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					CME/CE NEWSLETTER ISSUE 1
                                                                                                       CDI: Changing Epidemiology and Risk Factors
Release Date: June 30, 2008
Expiration Date: June 30, 2009




CDI: Changing Epidemiology
               and Risk Factors
FROM THE EDITOR’S DESK                                                                                                                IN THIS ISSUE . . .
Clostridium difficile is the leading cause of infectious healthcare-associated diarrhea in US                                            CME/CE Accreditation                                      2
hospitals. Not only has its incidence nearly tripled from 2000 to 2005 (Figure),1 but its severity
                                                                                                                                         The Evolving Epidemiology of CDI                          3
has also increased. It is now associated with greater morbidity and mortality and higher rates of
colectomies.2,3 It also prolongs hospitalization and results in significantly higher overall costs,                                      Pathogenesis of CDI                                       5
with one estimate of $3.2 billion attributed to CDI management in US hospitals in 2005.4
The increased severity of CDI may be related to the spread of an epidemic hypervirulent strain,                                          Risk Factors for CDI                                      6
BI/NAP1, which overproduces toxins A and B and produces an additional binary toxin.
This strain has been the main cause of outbreaks in hospitals and long-term care facilities in the
                                                                                                                                         Post Assessment and Evaluation Form                       9
US, Canada, and Europe.3,5 Recent evidence also suggests that CDIs are occurring in patients
                                                                                                                                         In Summary                                               11
with non-traditional risk factors—pregnant women, those without inpatient healthcare
exposure, or with no apparent history of recent antimicrobial use.                                                                       Post Assessment Questions                                11
Minimizing and preventing any potential CDI outbreak is possible. This requires, as a first step,
recognition by all healthcare professionals of the changing epidemiology of this disease.                                                About IMPACT–CDAD                                        12
The second step to achieve these goals is the application of infection control practices and good
antimicrobial stewardship tactics that have proven to be effective.
This series of newsletters aims to provide healthcare professionals with the latest information
on identifying, preventing, and treating CDIs.
Issue 1. CDI: Changing Epidemiology and Risk Factors
Issue 2. Preventing, Controlling, and Treating CDIs
We hope that you find these newsletters a valuable complement to your educational training
and an aid in the decision-making process for your patients.

                                                                                                                                      REFERENCES
Sincerely,
                                                                                                                                      1. McDonald LC, Owings M, Jernigan DB. Clostridium
                                                                          Figure. Rates of CDI in US hospitals, 1996–2005                difficile infection in patients discharged from US
                                                                                                                                         short-stay hospitals, 1996–2003. Emerg Infect Dis.
                                                                                                                                         2006;12:409-415.
                                Discharges per 100,000 Population




                                                                    120                                                               2. Muto CA, Pokrywka M, Shutt K, et al. A large outbreak
                                                                                                                                         of Clostridium difficile-associated disease with an
                                                                    100                                                                  unexpected proportion of deaths and colectomies at a
                                                                                   Any Listed                                            teaching hospital following increased fluoroquinolone
                                                                    80             Primary                                               use. Infect Control Hosp Epidemiol. 2005;26:273-280.
                                                                                                                                      3. Loo VG, Poirier L, Miller MA, et al. A predominantly clonal
                                                                    60                                                                   multi-institutional outbreak of Clostridium difficile-
                                                                                                                                         associated diarrhea with high morbidity and mortality.
                                                                                                                                         N Engl J Med. 2005;353:2442-2449.
Dale N. Gerding, MD                                                 40
                                                                                                                                      4. O’Brien JA, Lahue BJ, Caro JJ, Davidson DM.
Guest Editor                                                        20                                                                   The emerging infectious challenge of Clostridium
                                                                                                                                         difficile-associated disease in Massachusetts hospitals:
                                                                     0                                                                   clinical and economic consequences. Infect Control Hosp
                                                                                                                                         Epidemiol. 2007;28:1219-1227.
                                                                          1996   1997   1998 1999   2000   2001 2002 2003 2004 2005
                                                                                                                                      5. McDonald LC, Killgore GE, Thompson A, et al. An
                                                                                                    Year                                 epidemic, toxin gene-variant of Clostridium difficile.
                                                                                                                                         N Engl J Med. 2005;353:2433-2441.
                          Note: Based on Reference 1 and unpublished CDC data.




 Jointly sponsored by Center for Independent Healthcare Education, Medical Education Collaborative, and Vemco MedEd
                         Supported by an educational grant from Schering-Plough Corporation
     IMPACT–CDAD
     Implementing Multidisciplinary Prevention Approaches and Containment Tactics–C. difficile-Associated Disease


