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 After bacterial growth was observed, the blood component was immediately withdrawn from stock and a new sample was collected for a new culture, which also turned out positive.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.
