Pathogenesis and ToxinsNon-toxigenic Clostridium sordellii: Clinical and microbiological features of a case of cholangitis-associated bacteremia
Introduction
Clostridial species have long been identified as causative agents of human disease, but the importance of these toxigenic bacteria has gained recent attention due to the emergence and spread of pathogens like Clostridium difficile [1] and its close relative Clostridium sordellii [2], [3]. C. sordellii is a sporulating, anaerobic, gram positive bacterium that is often isolated from soil samples and sometimes causes highly lethal human infections [4]. This bacterium is known to cause gynecological infections following childbirth or abortion [5], [6], necrotizing soft tissue infections associated with the injection use of contaminated heroin [7], [8], [9], and post-operative infections complicating musculoskeletal transplants performed with contaminated graft material [10]. The incidence of C. sordellii infections is unclear, but an increasing number of cases has been reported over the past 10 years [11], [12], [13], [14], [15]. A recent report found that 1 in 200 deaths in women of reproductive age were associated with clostridial toxic shock, due to either C. sordellii or another clostridium, C. perfringens [3].
Perhaps two thirds of C. sordellii infections are associated with a clinically unique toxic shock syndrome (TSS), with mortalities exceeding 70% [4], [16]. However, this percentage may be overestimated, since it is likely that the most dramatic clinical cases (especially those associated with TSS) are reported, while infections that run a more benign course or have a positive outcome remain unpublished.
The pathogenesis of C. sordellii TSS has been a focus of recent studies [16], [17]. Though incompletely understood, the occurrence of TSS depends on the expression of one or both of the large glucosylating cytotoxins (TcsH and TcsL) of C. sordellii, which share structural and functional similarity to the large glucosylating cytotoxins of C. difficile (TcdA and TcdB, respectively). Both TcsH and TcsL intoxicate epithelial and endothelial cells by inactivating small GTPase proteins that are involved in maintaining cytoskeletal integrity [18], [19], [20]. Recent data suggest that C. sordellii TcsL is important for the development of TSS [17], [19], though almost nothing is known about the participation of TcsH.
Herein we present a case of invasive C. sordellii infection that was associated with neither TSS nor death. Molecular analyses demonstrated that this clinical strain lacked the tcsH and tcsL genes encoding TcsH and TcsL, respectively. This strain also lacked virulence in a mouse model of peritonitis. These data provide correlative support for the hypothesis that hemorrhagic and lethal toxins are important virulence determinants of the highly lethal and treatment-refractory TSS caused by C. sordellii. Knowledge gained from non-lethal C. sordellii infections such as this one provides new information regarding the pathogenesis of severe infections caused by this organism.
Section snippets
Institutional approval
This case report was reviewed and approved by the University of Michigan Institutional Review Board. Animals were treated according to National Institutes of Health guidelines for the use of experimental animals with the approval of the University of Michigan Committee for the Use and Care of Animals.
Animals
Eight-to-ten week old, female C57BL/6J mice were purchased from The Jackson Laboratory (Bar Harbor, ME).
Bacterial strains
C. sordellii strain HH-310 was isolated from anaerobic culture of a patient’s blood sample
Case report
An 81 year-old female presented with the acute onset of stabbing abdominal pain that emanated from her epigastrium and radiated to her right upper abdominal quadrant and back. This was initially intermittent but became continuous and was exacerbated with inspiration. It was associated with fever and chills. The patient had a history of hypertension, diabetes mellitus, coronary artery disease, portal vein thrombosis and a congenital disorder causing non-obstructive dilation of intrahepatic bile
Discussion
C. sordellii is an emerging pathogen associated with highly lethal bloodstream and soft tissue infections, particularly in young women following childbirth, abortion, or cervical procedures and also in injection drug users [3], [4]. Herein we describe a non-lethal case of invasive C. sordellii infection in the setting of polymicrobial bacterial cholangitis. This case was not associated with a stereotypical C. sordellii TSS and the patient had a favorable clinical outcome. Her initial sepsis
Acknowledgments
This work was supported by National Institutes of Health grant HL078727 (D.M.A.) and UL1RR024986 (S.T.W.) from the National Center for Research Resources. The non-animal research was supported by a Doris Duke Charitable Foundation Clinical Scientist Development Award (D.M.A.).
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