     CME/CE ACCREDITATION
     Statement of Need                                            Accreditation                                             Commercial Support
     Clostridium difficile-associated disease (CDAD) can                                                                    This activity is supported by an educational grant from
     significantly increase morbidity and mortality while         Physicians                                                Schering-Plough Corporation.
     resulting in excessive healthcare costs due to increased     This activity has been planned and implemented in
     length of stay in hospitals. In the US, the incidence and    accordance with the Essential Areas and policies of the
     severity of CDAD have increased substantially over           Accreditation Council for Continuing Medical              Disclosure Statement
     the past few years, possibly related to the spread of a      Education (ACCME) through the joint sponsorship of
     hypervirulent strain of C. difficile that is now present     Medical Education Collaborative (MEC) and Vemco           Medical Education Collaborative and Center for
     in most states.                                              MedEd. MEC is accredited by the ACCME to provide          Independent Healthcare Education require faculty,
                                                                  continuing medical education for physicians.              planners, and others who are in a position to control
     Education of all healthcare personnel can be invaluable                                                                the content of continuing education activities to
     in preventing or minimizing any potential CDAD               MEC designates this educational activity for a            disclose to the audience any real or apparent conflict of
     outbreaks. More stringent infection control policies         maximum of 1.0 AMA PRA Category 1 Credits™.               interest related to the activity. All identified conflicts
     have been shown to be an important preventative              Physicians should only claim credit commensurate          of interest are reviewed to ensure fair balance,
     measure. Recognizing patient risk factors can aid in         with the extent of their participation in the activity.   objectivity, and scientific rigor in all activities.
     early diagnosis while guidelines from the Infectious                                                                   The faculty is further required to disclose discussion of
     Diseases Society of America can serve as a basis for         For questions regarding the accreditation
                                                                                                                            off-label uses.
     selecting appropriate treatment for initial and              of this activity, please contact
     recurrent infections.                                        Medical Education Collaborative at
                                                                  (303) 420-3252 or inquire@meccme.org.                     Disclosures
     Target Audience                                              Pharmacists                                               Guest Editor of this Newsletter
     This newsletter is designed to meet the educational                Center for Independent Healthcare Education         Dale N. Gerding, MD serves on the advisory boards of
     needs of healthcare professionals who care for patients            (the Center) is accredited by the Accreditation     ViroPharma, Genzyme, Optimer, Salix, and Schering-
     in hospital settings and long-term care facilities.          Council for Pharmacy Education as a provider of           Plough. He has received grants/research support from
     Included are infectious diseases physicians, intensivists,   continuing pharmacy education. The Center has             ViroPharma, Genzyme, Optimer, and GOJO. He has
     hematology/oncology specialists, surgeons, hospital          assigned 1.0 contact hour (0.1 CEUs) of continuing        also served as a consultant and provided support
     epidemiologists, clinical pharmacists, infectious            pharmacy education credit to this activity.               related to patent licensing for ViroPharma.
     diseases pharmacists and pharmacy managers, nurse            ACPE Universal Program Number:
     managers, and nurse specialties such as critical care,       473-999-08-008-H01-P                                      Other faculty for the IMPACT–CDAD
     oncology, infection control, and geriatric.                                                                            Initiative
                                                                  Instructions for Credit                                   L. Clifford McDonald, MD does not have any relevant
                                                                                                                            financial relationships to disclose.
     Purpose Statement                                            There is no fee to participate in this educational
                                                                  activity. To receive a CME certificate or Statement of    Carlene A. Muto, MD, MS does not have any relevant
     The purpose of this newsletter is to equip healthcare                                                                  financial relationships to disclose.
                                                                  Credit, please complete the following steps:
     professionals to work together as a team to prevent
     and control the spread of C. difficile and appropriately     1. Review the CME/CE information including                Alla Paskovaty, PharmD does not have any relevant
     manage infections caused by this increasingly prevalent         the target audience, learning objectives, and          financial relationships to disclose.
     and resistant microorganism.                                    disclosures.
                                                                                                                            Anne Pohlman, RN, MS has served as a consultant for
                                                                  2. Read and review the online activity carefully.         Cardinal Health.
     Learning Objectives                                          3. Complete the post assessment, selecting the            Ron E. Polk, PharmD has served as a consultant for
     At the conclusion of this issue of the newsletter, readers      most appropriate response to each question.            Forest Laboratories, received grant/research support
     should be better able to:                                                                                              from ViroPharma, and has served on the Speakers
                                                                  4. Complete the Post Assessment and                       Bureau for Schering-Plough.
     • Describe the changing epidemiology of CDAD in the             Evaluation Form.
       hospital and community settings                                                                                      In this issue, no off-label use of antimicrobial agents
                                                                  5. Fax the Post Assessment and Evaluation Form to         is discussed.
     • Recognize risk factors associated with the increased          (908) 704-2424 or mail to Vemco MedEd, 245 US
                                                                     Highway 22, Suite 304, Bridgewater, NJ 08807.
       incidence of CDAD
                                                                     Documentation of credit will be mailed within
                                                                                                                            Planning Committee Members
                                                                     6–8 weeks following receipt of your materials.         Employees of Center for Independent Healthcare
     Author(s)                                                                                                              Education, Medical Education Collaborative, and
                                                                                                                            Vemco MedEd have no financial relationships to
     This newsletter is based on the scientific content that                                                                disclose.
     was presented at the IMPACT–CDAD meeting in
     Columbus, Ohio, on March 27, 2008. The faculty that
     participated in the live meeting (also available as on-                                                                Fee
     demand webcast at www.impactcdad.com) are listed
     on Page 12 of this newsletter. This newsletter is                                                                      There is no fee associated with this educational
     authored by the Guest Editor, Dale N. Gerding, MD,                                                                     activity.
     FACP, FIDSA, Professor of Medicine, Loyola University
     Chicago Stritch School of Medicine, Maywood, Illinois
     (Chair of the live meeting).




02
                                                                                                  CDI: Changing Epidemiology and Risk Factors


THE EVOLVING EPIDEMIOLOGY OF CDI
Historically and today, the major risk factors                                 CDI-associated mortality continues to                            6 months to 72 years (mean age, 26 years;
for CDI have been antimicrobial exposure,                                      increase with patient age. A study of CDI                        median age, 23 years). Eight of the 33 patients
hospitalization, and older age. However, recent                                patients from 12 Canadian hospitals revealed                     had no exposure to antimicrobial agents
CDI outbreaks caused by a hypervirulent strain                                 mortality rates typically <5% in patients ≤60                    while only four had close contact with a
indicate an evolving epidemiology. While use                                   years and >10% in those >80 years.2 CDI-                         patient with CDI. Clindamycin was the most
of nearly all antimicrobials continues to be                                   related death certificates nearly tripled in the                 frequently used antimicrobial (10 patients).
a major risk factor, CDI rates are increasing                                  US from 1999 (0.29 per 100,000 population)                       Fifteen patients required hospitalization
in patients of all ages in hospitals while                                     to 2002 (0.77 per 100,000 population) for all                    or an emergency room visit and 13 (39%)
community-associated disease and its severity                                  age groups, though the rate observed in men                      experienced a recurrence and required
is a growing concern.                                                          ≥90 years was extremely elevated (26.8 per                       antimicrobial therapy.
                                                                               100,000 population).3                                            Calculation of the CDI rate in the community
The Patient                                                                    Unfortunately, the peak of CDI rates has yet to                  in the Philadelphia area where this report
Older patients are still                                                       be reached in the US, and once the epidemic                      originated showed it was similar to the
at highest risk . . .                                                          does subside, it is unknown as to where CDI                      rate in a pre-paid health plan in Boston a
                                                                               rates will eventually stabilize.                                 decade earlier.5 A more recent report further
The elderly patient population remains at                                                                                                       described 10 pregnant women with severe
the greatest risk for CDI and its associated                                   Hospital and community . . .                                     CDI that resulted in 3 deaths and 3 stillborn
mortality, but CDI rates in younger patient                                    CDI has never been confined to the hospital                      births.6 The severity of CDI in so young a
populations over the past few years have                                       setting but it is now being reported in                          population is of most concern.
also increased. A study by Kralovic and                                        community populations previously at low
colleagues analyzed inpatient CDI rates in                                                                                                      These reports reflect a possibly changing
                                                                               risk. However, it is not yet clear whether the
VA medical centers throughout the US from                                                                                                       epidemiology of CDI that includes severe
                                                                               community CDI rates have increased beyond
1994 to 2004 by patient age. CDI rates were                                                                                                     disease in younger patients, some with no
                                                                               historical levels.
found to be fairly stable through most of                                                                                                       apparent recent history of antimicrobial
                                                                               A report published in 2005 identified 10                         use or of healthcare exposure. This evolving
the 1990s; however, from 2000 to 2004, they
                                                                               pregnant or peripartum women and 23                              epidemiology underscores the need for
nearly doubled regardless of the age group
                                                                               community-associated cases of CDI from                           surveillance and for clinicians to maintain
(Figure).1 Nonetheless, rates in patients over
                                                                               four states from May to June 2005.4 The age                      high suspicion of CDI and awareness of its
age 65 were two to four times higher than in
                                                                               for the non-peripartum cases ranged from                         potential severity.
the younger patients.



