Experience with Saccharomyces boulardii Probiotic in Oncohaematological Patients

Experience with Saccharomyces boulardii Probiotic in Oncohaematological Patients Probiotics & Antimicro. Prot. (2018) 10:350–355 DOI 10.1007/s12602-017-9332-4 Experience with Saccharomyces boulardii Probiotic in Oncohaematological Patients 1 2 2 Beata Sulik-Tyszka & Emilian Snarski & Magda Niedźwiedzka & 2 2 2 Małgorzata Augustyniak & Thorvald Nilsen Myhre & Anna Kacprzyk & 1 3 2 Ewa Swoboda-Kopeć & Marta Roszkowska & Jadwiga Dwilewicz-Trojaczek & 2 1,4 Wiesław Wiktor Jędrzejczak & Marta Wróblewska Published online: 25 September 2017 The Author(s) 2017. This article is an open access publication Abstract Very few reports have been published to date on however, they comprised Candida species: two C. glabrata, the bloodstream infections caused by Saccharomyces spp. one C. albicans, one C. krusei, one C. tropicalis and one in oncohaematological patients, and there are no guide- C. parapsilosis. There was no blood culture positive for lines on the use of this probiotic microorganism in this Saccharomyces spp. Our study indicates that despite colonisa- population. We describe the use of probiotic preparation tion of many oncohaematological patients with Saccharomyces containing Saccharomyces boulardii in a large group of spp., there were no cases of fungal sepsis caused by this oncohaematological patients. We retrospectively analysed species. the data from 32,000 patient hospitalisations at the hae- . . matological centre during 2011–2013 (including 196 Keywords Saccharomyces boulardii Probiotic . . haematopoietic stem cell transplant recipients) in a tertiary Leukaemia Lymphoma Haematology care university-affiliated hospital. During the study peri- od, 2270 doses of Saccharomyces boulardii probiotic were administered to the oncohaematological patients. In Introduction total, 2816 mycological cultures were performed, out of which 772 (27.4%) were positive, with 52 indicating Saccharomyces boulardii is a fungus classified as a yeast, digestive tract colonisation by Saccharomyces spp., which routinely cannot be distinguished from Saccharomyces mainly in patients with acute myeloid leukaemia (AML), cerevisiae and at present is regarded as a subtype of myelodysplastic syndrome (MDS) or multiple myeloma S. cerevisiae [1–6]. These yeasts are widespread in nature (MM). While colonised, they were hospitalised for and can be found on plants, fruit and in soil, being also used 1683 days and 416 microbiological cultures of their clin- in the baking and brewing industry [1, 2]. Usually, they are ical samples were performed. In the studied group of pa- considered to be nonpathogenic commensals of the digestive tients, there were six blood cultures positive for fungi; tract, administered as probiotics for several indications, in- cluding Clostridium difficile-associated disease [4, 7–16]. However, since the 1990s, an increasing number of publi- cations of fungemia and invasive infections caused by * Marta Wróblewska Saccharomyces cerevisiae (boulardii), particularly among in- martamwroblewska@gmail.com tensive care unit (ICU) patients and individuals with multiple co-morbidities, have been reported in literature in patients Department of Microbiology, Central Clinical Hospital in Warsaw, Warsaw, Poland treated with a probiotic preparation containing this yeast [1, 2, 5, 6, 11, 17–21]. Furthermore, it can also cause infections in Department of Haematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland otherwise healthy individuals [13, 17, 22–24]. Diarrhoea and colonisation of the gastrointestinal tract by Hospital Pharmacy, Central Clinical Hospital in Warsaw, Warsaw, Poland potentially pathogenic bacteria including Clostridium difficile are important problems in care of oncohaematological patients Department of Dental Microbiology, Medical University of Warsaw, 1a Banacha Street, 02-097 Warsaw, Poland treated for leukaemia and lymphoma [25]. One of the possible Probiotics & Antimicro. Prot. (2018) 10:350–355 351 approaches to this problem is to use probiotics containing and oncology ward from January 2011 until the end of Saccharomyces boulardii [26]. Both McFarland, and Videlock December 2013 in a tertiary care university-affiliated teaching and Cremonini in their meta-analyses comprising 5029 patients hospital (1050 beds). and 4138 patients, respectively, concluded that probiotic prepa- The data from the microbiology department was used to rations containing Saccharomyces boulardii reduced the inci- assess the