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Support Care Cancer (2000) 8 : 504–505
DOI 10.1007/s005209900123                  SHORT COMMUNICATION




Simone Cesaro                             Saccharomyces cerevisiae fungemia in a
Pierangelo Chinello
Lucia Rossi                               neutropenic patient treated with
Luigi Zanesco
                                          Saccharomyces boulardii




Published online: 7 March 2000            Abstract A case of Saccharomyces         of the central venous catheter. The
Q Springer-Verlag 2000                    fungemia in an 8-month-old baby          common biochemical characteris-
                                          affected by acute myeloid leukemia       tics make it difficult to differentiate
                                          while receiving intensive chemo-         between the strain of Saccharo-
                                          therapy is reported. The patient         myces cerevisiae and that of Sac-
                                          was receiving prophylaxis treat-         charomyces boulardii with routine
                                          ment with Saccharomyces boulardii        methods. In other cases, authors
S. Cesaro, M.D. (Y) 7 P. Chinello, M.D.   capsules (Codex) to prevent diarr-       demonstrated an identity between
L. Rossi, M.D. 7 L. Zanesco, M.D.         hea, which is commonly associated        the two strains with a more de-
II Clinic of Pediatrics, Pediatric
Oncology-Hematology Division,
                                          with this type of chemotherapy.          tailed analysis. These reports raise
Department of Pediatrics,                 Fever spiked just the day after          concern about the potential side
University of Padua, Via Giustiniani 3,   ending the chemotherapy course,          effects of such biotherapeutic
I-35128 Padua, Italy                      and a strain of Saccharomyces cere-      agents.
e-mail: scesaro6oncopedipd.org            visiae was isolated from blood cul-
Tel.: c39-049-8213579
Fax: 0039-049-8213510                     ture although the patient was also       Key words Infection 7
                                          receiving antifungal prophylaxis         Immunocompromised host 7
S. Cesaro, M.D. 7 P. Chinello, M.D.
L. Rossi, M.D. 7 L. Zanesco, M.D.
                                          with fluconazole. The patient re-        Saccharomyces boulardii 7
Microbiology Service, Padua Hospital,     covered, though still neutropenic,       Saccharomyces cerevisiae 7
I-35128 Padua, Italy                      with amphotericin-B and removal          Fungemia


Introduction                                                Case report
                                                            A 8-month-old baby affected by acute myeloid leukemia was
Saccharomyces boulardii is an essentially nonpathogen-      started on an intensive treatment protocol based on high doses of
ic yeast that is administered as a biotherapeutic agent     idarubicin, cytarabine, and etoposide (ICE). Common side effects
to treat diarrhea caused by Clostridium difficile or to     of this therapy are gastrointestinal symptoms such as mucositis,
prevent antibiotic-associated diarrhea [4, 5]. The taxon-   nausea and vomiting, and diarrhea. Codex capsules (Saccharo-
                                                            myces boulardii, SmithKline Beecham, Milan, Italy) were admin-
omic status of Saccharomyces boulardii is still uncer-      istered beforehand to preserve the nonpathogenic intestinal flora
tain, and originally it was described as Saccharomyces      [8] and to prevent antibiotic-associated diarrhea [4, 5]. As pro-
cerevisiae, a yeast used in the production of beer and      phylaxis, the patient was receiving cotrimoxazole (24 mg/kg three
baked food. Both yeasts have been associated with in-       times a week), paromomycin (20 mg/kg per day in three doses),
                                                            and fluconazole (6 mg/kg per day). The day after ending the sec-
vasive infection or fungemia in severely immunocom-         ond cycle of ICE, while the patient was neutropenic (WBC
promised hosts, but the common biochemical charac-          1300!10 9/l, 700 neutrophils 1300!10 9/l), fever spiked to 38.8 7C
teristics make it difficult to differentiate between the    and C-RP rose to 106 mg/l (normal value less than 6 mg/l). The
two strains [1, 3, 5–7].                                    patient was started empirically on antibiotics (ceftazidime and
                                                            amikacin). As the Saccharomyces cerevisiae strain was isolated in
   We describe a case of Saccharomyces cerevisiae fun-      a blood culture from the central venous catheter, amphotericin-B
gemia in an immunocompromised patient receiving             was added and Codex administration was withdrawn. The identif-
prophylaxis with Saccharomyces boulardii capsules.          ication of the strain was performed with API 32 C test strips,
505



(bioMèrieux, Marcy l’Etoile, France). The in vitro test confirmed      ing immunosuppressive therapy (steroids and cyclo-
susceptibility of the strain to amphotericin-B. Three days after       phosphamide) for polyarteritis nodosa, Bassetti et al.