                                                                       Figure. CDI rates in VA hospitals by age, 1994 –20041



                                                                 20
                                1000 Unique Persons Discharged




                                                                 18
                                                                 16          <45 years
                                                                             45–65 years
                                                                 14
                                        Rate of CDI per




                                                                             >65 years
                                                                 12
                                                                 10
                                                                  8

                                                                  6
                                                                  4
                                                                  2
                                                                  0
                                                                      1994   1995   1996   1997   1998     1999     2000   2001   2002   2003     2004

                                                                                                  Federal Fiscal Year




                                                                                                                                                                                                  03
     IMPACT–CDAD
     Implementing Multidisciplinary Prevention Approaches and Containment Tactics–C. difficile-Associated Disease



     The Pathogen:                                           Several typing methods have been used              REFERENCES
                                                                                                                1.   Kralovic SM, Danko LH, Simbartl MS, Roselle GA.
                                                             to characterize clinical isolates of the
     C. difficile Etiology                                   epidemic strain of C. difficile. The BI/NAP1
                                                                                                                     Clostridium difficile infection in VA medical centers
                                                                                                                     nationwide. Proceedings of the 15th Annual Scientific
                                                             epidemic strain belongs to toxinotype III               Meeting of the Society for Healthcare Epidemiology
     CDI is caused by the production of two                                                                          of America, Los Angeles, California, April 9–12, 2005.
     toxins—toxin A (an enterotoxin that causes              (compared to toxinotype 0 for typical clinical          Abstract 284.
     secretion of fluid into the colon) and toxin            isolates), ribotype 027 (as determined by          2.   Loo VG, Poirier L, Miller MA, et al. A predominantly
                                                                                                                     clonal multi-institutional outbreak of Clostridium
     B (a cytotoxin that causes cell damage to the           PCR ribotyping), group BI (characterized                difficile-associated diarrhea with high morbidity and
     lining of the colon). C. difficile’s ability to cause   by restriction endonuclease analysis),                  mortality. N Engl J Med. 2005;353:2442-2449.

     disease depends on the presence of an intact            and North American PFGE type 1                     3.   Wysowski DK. Increase in deaths related to
                                                                                                                     enterocolitis due to Clostridium difficile in the United
     pathogenicity locus (PaLoc) that consists of            (as determined by pulsed-field gel                      States, 1999–2002. Public Health Rep. 2006;121:361-
     5 genes responsible for toxin production.7              electrophoresis).8,9 It harbors the following           362.

     Strains that lack the entire PaLoc are typically        virulence characteristics: increased toxin         4.   Centers for Disease Control and Prevention (CDC).
                                                                                                                     Severe Clostridium difficile-associated disease in
     non-pathogenic, though a few strains do                 production, presence of the binary toxin,               populations previously at low risk—four States, 2005.
     contain atypical or variant toxin A or B genes          hypersporulation, and high-level resistance             MMWR Morb Mortal Wkly Rep. 2005;54:1201-1205.

                                                             to the fluoroquinolones. Toxin production by       5.   Hirschhorn LR, Trnka Y, Onderdonk A, et al.
     and are able to cause disease. A third toxin,                                                                   Epidemiology of community-acquired Clostridium
     binary toxin, may also be present though its            these strains can be 16- to 23-fold greater than        difficile-associated diarrhea. J Infect Dis. 1994;169:127-
                                                             that by other strains,8 and hypersporulation10          133.
     clinical significance is unknown.
                                                                                                                6.   Rouphael NG, O’Donnell JA, Bhatnagar J, et al.
                                                             may increase their capacity to spread through           Clostridium difficile-associated diarrhea: an emerging
                                                             environmental contamination.                            threat to pregnant women. Am J Obstet Gynecol. 2008.
                                                                                                                     April 5.
                                                                                                                7.   Spigaglia P, Mastrantonio P. Molecular analysis of the
                                                                                                                     pathogenicity locus and polymorphism in the
                                                                                                                     putative negative regulator of toxin production (TcdC)
                                                                                                                     among Clostridium difficile clinical isolates. J Clin
                                                                                                                     Microbiol. 2002;40:3470-3475.



            ViewPoint
                                                                                                                8.   Warny M, Pepin J, Fang A, et al. Toxin production by an
                                                                                                                     emerging strain of Clostridium difficile associated with
                                                                                                                     outbreaks of severe disease in North America and
                                                                                                                     Europe. Lancet. 2005;366:1079-1084.
                                                                                                                9.   McDonald LC, Killgore GE, Thompson A, et al. An

                       Is the BI/NAP1 epidemic
                                                                                                                     epidemic, toxin gene-variant of Clostridium difficile. N
                                                                                                                     Engl J Med. 2005;353:2433-2441.


                         strain really new?
                                                                                                                10. Fawley WN, Underwood S, Freeman J, et al. Efficacy of
                                                                                                                    hospital cleaning agents and germicides against
                                                                                                                    epidemic Clostridium difficile strains. Infect Control
                                                                                                                    Hosp Epidemiol. 2007;28:920-925.
          Though the BI/NAP1 strain is getting attention in recent years as the primary reason                  11. Gerding DN. Clindamycin, cephalosporins,
                                                                                                                    fluoroquinolones, and Clostridium difficile-associated
          for the increase in CDI rates and CDI epidemics in Europe, US, and Canada, the BI                         diarrhea: this is an antimicrobial resistance problem.
          strains were first identified in the 1980s.                                                               Clin Infect Dis. 2004;35:646-648.

