Streptococcus gallolyticus Bacteremia Detected in Apheresis Platelets and Its Link to Colonic Neoplasms

Abstract

Introduction Streptococcus gallolyticus belongs to the Streptococcus bovis complex, and it is a common bacterium colonizing the gastrointestinal tract. Its presence in the blood may suggest an underlying pathology such as a colonic neoplasm. We report herein a case of S. bovis bacteremia in an apheresis platelet donor, review similar cases in the literature, and suggest a flowchart for the management of similar cases in other blood donation centers.

Case Presentation A 61-year-old subject presented to a Hemotherapy Service to make an apheresis platelet donation. On quality control testing, S. gallolyticus was identified in hemoculture, and the donor was called back for follow-up. At first, a new hemoculture was requested, and the patient was referred to the outpatient department of infectious diseases to further investigate pathologies associated with S. gallolyticus. A subsequent colonoscopy investigation evidenced a polypoid structure in the ascending colon. Pathology reported the resected specimen as a low-grade tubular adenoma.

Conclusion Isolation of S. bovis in blood products requires further investigation and should be managed with precision by Hemotherapy Services. A standard protocol for the management of asymptomatic patients with S. bovis positive hemoculture, with the requests of a new blood culture, a colonoscopy, and an echocardiogram is crucial, as it may ensure early diagnosis and reduce morbidity and mortality.

Keywords

Streptococcus gallolyticus - Streptococcus bovis - colonic neoplasm - colorectal cancer - apheresis

Introduction

Streptococcus gallolyticus ssp. gallolyticus (formerly known as Streptococcus bovis type I) is a subspecies of the bacterial complex S. bovis found in the microbiota of the gastrointestinal tract in ∼ 2.5% to 15% of healthy individuals. However, its presence in the blood is not usual, and it indicates a pathological process.[1] Several studies point to its correlation with infectious endocarditis and colonic neoplasms. In addition, when an active infection by the bacteria is identified, the attending physician is responsible for a proper investigation to identify pathologies related to this microorganism.

We herein report a case of S. bovis bacteremia detected on a patient after an apheresis platelet donation which took place in a tertiary hospital in Southern Brazil, perform a literature review of similar cases, and suggest a flowchart for the management of this condition.

Case Report

A 61-year-old male subject attended a Hemotherapy Service in January 2019 to make a voluntary apheresis platelet donation. On the day after, (∼ 24 hours later) a closed-system sample was collected for quality control testing of the platelet sample, which consists of microbiological evaluation, platelet count, residual leukocyte count, and pH determination. Bacterial growth was observed both in aerobic and anaerobic bottles in the bacterial screening by the microbial detection system BACT/ALERT (bioMérieux SA, Marcy-l'Étoile, France). The bottles were then sent to our supporting laboratory for identification, and S. gallolyticus was isolated. After bacterial growth was observed, the blood component was immediately withdrawn from stock and a new sample was collected for a new culture, which also turned out positive. After that, the blood component was discarded, and the donor was called to return to the service for investigation.

Upon consultation, the donor was asymptomatic. He had made a whole blood donation in 2012 and red cell apheresis donations in 2016 and 2018, with no disturbances. The family history was positive for colon adenocarcinoma: his father, at 84 years old, had undergone curative treatment. He did not have a personal history of neoplasia and had never had a colonoscopy. At first, a new hemoculture was requested, and the donor was referred to the outpatient department of infectious diseases to investigate pathologies associated with S. gallolyticus infection.

In July 2019, the patient presented to the Hemotherapy Service for follow-up. Still asymptomatic, his new hemoculture came out negative for S. gallolyticus, and he was waiting for an appointment with the infectologist. In November 2019, the donor was called back for a consultation and a colonoscopy was requested, given the patient's known risk factors for colonic malignancies. The colonoscopy findings were of an 8-mm pedunculated polyp in the ascending colon, which was removed by electrocautery snare, and two wide stalk pedunculated polyps in the descending colon measuring 10 mm and 12 mm. The pathology report of the resected specimen showed low-grade tubular adenoma.

The patient herein reported gave his informed consent prior to inclusion in the study.