amphotericin-B was started, the central venous catheter was re-
moved owing to occlusion of the lumen while the patient was still      demonstrated an identical DNA-restriction pattern in
febrile. Thereafter, the fever resolved though the patient was still   the Saccharomyces strain isolated in the blood and in
neutropenic. A culture from the catheter tip was negative. No          that administered to the patient [4].
other cause or site of infection was found in spite of through             Overall, these reports raise concern about the poten-
anti-infective and daily clinical evaluation. The antifungal treat-
ment was carried out for 14 days until complete recovery from
                                                                       tial risks of giving biotherapeutic agents for fungemia
neutropenia. The patient carried on regularly with another che-        [1].
motherapy course, followed by transplantation of bone marrow               In our case we did not perform any DNA analysis of
from an HLA-matched sibling donor. The child is now alive and          the strain isolated from the blood (identified as Saccha-
well more than 3 years after receiving the transplant.                 romyces cerevisiae with API 32 test strips) and that of
                                                                       Saccharomyces boulardii (contained in Codex cap-
Discussion                                                             sules), because the method was not available at our la-
                                                                       boratory. However, the episode was interpreted as be-
The biotherapeutic agent Saccharomyces boulardii has                   ing related to the administration of Codex capsules, not
so far been largely considered a safe tool for prevention              only because of the difficulty of distinguishing the two
of antibiotic-associated diarrhea or treatment of diarr-               strains on the basis of biochemical characteristics but
hea due to Clostridium difficile [4]. The use of Saccha-               also because it is so rare for Saccharomyces cerevisiae
romyces boulardii capsules has been reported by sev-                   to be isolated from a blood culture. In our experience,
eral authors to be associated with infective complica-                 its isolation from a blood culture is exceptional and had
tions, however, ranging from vaginitis and endocarditis                never occurred before, even though Saccharomyces cer-
to fungemia in immunocompromised patients [1–3].                       evisiae commonly colonizes human mucosal surfaces.
Moreover, a case of Saccharomyces boulardii fungemia                   Surprisingly, the prophylaxis with fluconazole did not
in a nonimmunocompromised patient affected by                          prevent the patient from developing Saccharomyces
chronic obstructive pulmonary disease after enteral                    fungemia.
treatment with Saccharomyces boulardii capsules was                        In conclusion, the use of biotherapeutic agents for
described recently by Niault et al. [6].                               prophylaxis and treatment of antibiotic-associated
    A common feature of the case reports on Saccharo-                  diarrhea or for the prevention of infection by intestinal
myces boulardii fungemia is the routine identification                 bacterial pathogens and Candida spp. in the neutropen-
of the causative strain as Saccharomyces cerevisiae. In                ic patient should not be considered completely safe (at
fact, routine methods, such as the use of API 32 test                  least in immunosuppressed hosts). The impaired im-
strips, fail to distinguish between the two strains be-                mune response and disruption of the mucosal barriers
cause of their common biochemical characteristics.                     determined by chemotherapy could expose the patient
More detailed analysis of the strain isolated from blood               to the risk of severe infection. Since no guidelines are
and identified as Saccharomyces cerevisiae revealed the                reported on the use of biotherapeutic agents, physi-
same pattern as in the Saccharomyces boulardii strain                  cians must be aware that immunocompromised patients
administered orally or enterally to patients. Fredenucci               receiving broad-spectrum antibiotic treatment and with
et al., for example, found an identical pattern on                     mucositis or bowel disease can be at risk of fungemia.
pulsed-field gel electrophoresis for the Saccharomyces
strain isolated in a patient with fungemia and for that                Acknowledgement We thank Lucia Agostini for her skilful as-
contained in the capsules [3]. In an adult patient receiv-             sistance.