          Historic BI isolates (BI1 to BI5) were collected from 1984 to 1992. These strains
          produced binary toxin and contained the 18 bp deletion and a frame shift at
          position 117 in the tcdC gene that allowed for overproduction of toxin, similar to
          today’s strains.
          The main difference between these older strains and the current epidemic BI isolates
          (BI6 to BI25) is that the newer strains are almost always resistant to the newer
          fluoroquinolones (gatifloxacin and moxifloxacin) and exhibit greater resistance
          to older fluoroquinolones (ciprofloxacin and levofloxacin), whereas the older BI
          strains were susceptible to gatifloxacin and moxifloxacin.
          Evidence suggests that antimicrobial resistance may play an important role in the
          epidemiology of CDI.11 However, additional studies are needed to assess the impact
          of antimicrobial-resistant C. difficile and its ability to cause disease.




04
                                                                                     CDI: Changing Epidemiology and Risk Factors


PATHOGENESIS OF CDI                                                                                                             HOST PROTECTION FROM CDI1
Disruption of the normal intestinal flora is the precipitating antimicrobial event for CDI.                                           Normal bacterial flora in the
Anaerobic activity by the antimicrobial, once thought to be an important factor, is not                                               gastrointestinal tract can help
necessarily required for CDI—agents with poor anaerobic activity, such as some fluoroquinolones                                       prevent C. difficile colonization
and cephalosporins, are associated with CDI.1,2                                                                                       and overgrowth. Disruption
                                                                                                                                      of the bacterial flora—by
C. difficile resistance to the antimicrobial used may be important but is not always present—
                                                                                                                                      antimicrobial use for example—
ampicillin and amoxicillin use has been associated with CDI though resistance to these agents is
                                                                                                                                      can increase the risk of CDI
uncommon. Antimicrobial resistance allows the C. difficile strain to infect during antimicrobial
                                                                                                                                      during or after therapy as
therapy in the presence of the antibiotic as the intestinal flora is being disrupted, whereas both
                                                                                                                                      the normal flora tries to
resistant and susceptible strains can infect after termination of therapy when the antibiotic is
                                                                                                                                      re-establish in the intestines.
no longer present but intestinal flora has not yet re-established.
Colonization by C. difficile was thought to be a predisposing factor for CDI. However, data
compiled from four prospective studies of hospitalized patients showed that CDI in non-                                               If the normal intestinal flora
colonized patients was actually higher than in colonized patients (3.6% vs. 1.0%; P=.021).3                                           becomes disrupted, antibodies
The risk for colonized patients was also significantly less when only patients who received                                           to toxins in serum and in the
antimicrobials were analyzed (P=.024).                                                                                                intestinal mucosa can prevent
                                                                                                                                      infection if exposure to
Therefore, the latest model for CDI pathogenesis includes patient acquisition of C. difficile at
                                                                                                                                      C. difficile occurs. These
any time during hospitalization (Figure).4 Antimicrobial use by the patient disrupts the normal
                                                                                                                                      antibodies are probably
gastrointestinal flora and permits C. difficile colonization of the colon. CDI is predicted by
                                                                                                                                      first acquired during infancy
acquisition of a toxigenic strain of C. difficile and failure of the patient to mount an anamnestic
                                                                                                                                      as infants are frequently
toxin A antibody response. Asymptomatic C. difficile colonization occurs if there is an
                                                                                                                                      colonized by C. difficile but
immune response to toxin A of a toxigenic strain, or if the patient acquires a non-toxigenic
                                                                                                                                      do not become ill.
strain of C. difficile.
REFERENCES
                                                                                                                                REFERENCE
1. Muto CA, Pokrywka M, Shutt K, et al. A large outbreak of Clostridium difficile-associated disease with an unexpected
   proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect Control          1. Owens RC Jr, Donskey CJ, Gaynes RP, Loo VG,
   Hosp Epidemiol. 2005;26:273-280.                                                                                                Muto LA. Antimicrobial-associated risk factors
                                                                                                                                   for Clostridium difficile infection. Clin Infect Dis.
2. Walbrown MA, Aspinall SL, Bayliss NK, et al. Evaluation of Clostridium difficile-associated diarrhea with a drug formulary      2008;46(Suppl 1):S19-S31.
   change in preferred fluoroquinolones. J Manag Care Pharm. 2008;14:34-40.
3. Shim JK, Johnson S, Samore MH, Bliss DZ, Gerding DN. Primary symptomless colonization by Clostridium difficile and
   decreased risk of subsequent diarrhea. Lancet. 1998;351:633-636.
4. Poutanen SM, Simor AE. Clostridium difficile-associated diarrhea in adults. CMAJ. 2004;171:51-58.
                                                                                                                                 COMMON CLINICAL
                                                                                                                                 CHARACTERISTICS OF CDI1
                              Figure. Pathogenesis model for CDI4
                                                                                                                                 • Diarrhea associated with a
                                                                                                                                   history of antimicrobial use
                                                      C. difficile
                                                                                                                                   Diarrhea usually starts during
                        C. difficile
                        acquisition                   acquisition                                                                  or shortly after cessation of an
                                       Antimicrobial(s)                         Asymptomatic                                       antimicrobial regimen, but can
                                                                                  C. difficile                                     begin as much as 8 weeks following
                                                                                 colonization                                      termination of therapy.2
                                                                                                                                 • Abdominal cramps • Fever
                                                                                                                                 • Leukocytosis • Hypoalbuminemia
                                                                                   CDI
                        Hospitalization                                                                                          REFERENCES
                                                                                                                                 1. Bartlett JG, Gerding DN. Clinical recognition
                                                                                                                                    and diagnosis of Clostridium difficile infection.
                                                                                                                                    Clin Infect Dis. 2008;46(Suppl 1):S12-S18.
                            Acquisition of a toxigenic strain of C. difficile                                                    2. Mogg GA, Keighley MR, Burdon DW, et al.
                                                 and                                                                                Antibiotic-associated colitis—a review of 66
                                                                                                                                    cases. Br J Surg. 1979;66:738-742.
                  Failure to mount an anamnestic toxin A IgG antibody response

