis-associated infections [Table 1]. Upon this result, it can be argued that utilising automatised blood culture systems facilitates the cultivation of G. adiacens leading to frequent identification in intravascular infections. Except blood culture, the bacterium can be isolated from different clinical samples (peritoneal fluid, tissue samples, synovial fluid, abscess and pus) For treatment, penicillins or macrolides are used. Furthermore, for some cases, vancomycin, teicoplanin, rifampin and levofloxacin were used. When its susceptibility tests are examined, it is seen that it usually susceptible to penicillins, macrolides and glycopeptides.
Table 1: Review of current literature

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NVS are the members of oral, intestinal and genitourinary flora and were initially described as an etiological agent in a patient with IE. NVS may lead to septicaemia and endocarditis. For most cases, it is assumed that entry point is the oral cavity. By 16S rRNA sequencing, NVS are classified as Granulicatella and Abiotrophia spp. A. defective and G. adiacens can bind easily to extracellular matrix proteins and can cause serious infections.[2] Hence, these species are accepted as more virulent strains among the NVS species.

There are serious diagnostic difficulties because NVS have fastidious culturing and non-specific colony morphology. They need a medium supplemented with cysteine and pyridoxine for growing.[3] When the case reports are examined, it is seen that G. adiacens usually cause endocarditis and is isolated from blood cultures. Furthermore, the isolation chance can be rised with blood cultures containing 0.001% pyridoxal hydrochloride. For example, Hepburn et al. isolated G. adiacens from synovial fluid by inoculation it into blood culture bottles.[14] In our cases, the bacteria were isolated from blood and tissue samples, and isolates obtained from tissue samples were grew on 5% sheep blood agar without any additional supplement as in different reports.[5] The isolate obtained from blood sample did not grow on 5% sheep blood agar. It was inoculated on Schaedler agar and seen its growing after 48 h incubation in anaerobic conditions. We know classically NVS need cysteine and pyridoxine for growing. Schaedler agar contains L-cysteine. We think that some strains need additional nutrients while some strains can grow on 5% sheep blood agar easily without supplement.

Although there are some difficulties which are about diagnosis, new laboratory systems can detect these bacteria at species level. Ratcliffe et al. reported that the Vitek MS, the Bruker MS and the Vitek 2 system could correctly identify 10, 8 and 6 of 10 G. adiacens isolates, respectively.[4] Three G. adiacens isolates identified in our laboratory were detected by the Maldi-TOF Vitek MS (BioMerieux, France) system. We can say that this system really rises our detection chance of G. adiacens isolates.

The exact role of these bacteria in disease is unclear. However, clinicians should be aware of this organism's pathogenic potential although it is a member of normal flora. On the other hand, they can be easily overlooked because of their poor growth or non-growing on solid media. For all these reasons, appropriate supplemented media and a reliable detection system should be used to isolate these fastidious organisms.

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Conflicts of interest

There are no conflicts of interest.

 ~ References Top

Cargill JS, Scott KS, Gascoyne-Binzi D, Sandoe JA. Granulicatella infection: Diagnosis and management. J Med Microbiol 2012;61(Pt 6):755-61.  Back to cited text no. 1
Cerceo E, Christie JD, Nachamkin I, Lautenbach E. Central nervous system infections due to Abiotrophia and Granulicatella species: An emerging challenge? Diagn Microbiol Infect Dis 2004;48:161-5.  Back to cited text no. 2
Ruoff KL. Aerococcus, Abiotrophia, and other aerobic catalase-negative, Gram-positive cocci. In: Murray PR, Baron EJ, Jorgensen JH, Landry ML, Pfaller MA, editors. Manual of Clinical Microbiology. 9th ed. Washington, DC: ASM Press; 2007. p. 443-54.  Back to cited text no. 3
Ratcliffe P, Fang H, Thidholm E, Boräng S, Westling K, Özenci V. Comparison of MALDI-TOF MS and VITEK 2 system for laboratory diagnosis of Granulicatella and Abiotrophia species causing invasive infections. Diagn Microbiol Infect Dis 2013;77:216-9.  Back to cited text no. 4
Swain B, Otta S. Granulicatella adiacens – An unusual causative agent for carbuncle. Indian J Pathol Microbiol 2012;55:609-10.  Back to cited text no. 5
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Garibyan V, Shaw D. Bivalvular endocarditis due to Granulicatella adiacens. Am J Case Rep 2013;14:435-8.  Back to cited text no. 6
Shailaja TS, Sathiavathy KA, Unni G. Infective endocarditis caused by Granulicatella adiacens. Indian Heart J 2013;65:447-9.  Back to cited text no. 7
Mougari F, Jacquier H, Berçot B, Hannouche D, Nizard R, Cambau E, et al. Prosthetic knee arthritis due to Granulicatella adiacens after dental treatment. J Med Microbiol 2013;62(Pt 10):1624-7.  Back to cited text no. 8
Giuliano S, Caccese R, Carfagna P, Vena A, Falcone M, Venditti M. Endocarditis caused by nutritionally variant streptococci: A case report and literature review. Infez Med 2012;20:67-74.  Back to cited text no. 9
Quiroga B, Arroyo D, Verde E, Eworo A, Luño J. Infective endocarditis on a percutaneous prosthetic aortic valve with associated glomerulopathy due to Granulicatella adjacens. Braz J Infect Dis 2012;16:601-2.  Back to cited text no. 10
Adam EL, Siciliano RF, Gualandro DM, Calderaro D, Issa VS, Rossi F, et al. Case series of infective endocarditis caused by Granulicatella species. Int J Infect Dis 2015;31:56-8.  Back to cited text no. 11
Ku CA, Forcina B, LaSala PR, Nguyen J. Granulicatella adiacens, an unusual causative agent in chronic dacryocystitis. J Ophthalmic Inflamm Infect 2015;5:12.  Back to cited text no. 12
Padmaja K, Lakshmi V, Subramanian S, Neeraja M, Krishna SR, Satish OS. Infective endocarditis due to Granulicatella adiacens: A case report and review. J Infect Dev Ctries 2014;8:548-50.  Back to cited text no. 13
Hepburn MJ, Fraser SL, Rennie TA, Singleton CM, Delgado B Jr. Septic arthritis caused by Granulicatella adiacens: Diagnosis by inoculation of synovial fluid into blood culture bottles. Rheumatol Int 2003;23:255-7.  Back to cited text no. 14


  [Table 1]


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