total number of microbiological cultures performed dence of antibiotic-associated diarrhoea (AAD) [8, 27]. in the haematology and oncology department in the study However, there are concerns that probiotics might lead to period and find all of the patients who were colonised with severe invasive infections in some patients. This notion is fungi or had invasive fungal infections. Furthermore, we supported by some case reports of S. boulardii or analysed the medical charts of all the patients who were S. cerevisiae sepsis [1, 9, 18, 28]. This risk is emphasised in colonised with Saccharomyces boulardii in order to assess guidelines for infection prevention in haematological patients, their use of probiotics and antibiotics, the occurrence of colo- in which probiotics usage is generally contraindicated or their nisation and invasive infections caused by this yeast, as well possible use is not mentioned at all [29, 30]. Oral administra- as occurrence of neutropenia and previous treatment regimens tion of probiotic preparation containing live yeasts may pose a used in this group of recently treated immunocompromised particularly high risk to oncohaematological patients as they patients. Moreover, the data of the hospital pharmacy were often suffer from severe immune deficiency due to malignan- analysed to assess the total use of probiotics in the cy [29]. Furthermore, immunosuppressive treatment itself pre- haematology and oncology department. disposes these patients to infections and increases the risk of The Enterol 250 (Biocodex, France) was used as a spread of microorganisms within the host. It should also be probiotic preparation, containing 250 mg of lyophilised noted that oral mucositis and ulcers are very common in Saccharomyces boulardii in each tablet. oncohaematological patients. It may lead to yeast transloca- Specimens for microbiological cultures were taken from tion through the oral mucous membrane into the bloodstream, the patients as a standard procedure, according to the follow- causing fungaemia and invasive infections linked to an in- ing indications: a clinical suspicion of infection (fever > 38 °C creased mortality in this group of patients. or other signs of infection), diarrhoea and when a patient was However, the basis of the above-mentioned guidelines re- admitted for a high-toxicity treatment. As a routine procedure, lies on a limited number of published cases, and there is hardly surveillance oral and rectal swabs were taken. The patients any evidence from clinical trials to support this belief. The who received probiotics were treated according to the same guidelines are based on two reports published in 1996. In protocol as other patients and did not undergo any additional one of them, 55 cases of Lactobacillus infections were surveillance. reviewed—the mortality rate for the entire group was 6%; Mycological cultures of clinical specimens and identifica- however, there were no deaths among the patients with acute tion of strains of Saccharomyces spp. were done according to myeloid leukaemia (AML) (n =1),HIV(n = 3) and neutro- the standard laboratory procedures. Clinical samples were in- penic fever (n =3)[31]. In the other publication, a case was oculated onto Sabouraud agar supplemented with chloram- reported of a patient who developed Mucor spp. infection phenicol and gentamycin (bioMerieux), and incubated aerobi- 5 months after haematopoietic stem cell transplantation cally at 30 °C for 10 days. Identification of the strains of (HSCT) and was using an excess of oral herbal remedies with Saccharomyces spp. was done using API ID 32 C purified reishi mushrooms, extracts of ginseng and seaweed, (bioMerieux) tests and matrix-assisted laser desorption- and concentrated preparation of Lactobacillus bacteria [32]. ionisation time of flight mass spectrometry (MALDI-TOF Apart from the guidelines, there is at least one publication MS) (MALDI Microflex LT, Bruker, Germany). referring to a larger cohort of patients with sepsis caused by Saccharomyces boulardii (n = 37) [1]. In this publication, there was only one patient with AML and four patients with HIV infection in whom sepsis caused by this pathogen was Results confirmed—in all cases with favourable outcomes. In this study, we report our experience with a wide use of a During the study period (January 2011–December 2013), probiotic preparation containing Saccharomyces boulardii in there were 32,000 hospitalisations of haematological patients patients with haematological neoplasms. (including hospitalisations