Clostridium difficile Infections in Solid Organ Transplantation

Abstract

Clostridium difficile infection (CDI) is a common problem encountered in solid-organ transplant (SOT) recipients and the incidence is increasing. SOT recipients have an incidence of CDI that is higher than other postoperative patients, and this group has several unique risk factors that may contribute to more severe disease. Recent publications in nontransplant patients have indicated that treatment choices should be based on the severity of the illness (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). Although there continues to be a lack of well-designed, randomized, controlled trials to support the management decisions that must be made for SOT recipients with CDI, the available evidence is reviewed and summarized for these treatment guidelines. Clostridium difficile is a spore-forming, anaerobic, Gram-positive bacillus. It causes 6–25% of cases of antibiotic-associated diarrhea, up to 75% of antibiotic-associated colitis, and over 90% of cases of antibiotic-associated pseudomembranous colitis (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). C. difficile causes inflammatory diarrhea and colonic mucosal injury through production of two exotoxins, toxin A and toxin B, which trigger a cytotoxic response, neutrophilic infiltrate and cytokine release (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). The resulting inflammatory response results in the visible yellow plaques that form the characteristic pseudomembrane. This finding is less commonly seen in patients on immunosuppressive medications (2Nomura K Fujimoto Y Yamashita M et al.Absence of pseudomembranes in Clostridium difficile-associated diarrhea in patients using immunosuppression agents.Scand J Gastroenterol. 2009; 44: 74-78Crossref PubMed Scopus (60) Google Scholar). Although most strains of C. difficile produce both toxins A and B (toxigenic C. difficile), some produce only toxin B, and some do not produce any toxin. Strains that produce only toxin B can produce the same spectrum of illness as those that produce both toxins and are considered toxigenic. Strains that do not produce toxins A or B (nontoxigenic) are not capable of causing C. difficile infection (CDI). Some C. difficile strains also produce a binary toxin; however, what role this toxin plays in humans disease is not known (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). It is also important to note that 50% or more of patients in healthcare settings colonized with toxigenic C. difficile never develop CDI (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar,3Loo VG Bourgault AM Poirier L et al.Host and pathogen factors for Clostridium difficile infection and colonization.N Engl J Med. 2011; 365: 1693-1703Crossref PubMed Scopus (636) Google Scholar,4Clabots CR Johnson S Olson MM Peterson LR Gerding DN Acquisition of Clostridium difficile by hospitalized patients: Evidence for colonized new admissions as a source of infection.J Infect Dis. 1992; 166: 561-567Crossref PubMed Scopus (381) Google Scholar). Whether this proportion differs in SOT recipients is not known. The incidence and severity of CDI have increased dramatically since the year 2000 (5Loo VG Poirier L Miller MA et al.A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality.N Engl J Med. 2005; 353: 2442-2449Crossref PubMed Scopus (1689) Google Scholar). These changes in CDI epidemiology have been associated with the emergence of the North American pulsed field gel electrophoresis type 1 (NAP1)/restriction enzyme analysis type BI/PCR-ribotype 027 (NAP1/BI/027) strain of C. difficile (5Loo VG Poirier L Miller MA et al.A predominantly clonal multi-institutional outbreak of Clostridium difficile-associated diarrhea with high morbidity and mortality.N Engl J Med. 2005; 353: 2442-2449Crossref PubMed Scopus (1689) Google Scholar). CDI is a more frequently encountered problem in SOT recipients than other hospitalized populations. The incidence of CDI is estimated to be 3–19% in liver recipients, 3.5–16% in kidney recipients, 1.5–7.8% in pancreas–kidney recipients, 9% in intestinal recipients, 8–15% in heart recipients and 7–31% in lung recipients (6Boutros M Al Shaibi M Chan G et al.Clostridium difficile colitis: Increasing incidence, risk factors, and outcomes in solid organ transplant recipients.Transplantation. 