Discussion

Streptococcus bovis is a Gram-positive bacterium that belongs to group D streptococci. Currently, based on DNA studies, S. bovis is a complex comprising seven subspecies of bacteria. The most significant ones are S. gallolyticus ssp. gallolyticus (previously S. bovis type I), S. infantarius ssp. infantarius (previously S. bovis type II/1), S. gallolyticus ssp. pasteurian (previously S. bovis type II/2) and S. gallolyticus ssp. macedonicus.[2] [3] In humans, S. bovis acts as a commensal bacterium colonizing the colon.[1] [4] Studies[1] estimate that the prevalence of S. bovis in healthy human feces ranges from 5% to 60%.

Its presence in the blood is unusual and is correlated with hepatobiliary diseases, endocarditis, and colorectal lesions. Subtypes of S. bovis have already been related to the pathogenesis of some diseases: type-I bacteremia is mostly related to endocarditis and colorectal cancer (CRC), whereas the type-II subspecies are frequent in patients with hepatobiliary diseases.[1] [2] [5] Once the S. bovis complex is detected in the blood, the differentiation into subspecies must be performed because of its epidemiology.

We herein report a case of S. bovis bacteremia detected on a voluntary donor in an apheresis platelet sample. Platelet components have a much higher rate of bacterial contamination than any other blood component due to their storage at room temperature, although the S. bovis complex is not a regular cause of contamination in platelet units.[7] Possible sources of contamination in blood products include donor bacteremia, contamination during the blood collection procedure, contamination of collection bags, and contamination during processing and storage of blood products. Potential contamination of the platelet substrate through the equipment or the patient's skin is substantially reduced, since the collection of platelets by apheresis is performed with sterile and disposable materials, and adequate antisepsis is performed before all procedures. Therefore, when bacterial culture growth was detected in the donor sample, the service initiated an investigation of the donor, considering that the donor's bloodstream was the apparent source of the contamination of the platelet sample.

Although the pathomechanism is still to be fully uncovered, the link between S. bovis bacteremia and colonic malignancy has been strongly established in the last years, and S. gallolyticus ssp. gallolyticus seems to be particularly involved in the process. The most expressive evidence in the literature is regarding S. bovis infections such as infective endocarditis or bacteremia as having an etiological role in advanced intestinal polyps and CRC.[7] [8] However, it is not clear yet if the pathogen can promote the development of colon carcinoma or if the malignant lesion provides both a microenvironment and a pathway for the bacteria to grow and migrate into the bloodstream.[7] Boleij et al.[9] and Jans and Boleij[10] conducted meta-analyses that indicated a steady association between patients infected with S. bovis and colonic neoplasia. The median percentage of patients who had neoplasia was of 60%, and was higher for adenomas (43%) than for carcinomas (18%), but still largely exceeding the disease rate reported in the general asymptomatic population. This could point to S. bovis infection being associated with premalignant colonic lesions.

With increasing awareness of the association between fecal microbiota dysbiosis and the development of CRC, research was conducted, and the prevalence of S. bovis has been described to range from 15% to 62% in the gastrointestinal tract of healthy individuals.[7] [8] Despite that, Boltin et al.[11] were unable to find an association between colonic carriage of S. bovis and an increased risk of developing colon carcinoma in a long prospective study. Aware of these contradictions and others conflicting results, in 2015, Pasquereau-Kotula et al.[7] suggested S. bovis is “both a passenger and a cancer-promoting bacteria”; therefore, the pathogen is an auxiliary factor that accelerates the development of CRC.

In 2011, Lin C. et al.[12] reported a case of a 51-year-old male donor identified with S. bovis bacteremia in an apheresis platelet donation. Once the bacteria were isolated, an investigation was performed, and there were no other particularities on the physical or blood examinations. The fecal occult blood test was negative, and the level of carcinogenic antigen was within normal limits. Later, a colonoscopy revealed a colonic neoplasm, and a biopsy revealed the diagnosis of invasive adenocarcinoma. In 2014, Le Niger et al.[13] published an analysis of a case of an 80-year-old female with an asymptomatic rectal tumor that was discovered because of a platelet concentrate infected with S. gallolyticus. In this case, the patient only discovered the tumor because the Hemotherapy Service was aware of the correlation between platelet contamination and CRC and requested further investigation with colonoscopy.

