Bacteremia with the bovis group streptococci: species identification and association with infective endocarditis and with gastrointestinal disease

doi:10.1016/j.diagmicrobio.2016.02.019

Diagnostic Microbiology and Infectious Disease

Volume 85, Issue 2, June 2016, Pages 239-242

https://doi.org/10.1016/j.diagmicrobio.2016.02.019 Get rights and content

Highlights

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Sequencing of the ITS region identified 53 blood isolates of bovis group streptococci.
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S. gallolyticus subsp. gallolyticus seems associated with colorectal cancer.
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S. gallolyticus subsp. gallolyticus is associated with infective endocarditis.
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S. gallolyticus subsp. pasteurianus is associated with pancreatic malignancy.
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S. gallolyticus subsp. pasteurianus and S. lutetiensis have the highest mortality rate.

Abstract

DNA sequencing of the intergenic spacer (ITS) region was used to identify 53 blood culture isolates that had previously been designated to the bovis group streptococci and clinical data was collected retrospectively from patients’ records using a standardized protocol. ITS sequencing identified 19 (35.8%) isolates as Streptococcus gallolyticus subsp. gallolyticus, 12 (22.6%) as S. gallolyticus subsp. pasteurianus, two (3.8%) as S. gallolyticus subsp. macedonicus, seven (13.2%) as S. infantarius subsp. infantarius, 12 (22.6%) as S. lutetiensis and one (1.9%) as S. equinus. The association of S. gallolyticus subsp. gallolyticus with colorectal neoplasia and with infective endocarditis and the association between S. gallolyticus subsp. pasteurianus and pancreatic cancer were found to be clinically important. Also, a very high 1-year mortality rate with S. lutetiensis (66.7%) and S. gallolyticus subsp. pasteurianus (58.7%) bacteremia calls for intensive investigation for underlying disease focusing on the pancreas and the hepatobiliary system.

Introduction

Major changes in nomenclature of the bovis group streptococci have occurred during the past decades. Earlier the bovis group streptococci were phenotypically classified into three biotypes: Streptococcus bovis biotype I (mannitol fermentation positive), S. bovis biotype II/1 (mannitol negative and β-glucuronidase negative) and S. bovis biotype II/2 (mannitol negative and β-glucuronidase positive) (Beck et al., 2008). With the new nomenclature the following species and subspecies have been described: S. gallolyticus subsp. gallolyticus (former biotype I), S. infantarius subsp. infantarius (former biotype II/1), S. lutetiensis (former biotype II/2), S. gallolyticus subsp. pasteurianus (former biotype II/2), S. equinus and S. gallolyticus subsp. macedonicus (Poyart et al., 2002, Schlegel et al., 2000, Schlegel et al., 2003).

The species belonging to the bovis group streptococci have been associated with infective endocarditis (IE), cancer in various parts of the gastrointestinal tract and hepatobiliary disorders (Beck et al., 2008, Corredoira et al., 2008a, Romero et al., 2011). In 1951 McCoy and Mason (1951) were the first to report an association between IE caused by streptococci and colorectal cancer. Hoppes and Lerner (1974) reported 14 cases of bovis group streptococci IE with nine (64%) having concomitant gastrointestinal disease. Since then, several studies have established an association between bovis group streptococci bacteremia and colorectal cancer. In a meta-analysis, including 31 case series, Boleij et al. (2011a) found that 39% of patients with bovis group streptococci blood stream infection had concomitant adenomas or carcinomas. When only patients who had the colon investigated for disease were taken into account the median prevalence of colorectal cancer among patients with bovis group streptococci bacteremia increased to 60%. They also found a strongly increased risk among patients with S. bovis biotype I (SB I) compared with S. bovis biotype II (SB II) infected patients. In contrast, an association between SB II and non-colonic gastrointestinal cancers (pancreas and biliary tract) but also biliary tract infections has been documented by Corredoira et al., 2008a, Corredoira et al., 2014a.

