Rising Into Relevance: A Rare Case of Saccharomyces cerevisiae Pyelonephritis in an Immunosuppressed Patient With Exposure to Sourdough Starter

Abstract

Saccharomyces cerevisiae, commonly known as Baker’s yeast, has been used in breadmaking, winemaking, and beer brewing for centuries. Although not generally regarded as pathogenic, rare cases of invasive infections have occurred in patients predisposed by critical illness, immunosuppression, or prolonged antibiotic use. Using data collected from the electronic medical record and personal interactions with the patient, we present a case of complicated S cerevisiae urinary tract infection (UTI). We searched terms (and permutations of terms) including Saccharomyces cerevisiae, Baker’s or Brewer’s yeast, and urinary tract infection using PubMed to identify previously published evidence of invasive S cerevisiae infections. Our patient is a 30-year-old woman with a history of rheumatoid arthritis on methotrexate, and previous admission for Candida glabrata UTI requiring intravenous antifungal therapies, who presented to her gynecologist with complaints of vaginitis and flank pain. Vaginal and urine cultures grew S cerevisiae, and the patient was diagnosed with pyelonephritis and admitted for treatment. A further review of the patient’s history revealed daily exposure to S cerevisiae through baking sourdough bread. She was treated with 7 days of IV amphotericin deoxycholate and discharged on a 6-month course of suppressive oteseconazole for vulvovaginitis suppression. Saccharomyces cerevisiae is an exceedingly rare cause of invasive fungal UTI, with our literature review identifying only a few case reports of associated UTI and fungemia, all related to probiotic use. Our case emphasizes the importance of careful history taking and early diagnostic cultures in those at risk of invasive fungal infections.

Introduction

Saccharomyces cerevisiae, commonly known as Baker’s yeast or Brewer’s yeast, has been used in breadmaking, winemaking, and beer brewing for centuries. ¹ As a commensal pathogen of the skin, urogenital, gastrointestinal, and respiratory tract, and as a widely studied model eukaryotic organism, it has been considered to be Generally Regarded As Safe (GRAS) by the Food and Drug Administration.^1,2 Therapeutically, a subtype of S cerevisiae, Saccharomyces boulardii, can be taken as a probiotic dietary supplement and has been demonstrated to be effective in treating diarrhea.^3,4 Despite its widespread use and previous tolerance, there have been increasing reports of S cerevisiae pathogenicity. ⁵ Infections range from vaginitis to life-threatening fungemia, with most patients affected being immunocompromised, but others with no obvious predisposing factor. In this case report, we present a rare case of S cerevisiae pyelonephritis in an immunosuppressed patient with a prior history of Candida glabrata and S cerevisiae vaginitis with exposure to Baker’s yeast through sourdough breadmaking.

Case

A 30-year-old woman with a history of rheumatoid arthritis on long-term methotrexate and a previous hospital admission for a complicated fungal urinary tract infection (UTI) presented to her gynecologist with 1 week of vaginal discharge, vaginal pruritus, and bilateral flank pain. Urine and vaginal cultures were obtained, and she was started on intravaginal clotrimazole while awaiting results. The vaginal and urine cultures obtained by her gynecologist were notable for heavy growth of S cerevisiae that was susceptible to voriconazole, clotrimazole, flucytosine, and amphotericin B, and her infectious disease doctor was notified (Table 1). Due to a limited availability of outpatient flucytosine and rapid development of resistance with monotherapy and poor urinary concentration of other antifungals, the patient was admitted by infectious disease for intravenous amphotericin B deoxycholate.

Table 1.

Urine Culture Results With Sensitivity Testing. Fungal Culture: Heavy Growth Saccharomyces cerevisiae. Results of Antifungal Susceptibility Testing.

Drugs	Results: MIC values in μg/mL a	Interpretation
Amphotericin B (AMB)	0.25	No established breakpoints b
Nystatin (NYS)	2	No established breakpoints
5-Fluorocytosine (5-FC)	0.125	No established breakpoints
Ibrexafungerp	1	No established breakpoints
Fluconazole (FLU)	8 c	No established breakpoints
Voriconazole (VORI)	0.125	No established breakpoints
Clotrimazole (CLOT)	0.125	No established breakpoints

a

MIC values: Represent the minimum inhibitory concentrations of antifungal drugs.

b

No established breakpoints: Indicates that clinical breakpoints for the drug-organism combination have not been defined, and susceptibility should be interpreted in the context of clinical response.

c

Fluconazole has a high MIC (8 μg/mL), which may suggest potential resistance.

