Saccharomyces cerevisiae fungemia in a neutropenic patient treated ...

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neutropenic patient treated with. Saccharomyces boulardii. Published online: 7 March 2000. Q Springer-Verlag 2000. S. Cesaro, M.D. (И) 7 P. Chinello, M.D..
Support Care Cancer (2000) 8 : 504–505 DOI 10.1007/s005209900123

Simone Cesaro Pierangelo Chinello Lucia Rossi Luigi Zanesco

Published online: 7 March 2000 Q Springer-Verlag 2000

S. Cesaro, M.D. (Y) 7 P. Chinello, M.D. L. Rossi, M.D. 7 L. Zanesco, M.D. II Clinic of Pediatrics, Pediatric Oncology-Hematology Division, Department of Pediatrics, University of Padua, Via Giustiniani 3, I-35128 Padua, Italy e-mail: scesaro6oncopedipd.org Tel.: c39-049-8213579 Fax: 0039-049-8213510 S. Cesaro, M.D. 7 P. Chinello, M.D. L. Rossi, M.D. 7 L. Zanesco, M.D. Microbiology Service, Padua Hospital, I-35128 Padua, Italy

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Saccharomyces cerevisiae fungemia in a neutropenic patient treated with Saccharomyces boulardii

Abstract A case of Saccharomyces fungemia in an 8-month-old baby affected by acute myeloid leukemia while receiving intensive chemotherapy is reported. The patient was receiving prophylaxis treatment with Saccharomyces boulardii capsules (Codex) to prevent diarrhea, which is commonly associated with this type of chemotherapy. Fever spiked just the day after ending the chemotherapy course, and a strain of Saccharomyces cerevisiae was isolated from blood culture although the patient was also receiving antifungal prophylaxis with fluconazole. The patient recovered, though still neutropenic, with amphotericin-B and removal

of the central venous catheter. The common biochemical characteristics make it difficult to differentiate between the strain of Saccharomyces cerevisiae and that of Saccharomyces boulardii with routine methods. In other cases, authors demonstrated an identity between the two strains with a more detailed analysis. These reports raise concern about the potential side effects of such biotherapeutic agents. Key words Infection 7 Immunocompromised host 7 Saccharomyces boulardii 7 Saccharomyces cerevisiae 7 Fungemia

Introduction

Case report

Saccharomyces boulardii is an essentially nonpathogenic yeast that is administered as a biotherapeutic agent to treat diarrhea caused by Clostridium difficile or to prevent antibiotic-associated diarrhea [4, 5]. The taxonomic status of Saccharomyces boulardii is still uncertain, and originally it was described as Saccharomyces cerevisiae, a yeast used in the production of beer and baked food. Both yeasts have been associated with invasive infection or fungemia in severely immunocompromised hosts, but the common biochemical characteristics make it difficult to differentiate between the two strains [1, 3, 5–7]. We describe a case of Saccharomyces cerevisiae fungemia in an immunocompromised patient receiving prophylaxis with Saccharomyces boulardii capsules.

A 8-month-old baby affected by acute myeloid leukemia was started on an intensive treatment protocol based on high doses of idarubicin, cytarabine, and etoposide (ICE). Common side effects of this therapy are gastrointestinal symptoms such as mucositis, nausea and vomiting, and diarrhea. Codex capsules (Saccharomyces boulardii, SmithKline Beecham, Milan, Italy) were administered beforehand to preserve the nonpathogenic intestinal flora [8] and to prevent antibiotic-associated diarrhea [4, 5]. As prophylaxis, the patient was receiving cotrimoxazole (24 mg/kg three times a week), paromomycin (20 mg/kg per day in three doses), and fluconazole (6 mg/kg per day). The day after ending the second cycle of ICE, while the patient was neutropenic (WBC 1300!10 9/l, 700 neutrophils 1300!10 9/l), fever spiked to 38.8 7C and C-RP rose to 106 mg/l (normal value less than 6 mg/l). The patient was started empirically on antibiotics (ceftazidime and amikacin). As the Saccharomyces cerevisiae strain was isolated in a blood culture from the central venous catheter, amphotericin-B was added and Codex administration was withdrawn. The identification of the strain was performed with API 32 C test strips,

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(bioMèrieux, Marcy l’Etoile, France). The in vitro test confirmed susceptibility of the strain to amphotericin-B. Three days after amphotericin-B was started, the central venous catheter was removed owing to occlusion of the lumen while the patient was still febrile. Thereafter, the fever resolved though the patient was still neutropenic. A culture from the catheter tip was negative. No other cause or site of infection was found in spite of through anti-infective and daily clinical evaluation. The antifungal treatment was carried out for 14 days until complete recovery from neutropenia. The patient carried on regularly with another chemotherapy course, followed by transplantation of bone marrow from an HLA-matched sibling donor. The child is now alive and well more than 3 years after receiving the transplant.