2012; 93: 1051-1057Crossref PubMed Scopus (99) Google Scholar,7Riddle DJ Dubberke ER Clostridium difficile infection in solid organ transplant recipients.Curr Opin Organ Transplant. 2008; 13: 592-600Crossref PubMed Scopus (75) Google Scholar). This is higher than that seen in other hospitalized patient populations, where the incidence is typically <1% (8Zerey M Paton BL Lincourt AE Gersin KS Kercher KW Heniford BT The burden of Clostridium difficile in surgical patients in the United States.Surg Infect. 2007; 8: 557-566Crossref PubMed Scopus (139) Google Scholar,9Dubberke ER Butler AM Yokoe DS et al.Multicenter study of Clostridium difficile infection rates from 2000 to 2006.Infect Control Hosp Epidemiol. 2010; 31: 1030-1037Crossref PubMed Scopus (82) Google Scholar). Fulminant colitis develops in up to 8% of immunocompetent patients and 13% of SOT recipients with CDI (10Dallal RM Harbrecht BG Boujoukas AJ et al.Fulminant Clostridium difficile: An underappreciated and increasing cause of death and complications.Ann Surg. 2002; 235: 363-372Crossref PubMed Scopus (523) Google Scholar). The incidence of CDI in SOT recipients is highest within the first 3 months after the procedure, probably because of more frequent antimicrobial exposure, intense immunosuppression and increased exposure to the healthcare setting (6Boutros M Al Shaibi M Chan G et al.Clostridium difficile colitis: Increasing incidence, risk factors, and outcomes in solid organ transplant recipients.Transplantation. 2012; 93: 1051-1057Crossref PubMed Scopus (99) Google Scholar,10Dallal RM Harbrecht BG Boujoukas AJ et al.Fulminant Clostridium difficile: An underappreciated and increasing cause of death and complications.Ann Surg. 2002; 235: 363-372Crossref PubMed Scopus (523) Google Scholar). Late-onset CDI occurs months to years after the transplant and is usually associated with either antimicrobial exposure or intensified immunosuppression to treat graft rejection (10Dallal RM Harbrecht BG Boujoukas AJ et al.Fulminant Clostridium difficile: An underappreciated and increasing cause of death and complications.Ann Surg. 2002; 235: 363-372Crossref PubMed Scopus (523) Google Scholar). It is not known how the NAP1/BI/027 strain has the incidence and severity of CDI in SOT recipients to the exposure is the most important risk for of CDI DJ Dubberke ER Clostridium difficile infection in solid organ transplant recipients.Curr Opin Organ Transplant. 2008; 13: 592-600Crossref PubMed Scopus (75) Google Scholar). antimicrobial may to CDI, and are most frequently (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). The of antimicrobial and treatment have also been as risk factors (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). has been associated with CDI in immunocompetent with some have only of transplant recipients develop CDI have antimicrobial factors for Clostridium difficile infection.J Hosp Infect. PubMed Scopus Google Scholar). The with antimicrobial exposure in SOT recipients may be to in the and to immunosuppressive severe illness and surgical may also be an important in the of CDI in SOT The of the response is by a incidence of disease in patients are and lack Johnson S Gerding DN by Clostridium difficile and risk of PubMed Scopus Google Scholar). A response to C. difficile toxins after infection the of disease L M A of Clostridium difficile and of toxin Engl J Med. PubMed Scopus Google Scholar). The commonly associated with heart and liver may in a response and the incidence of CDI by in some patient M L et al.Clostridium difficile associated diarrhea in heart transplant the Transplant. 2007; PubMed Scopus Google Scholar). The of medications that as and is common in SOT recipients and may also as a risk for the of The of the is usually to of C. difficile and may of the form of the may also cause in the that can C. difficile to more the plays a role in CDI or is a for patients risk for CDI (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). risk factors commonly in the than years severe of a or and ER Y MA Clostridium difficile-associated disease in a setting of of risk Infect Dis. 2007; PubMed Scopus Google Scholar). SOT recipients frequently have a of these risk the of 1 are not to be risk for however, of C. difficile in this is common Johnson S Gerding DN by Clostridium difficile and risk of PubMed Scopus Google Scholar). this of C. difficile or toxins should not be to be the cause of diarrhea causes of diarrhea are exposure, or immunosuppression and are important risk factors for