Six months prior, the patient was admitted for refractory fungal vulvovaginitis and complicated C glabrata pyelonephritis. At that time, the patient reported nearly a 7-month history of flank pain, vaginal pruritus and discharge, and dysuria refractory to multiple courses of azole therapy. Urine cultures during that hospitalization were positive for azole-resistant C glabrata. Infectious disease was consulted and recommended treatment with a 7-day course of amphotericin B deoxycholate. The patient completed treatment with resolution of symptoms. Outpatient follow-up cultures were negative for C glabrata.

Upon arrival at the hospital, the patient reported subjective fever, bilateral flank pain, joint pain, and dysuria. In the setting of her infectious symptoms, the patient had stopped her methotrexate at the recommendation of her rheumatologist, leading to worsening rheumatic joint pain. On admission, her vital signs included a temperature of 37.1°C, heart rate of 72 beats per minute, blood pressure of 124/70 mmHg, respiratory rate of 18, and an SpO₂ of 99% on room air. Physical examination was remarkable for bilateral costovertebral angle and suprapubic tenderness to palpation. There was no abdominal distention, rebound, or guarding. Cardiac, pulmonary, and neurologic examinations were unremarkable. Complete blood count on admission demonstrated mild leukopenia with a white blood cell (WBC) count of 4.56 (normal: 4.80-10.80 K/cumm) and mild anemia with a hemoglobin of 11.8 (normal: 12.0-16.0 g/dL). Her comprehensive metabolic panel was unremarkable. Urinalysis demonstrated a specific gravity of 1.042 (normal: 1.003-1.030), <1 WBC (normal ≤ 3/HPF), few bacteria, few mucous, and 15 squamous epithelial cells (normal ≤ 5/HPF). Computed tomography of the abdomen and pelvis showed bilateral striated nephrograms and perinephric fat stranding, which, paired with her clinical presentation, was consistent with a diagnosis of fungal pyelonephritis (Figure 1).

Figure 1.

Initial CT abdomen/pelvis demonstrating striated nephrograms and perinephric fat stranding suggestive of pyelonephritis.

The patient was started on intravenous (IV) amphotericin B deoxycholate, which, despite its nephrotoxicity, was selected over liposomal amphotericin B for its superior urinary concentration. After initiation of antifungal therapy, her flank pain slowly improved as did her pelvic symptoms. Urine cultures collected upon admission resulted on hospital day 5 and confirmed S cerevisiae but also grew Klebsiella pneumoniae. Intravenous ertapenem for the Klebsiella was started once the care team was made aware of the urine culture result. Of note, the patient did have clinical improvement prior to the initiation of ertapenem. Discussion of possible sources of S cerevisiae exposure revealed that the patient had an active sourdough starter in her home which she fed and stirred daily. She completed a 7-day course of IV amphotericin B deoxycholate for the S cerevisiae and transitioned from IV ertapenem to ciprofloxacin (based on sensitivities) for a 10-day course of treatment for the Klebsiella. She was discharged home with close follow-up.

Discussion

Saccharomyces cerevisiae is a rare, but increasingly more prevalent, cause of fungal vaginitis and disseminated disease. ¹ Our case highlights the importance of recognizing S cerevisiae as a possible pathogen, as disseminated disease has contributed to death, septicemia, and postoperative complications in infected patients.^6-8 Our patient presented with several months of recurrent vaginitis refractory to antifungal treatment. Without performing a urine or vaginal culture, we are unable to determine whether the etiology of her recurrent infection was S cerevisiae, C glabrata, or other Candida species. As S cerevisiae vaginitis presents similar to Candida infections, increasing recognition of S cerevisiae as pathogenic can allow more prompt identification, lead to more timely treatment, and mitigate morbidity and mortality.