of 116 autologous and 82 alloge- neic transplant recipients and daycare unit stays). During this period, the only probiotic administered to the patients in the Patients and Methods haematology and oncology department was preparation con- taining Saccharomyces boulardii. The probiotic was given to The study is a retrospective analysis of the hospital and med- the patients once daily in the dose of 250 mg of lyophilised ical data of the patients who were treated at the haematology Saccharomyces boulardii. In total, during the study period, 352 Probiotics & Antimicro. Prot. (2018) 10:350–355 2270 doses of the preparation were administered to the pa- C. difficile-associated disease (CDAD) and recurrences of this tients on the ward (Table 1). condition; treatment of irritable bowel syndrome, traveller’s During the study, 2816 mycological cultures of the speci- diarrhoea and Crohn’s disease; and reduction of Helicobacter mens, collected from patients hospitalised in the department of pylori treatment-related symptoms, giardiasis and human im- haematology and oncology, were performed. There were 772 munodeficiency virus-related diarrhoea, as well as to preserve positive fungal cultures, comprising 48 rectal swab and 5 oral the intestinal bacterial flora during antibiotic therapy [1, 4, swab cultures positive for Saccharomyces boulardii, obtained 8–16, 26, 33]. Their mechanism of action is not fully under- from 38 patients during the study period. There were six blood stood, but it has been claimed that S. boulardii may directly cultures positive for fungi; however, they comprised Candida interact and inhibit C. difficile toxin A [15]. However, their species: two C. glabrata, one C. albicans,one C. krusei, one safety—particularly in imunocompromised patients—remains C. tropicalis and one C. parapsilosis. In the studied group of a controversial issue [1, 7, 16]. Several authors emphasise that patients, there was no blood culture positive for Saccharomyces caution is necessary when administering probiotics to the pa- spp. To put this data into the perspective, there were 22 blood tients with impaired immunity and risk-benefit potential cultures positive for Saccharomyces boulardii in patients should be evaluated [2, 5, 6, 10, 12, 32]. This is particularly hospitalised in other wards of the hospital—in internal medi- important while administering probiotics containing yeasts to cine wards (3 cases), in surgery wards (6 cases) and in the the immunocompromised patients [34]. Damage to the muco- intensive care unit (13 cases). sal barriers (e.g. mucositis and oral ulcers often seen in The basic demographic data of the population of colonised oncohaematological patients) as well as immunosuppression oncohaematological patients are shown in Table 2. The group due to the underlying condition or administered treatment of colonised patients consisted predominantly of patients with (apart from other risk factors) may contribute to invasive fun- AML, MDS or MM. Colonisation of these patients, detected in gal infections in this group of patients. the surveillance swabs taken during the whole hospitalisation To our knowledge, this is the first report of a wide usage of period, lasted on average for 1–4 weeks, rarely—for up to probiotics in oncohaematological patients. Interestingly, al- 3 months. They received the median of three chemotherapy though the use of this probiotic led in some patients to colo- cycles (range 0–16) prior to colonisation, and while colonised, nisation of the digestive tract with this yeast, there was no they were hospitalised for 1683 days, with 416 microbiologi- single case of sepsis caused by this microorganism in this cal cultures performed. We have analysed the use of probiotic high-risk population. in 23 of them for the median of 27 days (range 6–69 days) We have identified patients colonised with S. boulardii and accounting for 1019 doses of the preparation (45% of the analysed their probiotic use, which accounts for about half of probiotics used in the ward during the study period). The the use of probiotics in the ward. As this population was treat- ed with chemotherapy courses and had neutropaenia for probiotics were given due to diarrhoea (10 out of 23) or colo- nisation with Clostridium difficile with or without diarrhoea prolonged periods of time, it seems that S. boulardii has only (10 out of 23). As mentioned above, we did not identify any a limited ability to cause sepsis in this patient population de- invasive infections with Saccharomyces boulardii or with spite