Chang et al.[14] published a case in which S. bovis infection was identified in the donor after a patient went into septic shock due to the contaminated platelet transfusion. After the episode, they recommended that the patient perform a colonoscopy, in which a benign polyp was found and removed.[14] Haimowitz et al.[15] published a case report of a regular platelet donor who had a donated platelet sample that cultured positive for S. bovis. The woman was also asymptomatic and underwent a colonoscopy after the episode, which showed a mass with 3 cm in diameter in the sigmoid colon.

In addition to these reports, a retrospective study[16] published in 2013 followed blood donors for 14 years and detected S. bovis bacteremia in 16 of them (1 in 110,800 donations). From this group, eight underwent colonoscopy and, as a result, two patients were diagnosed with colonic carcinomas and four, with adenomas. The authors[16] also recommend donor follow-up once S. bovis bacteremia is detected. Moreover, data from the American Red Cross[17] showed that S. bovis contamination was detected in 14 apheresis platelet donations between 2004 and 2008. In this group, colonic cancer was found in four of the patients and colonic polyps, in another four.[17] Therefore, the importance of investigating the gastrointestinal tract becomes evident, due to the great relationship between bacteremia by S. bovis and intestinal tumor lesions.

In [Fig. 1], we present a flowchart for the management of S. bovis-positive platelet samples in our Hemotherapy Service as the association of S. gallolyticus with premalignant lesions and colorectal carcinoma is already well established in the literature. After the identification of bacteremia by S. gallolyticus, it is necessary to investigate organic damage related to these bacteria, mainly at the colonic level.[18] The diagnosis of CRC is made by colonoscopy, which offers direct visualization and detection of a colonic polyp (early stage) or advanced neoplasia, followed by biopsy of the changes for histopathological analysis.[19] Given this relationship, investigation for intestinal changes – with colonoscopy – in patients with serum contamination by S. gallolyticus, identified in blood control at the Hemotherapy Service, is paramount, as an early diagnosis and intervention reduce the risk of morbidity and mortality due to CRC.[20]

Fig. 1 After identification of S. bovis in blood culture, we suggest requesting a new hemoculture to assess the persistence of the pathogen in the blood, a colonoscopy, and an echocardiogram to investigate the presence of polyps in the intestine and infectious endocarditis, respectively. Finally, referral to an infectologist or gastroenterologist for follow-up.

In the context of blood-transfusion safety, identifying the microorganism involved is imperative to determine the most likely origin of the bacteremia, since the relationship involving S. bovis, infective endocarditis, and CRC is well established. Thus, screening for colorectal neoplasia with colonoscopy when S. gallolyticus is isolated in blood culture is essential, since early diagnosis reduces morbidity and mortality in CRC. We herein emphasize the need for a Hemotherapy Service to have a standard protocol for the management of these patients, requesting a new blood culture, a colonoscopy, and an echocardiogram.

Conflict of Interests

The authors have no conflict of interests to declare. All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

Availability of Data and Material

The data regarding the case presentation is available from the corresponding author upon reasonable request. All the literature data analyzed has been included in the present published article.

Code Availability

Not applicable.

Authors' Contributions

All authors contributed to the conception and design of the study. Material preparation and data collection and analysis were performed by Francisco Costa Beber Lemanski, Anna Laura Duro Barp, and Gabriela Kohl Hammacher. The first draft of the manuscript was written by Francisco Costa Beber Lemanski, Anna Laura Duro Barp, Gabriela Kohl Hammacher, Martina Estacia da Cas, Ana Paula dos Santos Voloski, and Cristine Moratelli Wink, and all authors commented on previous versions of the manuscript. Supervision was performed by Cristiane da Silva Rodrigues de Araújo and Adriano Pasqualotti. All authors read and approved the final manuscript.

Ethics Approval

All procedures involving human participants were performed in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The present study was approved by the Committee for Ethics in Research (CEP) of Hospital São Vicente de Paulo (No. 4.237.941).

Consent to Participate

Informed consent was obtained from the participant included in the study.

Consent for Publication

The participant has consented to the submission of the case report to the journal.