References
1. Aucott JN, Fayen J, Grossnickas H,          3. Fredenucci I, Chomarat M, Boucaud         6. Niault M, Thomas J, Prost F, Hojjat
   Morrisey A, Ledermann MM, Salata               C, Flandrois JP (1998) Saccharomyces         Ansari F, Kalfon P (1999) Fungemia
   RA (1990) Invasive infection with Sac-         boulardii fungemia in a patient receiv-      due to Saccharomyces species in a pa-
   charomyces cerevisiae: report of three         ing Ultra-levure therapy. Clin Infect        tient treated with enteral Saccharo-
   cases and review. Rev Infect Dis               Dis 27 : 222–223                             myces boulardii. Clin Infect Dis 28 : 930
   12 : 406–411                                4. Hogenauer C, Hammer HF, Krejs GJ,         7. Sobel JD, Vazquez J, Lynch M, Meri-
2. Bassetti S, Frei R, Zimmerli W (1998)          Reisinger EC (1998) Mechanism and            wether, Zervos MJ (1993) Vaginitis
   Fungemia with Saccharomyces cerevi-            management of antibiotic associated          due to Saccharomyces cerevisiae: epi-
   siae after treatment with Saccharo-            diarrhea. Clin Infect Dis 27 : 702–710       demiology, clinical aspect, and therapy.
   myces boulardii (abstract 14). Tenth        5. McFarland LV, Bernasconi P (1993)            Clin Infect Dis 16 : 93–99
   International Symposium on Infections          Saccharomyces boulardii: a review of      8. Vollaard EJ, Clasener HAL (1994)
   in the Immunocompromised Host, Da-             an innovative biotherapeutic agent.          Colonisation resistance. Antimicrob
   vos, Switzerland (International Immu-          Microb Ecol Health Dis 6 : 157–171           Agents Chemother 38 : 409–414
   nocompromised Host Society)

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  • 1. Support Care Cancer (2000) 8 : 504–505 DOI 10.1007/s005209900123 SHORT COMMUNICATION Simone Cesaro Saccharomyces cerevisiae fungemia in a Pierangelo Chinello Lucia Rossi neutropenic patient treated with Luigi Zanesco Saccharomyces boulardii Published online: 7 March 2000 Abstract A case of Saccharomyces of the central venous catheter. The Q Springer-Verlag 2000 fungemia in an 8-month-old baby common biochemical characteris- affected by acute myeloid leukemia tics make it difficult to differentiate while receiving intensive chemo- between the strain of Saccharo- therapy is reported. The patient myces cerevisiae and that of Sac- was receiving prophylaxis treat- charomyces boulardii with routine ment with Saccharomyces boulardii methods. In other cases, authors S. Cesaro, M.D. (Y) 7 P. Chinello, M.D. capsules (Codex) to prevent diarr- demonstrated an identity between L. Rossi, M.D. 7 L. Zanesco, M.D. hea, which is commonly associated the two strains with a more de- II Clinic of Pediatrics, Pediatric Oncology-Hematology Division, with this type of chemotherapy. tailed analysis. These reports raise Department of Pediatrics, Fever spiked just the day after concern about the potential side University of Padua, Via Giustiniani 3, ending the chemotherapy course, effects of such biotherapeutic I-35128 Padua, Italy and a strain of Saccharomyces cere- agents. e-mail: scesaro6oncopedipd.org visiae was isolated from blood cul- Tel.: c39-049-8213579 Fax: 0039-049-8213510 ture although the patient was also Key words Infection 7 receiving antifungal prophylaxis Immunocompromised host 7 S. Cesaro, M.D. 7 P. Chinello, M.D. L. Rossi, M.D. 7 L. Zanesco, M.D. with fluconazole. The patient re- Saccharomyces boulardii 7 Microbiology Service, Padua Hospital, covered, though still neutropenic, Saccharomyces cerevisiae 7 I-35128 Padua, Italy with amphotericin-B and removal Fungemia Introduction Case report A 8-month-old baby affected by acute myeloid leukemia was Saccharomyces boulardii is an essentially