In discussing identification of S cerevisiae, it is important to recognize risk factors associated with its pathogenicity. Immunocompromised status is considered the most important risk factor for infection, including those who are immunocompromised by disease, such as those with AIDS, history of solid organ transplant, diabetes, and malignancy or by medications or long-term antibiotic use.^1,9 In combination with immunocompromised status, infections have been linked to critical illness, central venous catheter use, intensive care unit admissions, and probiotic use. ⁹ In animal studies, CD-1 mice were able to clear nonvirulent strains of S cerevisiae, while more virulent isolates were able to persist and grow, suggesting that some strains may develop resistance to clearance by immunocompromised hosts. ¹⁰ Our patient had received several disease-modifying antirheumatic drugs (DMARDs) and non-DMARD drugs, such as methotrexate and glucocorticoids in treatment of her rheumatoid arthritis in the months leading up to her presentation. This therapy likely enabled a virulent strain of S cerevisiae to become pathogenic. In addition, while our patient’s urine culture showed heavy growth of S cerevisiae, her urinalysis results were not highly suggestive of fungal infection, which would be expected to show markers of an immune response and epithelial barrier breakdown. ¹¹ While her urinalysis showed elevated squamous epithelial cells (15/HPF), it is possible that the lack of WBC could be attributed to her preceding immunosuppressive therapy.

Saccharomyces cerevisiae remains a rare cause of clinically diagnosed vulvovaginitis. However, because it was not previously considered to be pathogenic, S cerevisiae often goes underdiagnosed or mis-diagnosed. Of those diagnosed with S cerevisiae vaginitis, many were found to be co-infected with C glabrata, another commensal vaginal pathogen. ¹¹ In addition, many patients with S cerevisiae vaginitis had a history of C glabrata vaginitis, suggesting that the latter may contribute to the pathogenicity of S cerevisiae. ¹ Infection with S cerevisiae is theorized to be the result of translocation through the gastrointestinal tract or the skin barrier. However, it is thought that S cerevisiae lacks epithelial adherence, as in vitro studies on epithelial barrier models demonstrated an inability of the organism to induce epithelial cytotoxicity or disruption of the gastrointestinal lumen. ¹² Therefore, damage of the skin and intestinal interface, whether obvious or microscopic, may be inherent to the pathogenicity of Saccharomyces. Central venous catheter use, recurrent vaginal infections, critical illness, and abdominal surgery all disrupt this barrier and have all been linked to patients with invasive disease.^8,12,13 Furthermore, probiotic supplementation with Saccharomyces species for treatment of diarrheal illness facilitates transfer of the pathogen from diet to bloodstream. ³

As its common name suggests, some cases of S cerevisiae vaginitis have been identified in those with exposure to Baker’s yeast, and it has been hypothesized that those with large exposure to S cerevisiae, perhaps through breadmaking, winemaking, or brewing, may be more prone to infection. ² Previously, there had been no known cases of immunocompetent patients developing S cerevisiae infections following overexposure. Rather, some cases have been reported of patients developing S cerevisiae vaginitis who have partners who work with Baker’s yeast, specifically a pizzeria.^1,2 This previously suggested that inoculation of the organism by a partner may carry more risk of infection than overexposure. However, our patient may be among the first to be infected following overexposure, as she frequently made sourdough bread at home and faced daily exposure through maintaining her sourdough starter.

Careful history taking is especially important in being able to identify a rare pathogen such as S cerevisiae. A careful medical history is required to identify risk factors for immunocompromising conditions, opportunities of disruption to the gastrointestinal or epithelial barrier, or additional supplements a patient may be taking, such as a probiotic or antibiotic. Including questions about sexual health and hobbies can be helpful in determining additional risk factors for S cerevisiae infection, such as overexposure or inoculation by a partner working with yeast. We believe that through thorough history taking, we were able to help our patient receive a timely diagnosis and necessary treatment.

Our case report identifies a need for S cerevisiae to be considered a fungal pathogen and the importance of a thorough history. Current studies are focused on genome wide investigations into S cerevisiae virulence and pathogenic characteristics. Further studies are needed to better identify risk factors for disease and the true epidemiology of pathogenic S cerevisiae infections.