The described associations have not been consistent in different studies. More data is needed in order to refine and optimize diagnostic procedures so as to correlate specific species and subspecies belonging to the bovis group streptococci to the different clinical syndromes. To establish clear associations between certain species and subspecies of the bovis group streptococci and specific diseases, correct species identification is of the utmost importance. Correct identification of the bovis group streptococci is difficult, but recently molecular methods have been used to clearly distinguish the different species and subspecies. DNA sequencing is an excellent tool for identification of bacteria. Partial DNA sequencing of the 16S rRNA gene is widely used for this purpose. However, for exact identification of non-hemolytic streptococci alternative sequencing targets such as the 16S-23S intergenic spacer (ITS) region seems more accurate (Marmolin et al., 2012, Nielsen et al., 2009).

The purpose of this study was to apply DNA sequencing of the ITS region for identification of species and subspecies belonging to the bovis group streptococci isolated from blood cultures and to investigate possible associations with infective endocarditis and gastrointestinal disease and to evaluate mortality with the different species.

Section snippets

Methods

Sixty-six blood culture isolates, which had previously been designated to the bovis group streptococci, was obtained from the Department of Clinical Microbiology, Odense University Hospital (n = 21) from the period 2004–2011 and from the Department of Clinical Microbiology, Slagelse Hospital (n = 45) from the period 1990–2011. The blood culture system used in Odense was BD BACTEC^TM 9240, Becton Dickinson, Franklin Lakes, NJ. and in Slagelse BacT/ALERT® 3D from bioMérieux. Of the 66 isolates, 53

Results

The demographical data of the patients included in the study is shown in Table 1.

Except from one patient, all patients included in the study had two or more positive 10 ml blood culture bottles. The bacterial species and subspecies identified by DNA sequencing of the ITS region are shown in Table 2.

Forty-four (83%) patients had further investigation because of blood culture findings. Fifteen (28.3%) underwent dental examination, 12 (22.6%) gastroscopy, 17 (32.1%) colonoscopy, 11 (20.8%)

Discussion

Bacteremia with the bovis group streptococci has been associated with IE and various abdominal cancers. A clear association between individual species in the group and IE or specific types of cancer remains to be established. In this study we identified blood culture isolates of the bovis group streptococci by molecular techniques and linked them to presence of IE or gastrointestinal disease.

In the study we found that approximately one third of all patients with bovis group streptococci

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Ethics aspect

Ethical approval permitting the review of patients’ records was obtained from the appropriate ethics committees.

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Clinical importance of Streptococcus gallolyticus infection among colorectal cancer patients: Systematic review and meta-analysis
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Novel clues on the specific association of Streptococcus gallolyticus subsp. gallolyticus with colorectal cancer
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Association between Streptococcus infantarius (formerly S. bovis II/1) bacteremia and noncolonic cancer
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Characteristics of Streptococcus bovis endocarditis and its differences with Streptococcus viridans endocarditis
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Is colonoscopy necessary in cases of infection by Streptococcus bovis biotype II

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Cited by (30)