nonpathogen- started on an intensive treatment protocol based on high doses of ic yeast that is administered as a biotherapeutic agent idarubicin, cytarabine, and etoposide (ICE). Common side effects to treat diarrhea caused by Clostridium difficile or to of this therapy are gastrointestinal symptoms such as mucositis, prevent antibiotic-associated diarrhea [4, 5]. The taxon- nausea and vomiting, and diarrhea. Codex capsules (Saccharo- myces boulardii, SmithKline Beecham, Milan, Italy) were admin- omic status of Saccharomyces boulardii is still uncer- istered beforehand to preserve the nonpathogenic intestinal flora tain, and originally it was described as Saccharomyces [8] and to prevent antibiotic-associated diarrhea [4, 5]. As pro- cerevisiae, a yeast used in the production of beer and phylaxis, the patient was receiving cotrimoxazole (24 mg/kg three baked food. Both yeasts have been associated with in- times a week), paromomycin (20 mg/kg per day in three doses), and fluconazole (6 mg/kg per day). The day after ending the sec- vasive infection or fungemia in severely immunocom- ond cycle of ICE, while the patient was neutropenic (WBC promised hosts, but the common biochemical charac- 1300!10 9/l, 700 neutrophils 1300!10 9/l), fever spiked to 38.8 7C teristics make it difficult to differentiate between the and C-RP rose to 106 mg/l (normal value less than 6 mg/l). The two strains [1, 3, 5–7]. patient was started empirically on antibiotics (ceftazidime and amikacin). As the Saccharomyces cerevisiae strain was isolated in We describe a case of Saccharomyces cerevisiae fun- a blood culture from the central venous catheter, amphotericin-B gemia in an immunocompromised patient receiving was added and Codex administration was withdrawn. The identif- prophylaxis with Saccharomyces boulardii capsules. ication of the strain was performed with API 32 C test strips,
  • 2. 505 (bioMèrieux, Marcy l’Etoile, France). The in vitro test confirmed ing immunosuppressive therapy (steroids and cyclo- susceptibility of the strain to amphotericin-B. Three days after phosphamide) for polyarteritis nodosa, Bassetti et al. amphotericin-B was started, the central venous catheter was re- moved owing to occlusion of the lumen while the patient was still demonstrated an identical DNA-restriction pattern in febrile. Thereafter, the fever resolved though the patient was still the Saccharomyces strain isolated in the blood and in neutropenic. A culture from the catheter tip was negative. No that administered to the patient [4]. other cause or site of infection was found in spite of through Overall, these reports raise concern about the poten- anti-infective and daily clinical evaluation. The antifungal treat- ment was carried out for 14 days until complete recovery from tial risks of giving biotherapeutic agents for fungemia neutropenia. The patient carried on regularly with another che- [1]. motherapy course, followed by transplantation of bone marrow In our case we did not perform any DNA analysis of from an HLA-matched sibling donor. The child is now alive and the strain isolated from the blood (identified as Saccha- well more than 3 years after receiving the transplant. romyces cerevisiae with API 32 test strips) and that of Saccharomyces boulardii (contained in Codex cap- Discussion sules), because the method was not available at our la- boratory. However, the episode was interpreted as be- The biotherapeutic agent Saccharomyces boulardii has ing related to the administration of Codex capsules, not so far been largely considered a safe tool for prevention only because of the difficulty of distinguishing the two of antibiotic-associated diarrhea or treatment of diarr- strains on the basis of biochemical characteristics but hea due to Clostridium difficile [4]. The use of