Probiotic paradox: Saccharomyces cerevisiae fungemia after S. boulardii use in severe pancreatitis

Abstract

Background

Saccharomyces boulardii is a widely used probiotic for managing antibiotic-associated diarrhea and other gastrointestinal disorders. While considered safe in immunocompetent individuals, its use in critically ill patients has been increasingly associated with invasive fungal infections, particularly Saccharomyces cerevisiae fungemia.

Case presentation

We report the case of a 46-year-old male admitted with severe necrotizing biliary pancreatitis, complicated by pancreatic necrosis, portal vein thrombosis, and a suspected duodenal fistula. Following emergency necrosectomy, the patient required prolonged ICU care with enteral and parenteral nutrition via jejunostomy and central venous catheter. On postoperative day 7, he developed watery diarrhoea and was started on S. boulardii (Econorm) probiotics. By day 14, he developed high-grade fever, hypotension, and leucocytosis. Blood cultures from both central and peripheral lines grew S. cerevisiae, confirmed by MALDI-TOF. The isolate was sensitive to amphotericin B, fluconazole, and caspofungin. The probiotic was discontinued, central line removed, and caspofungin initiated, resulting in clinical improvement and sterile follow-up cultures.

Discussion and conclusion

Though rare, fungemia due to S. boulardii can be life-threatening, particularly in ICU settings where multiple risk factors coexist. Proposed mechanisms include gut translocation and catheter contamination during probiotic handling. This case underscores the need for caution in using yeast-based probiotics in critically ill patients. Lactobacillus-based formulations are safer alternatives. Strict infection control, microbiology communication, and heightened clinical awareness are essential to mitigate risk.

Introduction

Probiotics containing Saccharomyces boulardii, a subtype of S. cerevisiae, commonly known as Bakers’ or Brewers’ yeast, are commonly used to prevent or manage antibiotic-associated diarrhoea, Clostridium difficile infection, and other gastrointestinal disorders [1]. It is generally considered safe, because it is a non-pathogenic yeast that does not colonize permanently, lacks virulence factors [2]. It is rarely associated with systemic infection in immunocompetent individuals, their use in critically ill or immunocompromised patients has been increasingly associated with adverse events, including Saccharomycesfungemia [3].

A few case reports have documented S. boulardii-associated fungemia in intensive care unit (ICU) patients, often leading to systemic infections, septic shock, and in some instances, mortality. Risk factors include the presence of central venous catheters (CVCs), impaired mucosal barriers, broad-spectrum antibiotic use, gastrointestinal pathology, and immunosuppression [4].

This report uniquely describes fungemia following S. boulardii use in a patient with severe necrotizing pancreatitis with duodenal fistula, underscoring that profound gut barrier disruption—even in the absence of classic immunosuppression—can precipitate systemic Saccharomyces infection. Moreover, it offers the published evidence of successful caspofungin therapy for Saccharomyces fungemia, broadening our antifungal armamentarium against similar infections.

Case description

A 46-year-old previously healthy male presented with sudden-onset epigastric abdominal pain and distension. Evaluation with contrast-enhanced CT revealed severe acute necrotizing biliary pancreatitis with a Computed Tomography Severity Index (CTSI) of 8. Imaging demonstrated pancreatic ascites, peripancreatic fluid collections, and thrombosis of the portal and splenic veins. He was admitted to the intensive care unit (ICU) for hemodynamic monitoring and organ support. Initial management included fluid resuscitation, bowel rest, and parenteral nutrition. Due to rising leucocytosis, fever, and clinical deterioration, he was empirically started on broad-spectrum intravenous antibiotics. His antimicrobial regimen was progressively escalated to high-grade agents including meropenem (1 g IV every 8 h), tigecycline (100 mg loading followed by 50 mg twice daily) to ensure extended-spectrum gram-negative coverage including multidrug-resistant organisms. Inj. Fluconazole and Amphotericin B were given as a prophylaxis for fungal infection.

Despite maximal medical management, the patient developed worsening sepsis with features of systemic inflammatory response and abdominal tenderness. A repeat CT abdomen revealed an infected necrotic pancreatic collection. Interventional radiology-guided percutaneous catheter drainage (PCD) was performed, yielding purulent material. However, due to persistent fever, and suspicion of a pancreatic fistula, the patient was taken up for emergency surgical intervention. Intraoperatively, dense vascular adhesions, along with solid necrotic tissue in the lesser sac and infected ascites were noted. The surgical procedure included exploratory laparotomy, adhesiolysis, omentectomy, cholecystectomy, necrosectomy, and feeding jejunostomy.