Improved identification of Streptococcus bovis-Streptococcus equinus-complex species and subspecies by MALDI-TOF MS using a novel library
2023, Diagnostic Microbiology and Infectious Disease
To develop an in-house matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) library for improved identification of species and subspecies of the Streptococcus bovis/Streptococcus equinus-complex (SBSEC).
A total of 236 SBSEC isolates from blood stream infections and culture collections, determined by whole genome sequencing to subspecies level, were grown in brain heart infusion broth. Mass spectra were collected using the Bruker MALDI Biotyper system after ethanol-formic acid extraction. Main spectral profiles from 117 isolates were used to create the “SBSEC-CMRS library.” The remaining 119 spectra were used for evaluation of Bruker MALDI Biotyper (MBT) Compass Library Revision K (2022) and the SBSEC-CMRS library.
The Bruker library correctly identified species and subspecies in 72 of 119 (61 %) isolates, while the SBSEC-CMRS library identified 116 of 119 (97 %), using a cutoff score of ≥2.0.
The SBSEC-CMRS library showed sufficient diagnostic accuracy, and can be implemented in clinical practice for SBSEC species and subspecies identification.
Species and biotypes of Streptococcus bovis causing infective endocarditis
2023, Enfermedades Infecciosas y Microbiologia Clinica
Citation Excerpt :
A variable proportion of bacteremic cases have been associated with infectious endocarditis (IE) and colorectal cancer (CRC), depending mainly on the prevalence of S. gallolyticus subsp. gallolyticus (SGG), which is the species with strongest association to both entities.3,12–14 SBEC is the fifth leading cause of IE in the world,15 although its frequency varies among countries and geographic areas.12,17 Its prevalence is higher in Europe than in the USA, being a very frequent cause of IE in some areas of southern Europe.17
Streptococcus bovis/equinus complex (SBEC) is a major cause of infective endocarditis (IE), although its incidence varies greatly depending on the geographical area. The characteristics of IE caused by Streptococcus gallolyticus susp. gallolyticus are well known; there are hardly any descriptions of IE caused by other species or biotypes.
Retrospective cohort study, from 1990 to 2019, of all SBEC IE in adults in three Spanish hospitals, Lugo (LH), Barcelona (BH) and Ferrol (FH) where the population is mainly rural, urban and mixed, respectively. The incidence of IE was analyzed in 3 areas. Clinical characteristics of IE (277 cases, 258 biotyped) were compared according to SBEC species and biotypes.
There are significant differences between the incidence of SBEC IE in HL (27.9/10⁶) vs. HF and HB (8.8 and 7,1, respectively, p < 0.001). We found significant differences (SbI vs. SbII) in mean age (68.5 vs. 73 years; p < 0.01), duration of symptoms before diagnosis (46.9 ± 46.5 vs. 30.4 ± 40.9 days; p < 0.01), presence of comorbidities: 39.1% (78) vs. 54.2% (32; p < 0.04), predisposing heart illness:62.3% (124) vs. 81.3% (48; p < 0.006), particularly, prosthetic or intravascular devices IE: 24.6% (49) vs. 52.4% (31; p < 0.001), bi-valve involvement:23.6% (47) vs. 11.8% (7; p < 0.05) and heart failure: 24.6% (49) vs. 38.9% (23; p < 0.03). There were no significant differences in embolic events, need for surgery or mortality. The association with CRC was high in both groups: 77.7% vs. 66.6%.
IE due to SBEC has geographical variations in incidence and different clinical characteristics among biotypes. The association with CRC was high.
El complejo Streptococcus bovis/equinus (SBEC) es una de las principales causas de endocarditis infecciosa (EI), aunque su incidencia es muy variable según la zona geográfica. Las características de EI causada por Streptococcus gallolyticus subsp. gallolyticus son bien conocidas; apenas hay descripciones de EI causada por otras especies o biotipos.
Estudio de cohorte retrospectivo, desde 1990 hasta 2019, de todas las EI por SBEC en adultos en 3 hospitales españoles, Lugo (LH), Barcelona (BH) y Ferrol (FH) donde la población es mayoritariamente rural, urbana y mixta, respectivamente. Se analizó la incidencia de EI en 3 áreas. Se compararon las características clínicas de EI (277 casos, 258 biotipados) según las especies y biotipos de SBEC.
Existen diferencias significativas entre la incidencia de EI por SBEC en HL (27,9/10⁶) vs. HF y HB (8,8 y 7,1, respectivamente, p < 0,001). Encontramos diferencias significativas (SbI vs. SbII) en edad media (68,5 vs. 73 años; p < 0,01), duración de los síntomas antes del diagnóstico (46,9 ± 46,5 vs. 30,4 ± 40,9 días; p < 0,01); comorbilidades: 39,1 (78) vs. 54,2% (32; p < 0,04); enfermedad cardíaca predisponente: 62,3 (124) vs. 81,3% (48; p < 0,006), en particular, EI protésica o sobre dispositivos intravasculares: 24,6 (49) vs. 52,4% (31; p < 0,001); afectación bivalva: 23,6 (47) vs. 11,8% (7; p < 0,05) e insuficiencia cardiaca: 24,6 (49) vs. 38,9% (23; p < 0,03). No hubo diferencias significativas en cuanto a eventos embólicos, necesidad de cirugía o mortalidad. La asociación con el CCR fue alta en ambos grupos: 77,7 vs. 66,6%.
La EI por SBEC tiene variaciones geográficas en la incidencia y diferentes características clínicas entre los biotipos. La asociación con el CCR fue elevada.
Clustering of Streptococcus gallolyticus subspecies pasteurianus bacteremia and meningitis in neonates
2021, Journal of Microbiology, Immunology and Infection
Citation Excerpt :
In children, SGSP was the most common subspecies from the S. bovis group that predominantly infected infants. In contrast to that in children, SGSP, SGSG, and S. infantarius can infect adults.8,11,12,22 Bacteremia and meningitis were the most common clinical syndromes associated with S. bovis group infection in infants, according to the reviews of case series.23,24
Although Streptococcus gallolyticus subspecies pasteurianus (SGSP) is a rare pathogen in children, it can cause invasive infections among neonates and infants. Herein, we report bacteremia/meningitis caused by SGSP in three neonates and review the literature on bacteremia and/or meningitis caused by this organism.
