Name of Presentation

Name of Presentation

Use of Cultured Yogurt Causing Septic Shock and Intra-abdominal Abscesses Justin Fernandez, M.D., Maha Assi, M.D., M.P.H. KU School of Medicine-Wichita 1 DISCLOSURE I have no actual or potential conflict of interest in relation to this topic/presentation. 2 INTRODUCTION Brewers/bakers yeast, yogurts Probiotic live, beneficial Lactobacillus

http://www.nutraingredients.com, http://www.art.com/ S. cerevisiae 3 PRODUCT CONTENTS Activia yogurt Bifidobacterium - Dannon lactis COST $0.70 / cup 100 million / gram

Culturelle capsules Lactobacillus rhamnosus $1.06 / capsule 10 billion / capsule Jarrow capsules Saccharomyces boulardi $0.20 / capsule 5 billion / capsule

4 Patient 1: 65 M STEM CELL Abdominal pain / fever Indwelling catheter Yogurt ingestion CDAD Previous bowel surgery Septic Shock / Respiratory failure

Lactobacillus Patient 3: 66 F LIVER

Abdominal abscess S. cerevisiae Patient 2: 55 F KIDNEY 5

PRESENTATION Asymptomatic <---------------> Septicemia Pneumonia Abscess Endocarditis 6 Patients with fungemia caused by S. cerevisiae (60): ICU 60% Enteral/parenteral nutrition 71% Use of probiotics 26% Saccharomyces cerevisiae Fungemia: An Emerging Infectious Disease, Munoz et al. Madrid, Spain, 2003 7 Patients with invasive Saccharomyces infections (91):

Central venous catheter 95% Previous antibiotics 87% Digestive tract disease 64% Invasive Saccharomyces Infection: A Comprehensive Review, Enache et al. Paris, France, 2005 8 Patients with Lactobacillus bacteremia (89): Fatal conditions 80-90% Previous antibiotic use 52%

Mechanically ventilated 45% Lactobacillus Bacteremia, Clinical Significance, and Patient Outcome, Salminen et al. Tampere, Finland, 2004 9 Patients with Lactobacillus bacteremia: Lactobacillus Bacteremia and Endocarditis: Review of 45 Cases, Rola et al. Cleveland, Ohio, 1997 10 WHY HAPPENING?

Higher population at risk Immunosuppressive drugs Broad spectrum antiobiotics Parenteral nutrition 11 WHY RELEVANT? Ubiquitous An Emerging Infectious Disease 50 40 30 20 10 0 1970-1980

Reported Cases 1981-1990 1991-2004 Saccharomyces cerevisiae Fungemia: An Emerging Infectious Disease, Munoz et al. Madrid, Spain 12 OFFICIAL RECOMMENDATION (IDSA) Saccharomyces + po Vancomycin C. diff recurrences Potential fungemia if immunocompromised Avoid if critically ill No compelling evidence with other probiotics http://www.idsociety.org 13

SAFE? ORGANIZATION ANTIBIOTIC ASSOCIATED DIARRHEA CLOSTRIDIUM DIFFICILE ASSOCATED DIARRHEA (CDAD) ACP (Dr. Thomas Fekete 2013) Yes with caution UK Health Protection Agency

Does not recommend use Society for Healthcare Epidemiology of America Does not recommend use Infectious Diseases Society of America Does not recommend use World Gastroenterology Organization Strong evidence Safe to use

14 LOCAL and NATIONAL HOSPITAL LOCATION GENERAL PRACTICE Via Christi Medical Center Wichita, KS <50% of time Wesley Medical Center

Wichita, KS 50% KU Medical Center Kansas City, KS <50% (last ditch effort) UCLA Medical Center Santa Monica, CA Very common, continued in house if pt taking as outpatient

New York Presbyterian Medical Center New York, NY make probiotics a habit, caution if immunocompromised 15 CONCLUSION BENEFIT should clearly outweigh RISK HOWEVERIF Immunocompromised Bowel compromise Comorbidities Central Venous Catheter