Postoperatively, the patient was managed in the ICU with elective ventilation for 72 h and required vasopressor support for seven days. Enteral feeding via the jejunostomy was initiated gradually along with continuation of supportive parenteral nutrition via central venous catheter in view of suspicious duodenal fistula presented as bilious drain output. Around postoperative day 7, he developed new-onset watery diarrhoea, presumed to be antibiotic-associated. In accordance with routine supportive measures, the patient was started on probiotic sachets (containing Saccharomyces boulardii, 250 mg) administered thrice daily through the jejunostomy tube. Stool sample for Clostridium difficile toxins was sent which was found to be negative.

While the diarrhoea showed initial improvement, the patient experienced recurrence of high-grade fever, leucocytosis, and hypotension by postoperative day 14. Blood cultures obtained from both peripheral veins and the central venous catheter showed growth of Saccharomyces cerevisiae. The organism was identified by Matrix-Assisted Laser Desorption Ionization Time-of-Flight (MALDI-TOF) mass spectrometry [5]. (Table 1) Given the close temporal relationship—seven days after initiating the probiotic—and absence of other fungal risk factors, the diagnosis of S. cerevisiae fungemia secondary to S. boulardii probiotic use was established. The probiotic was immediately discontinued and the central line was removed.

Table 1.

Summary of blood culture findings and antifungal susceptibility for saccharomyces cerevisiae.

Parameter	Result
Sample Sources	Central line and right peripheral vein
Time to Positivity	96 h
Organism Identified	Saccharomyces cerevisiae
Identification Methods	MALDI-TOF
Sensitivity
Antifungal Agent	MIC (µg/mL)	Interpretation
Caspofungin	0.25	Sensitive
Amphotericin B	0.064	Sensitive
Fluconazole	64	Resistant
5-Flucytosine	1	Sensitive
Micafungin	0.25	Sensitive
Voriconazole	1	Resistant

The patient was initiated on intravenous Caspofungin as per scheduled doses. Fever subsided within 72 h of starting antifungal therapy, and subsequent blood cultures returned sterile. His clinical condition gradually improved, enteral nutrition was resumed, and he was eventually weaned off ICU care and discharged in a stable condition.

Discussion

According to the Food and Agriculture Organization of the United Nations and the World Health Organization, probiotics are defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host.” [6] These microorganisms are typically bacteria or yeasts that inhabit the gastrointestinal tract and support various physiological processes, including modulation of immunity, maintenance of mucosal integrity, and inhibition of pathogenic colonization. Though bacterial species dominate the gut microbiota, fungi constitute approximately less than 0.1 % of it. This fungal component, known as the mycobiota, is highly individual and primarily composed of Candida and Saccharomyces species in healthy individuals [7].

Indications for use and mechanism of action

Probiotics are commonly prescribed for multiple gastrointestinal and systemic conditions. The most well-established indications include antibiotic-associated diarrhea, prevention of Clostridioides difficile infection, traveller’s diarrhoea, and supportive management in irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and enteral feeding-related diarrhea [8]. Mechanistically, probiotics contribute to health by enhancing mucosal barrier function, competing with pathogens for adhesion and nutrients, producing antimicrobial peptides, and modulating the host’s immune responses. Certain strains like Saccharomyces boulardii also produce proteases that degrade bacterial toxins, making them particularly useful in infections such as C. difficile colitis [9].

Options available

Probiotics are available in single- or multi-strain formulations and in various delivery forms such as capsules, sachets, and fermented foods. Commonly used probiotic organisms include Lactobacillus Rhamnosus GG, Bifidobacterium bifidum, Saccharomyces boulardii, and multi-strain combinations [10]. Among these, S. boulardii, a yeast strain of S. cerevisiae, is notable for its ability to survive gastric acid, its resistance to antibiotics, and its immune-modulating properties. It is commercially available and routinely used in clinical practice for the prevention and treatment of diarrhea from various causes.

Recommended dose and safety

The typical adult dosage of S. boulardii ranges from 250 to 500 mg once or twice daily, often administered for a duration of 7–14 days depending on the indication [11]. In immunocompetent patients, S. boulardii has an excellent safety profile. However, its use in critically ill or immunocompromised individuals has been increasingly scrutinized due to reports of systemic infections. In our case we have used the dose 250 mg thrice a day, which falls within the range of routinely recommended dosing regimens. Notably, the first documented case of Saccharomyces-related fungemia was reported in 1970, involving a patient with a prosthetic mitral valve, which brought early attention to the potential for systemic infection even from presumed non-pathogenic strains [12]. Since then, multiple cases have demonstrated that S. cerevisiae can lead to severe systemic infections such as fungemia, endocarditis, liver abscess, pneumonia, peritonitis, and even septic shock [13].