Three neonates, referred from an obstetrics clinic within a 2-month period, presented with invasive SGSP infections. The bacterial isolates were analyzed using Bruker Biotyper MALDI-TOF, sequencing of 16S rRNA and sodA genes (encoding manganese dependent superoxide dismutase), and PCR restriction fragment length polymorphism assay of groESL gene. Molecular typing was performed to evaluate the genetic relatedness.
The median onset age of infection in the three neonates was 3 days (range 2–5 days). They were delivered through cesarean section in the same operation room under different doctors, and were cared for by different nurses. Patient A presented with bacteremia, patient B with bacteremia and meningitis, and patient C with meningitis. Four isolates were identified as SGSP and were susceptible to penicillin G, cefotaxime, and vancomycin. All patients were treated with ampicillin plus cefotaxime for 14 days, and no complications were observed. The molecular typing results suggested that all isolates belonged to a single clone, which indicated the possibility of an outbreak in the obstetrics clinic.
Infection by a rare pathogen such as SGSP in multiple patients belonging to a single healthcare unit indicates that detailed investigation and stringent infection control policy are necessary for preventing further outbreaks of such diseases.
Detection of biofilm formation, virulence factor genes, antibiotic-resistance, adherence properties, and some beneficial properties of cheese origin S. infantarius, S. gallolyticus, and S. lutetiensis strains belonging to the S. bovis/S. equinus complex
2021, LWT
Citation Excerpt :
Current nomenclature includes the species and subspecies of S. equinus, S. lutetiensis, S. gallolyticus subsp. macedonicus, S. gallolyticus subsp. pasteurianus, S. gallolyticus subsp. gallolyticus, and S. infantarius subsp. infantarius under the group named SBSEC (Marmolin et al., 2016; Schlegel, Grimont, Ageron, Grimont, & Bouvet, 2003). Several studies have shown that some strains of S. lutetiensis, previously known as S. bovis type II/2, cause bacteremia (Almuzara et al., 2013; Marmolin et al., 2016). Notwithstanding, S. lutetiensis strains have been frequently isolated from fermented foods such as various artisanal cheeses, fermented flour of finger millet (Divisekera et al., 2019; Gaglio et al., 2014; Medeiros et al., 2016).
This study was conducted to determine whether the potential health benefits of cheese-related Streptococcus (S.) infantarius, S. gallolyticus, and S. lutetiensis strains taxonomically belonging to the S. bovis/S. equinus complex (SBSEC) could be addressed without safety concern. All strains showed antagonistic effect against Staphylococcus (S.) aureus ATCC 25923 and produced a high amount of exopolysaccharide (293.48–365.95 μg/mL). Moreover, they presented high hydrophobicity towards n-hexadecane and xylene. The highest cholesterol assimilation (13.95–19.30%) and β-galactosidase activity (35.17–43.33 MU) were determined in isolates 930 and 120. Besides, all isolates neither showed hemolytic activity nor harbored virulence genes (asa1, gelE, cylA, cylB, epfSTR, hylSTR, mrpSTR, slySTR, bay046STR). However, only isolate 937 harbored the arcSTR virulence gene. Besides, isolates 937 and 120 were observed to degrade arginine. All isolates, except for isolate 937, were susceptible to penicillin, ampicillin, chloramphenicol, and vancomycin. All isolates had biofilm-forming capability. Considering all benefits and safety features, isolate 930 can be suggested for further in vivo and in situ investigations. This study does not claim that the SBSEC group bacteria, which are associated with many diseases, are actually beneficial, but only supports the view that clinical origin SBSEC group bacteria can be evaluated differently from those isolated from fermented products.
Species identification of Streptococcus bovis group isolates causing bacteremia: a comparison of two MALDI-TOF MS systems
2017, Diagnostic Microbiology and Infectious Disease
Identification, antimicrobial resistance and molecular characterization of the human emerging pathogen Streptococcus gallolyticus subsp. pasteurianus
2016, Diagnostic Microbiology and Infectious Disease
Citation Excerpt :
In fact, after the introduction of the new nomenclature of S. bovis strains, it became clear that SGSG represent the major cause of infective endocarditis and bacteremia, the latter that is often associated with colorectal cancer (Boleij et al., 2011a, 2011b; Vaska and Faoagali, 2009). SGSP seem instead related to immunosuppressive comorbidities, polymicrobial bacteraemia and concomitant biliary-pancreatic diseases, urinary tract infection (UTI), osteoarticular infections, and meningitis, mostly in elderly patients (Corredoira et al., 2014; Dekker and Lau, 2016; Fernandez-Ruiz et al., 2010; García-País et al., 2016; Marmolin et al., 2016; Matesanz et al., 2015; Romero et al., 2011; van Samkar et al., 2015). Phenotypic biochemical methods have been largely used for streptococci identification in routine diagnostic laboratories, though they are time-consuming and have limited differentiation capacity due to phenotypic trait variability (Isaksson et al., 2015; Teles et al., 2011).
This study aimed to retrospectively identify 22 Streptococcus bovis clinical strains based on the new taxonomy, as well as to investigate their antibiotic-resistance and clonality. Strains were identified by Phoenix100 system, 16S rRNA sequencing, and two MALDI-TOF MS platforms (Bruker Biotyper, Vitek MS). Antibiotic resistance was determined both phenotypically and genotypically, and clonality was assessed by PFGE. Most of strains (63.6%) were isolated from urine, and diabetes was the most common underlying disease (31.8%). Phoenix100 system revealed all strains belonged to biotype II, and 16S rRNA sequencing identified all strains as S. gallolyticus subsp pasteurianus (SGSP). Although both MALDI-TOF MS systems correctly identified isolates to the species level, only Bruker Biotyper accurately identified to the subspecies level. Erythromycin-resistant strains (31.8%) were also clindamycin-resistant and positive for erm(B). Strains resistant to tetracycline (68.2%) were also resistant to erythromycin. PFGE showed high genetic variability identifying 17 different pulsotypes, most of which single.