Discussion The biotherapeutic agent Saccharomyces boulardii has so far been largely considered a safe tool for prevention of antibiotic-associated diarrhea or treatment of diarrhea due to Clostridium difficile [4]. The use of Saccharomyces boulardii capsules has been reported by several authors to be associated with infective complications, however, ranging from vaginitis and endocarditis to fungemia in immunocompromised patients [1–3]. Moreover, a case of Saccharomyces boulardii fungemia in a nonimmunocompromised patient affected by chronic obstructive pulmonary disease after enteral treatment with Saccharomyces boulardii capsules was described recently by Niault et al. [6]. A common feature of the case reports on Saccharomyces boulardii fungemia is the routine identification of the causative strain as Saccharomyces cerevisiae. In fact, routine methods, such as the use of API 32 test strips, fail to distinguish between the two strains because of their common biochemical characteristics. More detailed analysis of the strain isolated from blood and identified as Saccharomyces cerevisiae revealed the same pattern as in the Saccharomyces boulardii strain administered orally or enterally to patients. Fredenucci et al., for example, found an identical pattern on pulsed-field gel electrophoresis for the Saccharomyces strain isolated in a patient with fungemia and for that contained in the capsules [3]. In an adult patient receiv-

ing immunosuppressive therapy (steroids and cyclophosphamide) for polyarteritis nodosa, Bassetti et al. demonstrated an identical DNA-restriction pattern in the Saccharomyces strain isolated in the blood and in that administered to the patient [4]. Overall, these reports raise concern about the potential risks of giving biotherapeutic agents for fungemia [1]. In our case we did not perform any DNA analysis of the strain isolated from the blood (identified as Saccharomyces cerevisiae with API 32 test strips) and that of Saccharomyces boulardii (contained in Codex capsules), because the method was not available at our laboratory. However, the episode was interpreted as being related to the administration of Codex capsules, not only because of the difficulty of distinguishing the two strains on the basis of biochemical characteristics but also because it is so rare for Saccharomyces cerevisiae to be isolated from a blood culture. In our experience, its isolation from a blood culture is exceptional and had never occurred before, even though Saccharomyces cerevisiae commonly colonizes human mucosal surfaces. Surprisingly, the prophylaxis with fluconazole did not prevent the patient from developing Saccharomyces fungemia. In conclusion, the use of biotherapeutic agents for prophylaxis and treatment of antibiotic-associated diarrhea or for the prevention of infection by intestinal bacterial pathogens and Candida spp. in the neutropenic patient should not be considered completely safe (at least in immunosuppressed hosts). The impaired immune response and disruption of the mucosal barriers determined by chemotherapy could expose the patient to the risk of severe infection. Since no guidelines are reported on the use of biotherapeutic agents, physicians must be aware that immunocompromised patients receiving broad-spectrum antibiotic treatment and with mucositis or bowel disease can be at risk of fungemia. Acknowledgement We thank Lucia Agostini for her skilful assistance.

References 1. Aucott JN, Fayen J, Grossnickas H, Morrisey A, Ledermann MM, Salata RA (1990) Invasive infection with Saccharomyces cerevisiae: report of three cases and review. Rev Infect Dis 12 : 406–411 2. Bassetti S, Frei R, Zimmerli W (1998) Fungemia with Saccharomyces cerevisiae after treatment with Saccharomyces boulardii (abstract 14). Tenth International Symposium on Infections in the Immunocompromised Host, Davos, Switzerland (International Immunocompromised Host Society)

3. Fredenucci I, Chomarat M, Boucaud C, Flandrois JP (1998) Saccharomyces boulardii fungemia in a patient receiving Ultra-levure therapy. Clin Infect Dis 27 : 222–223 4. Hogenauer C, Hammer HF, Krejs GJ, Reisinger EC (1998) Mechanism and management of antibiotic associated diarrhea. Clin Infect Dis 27 : 702–710 5. McFarland LV, Bernasconi P (1993) Saccharomyces boulardii: a review of an innovative biotherapeutic agent. Microb Ecol Health Dis 6 : 157–171

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