                                                                                                                                                                                           05
     IMPACT–CDAD
     Implementing Multidisciplinary Prevention Approaches and Containment Tactics–C. difficile-Associated Disease


     RISK FACTORS FOR CDI
                                              Antimicrobial-associated                           infections. Analyses of CDI outbreaks caused
                                                                                                 by a clindamycin-resistant C. difficile strain14
       Traditional                            Risk Factors                                       showed that clindamycin use increased the
       Risk Factors1–4                        The role of antimicrobials in causing CDI is       risk of CDI. Consequently, clindamycin
       • Antimicrobial use                    not a new discovery. Antimicrobial-associated      use in hospitals decreased, which resulted
                                              pseudomembranous colitis has been                  in the resolution of outbreaks, decreased
       • Prolonged stay in the hospital       reported as early as 1960.10 Prior antimicrobial   prevalence of the dominant clindamycin-
         or long-term care facility           use is undoubtedly a major risk factor             resistant epidemic strain, and decreased rates
       • Having a CDI-infected                for CDI as demonstrated by clinical and            of clindamycin-associated CDI.
         roommate in the hospital             animal studies as well as observations of a
                                              relatively low incidence of CDI in patients        Cephalosporins
       • Advanced age                         not exposed to antimicrobials. The challenge       The risk of antimicrobial-associated CDI
       • Serious underlying illness           lies in determining whether there are              increases if the C. difficile strain is resistant
         or immunosuppression                 significant differences among antimicrobials       to the antimicrobial used.14,15 C. difficile is
                                              in causing CDI, particularly among agents          universally resistant to the cephalosporins,
       • Gastrointestinal surgery             within a class.                                    so as these agents became the ‘workhorse’
         or manipulation                                                                         antimicrobials in hospitals in the 1990s,
                                              Challenges in determining
                                                                                                 they were implicated as risk factors for CDI.
                                              differences among antimicrobials in                Second- and third-generation cephalosporins,
                                              causing CDI                                        such as cefotaxime, ceftazidime, and
      Non-Traditional                         Studies attempting to draw such conclusions        cefuroxime, were strongly associated with
                                                                                                 CDI in one meta-analysis.1 Recent outbreaks
      Risk Factors                            are often limited by their design and
                                                                                                 have attributed cephalosporin use as a major
                                              confounding variables and their conclusions
      • Use of proton pump inhibitors         are often conflicting or misleading for various    risk factor,16,17 and CDI rates tend to be lower
        (PPIs)                                reasons.11 Moreover, systematic reviews and        when use of these agents is limited in response
        Results from several studies          meta-analyses comment on the poor quality          to an outbreak.4,18
        that have analyzed the role of        of available data.1,12,13                          Fluoroquinolones
        PPIs in the development of            Several patient variables can have substantial     In the early 1990s, case reports involving
        CDI have been conflicting.5–7 It      consequences when studying the association         ciprofloxacin and ofloxacin linked the
        will be important to more fully       of antimicrobials and CDI. The dose and            fluoroquinolones with CDI.19,20 More attention
        understand the mechanism              duration of antimicrobial treatment are            was paid to these agents only after many
        by which these agents can             important factors. A large proportion              CDI outbreaks in hospitals were reported.
        predispose patients to CDI—           of patients is typically given multiple            Some of these outbreaks followed formulary
        reduced protection from spore-        antimicrobials, making it challenging to           changes involving a switch to a preferred
        forming bacteria by gastric acid      attribute CDI to a particular agent. The           fluoroquinolone.
        suppression or antibiotic effect.     susceptibility of the infecting C. difficile
                                              strain can also be critical and should take        Can we differentiate among the
      • Aging of the inpatient hospital       into account that susceptibility of the            fluoroquinolones with respect to
        population8                           dominant strain may differ when comparing          their associated CDI risk?
      • Spread of the hypervirulent           different studies. Each of these variables
                                              provides a challenge when designing a study        An outbreak at the University of Pittsburgh
        strain of C. difficile 9                                                                 Medical Center during 2000–2002 was
                                              to understand the association between
        Virulence is an important                                                                associated with a formulary switch in 1998–
                                              antimicrobial use and CDI.
        determinant of disease. Greater                                                          1999 from ciprofloxacin to levofloxacin, and
        production of toxins by the BI/       Clindamycin                                        from ceftazidime to cefepime.16 Following
        NAP1 strain may be related to         Clindamycin was commonly used in hospitals         the formulary change, fluoroquinolone use
        increased incidence and severity      during the 1970s and 1980s for anaerobic           increased significantly, which preceded the
        of disease.



06
                                                                              CDI: Changing Epidemiology and Risk Factors