THEN CAUTION!!! 16 NO INTERVENTION IS BENIGN 17 REFERENCES 1. Stein PD, Folkens AT, Hruska KA. Saccharomyces fungemia. Chest 1970; 58:1735 2. Saccharomyces boulardii in critically ill patients. Intensive Care Med 2002; 28:797801. , Piarroux R, Millon L, Bardonnet K, Vagner O, Koenig H. Are live saccharomyces yeasts harmful to patients? Lancet 1999; 353:18512 Rees JR, Pinner RW, Hajjeh RA, Brandt ME, Reingold AL 3. The epidemiological features of invasive mycotic infections in the San Francisco Bay Area, 19921993: results of population-based laboratory active surveillance. Clin Infect Dis 1998; 27:113847. Stein PD, Folkens AT, Hruska KA. Saccharomyces fungemia. Chest 1970; 58:1735 4. Seven cases of fungemia with Saccharomyces boulardii in critically ill patients. Intensive Care Med 2002; 28:797801. , Piarroux R, Millon L, Bardonnet K, Vagner O, Koenig H. 5. Are live saccharomyces yeasts harmful to patients? Lancet 1999; 353:18512 6. Rees JR, Pinner RW, Hajjeh RA, Brandt ME, Reingold AL. The epidemiological features of invasive mycotic infections in the San Francisco Bay Area, 1992

1993: results of population-based laboratory active surveillance. Clin Infect Dis 1998; 27:113847. 7. Hennequin C, Kauffmann-Lacroix C, Jobert A, et al. Possible role of catheters in Saccharomyces boulardii fungemia. Eur J Clin Microbiol Infect Dis 2000; 19:1620 8. Piarroux R, Millon L, Bardonnet K, Vagner O, Koenig H. Are live saccharomyces yeasts harmful to patients? Lancet 1999; 353:18512. 9. Perapoch J, Planes AM, Querol A, et al. Fungemia with Saccharomyces cerevisiae in two newborns, only one of whom had been treated with ultra-levura. Eur J Clin Microbiol Infect Dis 2000; 19:46870 10. Hennequin C, Kauffmann-Lacroix C, Jobert A, et al. Possible role of catheters in Saccharomyces boulardii fungemia. Eur J Clin Microbiol Infect Dis 2000; 19:1620 18 11. Saccharomyces cerevisiae Fungemia: An Emerging Infectious Disease Patricia Mun oz,1 Emilio Bouza,1 Manuel Cuenca-Estrella,3 Jose Mara Eiros,1 Maria Jesus Pe rez,2 Mar Sanchez-Somolinos,1 Cristina Rincon,2 Javier Hortal,2 and Teresa Pelaez1 Departments of 1Clinical Microbiology and Infectious Diseases and 2Heart Surgery, Hospital General Universitario Gregorio Maranon,Universidad Complutense, and 3Centro Nacional de Microbiologa, Instituto de Salud Carlos III, Madrid, Spain 12. Salonen JH, Richardson MD, Gallacher K, et al. Fungal colonization of haematological patients receiving cytotoxic chemotherapy: emergence emergenceof azole-resistant Saccharomyces cerevisiae. J Hosp Infect 2000; 45:293301 13. Jensen DP, Smith DL. Fever of unknown origin secondary to brewers yeast ingestion. Arch Intern Med 1976; 136:3323.

14. McCusker JH, Clemons KV, Stevens DA, Davis RW. Saccharomyces cerevisiae virulence phenotype as determined with CD-1 mice is associated with the ability to grow at 42 degrees C and form pseudohyphae. Infect Immun 1994; 62:544755 15. Wheeler RT, Kupiec M, Magnelli P, Abeijon C, Fink GR. A Saccharomyces cerevisiae mutant with increased virulence. Proc Natl Acad Sci U S A 2003; 100:276670 16. Invasive Saccharomyces Infection: A Comprehensive Review Adela Enache-Angoulvant1,2 and Christophe Hennequin1,2 1Laboratoire de Parasitologie, Faculte de Medecine Pierre et Marie Curie, Universite Pierre et Marie Curie, and 2Service de Parasitologie, Hopital Tenon, Paris, France 17. Eng RHK, Drehmel R, Smith SM, Goldstein EJC. Saccharo- myces cerevisiae infections in man. Sabouraudia 1984; 22: 4037 18. J. S. Williams, G. J. Mufti,* S. Powell, J. R. Salisbury and E. M. Higgins Departments of Dermatology, *Haematological Medicine, and Histopathology, Kings College Hospital, London, UK 19. Two Cases of Vaginitis Caused by Itraconazole-Resistant Saccharomyces cerevisiae and a Review of Recently Published Studies Vincenzo Savini Chiara Catavitello Assunta Manna Marzia Talia Fabio Febbo Andrea Balbinot Francesco DAntonio Giovanni Di Bonaventura Claudio Celentano Marco Liberati Raffaele Piccolomini Domenico DAntonio 19 20. Rosa de Llanos a, Amparo Querol a, Javier Peman b, Miguel Gobernado b, Maria Teresa Fernandez-Espinar a, a Departamento de Biotecnologia, a Departamento de Biotecnologia, Instituto de Agroquimica y Tecnologia de los Alimentos (CSIC), 46100 Burjassot, Valencia, Spain b Servicio de Microbiologia, Hospital Universitario La