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Clinical StudyBacteremia with the bovis group streptococci: species identification and association with infective endocarditis and with gastrointestinal disease

Highlights

Abstract

Introduction

Section snippets

Methods

Results

Discussion

Conflicts of Interest

Ethics aspect

Lancet Infect Dis

Clin Microbiol Infect

J Infect

J Infect

Streptococcus bovis bacteremia: Association with gastrointestinal and liver disease in a predominantly Hispanic population

South Med J

Comprehensive study of strains previously designated Streptococcus bovis consecutively isolated from human blood cultures and emended description of Streptococcus gallolyticus and Streptococcus infantarius subsp. coli

J Clin Microbiol

Clinical importance of Streptococcus gallolyticus infection among colorectal cancer patients: Systematic review and meta-analysis

Clin Infect Dis

Novel clues on the specific association of Streptococcus gallolyticus subsp. gallolyticus with colorectal cancer

J Infect Dis

Association between Streptococcus infantarius (formerly S. bovis II/1) bacteremia and noncolonic cancer

J Clin Microbiol

Characteristics of Streptococcus bovis endocarditis and its differences with Streptococcus viridans endocarditis

Eur Clin Microbiol Infect Dis

Is colonoscopy necessary in cases of infection by Streptococcus bovis biotype II

Eur J Clin Microbiol Infect Dis

Clinical Study
Bacteremia with the bovis group streptococci: species identification and association with infective endocarditis and with gastrointestinal disease