International Journal of Infectious Diseases 31 (2015) 56–58

Contents lists available at ScienceDirect

International Journal of Infectious Diseases

jou rnal homepage: www.elsevier.com/locate/ijid

Case Report

Case series of caused by

Eduardo Leal Adam *, Rinaldo Focaccia Siciliano, Danielle Menosi Gualandro,

Daniela Calderaro, Victor Sarli Issa, Flavia Rossi, Bruno Caramelli, Alfredo Jose Mansur,

Tania Mara Varejao Strabelli

Heart Institute (InCor), University of Sao Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar, 44, Bloco 1, sala CCIH, Cerqueira Cesar–SP, Sao Paulo,

05403-000, Brazil

A R T I C L E I N F O S U M M A R Y

Article history: Background: Nutritionally variant streptococci (NVS) are Gram-positive cocci characterized by their

Received 23 July 2014

dependence on pyridoxal or cysteine supplementation for growth in standard blood culture media. They

Received in revised form 27 September 2014

are responsible for severe infections in immunocompetent and immunosuppressed hosts, including

Accepted 6 October 2014

infective endocarditis (IE). NVS have been divided into two different genera, Granulicatella and .

Corresponding Editor: Eskild Petersen,

Methods: We report four cases of IE caused by Granulicatella species, including clinical presentation,

Aarhus, Denmark

echocardiographic characteristics, treatments received, and outcomes. We also performed a literature

search for previously reported cases of IE caused by Granulicatella species to better characterize this Keywords: condition.

Granulicatella spp

Results: A total of 29 cases of Granulicatella endocarditis were analyzed, including the four newly

Endocarditis

reported cases. The aortic (44%) and mitral (38%) valves were those most commonly affected.

Nutritionally variant streptococci

Multivalvular involvement was observed in 13% of cases. The mean vegetation length was 16 mm.

Complications were frequent, including heart failure (30%), embolism (30%), and perivalvular abscess

(11%). The most frequent antibiotic regimen (85%) was or one of its derivatives plus

gentamicin. The mortality rate was 17%.

Conclusions: Endocarditis due to Granulicatella species is a rare and severe condition. Complications are

frequent despite the use of appropriate antibiotic regimens.

ß 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-

nc-nd/3.0/).

1. Introduction After the subsequent division of the NVS into different genera,

their most recent classification was proposed by Collins and

Nutritionally variant streptococci (NVS) were first described in Lawson in 2000 based on 16S rRNA gene sequencing, as follows:

1961 by Frenkel and Hirsch as fastidious organisms that showed Granulicatella genus, comprising , Granuli-

1

satellitism around colonies of other . These Gram-positive catella elegans, and Granulicatella balaenopterae; and Abiotrophia

2

cocci were characterized by their dependence on pyridoxal or genus, comprising solely Abiotrophia defectiva.

cysteine supplementation for growth in standard blood culture Although more than 100 cases of IE caused by NVS have been

media. Although part of the normal oral, gastrointestinal, and reported to date, we found only 25 cases of IE caused specifically by

genitourinary microbiota, NVS can cause severe infections in both Granulicatella sp since their division into the different genera and

3–21

immunocompetent and immunosuppressed hosts. NVS are also species (Table 1). In the present article, we report four cases of

described as a cause of culture-negative infective endocarditis (IE), IE caused by Granulicatella species from our institution and provide

due to their slow growth and requirement for special media for a brief review of the literature.

identification. Other conditions related to NVS include primary

bloodstream infections in neutropenic patients, central nervous

system infections, osteomyelitis, septic arthritis, chronic sinusitis,

2. Case reports

and endophthalmitis.

2.1. Case 1

A 31-year-old male presented with a history of fever, fatigue,

* Corresponding author. Tel.: +55 11 982283377; fax: +55 11 26615538.

E-mail address: [email protected] (E.L. Adam). and lower extremity edema of 15 days duration. The patient

http://dx.doi.org/10.1016/j.ijid.2014.10.023

1201-9712/ß 2014 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND

license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

E.L. Adam et al. / International Journal of Infectious Diseases 31 (2015) 56–58 57

Table 1

Cases of Granulicatella spp endocarditis reported to date

Reference Age, years Sex Valve Vegetation Complications Antibiotics Valve surgery Outcome

size (mm)

[3] 38 NR Aortic NR NR PT, VAN, GEN Yes Survived

[4] 71 F Aortic (prosthetic) NR None PEN, GEN Yes Survived

[5] 29 M Aortic 14 Heart failure AMOX, GEN Yes Survived

[6] 68 M Pacemaker lead NR Osteomyelitis PEN, GEN, RIF No Survived

[7] 57 M No vegetation No vegetation CNS embolism AMP, GEN No Survived

[8] 85 M NR NR NR NR NR Died

[9] 53 F NR NR NR PEN, GEN Yes Survived

[10] 18 M Pulmonic (prosthetic) NR None VAN, GEN, RIF No Survived

[11] 77 F Aortic NR None VAN, AMP, GEN No Survived

[12] 43 M Aortic (prosthetic) NR Abscess PEN, GEN No Survived

[13] 18 F Mitral 16 Heart failure PEN, GEN Yes Survived

[13] 61 M Mitral and tricuspid 20 Heart failure PEN, GEN Yes Survived

[13] 30 M Mitral 11 CNS embolism PEN, GEN, CEF Yes Survived

[13] 28 F Mitral and aortic 13 Heart failure, peripheral embolism PEN, GEN, TEI, VAN Yes Survived