severity of their clinical condition. The main indication Saccharomyces cerevisiae in this group of patients. for Saccharomyces boulardii use was diarrhoea or colonisa- tion with Clostridium difficile. However, with the study de- sign, we did not assess the effectiveness of the probiotic prep- Discussion aration for this indication. Despite the fact that oncohaematological patients in the Probiotics have been used safely for years, and at present, they studied population were intensively treated with antibiotics are indicated for therapy or prophylaxis of many diseases, (97%) and antifungals (90%) during the period of colonisation such as enteral nutrition-related diarrhoea; prevention of with Saccharomyces boulardii, we did not notice any effect of Table 1 Use of the probiotics Number of Number of Total number Number of Number of containing Saccharomyces doses of the patients with of days of mycological cultures invasive boulardii, occurrence of probiotic to colonisation observation performed in the infections by colonisation with this the patients of the digestive of colonised study period in Saccharomyces microorganism and invasive during the study tract (detected patients hospitalised spp. (sepsis or infections in oncohaematological in oral swabs or oncohaematological systemic patients stool samples) patients infection) 2270 38 1683 2816 0 The cultures of oral swabs and stool samples were performed for various indications Probiotics & Antimicro. Prot. (2018) 10:350–355 353 Table 2 General data of the Characteristics Colonised patients (n =38) colonised patients included in the and number of hospitalisations study (n =53) Median age on admission in years (range) 61 (19–81) Median hospital stay in days (range) 36 (2–112) Gender, n (%) Female 20 (53) Male 18 (47) Disease, n (%) Acute myeloid leukaemia 11 (29) Myelodysplastic syndromes 7 (18) Multiple myeloma 7 (18) Lymphoma 4 (11) Chronic myelo-monocytic leukaemia 2 (5) Acute lymphoblastic leukaemia 2 (5) Other 5 (14) Cause of hospitalisation, n (%) Chemotherapy 26 (68) Haematopoietic stem cell transplantation 5 (14) Other 7 (18) Probiotic use, n (%) 26 (72) Duration of use of probiotic in days (range) 27 (6–69) Indication for Saccharomyces boulardii probiotic, n (%) Diarrhoea 10 (43) Clostridium difficile (with or without diarrhoea) 10 (43) Unknown 3 (14) Median number of microbiological cultures 8(1–41) per patient during hospitalisation (range) Median number of mycological stool cultures 3(0–8) per patient during hospitalisation (range) Neutropaenia during S. boulardii colonisation, n (%) 14 (36) Antibiotic treatment at the time of 38 (97) S. boulardii colonisation, n (%) Median number of antibiotics used during 5(0–10) hospitalisation (range) Antifungal prophylaxis/treatment at the time 34 (89) of S. boulardii colonisation, n (%) Presence of the central venous catheter, n (%) 26 (63) Parenteral nutrition at any time during hospitalisation, n (%) 7 (18) Fever during hospitalisation, n (%) 26 (74) Body mass index (BMI) < 18.5, n (%) 7 (21) As some medical records were not complete, the percentages given in italics are the percentage of data from complete records of this parameter this treatment on occurrence of invasive infections in this pop- hospitalised for bone marrow transplantation, S. cerevisiae ulation, although invasive Saccharomyces boulardii infections was isolated only once, despite weekly surveillance cultures were recorded in patients hospitalised in other wards of the (primarily of stool and throat swab specimens) during hospital during the study period. Salonen et al. in a study in- hospitalisation [36]. It is possible that antifungal treatment or volving patients with haematological diseases reported isola- prophylaxis—administered as a routine regimen to tion of S. cerevisiae from throat,stool,urine,andperineum oncohaematological patients—prevented in our patients pro- samples in 16, 23, 10 and 20% of the patients, respectively gression of S. boulardii colonisation to an invasive infection. [35]. Interestingly, in another study, among 70 patients In empiric therapy in these patients, voriconazole is used, 354 Probiotics & Antimicro. Prot. (2018) 10:350–355 Saccharomyces cerevisiae fungemia: an emerging infectious dis- which is active against Aspergillus spp., Candida krusei and ease. Clin Infect Dis 40:1625–1634. https://doi.org/10.1086/ Candida glabrata, and it may have also prevented invasive infections of S. boulardii/S. cerevisiae aetiology. Indeed, 3. 