C. difficile outbreak by 9 months (Figure 1).       and colleagues analyzed antimicrobial use and                                                                                                                             difference in CDI rates when comparing
Cephalosporin and clindamycin use did not           CDI rates for 6 months before and 6 months                                                                                                                                each of the fluoroquinolones. The authors
change significantly. A matched case–control        after a formulary change from levofloxacin to                                                                                                                             concluded that the increased rate of CDI was
study using multivariate analysis identified        gatifloxacin as the preferred fluoroquinolone.24                                                                                                                          not attributed to the addition of gatifloxacin
levofloxacin use as an independent risk factor      Analysis of 505 cases of CDI showed an overall                                                                                                                            to the formulary.
(OR 2.0), though use of ceftriaxone (OR 5.4)        increase in CDI rates following the formulary                                                                                                                             A prospective study and case–control analysis
and clindamycin (OR 4.8) was more strongly          switch (Figure 2). CDI incidence increased                                                                                                                                attempted to identify risk factors for CDI in
associated with CDI. Other drugs identified as      significantly following the switch for patients                                                                                                                           12 Quebec hospitals.17 Analysis of over 1700
independent risk factors included H2 blockers       using fluoroquinolones in general and for                                                                                                                                 episodes of CDI revealed cephalosporin
(OR 2.0) and PPIs (OR 2.4). It is important         levofloxacin (P<.001), but not ciprofloxacin.                                                                                                                             and fluoroquinolone use as the strongest
to note that levofloxacin was the most widely       Following the switch, there was no significant                                                                                                                            risk factors for infection among the
prescribed antimicrobial during the study                                                                                                                                                                                     antimicrobials analyzed.
period—present in 59% of the cases.
Analysis of risk factors for the Quebec outbreak
                                                      LIMITATIONS OF STUDIES
revealed similar results. Fluoroquinolone             ATTEMPTING TO ASSESS
use (predominantly ciprofloxacin and                  CDI RISK WITH
                                                                                                                                                                                                                                             FACTORS THAT IMPACT
levofloxacin) was most strongly associated            ANTIMICROBIAL AGENTS
with CDI (adjusted hazard ratio of 3.44).2                                                                                                                                                                                                   STUDYING THE ASSOCIATION
                                                      • Lack of prospective, randomized                                                                                                                                                      BETWEEN ANTIMICROBIAL
However, later correspondence regarding that
study suggested that poor infection control             controlled studies                                                                                                                                                                   USE AND CDI
procedures and not fluoroquinolone use                • Failure to achieve adequate                                                                                                                                                          • Patient variables: co-morbid
contributed to the Quebec outbreak.21,22                population sizes for the                                                                                                                                                               conditions, immune status,
A report by Gaynes and colleagues showed                antimicrobials being investigated                                                                                                                                                      age, concomitant medications
how an outbreak of CDI coincided with                 • Use of study designs that lack                                                                                                                                                         (such as PPIs), length of stay
a formulary change from levofloxacin to
                                                        appropriate statistical analyses                                                                                                                                                       (ICU and hospital)
gatifloxacin in a long-term care facility and its
adjacent hospital.3 Return to levofloxacin as         • Inadequate group selection of                                                                                                                                                        • Dose and duration of
the preferred fluoroquinolone after 9 months            controls in case–control studies                                                                                                                                                       antimicrobial treatment
resulted in a corresponding decrease in CDI           • Failure to adjust for substantial                                                                                                                                                    • Susceptibility of the infecting
rates to near baseline levels. It is noteworthy
                                                        confounding variables                                                                                                                                                                  C. difficile strain
that the increase in CDI rates reported during
gatifloxacin use was the result of only 4
additional cases compared to the previous 9
months. Increased infection control efforts                                                         Figure 1. Total fluoroquinolone usage (DDD) and
at the institutions prior to the switch back                                                    incidence of nosocomial CDI cases at the University of
to levofloxacin may have also confounded                                                        Pittsburgh Medical Center, January 1996 to April 200116
any interpretation.
Biller and colleagues also reported an outbreak
                                                                           4000                                                                                                                                                                                                                                                                                               30
                                                                                                                                     Quinolone IV/PO                                                                                CDI cases
                                                                           3500

of CDI at one hospital after a formulary                                                                                                                                                                                                                                                                                                                                      25
                                                                                                                                                                                                                                                                                                                                                                                   No. of Cases




                                                                           3000
                                                              Total DDDs




change from levofloxacin to moxifloxacin.23                                2500
                                                                                                                                                                                                                                                                                                                                                                              20



However, a change back to levofloxacin did                                 2000                                                                                                                                                                                                                                                                                               15

                                                                           1500
not reduce the incidence of CDI and the                                    1000
                                                                                                                                                                                                                                                                                                                                                                              10


authors concluded that substituting one                                     500
                                                                                                                                                                                                                                                                                                                                                                              5


fluoroquinolone with another in the class is                                  0                                                                                                                                                                                                                                                                                               0
                                                                                  January ‘96


                                                                                                April ‘96


                                                                                                            July ‘96


                                                                                                                       October ‘96


                                                                                                                                      January ‘97


                                                                                                                                                    April ‘97


                                                                                                                                                                July ‘97


                                                                                                                                                                           October ‘97


                                                                                                                                                                                         January ‘98


                                                                                                                                                                                                       April ‘98


                                                                                                                                                                                                                   July ‘98


                                                                                                                                                                                                                               October ‘98


                                                                                                                                                                                                                                              January ‘99


                                                                                                                                                                                                                                                            April ‘99


                                                                                                                                                                                                                                                                        July ‘99


                                                                                                                                                                                                                                                                                   October ‘99


                                                                                                                                                                                                                                                                                                 January ‘00


                                                                                                                                                                                                                                                                                                               April ‘00


                                                                                                                                                                                                                                                                                                                           July ‘00


                                                                                                                                                                                                                                                                                                                                      October ‘00


                                                                                                                                                                                                                                                                                                                                                    January ‘01


                                                                                                                                                                                                                                                                                                                                                                  April ‘01




unlikely to control outbreaks without limiting
overall use of the fluoroquinolones.
                                                                                                                                                                                                                   Month and Year
In one of the larger studies that involved 10 VA
medical centers in northeastern US, Walbrown                Note: Arrow depicts time of formulary change.




                                                                                                                                                                                                                                                                                                                                                                                                  07
     IMPACT–CDAD
     Implementing Multidisciplinary Prevention Approaches and Containment Tactics–C. difficile-Associated Disease