CDI CDI is by the of toxigenic C. difficile in the of a Recent evidence that is to C. difficile more as are ER L et of on of for Clostridium difficile 2011; PubMed Scopus Google Scholar). SOT patients may have an transplant should not The for C. difficile toxin in is the and the for toxin C. difficile is toxigenic toxin in have of because is and the of (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). of C. difficile by for toxin It is for to and is an important for to a of American of in the United available for C. difficile toxin Clostridium difficile is and 2009; PubMed Scopus Google Scholar). These a of results and are are only with to rates S of of for Clostridium difficile J Med. PubMed Scopus Google and may ER L et of on of for Clostridium difficile 2011; PubMed Scopus Google Scholar). with the the of a toxin is than and the of a and treatment decisions after an toxin should be based on the of CDI than the (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). It is important to note some only toxin These strains that produce only toxin may be a common for CDI, more are to a that new Clostridium difficile is and 2009; PubMed Scopus Google Scholar). for the of a common by both toxigenic and C. is the for of the new for the of for and however, as not toxigenic strains from toxin is for those that are (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). The of toxigenic C. difficile in has been by several to the and have been both as a as as to the of toxigenic C. difficile in of for of Clostridium difficile 2011; 13: PubMed Scopus Google Scholar). the of using for C. difficile in of with a and a toxin for of toxigenic Clostridium difficile infection.J 2010; PubMed Scopus Google of for of the with toxin and in of Clostridium difficile infection.J 2008; PubMed Scopus Google the can be as as for the of CDI, and is the most of ER L et of on of for Clostridium difficile 2011; PubMed Scopus Google Scholar). The is to of C. difficile in of what or an should be for only patients for there is a for cases where the of CDI is or the of results in a lack of diarrhea, to on and and are typically in severe colitis, in the of diarrhea (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). and a can be seen in SOT recipients with of severe colitis and These and usually organ A high of for CDI is in SOT patients with these and should be with the C. difficile available and of for C. difficile toxins should only be in patients have that is not the is should be only there is a high of for CDI and results management toxin is not indicated for cytotoxic based and of for the of toxin the of should be and in a patient with should the to CDI a lack of diarrhea The of CDI is the cause of these of CDI can be severe and severe with (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). there are to patients as CDI is typically patients with diarrhea and also with and CDI and or other with and patients with are increased risk for severe disease (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). disease with the of severe disease by as to The disease severity may should frequently and The first that should in any patient with CDI is of the antimicrobial antimicrobial on the in of immunocompetent patients to the NAP1/BI/027 (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). antimicrobial must be in to treat may to a more or an antimicrobial with less with guidelines support the on the severity of CDI (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google is for disease in both the and SOT and the colonic also in the This of has not been is by several S Peterson LR Gerding DN and Clostridium difficile-associated diarrhea or Infect Dis. PubMed Scopus Google Scholar). has also been a that the of the incidence of have not this Al MM and with in patients or treatment for Clostridium difficile-associated Control Hosp Epidemiol. 