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Probiotics & Antimicro. Prot. (2018) 10:350–355 DOI 10.1007/s12602-017-9332-4 Experience with Saccharomyces boulardii Probiotic in Oncohaematological Patients 1 2 2 Beata Sulik-Tyszka & Emilian Snarski & Magda Niedźwiedzka & 2 2 2 Małgorzata Augustyniak & Thorvald Nilsen Myhre & Anna Kacprzyk & 1 3 2 Ewa Swoboda-Kopeć & Marta Roszkowska & Jadwiga Dwilewicz-Trojaczek & 2 1,4 Wiesław Wiktor Jędrzejczak & Marta Wróblewska Published online: 25 September 2017 The Author(s) 2017. This article is an open access publication Abstract Very few reports have been published to date on however, they comprised Candida species: two C. glabrata, the bloodstream infections caused by Saccharomyces spp. one C. albicans, one C. krusei, one C. tropicalis and one in oncohaematological patients, and there are no guide- C. parapsilosis. There was no blood culture positive for lines on the use of this probiotic microorganism in this Saccharomyces spp. Our study indicates that despite colonisa- population. We describe the use of probiotic preparation tion of many oncohaematological patients with Saccharomyces containing Saccharomyces boulardii in a large group of spp., there were no cases of fungal sepsis caused by this oncohaematological patients. We retrospectively analysed species. the data from 32,000 patient hospitalisations at the hae- . . matological centre during 2011–2013 (including 196 Keywords Saccharomyces boulardii Probiotic . . haematopoietic stem cell transplant recipients) in a tertiary Leukaemia Lymphoma Haematology care university-affiliated hospital. During the study peri- od, 2270 doses of Saccharomyces boulardii probiotic were administered to the oncohaematological patients. In Introduction total, 2816 mycological cultures were performed, out of which 772 (27.4%) were positive, with 52 indicating Saccharomyces boulardii is a fungus classified as a yeast, digestive tract colonisation by Saccharomyces spp., which routinely cannot be distinguished from Saccharomyces mainly in patients with acute myeloid leukaemia (AML), cerevisiae and at present is regarded as a subtype of myelodysplastic syndrome (MDS) or multiple myeloma S. cerevisiae [1–6]. These yeasts are widespread in nature (MM). While colonised, they were hospitalised for and can be found on plants, fruit and in soil, being also used 1683 days and 416 microbiological cultures of their clin- in the baking and brewing industry [1, 2]. Usually, they are ical samples were performed. In the studied group of pa- considered to be nonpathogenic commensals of the digestive tients, there were six blood cultures positive for fungi; tract, administered as probiotics for several indications, in- cluding Clostridium difficile-associated disease [4, 7–16]. However, since the 1990s, an increasing number of publi- cations of fungemia and invasive infections caused by * Marta Wróblewska Saccharomyces cerevisiae (boulardii), particularly among in- martamwroblewska@gmail.com tensive care unit (ICU) patients and individuals with multiple co-morbidities, have been reported in literature in patients Department of Microbiology, Central Clinical Hospital in Warsaw, Warsaw, Poland treated with a probiotic preparation containing this yeast [1, 2, 5, 6, 11, 17–21]. Furthermore, it can also cause infections in Department of Haematology, Oncology and Internal Diseases, Medical University of Warsaw, Warsaw, Poland otherwise healthy individuals [13, 17, 22–24]. Diarrhoea and colonisation of the gastrointestinal tract by Hospital Pharmacy, Central Clinical Hospital in Warsaw, Warsaw, Poland potentially pathogenic bacteria including Clostridium difficile are important problems in care of oncohaematological patients Department of Dental Microbiology, Medical University of Warsaw, 1a Banacha Street, 02-097 Warsaw, Poland treated for leukaemia and lymphoma [25]. One of the possible Probiotics & Antimicro. Prot. (2018) 10:350–355 351 approaches to this problem is to use probiotics containing and oncology ward from January 2011 until the end of Saccharomyces boulardii [26]. Both McFarland, and Videlock December 2013 in a tertiary care university-affiliated teaching and Cremonini in their meta-analyses comprising 5029 patients hospital (1050 beds). and 4138 patients, respectively, concluded that probiotic prepa- The data from the microbiology department was used to rations containing Saccharomyces boulardii reduced the inci- assess the total number of microbiological cultures performed dence of antibiotic-associated diarrhoea (AAD) [8, 27]. in the haematology and oncology