[14] 47 M Mitral 15 CNS embolism NR Yes Survived

[15] 31 M Mitral 10 CNS embolism OXA, GEN Yes Survived

[16] 71 M Mitral 20 Peripheral embolism AMP, GEN No Survived

[17] 81 M Mitral 18 Heart failure AMP, GEN No Survived

[18] 58 M Mitral NR None VAN, GEN No Survived

[18] 63 M Mitral and aortic NR Heart failure AMOX, GEN Yes Survived

[18] 38 F Tricuspid NR None AMOX, GEN No Survived

[18] 63 F Mitral and tricuspid NR None AMOX, GEN No Died

[19] 40 M Aortic 15 Abscess, heart failure VAN, AMP, GEN Yes Survived

[20] 32 F Tricuspid NR None LEV, PEN No Survived

[21] 86 M Aortic (prosthetic) NR None DAP, CEF No Died

This report 31 M Aortic 21 Abscess, fistula CEF, OXA, GEN, TEI Yes Survived

This report 64 M Aortic 26 Heart failure CEF, OXA, GEN, TEI, VAN Yes Died

This report 75 M Aortic 19 CNS and spleen embolism CEF, PEN, GEN No Died

This report 59 F Aortic 8 Kidney and spleen embolism CEF, GEN, VAN Yes Survived

F, female; M, male; NR, not reported; CNS, central nervous system; PT, piperacillin–tazobactam; VAN, vancomycin; GEN, gentamicin; PEN, penicillin; AMOX, amoxicillin; RIF,

rifampin; AMP, ampicillin; CEF, ceftriaxone; TEI, teicoplanin; OXA, oxacillin; LEV, levofloxacin; DAP, daptomycin.

reported an unintentional 6-kg weight loss in the preceding 2.3. Case 3

months. An echocardiogram showed a bicuspid aortic valve with

severe regurgitation and a 21-mm mobile vegetation. There was a A previously hypertensive 75-year-old male was admitted for

cavity suggestive of abscess formation in the mitro-aortic region investigation of weight loss and fatigue that had started after an

and a fistula from the aorta to the left ventricle. Ceftriaxone, ischemic stroke 3 months before. His laboratory examinations

oxacillin, and gentamicin were started. Surgery was performed for showed anemia, acute renal failure, and hematuria with dysmorphic

correction of the local complications and valve replacement. After features. An echocardiogram showed severe aortic regurgitation

identification of Granulicatella sp in blood cultures, the antibiotic along with a 19-mm vegetation, and blood cultures were positive for

regimen was changed to teicoplanin and gentamicin. The patient G. adiacens in two samples. Penicillin and gentamicin were initiated.

was discharged home after 4 weeks of combined antibiotic The patient developed embolization to the spleen, seizures, and

therapy. hemodynamic instability, leading to death 3 weeks later.

2.2. Case 2 2.4. Case 4

A 64-year-old male with a past medical history of diabetes, A 59-year-old female, with a prior history of hypothyroidism

obesity, and two coronary artery bypass surgeries was admitted for and dyslipidemia, reported fever and a 5-kg weight loss over a 5-

evaluation of effort-induced dyspnea in the 30 days prior to month period. Two weeks prior to admission, she had developed

hospital presentation. The patient reported a weight loss of 25 kg left abdominal pain, lower extremity edema, and petechiae.

in the past 6 months. Physical examination showed signs of Abdominal computed tomography showed embolization to the

pulmonary edema and poor dental hygiene. An echocardiogram spleen and left kidney. An echocardiogram identified a bicuspid

revealed two vegetations in the aortic valve and moderate valve aortic valve with severe regurgitation and a vegetation measuring

regurgitation. The initial empiric treatment for the IE was 8 mm in diameter. Six blood cultures revealed Granulicatella

ceftriaxone, oxacillin, and gentamicin. On the seventh day of spp. After 2 weeks of treatment with ceftriaxone and gentamicin,

antibiotic therapy, the patient developed cardiogenic shock, the fever recurred and an echocardiogram showed an increase in

requiring emergency valve replacement surgery. G. adiacens was the vegetation size to 12 mm. Valve replacement surgery was

identified in six blood cultures. Postoperatively, the antibiotic performed. The patient received treatment with vancomycin and

regimen was changed to teicoplanin and maintained for 6 weeks. gentamicin for 30 days and was discharged home asymptomatic.

The patient developed acute renal failure requiring hemodialysis

and multiple hospital-acquired infections, which were treated 3. Discussion

with vancomycin, meropenem, polymyxin, and fluconazole. He

progressed to refractory septic shock and died 5 months after the A subacute or even chronic presentation of IE caused by

surgery. Granulicatella sp has most often been described in the literature.

58 E.L. Adam et al. / International Journal of Infectious Diseases 31 (2015) 56–58

Indeed, all of our patients presented a history of a few months of Conflict of interest: All authors report no conflicts.

constitutional symptoms such as weight loss, anorexia, and fever,

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