Saccha- also because it is so rare for Saccharomyces cerevisiae romyces boulardii capsules has been reported by sev- to be isolated from a blood culture. In our experience, eral authors to be associated with infective complica- its isolation from a blood culture is exceptional and had tions, however, ranging from vaginitis and endocarditis never occurred before, even though Saccharomyces cer- to fungemia in immunocompromised patients [1–3]. evisiae commonly colonizes human mucosal surfaces. Moreover, a case of Saccharomyces boulardii fungemia Surprisingly, the prophylaxis with fluconazole did not in a nonimmunocompromised patient affected by prevent the patient from developing Saccharomyces chronic obstructive pulmonary disease after enteral fungemia. treatment with Saccharomyces boulardii capsules was In conclusion, the use of biotherapeutic agents for described recently by Niault et al. [6]. prophylaxis and treatment of antibiotic-associated A common feature of the case reports on Saccharo- diarrhea or for the prevention of infection by intestinal myces boulardii fungemia is the routine identification bacterial pathogens and Candida spp. in the neutropen- of the causative strain as Saccharomyces cerevisiae. In ic patient should not be considered completely safe (at fact, routine methods, such as the use of API 32 test least in immunosuppressed hosts). The impaired im- strips, fail to distinguish between the two strains be- mune response and disruption of the mucosal barriers cause of their common biochemical characteristics. determined by chemotherapy could expose the patient More detailed analysis of the strain isolated from blood to the risk of severe infection. Since no guidelines are and identified as Saccharomyces cerevisiae revealed the reported on the use of biotherapeutic agents, physi- same pattern as in the Saccharomyces boulardii strain cians must be aware that immunocompromised patients administered orally or enterally to patients. Fredenucci receiving broad-spectrum antibiotic treatment and with et al., for example, found an identical pattern on mucositis or bowel disease can be at risk of fungemia. pulsed-field gel electrophoresis for the Saccharomyces strain isolated in a patient with fungemia and for that Acknowledgement We thank Lucia Agostini for her skilful as- contained in the capsules [3]. In an adult patient receiv- sistance. References 1. Aucott JN, Fayen J, Grossnickas H, 3. Fredenucci I, Chomarat M, Boucaud 6. Niault M, Thomas J, Prost F, Hojjat Morrisey A, Ledermann MM, Salata C, Flandrois JP (1998) Saccharomyces Ansari F, Kalfon P (1999) Fungemia RA (1990) Invasive infection with Sac- boulardii fungemia in a patient receiv- due to Saccharomyces species in a pa- charomyces cerevisiae: report of three ing Ultra-levure therapy. Clin Infect tient treated with enteral Saccharo- cases and review. Rev Infect Dis Dis 27 : 222–223 myces boulardii. Clin Infect Dis 28 : 930 12 : 406–411 4. Hogenauer C, Hammer HF, Krejs GJ, 7. Sobel JD, Vazquez J, Lynch M, Meri- 2. Bassetti S, Frei R, Zimmerli W (1998) Reisinger EC (1998) Mechanism and wether, Zervos MJ (1993) Vaginitis Fungemia with Saccharomyces cerevi- management of antibiotic associated due to Saccharomyces cerevisiae: epi- siae after treatment with Saccharo- diarrhea. Clin Infect Dis 27 : 702–710 demiology, clinical aspect, and therapy. myces boulardii (abstract 14). Tenth 5. McFarland LV, Bernasconi P (1993) Clin Infect Dis 16 : 93–99 International Symposium on Infections Saccharomyces boulardii: a review of 8. Vollaard EJ, Clasener HAL (1994) in the Immunocompromised Host, Da- an innovative biotherapeutic agent. Colonisation resistance. Antimicrob vos, Switzerland (International Immu- Microb Ecol Health Dis 6 : 157–171 Agents Chemother 38 : 409–414 nocompromised Host Society)