department in the study However, there are concerns that probiotics might lead to period and find all of the patients who were colonised with severe invasive infections in some patients. This notion is fungi or had invasive fungal infections. Furthermore, we supported by some case reports of S. boulardii or analysed the medical charts of all the patients who were S. cerevisiae sepsis [1, 9, 18, 28]. This risk is emphasised in colonised with Saccharomyces boulardii in order to assess guidelines for infection prevention in haematological patients, their use of probiotics and antibiotics, the occurrence of colo- in which probiotics usage is generally contraindicated or their nisation and invasive infections caused by this yeast, as well possible use is not mentioned at all [29, 30]. Oral administra- as occurrence of neutropenia and previous treatment regimens tion of probiotic preparation containing live yeasts may pose a used in this group of recently treated immunocompromised particularly high risk to oncohaematological patients as they patients. Moreover, the data of the hospital pharmacy were often suffer from severe immune deficiency due to malignan- analysed to assess the total use of probiotics in the cy [29]. Furthermore, immunosuppressive treatment itself pre- haematology and oncology department. disposes these patients to infections and increases the risk of The Enterol 250 (Biocodex, France) was used as a spread of microorganisms within the host. It should also be probiotic preparation, containing 250 mg of lyophilised noted that oral mucositis and ulcers are very common in Saccharomyces boulardii in each tablet. oncohaematological patients. It may lead to yeast transloca- Specimens for microbiological cultures were taken from tion through the oral mucous membrane into the bloodstream, the patients as a standard procedure, according to the follow- causing fungaemia and invasive infections linked to an in- ing indications: a clinical suspicion of infection (fever > 38 °C creased mortality in this group of patients. or other signs of infection), diarrhoea and when a patient was However, the basis of the above-mentioned guidelines re- admitted for a high-toxicity treatment. As a routine procedure, lies on a limited number of published cases, and there is hardly surveillance oral and rectal swabs were taken. The patients any evidence from clinical trials to support this belief. The who received probiotics were treated according to the same guidelines are based on two reports published in 1996. In protocol as other patients and did not undergo any additional one of them, 55 cases of Lactobacillus infections were surveillance. reviewed—the mortality rate for the entire group was 6%; Mycological cultures of clinical specimens and identifica- however, there were no deaths among the patients with acute tion of strains of Saccharomyces spp. were done according to myeloid leukaemia (AML) (n =1),HIV(n = 3) and neutro- the standard laboratory procedures. Clinical samples were in- penic fever (n =3)[31]. In the other publication, a case was oculated onto Sabouraud agar supplemented with chloram- reported of a patient who developed Mucor spp. infection phenicol and gentamycin (bioMerieux), and incubated aerobi- 5 months after haematopoietic stem cell transplantation cally at 30 °C for 10 days. Identification of the strains of (HSCT) and was using an excess of oral herbal remedies with Saccharomyces spp. was done using API ID 32 C purified reishi mushrooms, extracts of ginseng and seaweed, (bioMerieux) tests and matrix-assisted laser desorption- and concentrated preparation of Lactobacillus bacteria [32]. ionisation time of flight mass spectrometry (MALDI-TOF Apart from the guidelines, there is at least one publication MS) (MALDI Microflex LT, Bruker, Germany). referring to a larger cohort of patients with sepsis caused by Saccharomyces boulardii (n = 37) [1]. In this publication, there was only one patient with AML and four patients with HIV infection in whom sepsis caused by this pathogen was Results confirmed—in all cases with favourable outcomes. In this study, we report our experience with a wide use of a During the study period (January 2011–December 2013), probiotic preparation containing Saccharomyces boulardii in there were 32,000 hospitalisations of haematological patients patients with haematological neoplasms. (including hospitalisations of 116 autologous and 82 alloge- neic transplant recipients and daycare unit stays). During this period, the only probiotic administered