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

Brewer’s/baker’s yeast, yogurts Probiotic – live, beneficial 3 INTRODUCTION LactobacillusS. cerevisiae

PRODUCTCONTENTSCOST Activia yogurt - Dannon Bifidobacterium lactis 100 million / gram $0.70 / cup Culturelle capsules Lactobacillus rhamnosus 10 billion / capsule $1.06 / capsule Jarrow capsules Saccharomyces boulardi 5 billion / capsule $0.20 / capsule 4

Patient 1: 65 M STEM CELL Patient 2: 55 F KIDNEY Patient 3: 66 F LIVER Abdominal pain / fever ✔✔✔ Indwelling catheter ✔✔✔ Yogurt ingestion ✔✔✔ CDAD ✔ Previous bowel surgery ✔✔ Septic Shock / Respiratory failure ✔ Abdominal abscess ✔✔ S. cerevisiae ✔✔ Lactobacillus ✔ 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% 7 Saccharomyces cerevisiae Fungemia: An Emerging Infectious Disease, Munoz et al. Madrid, Spain, 2003

Patients with invasive Saccharomyces infections (91): Central venous catheter – 95% Previous antibiotics – 87% Digestive tract disease – 64% 8 Invasive Saccharomyces Infection: A Comprehensive Review, Enache et al. Paris, France, 2005

9 Lactobacillus Bacteremia, Clinical Significance, and Patient Outcome, Salminen et al. Tampere, Finland, 2004 Patients with Lactobacillus bacteremia (89): Fatal conditions – 80-90% Previous antibiotic use – 52% Mechanically ventilated – 45%

Lactobacillus Bacteremia and Endocarditis: Review of 45 Cases, Rola et al. Cleveland, Ohio, Patients with Lactobacillus bacteremia:

WHY HAPPENING? Higher population at risk Immunosuppressive drugs Broad spectrum antiobiotics Parenteral nutrition 11

WHY RELEVANT? Ubiquitous “An Emerging Infectious Disease” 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 13

SAFE? ORGANIZATIONA NTIBIOTIC A SSOCIATED D IARRHEA C LOSTRIDIUM DIFFICILE A SSOCATED D IARRHEA (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

HOSPITALLOCATIONGENERAL PRACTICE Via Christi Medical CenterWichita, KS<50% of time Wesley Medical CenterWichita, KS50% KU Medical CenterKansas City, KS<50% (“last ditch effort”) UCLA Medical CenterSanta Monica, CAVery 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 LOCAL and NATIONAL

CONCLUSION BENEFIT should clearly outweigh RISK HOWEVER…IF Immunocompromised Bowel compromise Comorbidities Central Venous Catheter THEN… CAUTION!!! 16

NO INTERVENTION IS BENIGN 17

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20. Rosa de Llanos a, Amparo Querol a, Javier Pemán b, Miguel Gobernado b, María Teresa Fernández-Espinar a, a Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de los Alimentos (CSIC), Burjassot, Valencia, Spain b Servicio de Microbiología, Hospital Universitario La Fe, Valencia, Spain Received 2 December 2005; received in revised form 1 March 2006; accepted 25 April Guslandi M., G. Mezzi, M. Sorghi, and P. A. Testoni Saccharomyces boulardii in maintenance treatment of Crohn’s disease. Dig. Dis. Sci. 68: 5998– Hennequin, C., C. Kauffmann-Lacroix, A. Jobert, J. P. Viard, C. Ricour, J. L. Jacquemin, and P. Berche Possible role of catheters in Saccharomyces boulardii fungemia. Eur. J. Clin. Microbiol. Infect. Dis. 19:16– 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; 58:173–5 25. Saccharomyces cerevisiae Fungemia After Saccharomyces boulardii Treatment in Immunocompromised Patients Riquelme, Arnoldo J. M.D.; Calvo, Mario A. M.D.; Guzmán, Ana M. M.D.; Depix, María S.; García, Patricia M.D.; Pérez, 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: 5225– 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: 5225–32 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, Hoˆpital 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: 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 Järvinen1 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

QUESTIONS 22

MECHANISM 23