Fe, Valencia, Spain Received 2 December 2005; received in revised form 1 March 2006; accepted 25 April 2006 21. Guslandi M., G. Mezzi, M. Sorghi, and P. A. Testoni. 2000. Saccharomyces boulardii in maintenance treatment of Crohns disease. Dig. Dis. Sci. 68: 5998 6004 22. Hennequin, C., C. Kauffmann-Lacroix, A. Jobert, J. P. Viard, C. Ricour, J. L. Jacquemin, and P. Berche. 2000. Possible role of catheters in Saccharomyces boulardii fungemia. Eur. J. Clin. Microbiol. Infect. Dis. 19:1620 23. Outbreak of Saccharomyces cerevisiae Subtype boulardii Fungemia in Patients Neighboring Those Treated with a Probiotic Preparation of the Organism Marco Cassone,1* Pietro Serra,1 Francesca Mondello,2 Antonietta Girolamo,2 Sandro Scafetti,3 Eleonora Pistella,1 and Mario Venditti1 III Clinica Medica, Dipartimento di Medicina Clinica, Universita` degli Studi di Roma La Sapienza,1 Dipartimento di Malattie infettive, parassitarie ed immunomediate, Istituto Superiore di Sanita`,2 and Reparto di Rianimazione e Terapia Intensiva, Ospedale Sandro Pertini,3 Rome, Italy 24. Stein P, Folkens A, Hruska K. Saccharomyces fungemia. Chest 1970; 58:1735 25. Saccharomyces cerevisiae Fungemia After Saccharomyces boulardii Treatment in Immunocompromised Patients Riquelme, Arnoldo J. M.D.; Calvo, Mario A. M.D.; Guzman, Ana M. M.D.; Depix, Maria S.; Garcia, Patricia M.D.; Prez, Carlos M.D.; Arrese, Marco M.D.; Abarca, Jaime A. M.D. 26. Castagliuolo I, LaMont JT, Nikulasson ST, Pothoulakis C. Saccharomyces boulardii pro- tease inhibits Clostridium difficile toxin A effects in the rat ileum. Infect Immun 1996; 64: 522532 27. Castagliuolo I, LaMont JT, Nikulasson ST, Pothoulakis C. Saccharomyces boulardii pro- tease inhibits Clostridium difficile toxin A effects in the rat ileum. Infect Immun 1996; 64: 522532 20

28. Saccharomyces cerevisiae Fungemia: An Adverse Effect of Saccharomyces boulardii Probiotic Administration Raoul Herbrecht and Yasmine Nivoix Department of Hematology and Oncology and Pharmacy, Hopital de Hautepierre, Strasbourg, France 29. Shadi Hamoud MD1, Zohar Keidar MD2 and Tony Hayek MD1 Departments of 1Internal Medicine E and 2Nuclear Medicine, Rambam Medical Center, Haifa, Israel 30. Aguirre M, Collins MD. Lactic acid bacteria and human clinical infection. J Appl Bacteriol 1993;75:95-107 31. Lactobacillus Bacteremia, Clinical Significance, and Patient Outcome, with Special Focus on Probiotic L. Rhamnosus GG Minna K. Salminen1, Hilpi Rautelin2, Soile Tynkkynen3, Tuija Poussa4, Maija Saxelin3, Ville Valtonen1, and Asko Jrvinen1 32. Probiotics in the prevention of antibiotic-associated diarrhoea and Clostridium difficile infection Mary Hickson 33. Lactobacillus Bacteremia and Endocarditis: Review of 45 Cases Rola N. Husni, Steven M. Gordon, John A. Washington, From the Departments of Infectious Diseases and Clinical Pathology, and David L. Longworth The Cleveland Clinic Foundation, Cleveland, Ohio 34. Probiotics for the Prevention and Treatment of Antibiotic-Associated DiarrheaA Systematic Review and Meta-analysis FREESusanne Hempel, PhD; Sydne J. Newberry, PhD; Alicia R. Maher, MD; Zhen Wang, PhD; Jeremy N. V. Miles, PhD; Roberta Shanman, MS; Breanne Johnsen, BS; Paul G. Shekelle, MD, PhD 35. http://www.idsociety.org 21

QUESTIONS 22

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