to the patients in the Patients and Methods haematology and oncology department was preparation con- taining Saccharomyces boulardii. The probiotic was given to The study is a retrospective analysis of the hospital and med- the patients once daily in the dose of 250 mg of lyophilised ical data of the patients who were treated at the haematology Saccharomyces boulardii. In total, during the study period, 352 Probiotics & Antimicro. Prot. (2018) 10:350–355 2270 doses of the preparation were administered to the pa- C. difficile-associated disease (CDAD) and recurrences of this tients on the ward (Table 1). condition; treatment of irritable bowel syndrome, traveller’s During the study, 2816 mycological cultures of the speci- diarrhoea and Crohn’s disease; and reduction of Helicobacter mens, collected from patients hospitalised in the department of pylori treatment-related symptoms, giardiasis and human im- haematology and oncology, were performed. There were 772 munodeficiency virus-related diarrhoea, as well as to preserve positive fungal cultures, comprising 48 rectal swab and 5 oral the intestinal bacterial flora during antibiotic therapy [1, 4, swab cultures positive for Saccharomyces boulardii, obtained 8–16, 26, 33]. Their mechanism of action is not fully under- from 38 patients during the study period. There were six blood stood, but it has been claimed that S. boulardii may directly cultures positive for fungi; however, they comprised Candida interact and inhibit C. difficile toxin A [15]. However, their species: two C. glabrata, one C. albicans,one C. krusei, one safety—particularly in imunocompromised patients—remains C. tropicalis and one C. parapsilosis. In the studied group of a controversial issue [1, 7, 16]. Several authors emphasise that patients, there was no blood culture positive for Saccharomyces caution is necessary when administering probiotics to the pa- spp. To put this data into the perspective, there were 22 blood tients with impaired immunity and risk-benefit potential cultures positive for Saccharomyces boulardii in patients should be evaluated [2, 5, 6, 10, 12, 32]. This is particularly hospitalised in other wards of the hospital—in internal medi- important while administering probiotics containing yeasts to cine wards (3 cases), in surgery wards (6 cases) and in the the immunocompromised patients [34]. Damage to the muco- intensive care unit (13 cases). sal barriers (e.g. mucositis and oral ulcers often seen in The basic demographic data of the population of colonised oncohaematological patients) as well as immunosuppression oncohaematological patients are shown in Table 2. The group due to the underlying condition or administered treatment of colonised patients consisted predominantly of patients with (apart from other risk factors) may contribute to invasive fun- AML, MDS or MM. Colonisation of these patients, detected in gal infections in this group of patients. the surveillance swabs taken during the whole hospitalisation To our knowledge, this is the first report of a wide usage of period, lasted on average for 1–4 weeks, rarely—for up to probiotics in oncohaematological patients. Interestingly, al- 3 months. They received the median of three chemotherapy though the use of this probiotic led in some patients to colo- cycles (range 0–16) prior to colonisation, and while colonised, nisation of the digestive tract with this yeast, there was no they were hospitalised for 1683 days, with 416 microbiologi- single case of sepsis caused by this microorganism in this cal cultures performed. We have analysed the use of probiotic high-risk population. in 23 of them for the median of 27 days (range 6–69 days) We have identified patients colonised with S. boulardii and accounting for 1019 doses of the preparation (45% of the analysed their probiotic use, which accounts for about half of probiotics used in the ward during the study period). The the use of probiotics in the ward. As this population was treat- ed with chemotherapy courses and had neutropaenia for probiotics were given due to diarrhoea (10 out of 23) or colo- nisation with Clostridium difficile with or without diarrhoea prolonged periods of time, it seems that S. boulardii has only (10 out of 23). As mentioned above, we did not identify any a limited ability to cause sepsis in this patient population de- invasive infections with Saccharomyces boulardii or with spite severity of their clinical condition. The main indication Saccharomyces cerevisiae in this group of patients. for Saccharomyces boulardii