2009; PubMed Scopus Google Scholar). A of in SOT recipients is an with medications as or that of should be are to the guidelines on and in this for is the for severe response rates with to in severe disease. that of patients with severe CDI with only of patients with K an for Clostridium difficile-associated Opin 2008; A of and for the treatment of Clostridium difficile-associated diarrhea, by disease Infect Dis. 2007; PubMed Scopus Google Scholar). These same to the two antimicrobial in disease K an for Clostridium difficile-associated Opin 2008; A of and for the treatment of Clostridium difficile-associated diarrhea, by disease Infect Dis. 2007; PubMed Scopus Google Scholar). typically is in because higher have increased and J B of antibiotic-associated Clostridium difficile colitis with of two J Med. PubMed Scopus Google Scholar). This that are of than the of C. difficile MA Johnson S Gerding DN of antimicrobial toxigenic Clostridium difficile from to 2007; PubMed Scopus Google Scholar). The of for is in or from with in to not in the and should never be to treat for the treatment of CDI et for infection with Clostridium difficile in and the A controlled Infect Dis. 2012; PubMed Scopus Google Miller MA et for Clostridium difficile Engl J Med. 2011; PubMed Scopus Google Scholar). is a the United is as a in as a with high colonic and on It has been in patients with or 1 of response, rates of as with et for infection with Clostridium difficile in and the A controlled Infect Dis. 2012; PubMed Scopus Google Miller MA et for Clostridium difficile Engl J Med. 2011; PubMed Scopus Google Scholar). to and lack of in SOT has rates in patients are on for other to Miller MA K et of as for Clostridium difficile infection in for other Infect Dis. 2011; PubMed Scopus Google Scholar). cases of severe CDI with may the of by the from the of these patients, of may be in an to the that of be in the as as also support the of by in cases of A Clostridium difficile colitis: The role of J Med. 2002; PubMed Scopus Google Scholar). surgical as are role in the management of CDI is and colonic An to for the treatment of Clostridium difficile associated Surg. 2011; PubMed Scopus Google Scholar). from colonic have been of should this A Clostridium difficile colitis: The role of J Med. 2002; PubMed Scopus Google Scholar). should also be with in an to to the of infection in more severe may be treatment in patients with severe CDI and surgical may be a than of immunocompetent patients with CDI develop pseudomembranous colitis that however, is in up to 13% of SOT recipients with CDI (10Dallal RM Harbrecht BG Boujoukas AJ et al.Fulminant Clostridium difficile: An underappreciated and increasing cause of death and complications.Ann Surg. 2002; 235: 363-372Crossref PubMed Scopus (523) Google Scholar). within the first of a to to or may in patients with severe disease (10Dallal RM Harbrecht BG Boujoukas AJ et al.Fulminant Clostridium difficile: An underappreciated and increasing cause of death and complications.Ann Surg. 2002; 235: 363-372Crossref PubMed Scopus (523) Google Scholar). and may be in of surgical to and to are associated with to these should be higher risk for postoperative those for a other than CDI, and support to DS of after for Clostridium difficile Surg. 2008; PubMed Scopus Google Scholar). has been with in the treatment of is known to C. difficile is only by and A analysis of patients with severe CDI not any to with antimicrobial however, this study not for the from of to et al.Clinical outcomes of in severe Clostridium difficile associated J Infect 2007; PubMed Scopus Google Scholar). a of heart transplant recipients with a incidence of CDI in the patients with M L et al.Clostridium difficile associated diarrhea in heart transplant the Transplant. 2007; PubMed Scopus Google however, these results not this a treatment that is be to of patients with CDI (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). with have less of CDI, to have not transplant recipients Miller MA et for Clostridium difficile Engl J Med. 2011; PubMed Scopus Google Scholar). of the first should be by the disease severity as is not to the of antimicrobial to the first of treatment (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). of patients with has not been there are of with either a or of should not be or pulsed (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). for is in 1 and the after the of for is for a for a and or 3 for (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). or 3 for have outcomes and The of both the and the is that C. difficile be in of the (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). has been in the of with in to the of CDI and in patients from disease have a after treatment with or (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). have not been in trials and has not been with also the risk of from the in this (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google AE infection in a Infect. PubMed Scopus Google Scholar). in immunocompetent (1Cohen SH Gerding DN Johnson S et al.Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA).Infect Control Hosp Epidemiol. 2010; 31: 431-455Crossref PubMed Scopus (2527) Google Scholar). to of in because of risk of also to in SOT recipients the of in SOT recipients and for and have also been as in and since the C. difficile toxins in have should be the are in with since has been to with in and may in in to other A may be of to there are for the and of et of in an Clostridium difficile from a Infect Dis. 2009; PubMed Scopus Google S M Gerding DN of Clostridium difficile associated diarrhea by with and Infect Dis. 2007; 44: PubMed Scopus Google Scholar). with CDI and diarrhea should be for other causes of diarrhea, with other as or infection with or with or and causes as other or colitis may should be first that should in any patient with CDI is of the antimicrobial CDI, the of The of is for and for patients to severe CDI, is the treatment of The of is for and for patients to cases of severe CDI with the of may be increased up to may be by and may be should be considered in cases of CDI from of CDI may to of either in a or of in solid-organ transplant recipients is not is evidence to of or in the treatment of or and may be to the risk of or the of antimicrobial of CDI is a infection and and the ER Gerding DN et to Clostridium difficile in Control Hosp Epidemiol. 2008; PubMed Scopus Google Scholar). should an role on the CDI CDI is in to infection of CDI must on the risk factors for the disease in patients that C. The most risk for CDI antimicrobial exposure, to antimicrobial have in the of antimicrobial through of and antimicrobial This in the incidence of CDI by a the outbreak in L B J of a in the of on the of an of Clostridium difficile-associated disease by the Infect Dis. 2007; PubMed Scopus Google Scholar). that spectrum antimicrobial antimicrobial also in in the incidence of CDI L B J of a in the of on the of an of Clostridium difficile-associated disease by the Infect Dis. 2007; PubMed Scopus Google Scholar). that only antimicrobial as and also with in CDI other L et of antimicrobial in Infect Dis. PubMed Google Scholar). is known C. CDI can be by any antimicrobial and is that antimicrobial be with the of the disease. with C. difficile also to be of CDI after a patient is the of the or toxin in an patient not be cause for DN to and Clostridium difficile Infect Dis. 2008; PubMed Scopus Google Scholar). The of as a has also in several and there are that support the of as may be in the has not and this antimicrobial through antimicrobial the incidence of CDI risk factors for the of CDI, as or should be and are in to the of C. difficile within with CDI should be as as to the of C. should be diarrhea or a after diarrhea and ER Gerding DN et to Clostridium difficile in Control Hosp Epidemiol. 2008; PubMed Scopus Google Scholar). An of and CDI is the of after for a patient with do not C. difficile and are less than and C. difficile VG S with and is to and for of Clostridium Control Hosp Epidemiol. 2009; PubMed Scopus Google Scholar). several have to either an in CDI with or a in CDI with and ER Gerding DN et to Clostridium difficile in Control Hosp Epidemiol. 2008; PubMed Scopus Google Scholar). several of these a in to other antimicrobial is are an form of are for a patient with and should be considered where other are not CDI incidence ER Gerding DN et to Clostridium difficile in Control Hosp Epidemiol. 2008; PubMed Scopus Google Scholar). C. difficile are known to the are to and are capable of for months on within a It is not with is is to disease Whether to or a new as or to C. difficile should be to the ER Gerding DN et to Clostridium difficile in Control Hosp Epidemiol. 2008; PubMed Scopus Google of and the incidence of CDI through patient of C. difficile of are with in C. difficile after and may be for are with to CDI, the to CDI, treatment for and severe CDI with and to This is for both immunocompetent and patient populations. on CDI should on the as the of C. difficile from not to on the patient and outcomes should be as are to severe from CDI, with that treatment based on this results in to patients highest risk for CDI and to CDI are are to to CDI and to are This from a by Dubberke and in the American of 2009; and by the American Society of Society of The of this have of to as by the American of Dubberke is a for and support from and