Risks in ICU and critically Ill patients

The risk of probiotic-associated fungemia is significantly heightened in critically ill patients, particularly those with indwelling vascular catheters, those on immunosuppressants, or those receiving multiple broad-spectrum antibiotics. ICU patients often have disrupted mucosal integrity and altered immune responses, which further increase their susceptibility [3], [4]. Recognizing these risks, the European Medicines Agency (EMA) issued a warning in 2017 advising against the use of S. boulardii-based probiotics in patients with CVCs or in ICU settings. This was in line with earlier concerns raised by researchers like Muñoz et al., who linked probiotic administration to fungemia in hospitalized patients [14].

Mechanisms of fungemia

In a comprehensive review of more than 90 cases of S. cerevisiae fungemia, the most consistent risk factor identified was the use of probiotics containing S. boulardii [13]. Notably, the majority of patients had central venous catheters and had been treated with broad-spectrum antibiotics. In another review of Fungemia was typically detected a median of 10 days after the initiation of the probiotic, with a wide range from 4 to 300 days which also corelates in our case, where the fungemia was detected after 7 days of the probiotic use [14]. The mechanisms proposed for the development of fungemia include direct translocation of the yeast across a compromised intestinal barrier or external contamination of central venous lines through aerosolized probiotic powder or colonized hands of healthcare workers. These routes highlight the potential for both endogenous and exogenous sources of infection in at-risk patients. Our patient was operated case of acute necrotizing pancreatitis with suspected duodenal fistula, with prolonged hospital stay, on multiple broad-spectrum antibiotic agents and central venous access. The Fungemia in our patient may either be due to translocation of the fungus due to weak gut mucosal barrier or due to contamination of central venous access directly or by the hands of a healthcare worker.

Current guidelines for use and recommendations

Management of S. cerevisiae fungemia involves prompt discontinuation of the probiotic, removal of any suspected central lines, and initiation of antifungal therapy. Amphotericin B and fluconazole have been the most commonly used antifungal agents, though the absence of defined MIC breakpoints for Saccharomyces species presents a challenge [15]. Interestingly, caspofungin and other echinocandins have not yet been adequately studied in this context, except some reported cases supporting the use [16]. In our case, the organism identified was found to be sensitive to Caspofungin, Amphotericin and Fluconazole. As the patient already received rest antifungal agents, Inj. Caspofungin was prescribed.

To minimize the risk of such complications, several best practices are recommended. Saccharomyces-based probiotics should be strictly avoided in patients with known or suspected immunocompromise or those with central lines. When necessary, probiotics should be administered in capsule form rather than sachets to limit aerosolization, and preparation should occur outside the patient’s room using strict aseptic technique with appropriate glove changes [17]. Lactobacillus-based formulations are generally considered safer alternatives in high-risk patients [18]. It is also important for clinicians to inform microbiology labs about the use of Saccharomyces supplements to aid in the rapid differentiation from Candida species when yeast is isolated in cultures. After line removal, catheter tip cultures should be sent to help identify the source of fungemia, whether translocation from the gut or external contamination. Finally, there is a pressing need for regulatory bodies to require warning labels on S. boulardii products and to define standardized antifungal susceptibility breakpoints for Saccharomyces spp.

Conclusion

This case illustrates that Saccharomyces cerevisiae fungemia, though rare, can occur following S. boulardii probiotic use in critically ill patients, particularly those with central venous catheters, compromised gut integrity, and broad-spectrum antibiotic exposure. While generally safe in healthy individuals, S. boulardii should be avoided in high-risk ICU settings. Early recognition, withdrawal of the probiotic, removal of invasive devices, and timely antifungal therapy are essential for favourable outcomes. Safer alternatives, such as Lactobacillus-based probiotics, should be preferred in vulnerable populations.

Ethical approval

Ethical approval was not required for a single anonymized case report as per institutional policy.

Author contributions

Vidit Dholakia (VD), Soumyadip Sain (SS) and Suvendu Sekhar Jena (SJ) were responsible for clinical management of the patient, collection of case data, and preparation of the case narrative. SS and VD performed the literature review and drafted the manuscript. Suvendu Sekhar Jena (SJ) contributed to clinical interpretation, postoperative management, and manuscript review. Samiran Nundy (SN) supervised the work, provided critical commentary, and approved the final manuscript. All authors read and approved the final version of the manuscript.

Consent

Written informed consent was obtained from the patient for publication of the case details and any accompanying clinical information.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

CRediT authorship contribution statement

Soumyadip Sain: Writing – original draft, Formal analysis, Data curation, Conceptualization. Vidit Dholakia: Writing – original draft, Methodology, Investigation, Formal analysis, Data curation. Samiran Nundy: Writing – review & editing, Validation, Supervision, Resources. Suvendu Sekhar Jena: Writing – review & editing, Supervision, Project administration, Investigation, Formal analysis.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.