use was diarrhoea or colonisa- tion with Clostridium difficile. However, with the study de- sign, we did not assess the effectiveness of the probiotic prep- Discussion aration for this indication. Despite the fact that oncohaematological patients in the Probiotics have been used safely for years, and at present, they studied population were intensively treated with antibiotics are indicated for therapy or prophylaxis of many diseases, (97%) and antifungals (90%) during the period of colonisation such as enteral nutrition-related diarrhoea; prevention of with Saccharomyces boulardii, we did not notice any effect of Table 1 Use of the probiotics Number of Number of Total number Number of Number of containing Saccharomyces doses of the patients with of days of mycological cultures invasive boulardii, occurrence of probiotic to colonisation observation performed in the infections by colonisation with this the patients of the digestive of colonised study period in Saccharomyces microorganism and invasive during the study tract (detected patients hospitalised spp. (sepsis or infections in oncohaematological in oral swabs or oncohaematological systemic patients stool samples) patients infection) 2270 38 1683 2816 0 The cultures of oral swabs and stool samples were performed for various indications Probiotics & Antimicro. Prot. (2018) 10:350–355 353 Table 2 General data of the Characteristics Colonised patients (n =38) colonised patients included in the and number of hospitalisations study (n =53) Median age on admission in years (range) 61 (19–81) Median hospital stay in days (range) 36 (2–112) Gender, n (%) Female 20 (53) Male 18 (47) Disease, n (%) Acute myeloid leukaemia 11 (29) Myelodysplastic syndromes 7 (18) Multiple myeloma 7 (18) Lymphoma 4 (11) Chronic myelo-monocytic leukaemia 2 (5) Acute lymphoblastic leukaemia 2 (5) Other 5 (14) Cause of hospitalisation, n (%) Chemotherapy 26 (68) Haematopoietic stem cell transplantation 5 (14) Other 7 (18) Probiotic use, n (%) 26 (72) Duration of use of probiotic in days (range) 27 (6–69) Indication for Saccharomyces boulardii probiotic, n (%) Diarrhoea 10 (43) Clostridium difficile (with or without diarrhoea) 10 (43) Unknown 3 (14) Median number of microbiological cultures 8(1–41) per patient during hospitalisation (range) Median number of mycological stool cultures 3(0–8) per patient during hospitalisation (range) Neutropaenia during S. boulardii colonisation, n (%) 14 (36) Antibiotic treatment at the time of 38 (97) S. boulardii colonisation, n (%) Median number of antibiotics used during 5(0–10) hospitalisation (range) Antifungal prophylaxis/treatment at the time 34 (89) of S. boulardii colonisation, n (%) Presence of the central venous catheter, n (%) 26 (63) Parenteral nutrition at any time during hospitalisation, n (%) 7 (18) Fever during hospitalisation, n (%) 26 (74) Body mass index (BMI) < 18.5, n (%) 7 (21) As some medical records were not complete, the percentages given in italics are the percentage of data from complete records of this parameter this treatment on occurrence of invasive infections in this pop- hospitalised for bone marrow transplantation, S. cerevisiae ulation, although invasive Saccharomyces boulardii infections was isolated only once, despite weekly surveillance cultures were recorded in patients hospitalised in other wards of the (primarily of stool and throat swab specimens) during hospital during the study period. Salonen et al. in a study in- hospitalisation [36]. It is possible that antifungal treatment or volving patients with haematological diseases reported isola- prophylaxis—administered as a routine regimen to tion of S. cerevisiae from throat,stool,urine,andperineum oncohaematological patients—prevented in our patients pro- samples in 16, 23, 10 and 20% of the patients, respectively gression of S. boulardii colonisation to an invasive infection. [35]. Interestingly, in another study, among 70 patients In empiric therapy in these patients, voriconazole is used, 354 Probiotics & Antimicro. Prot. (2018) 10:350–355 Saccharomyces cerevisiae fungemia: an emerging infectious dis- which is active against Aspergillus spp., Candida krusei and ease. Clin Infect Dis 40:1625–1634. https://doi.org/10.1086/ Candida glabrata, and it may have also prevented invasive infections of S. boulardii/S. cerevisiae aetiology. Indeed, 3. 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Probiotics and Antimicrobial ProteinsSpringer Journals

Published: Sep 25, 2017

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