Probiotic-Associated Bifidobacterium Septic Prosthetic Joint Arthritis Larry M. Bush, MD, FACP,*Þþ Kleper N.F. De Almeida, MD,Þþ Gregory Martin, MD,þ and Maria T. Perez, MD, FCAP§ Abstract: Probiotics are claimed to provide some preventative and/or therapeutic health benefits. However, many of these assertions are based on scarce or no objective data. Generally believed to be safe, few ad- verse events have been associated with their use. We report the first case of septic prosthetic joint arthritis due to Bifidobacterium species pre- sumed secondary to probiotic consumption. Key Words: probiotic, bifidobacteria, septic prosthetic joint arthritis (Infect Dis Clin Pract 2014;22: e39Ye41) T he United States currently leads in the fastest growth of probiotic sales worldwide, which includes supplements and foods. In fact, by current estimated projections, it is predicted that a doubling of this multibillion dollar market will be achieved by the year 2016. 1 Here in the United States, most probiotic products are comprised of either a single microbe or combination of species from the genera Lactobacillus, Bifidobacterium, and Saccharomyces and are distributed in the form of capsules or powder preparations. Although probiotics have been defined by the Food and Agriculture Organization of the United Nations and the World Health Organization as ‘‘live microorganisms that, when administered in adequate amounts, confer a health benefit on the host,’’ 2 the results of efficacy studies found in peer-reviewed journals, for the most part, have not proven this proposed attribute of probiotics to be indisputably true. Placebo- controlled randomized clinical trial validation of the benefits of probiotics has been reported for specific functional gastrointesti- nal disorders, such as acute infectious and antibiotic-associated diarrhea. 3 In addition, a recent meta-analysis concluded that moderate-quality evidence exists suggesting that probiotic pro- phylaxis results in a large reduction in Clostridium difficile dis- ease in persons taking antibiotics for various infections. 4 These ‘‘good’’ bacteriaYladen supplements and capsules are also often taken as treatment for a variety of conditions including allergic rhinitis, atopic dermatitis, bacterial vaginosis, lactose intolerance, and asthma. 5 However, several meta-analyses and systematic re- views have concluded that the probiotics investigated were either ineffective or lacked sufficient evidence to support manufacturer’s claims that ingestion of these microorganisms either prevented, cured, mitigated, or treated any one of a proposed array of medical conditions. 6,7 Furthermore, because most probiotics are cur- rently marketed as food ingredients or dietary supplements, the regulatory role of the US Food and Drug Administration (FDA) is limited to the labeling and safety of these products. The manu- facturers of foods and supplements are not required to obtain premarket approval of claims of efficacy or safety; hence, FDA regulations do not address the verification of any assertions of efficacy. 2 Consequently, the consumer is left alone to determine the validity of any proposed benefit offered by the manufacturer when taking the probiotic, generally with little or no objective data to rely on when making this decision. The FDA has the authority to assign ‘‘generally recognized as safe’’ (GRAS) status to probiotics. However, this status re- lates to probiotics as dietary supplements included in foods or drinks but does not necessarily mean that they have GRAS status for use in a capsule or powder format. 8 Thus, it is left to the discretion of the company that manufactures and distributes these over-the-counter probiotic capsules to decide if ingestion of the supplement places the individual at any risk when their product is taken for any of the myriad of uses advertised and stated on the label. 9 Historically, based on the widespread and growing use of probiotics, related infections and toxicities have infrequently been reported. Nonetheless, it has been suggested that caution is warranted when probiotics are used in certain pa- tient populations deemed more vulnerable to subsequent compli- cations including immunocompromised hosts, premature infants, elderly patients, and those with short bowel syndrome, central venous catheters, abnormal cardiac valves, or prosthetic material or hardware. 10 We recently cared for a woman who developed septic arthritis with Bifidobacterium species after a total hip arthroplasty, which we believe to be related to daily probiotic in- gestion that she began shortly after her orthopedic operation. CASE REPORT A 52-year-old woman underwent a total hip arthroplasty for osteoarthritis followed by a reoperation to correct a dis- crepancy in extremity length. Three years later, her metal-on- metal implant was recalled during which time she had begun to demonstrate symptoms of metallosis, requiring the need for a revision total hip replacement. Subsequently, she experienced multiple hip joint disloca- tions, culminating in a third surgical procedure whereupon her hip joint was converted to a constrained liner. Approximately 3 months after her last operation, she complained of new pain in the operated hip along with low-grade fever and malaise. On physical examination, the surgical hip wound was closed, but was found to be erythematous, warm, fluctuant, and tender. Using sterile technique, the prosthetic joint was aspirated, yielding a sample of cloudy fluid. Analysis of the fluid demonstrated 16,280 white blood cells per cubic millimeter, 97% of which were poly- morphonuclear cells. Although the Gram stain of the fluid re- vealed moderate white blood cells, no organisms were observed. However, Bifidobacterium species was isolated from the cultured synovial fluid sample. Upon further questioning, the patient re- lated that shortly after her third joint revision surgery, she began taking daily probiotic capsules, as she was encouraged by the CASE REPORT Infectious Diseases in Clinical Practice & Volume 22, Number 4, July 2014 www.infectdis.com e39 From the *Charles E. Schmidt College of Medicine, Florida Atlantic University, Boca Raton, FL, †University of Miami-Miller School of Medi- cine, Miami, FL; ‡JFK Medical Center, Palm Beach County, FL and §Inte- grated Regional Laboratory Pathology Services, JFK Medical Center, Palm Beach County, FL. Correspondence to: Larry M. Bush, MD, FACP, Comprehensive Infectious Diseases, LLC, 5503 South Congress Ave, Suite 104, Atlantis, FL 33462. E-mail: drlarry561@aol.com. The authors have no funding or conflicts of interest to disclose. Copyright * 2013 by Lippincott Williams & Wilkins ISSN: 1056-9103 Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.