     The authors differentiated risk among the                                    REFERENCES
                                                                                  1. Bignardi GE. Risk factors for Clostridium difficile             8. US Department of Health and Human Services.
     fluoroquinolones and found that use of                                          infection. J Hosp Infect. 1998;40:1-15.                             Changing demographics and the implications for
     ciprofloxacin, moxifloxacin, or gatifloxacin                                 2. Pepin J, Saheb N, Coulombe MA, et al. Emergence of
                                                                                                                                                         physicians, nurses, and other health workers. Available
                                                                                                                                                         at: http://bhpr.hrsa.gov/healthworkforce/reports/
     were significant risk factors, but that use of                                  fluoroquinolones as the predominant risk factor for
                                                                                                                                                         changedemo/default.htm. Accessed: April 17, 2008.
                                                                                     Clostridium difficile-associated diarrhea: a cohort study
     levofloxacin was not a statistically significant                                during an epidemic in Quebec. Clin Infect Dis.                  9. McDonald LC, Killgore GE, Thompson A, et al. An
     risk factor, most likely because of the small                                   2005;41:1254-1260.                                                  epidemic, toxin gene-variant of Clostridium difficile. N
                                                                                                                                                         Engl J Med. 2005;353:2433-2441.
     number of patients exposed to this agent.11,17                               3. Gaynes R, Rimland D, Killum E, et al. Outbreak of
                                                                                     Clostridium difficile infection in a long-term care facility:   10. Valberg LS, Truelove SC. Noninfective
                                                                                     association with gatifloxacin use. Clin Infect Dis.                 pseudomembranous colitis following antibiotic
     Given the preceding evidence, it may be safe to                                 2004;38:640-645.                                                    therapy. Am J Dig Dis. 1960;5:728-738.
     conclude that the use of any fluoroquinolone                                 4. Muto CA, Blank MK, Marsh JW, et al. Control of an               11. Owens RC Jr, Donskey CJ, Gaynes RP, Loo VG, Muto CA.
     can increase the risk of CDI and insufficient                                   outbreak of infection with the hypervirulent Clostridium            Antimicrobial-associated risk factors for Clostridium
                                                                                     difficile BI strain in a university hospital using a                difficile infection. Clin Infect Dis. 2008;46(Suppl
     data are available to allow any meaningful                                      comprehensive “bundle” approach. Clin Infect Dis.                   1):S19-S31.
     differentiation of risk among the agents in                                     2007;45:1266-1273.                                              12. Thomas C, Stevenson M, Riley TV. Antibiotics and
                                                                                  5. Dial S, Delaney JAC, Schneider V, Suissa S. Proton pump             hospital-acquired Clostridium difficile-associated
     this class. The increased association between                                                                                                       diarrhea: a systematic review. J Antimicrob Chemother.
                                                                                     inhibitor use and risk of community-acquired
     fluoroquinolone use and CDI may be related                                      Clostridium difficile-associated disease defined by                 2003;51:1339-1350.
     to high-level resistance by the epidemic                                        prescription for oral vancomycin therapy. CMAJ.                 13. Davey P, Brown E, Fenelon L, et al. Systematic review of
                                                                                     2006;175:745-748.                                                   antimicrobial drug prescribing in hospitals. Emerg Infect
     BI/NAP1 strains to all fluoroquinolones.                                     6. Dial S, Delaney JA, Barkun AN, Suissa S. Use of gastric             Dis. 2006;12:211-216.
     Therefore, the best strategy to reduce CDI risk                                 acid-suppressive agents and the risk of community-              14. Johnson S, Samore MH, Farrow KA, et al. Epidemics of
                                                                                     acquired Clostridium difficile-associated disease. JAMA.            diarrhea caused by a clindamycin-resistant strain of
     is not to switch from one fluoroquinolone to                                    2005;294:2989-2995.                                                 Clostridium difficile in four hospitals. N Engl J Med.
     another member in this class, but to reduce                                  7. Lowe DO, Mamdani MM, Kopp A, Low DE, Juurlink DN.                   1999;341:1645-1651.
     overall fluoroquinolone use in patients at risk                                 Proton pump inhibitors and hospitalization for                  15. Gerding DN. Clindamycin, cephalosporins,
                                                                                     Clostridium difficile-associated disease: a population-             fluoroquinolones, and Clostridium difficile-associated
     for this disease.                                                               based study. Clin Infect Dis. 2006;43:1272-1276.                    diarrhea: this is an antimicrobial resistance problem.
                                                                                                                                                         Clin Infect Dis. 2004;38:646-648.
                                                                                                                                                     16. Muto CA, Pokrywka M, Shutt K, et al. A large outbreak of
                                                                                                                                                         Clostridium difficile-associated disease with an
                           Figure 2. Evaluation of CDI following a formulary                                                                             unexpected proportion of deaths and colectomies at a
                                                                                                                                                         teaching hospital following increased fluoroquinolone
                           change in preferred fluoroquinolones24                                                                                        use. Infect Control Hosp Epidemiol. 2005;26:273-280.
                                                                                                                                                     17. Loo VG, Poirier L, Miller MA, et al. A predominantly
                                                               12                                                                                        clonal multi-institutional outbreak of Clostridium
                                                                       All Antibiotics
                                                                       All Fluoroquinolones       *                                                      difficile-associated diarrhea with high morbidity and
                                                                                                                                                         mortality. N Engl J Med. 2005;353:2442-2449.
                                  Cases/1000 Antibiotic Days




                                                               10
                                                                       Ciprofloxacin
                                                                                                                                                     18. Settle CD, Wilcox MH, Fawley WN, et al. Prospective
                                                                       Levofloxacin                                                                      study of the risk of Clostridium difficile diarrhea in
                                                                8


                                                                6
                                                                       Gatifloxacin
                                                                                           *                                                             elderly patients following treatment with cefotaxime or
                                                                                                                                                         piperacillin–tazobactam. Aliment Pharmacol Ther.
                                                                                                                                                         1998;12:1217-1223.
                                                                                                                                                     19. Dan M, Samra Z. Clostridium difficile colitis associated
                                                                4
                                                                                       *                                                                 with ofloxacin therapy. Am J Med. 1989;87:479.
                                                                                                                                                     20. Cain DB, O’Connor ME. Ciprofloxacin and
                                                                2
                                                                                                                                                         pseudomembranous colitis. Lancet. 1990;336:1509-
                                                                                                                                                         1510.
                                                                0
                                                                    Pre-switch             Post-switch                                               21. Weiss K. Poor infection control, not fluoroquinolones,
                                                                                                                                                         likely to be primary cause of Clostridium difficile-
                                *P<.0001                                                                                                                 associated diarrhea outbreaks in Quebec. Clin Infect Dis.
                                                                                                                                                         2006;42:725-727.




              ViewPoints
                                                                                                                                                     22. Beaulieu M, Thirion DJG, Williamson D, Pichette G.
                                                                                                                                                         Clostridium difficile-associated diarrhea outbreaks: the
                                                                                                                                                         name of the game is isolation and cleaning. Clin Infect
                                                                                                                                                         Dis. 2006;42:725.
                                                                                                                                                     23. Biller P, Shank B, Lind L, et al. Moxifloxacin therapy as a
                                                                                                                                                         risk factor for Clostridium difficile-associated disease
                                                                                                                                                         during an outbreak: attempts to control a new
              “... if any fluoroquinolone restriction is going to                                                                                        epidemic strain. Infect Control Hosp Epidemiol.
                                                                                                                                                         2007;28:198-201.
               contribute to control, it is likely to be restriction                                                                                 24. Walbrown MA, Aspinall SL, Bayliss NK, et al. Evaluation
               or reduced use of all fluoroquinolones.”25                                                                                                of Clostridium difficile-associated diarrhea with a drug
                                                                                                                                                         formulary change in preferred fluoroquinolones. J
                                                                                                                                                         Manag Care Pharm. 2008;14:34-40.
              “Switching from one quinolone to another is futile...                                                                                  25. Blossom DB, McDonald LC. The challenges posed by
                                                                                                                                                         reemerging Clostridium difficile infection. Clin Infect Dis.
               quinolones share equal risk for CDI, and nearly all                                                                                       2007;45:222-227.