• References

• 1 Jans C, Boleij A. The Road to Infection: Host-Microbe Interactions Defining the Pathogenicity of Streptococcus bovis/Streptococcus equinus Complex Members. Front Microbiol 2018; 9: 603
• 2 Ben-Chetrit E, Wiener-Well Y, Kashat L, Yinnon AM, Assous MV. Streptococcus bovis new taxonomy: does subspecies distinction matter?. Eur J Clin Microbiol Infect Dis 2017; 36 (02) 387-393
• 3 Kaindi DWM, Kogi-Makau W, Lule GN. et al. Colorectal cancer-associated Streptococcus infantarius subsp. infantarius differ from a major dairy lineage providing evidence for pathogenic, pathobiont and food-grade lineages. Sci Rep 2018; 8 (01) 9181
• 4 Jans C, Meile L, Lacroix C, Stevens MJ. Genomics, evolution, and molecular epidemiology of the Streptococcus bovis/Streptococcus equinus complex (SBSEC). Infect Genet Evol 2015; 33: 419-436
• 5 Corredoira J, Grau I, Garcia-Rodriguez JF. et al. The clinical epidemiology and malignancies associated with Streptococcus bovis biotypes in 506 cases of bloodstream infections. J Infect 2015; 71 (03) 317-325
• 6 White SK, Schmidt RL, Walker BS, Metcalf RA. Bacterial contamination rate of platelet components by primary culture: a systematic review and meta-analysis. Transfusion 2020; 60 (05) 986-996
• 7 Pasquereau-Kotula E, Martins M, Aymeric L, Dramsi S. Significance of Streptococcus gallolyticus subsp. gallolyticus association with colorectal cancer. Front Microbiol 2018; 9 (APR): 614
• 8 Murinello A, Ho C, Tavares P. et al. Streptococcus Gallolyticus Bacteraemia associated with colonic adenomatous polyps. J Port Gastrenterologia. 2006; 13 (03) 152-158
• 9 Boleij A, van Gelder MMHJ, Swinkels DW, Tjalsma H. Clinical Importance of Streptococcus gallolyticus infection among colorectal cancer patients: systematic review and meta-analysis. Clin Infect Dis 2011; 53 (09) 870-878
• 10 Jans C, Boleij A. The Road to Infection: Host-Microbe Interactions Defining the Pathogenicity of Streptococcus bovis/Streptococcus equinus Complex Members. Front Microbiol 2018; 9: 603
• 11 Boltin D, Goldberg E, Bugaevsky O. et al. Colonic carriage of Streptococcus bovis and colorectal neoplasia: a prospective 17-year longitudinal case-control study. Eur J Gastroenterol Hepatol 2015; 27 (12) 1449-1453
• 12 Lin CY, Tseng SB, Lu PL. et al. Isolation of Streptococcus bovis from apheresis platelets of asymptomatic donor warranted colonoscopy investigation: case report and literature review. Transfusion 2011; 51 (09) 2023-2027
• 13 Le Niger C, Dalbies F, Narbonne V. et al. Infection bactérienne à Streptococcus gallolyticus transmise par transfusion d'un concentré de plaquettes : à propos d'un cas. [Transfusion-transmitted bacterial infection of a apheresis platelet concentrate with Streptococcus gallolyticus: Analysis of one case] Transfus Clin Biol 2014; 21 (03) 107-110
• 14 Chang AH, Kirsch CM, Mobashery N, Johnson N, Levitt LJ. Streptococcus bovis septic shock due to contaminated transfused platelets. Am J Hematol 2004; 77 (03) 282-286
• 15 Haimowitz MD, Hernandez LA, Herron Jr RM. A blood donor with bacteraemia. Lancet 2005; 365 (9470): 1596
• 16 Lee CK, Chan HM, Ho PL. et al. Long-term clinical outcomes after Streptococcus bovis isolation in asymptomatic blood donors in Hong Kong. Transfusion 2013; 53 (10) 2207-2210
• 17 Eder AF, Goldman M. How do I investigate septic transfusion reactions and blood donors with culture-positive platelet donations?. Transfusion 2011; 51 (08) 1662-1668
• 18 Wong HK, Ho PL, Lee CK. Streptococcus gallolyticus Bacteremia and Colorectal Carcinoma. Gastroenterology 2019; 156 (01) 291-292
• 19 Dekker E, Tanis PJ, Vleugels JLA, Kasi PM, Wallace MB. Colorectal cancer. Lancet 2019; 394 (10207): 1467-1480
• 20 Issa IA, Noureddine M. Colorectal cancer screening: An updated review of the available options. World J Gastroenterol 2017; 23 (28) 5086-5096

Publication History

Received: 09 May 2022

Accepted: 07 June 2022

Article published online:
20 July 2022