               BI/NAP1 epidemic strains are resistant.”11

08
                                                                        CDI: Changing Epidemiology and Risk Factors

                                                                                                                         IMPACT–CDAD Newsletter Issue 1

Post Assessment and Evaluation Form                                                                             CDI: Changing Epidemiology and Risk Factors
                                                                                                                 MEC Serial # 7369 Center Serial # CV3077/1



                                                          OVERALL ACTIVITY EVALUATION

Select your professional title:               o Pharmacist        o Physician        o Other
Answer Key to Post Assessment Questions on Page 11
1.         2.        3.        4.        5.        6.        7.         8.      9.      10.


     OBJECTIVES: Upon completion of this activity, are you able to                                   Yes               Somewhat                 No
     1. Describe the changing epidemiology of
        CDAD in the hospital and community settings                                                       5        4       3         2           1
     2. Recognize risk factors associated with the
        increased incidence of CDAD                                                                       5        4       3         2           1
     If you answered “No” to any objective, please explain.




     CONTENT: Please evaluate the content of this activity.                                          Yes               Somewhat                 No
     3. This activity met my expectations.                                                                5        4       3         2          1
     4. The content was relevant to my practice.                                                          5        4       3         2          1
     5. This activity was fair and balanced.                                                              5        4       3         2          1
     6. This activity was without commercial bias.                                                        5        4       3         2          1
     7. I learned something that I can apply to my practice.                                              5        4       3         2          1
     If you answered “No” to Number 6, please explain.




     If you answered “Yes” to Number 7, how will you change your practice based on what you learned?




     8. What degree of confidence do you have that you will apply what you have learned to your practice?
     o 100% o 75% o 50% o 25% o 0%
     SCIENTIFIC CONTENT: Please rate the content.                                             Excellent       Good       Average         Fair    Poor
     9. The scientific content of this activity was                                              5             4            3             2          1
     10. The level of expertise of the author(s) of this activity was                            5             4            3             2          1




                                                                                                                                                              09
     IMPACT–CDAD
     Implementing Multidisciplinary Prevention Approaches and Containment Tactics–C. difficile-Associated Disease


       FUTURE EDUCATIONAL ACTIVITIES
       11. What types of educational activities do you prefer?
       o Live meetings o Live webcasts o Audioconferences o Podcasts o On-line archived presentations
       o CE monographs o CE supplements to journals o Newsletters o Other:
       12. What topics would be of the greatest interest and clinical use to you?




       13. What are your suggestions for improving this activity?




       14. Do you have any additional comments?




                                                              CREDIT APPLICATION
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     Address
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     E-mail address                                                                            May we contact you by e-mail?   o Yes o No
     Please check the type of credit you are requesting.   o ACPE        o AMA

     I certify that I have read this issue “CDI: Changing Epidemiology and Risk Factors”.
     Date:                                                          Time Spent:
     Signature                                                    Date

     In order to receive your CME certificate or Statement of Credit, complete the Post Assessment and Evaluation Form (Pages 9 and 10)
     including the Credit Application section and sign. Fax the Post Assessment and Evaluation Form to (908) 704-2424 or mail to
     Vemco MedEd, 245 US Highway 22, Suite 304, Bridgewater, NJ 08807. Documentation of credit will be mailed within 6–8 weeks
     following receipt of your materials.
     For questions regarding the ACPE accreditation of this activity, please contact Center for Independent Healthcare Education at
     (908) 797-1240 or info@jointsponsor.com. For questions regarding the AMA accreditation of this activity, please contact
     Medical Education Collaborative at (303) 420-3252 or inquire@meccme.org.




10
                                                               CDI: Changing Epidemiology and Risk Factors


IN SUMMARY . . .
The increasing rates of CDI since 2000 have challenged the healthcare community to keep abreast with the evolving epidemiology of this
disease and its various non-traditional risk factors. While advanced age, hospitalization, and antimicrobial use remain the major risk factors,
the spread of a hypervirulent strain may have broadened the population at risk. Controlling and preventing the spread of this pathogen require
a multidisciplinary approach involving stringent infection control tactics combined with antimicrobial stewardship—these will be discussed
in the next issue of this newsletter. As new information on the diagnosis, prevention, and management of CDI becomes available, healthcare
professionals need to stay informed to provide the best possible care for their patients.




Post Assessment Questions
1. Rates of CDI in US hospitals have            5. Which of the following may decrease the       8. Compared to earlier C. difficile strains,
   increased from 2000 to 2005 by . .              risk for CDI in a hospitalized patient?          the hypervirulent strain has all of the
                                                                                                    following characteristics except . . .
   a. 25%                                          a. Use of an antimicrobial agent with
                                                      anaerobic activity                            a. Increased resistance to the
   b. 50%
                                                                                                       fluoroquinolones
                                                   b. Colonization by C. difficile
   c. 100%
                                                                                                    b. Hypersporulation
                                                   c. Acquisition of a C. difficile strain
   d. 200%
                                                      that is resistant to the antimicrobial        c. Increased toxin production
                                                      administered
2. The group BI genotype, commonly                                                                  d. Increased resistance to vancomycin
   associated with the epidemic strain of          d. Use of an antimicrobial agent with poor
   C. difficile, was first isolated in . . .          anaerobic activity                         9. A CDI outbreak at the University of
                                                                                                    Pittsburgh Medical Center was preceded
   a. 1970s
                                                6. Recently, a number of cases of CDI               by all of the following except . . .
   b. 1980s                                        have been reported in which patient
                                                                                                    a. A formulary change from
                                                   population previously considered low
   c.1990s                                                                                             ciprofloxacin to levofloxacin
                                                   risk for this disease . . .
   d. 2000s                                                                                         b. A formulary change from
                                                   a. Peripartum women
                                                                                                       ceftazidime to cefepime
3. The epidemic BI/NAP1 strain of                  b. Agricultural workers
                                                                                                    c. An increase in clindamycin usage
   C. difficile normally produces all of           c. High school wrestlers
   the following toxins except . . .                                                                d. An increase in total
                                                   d. Patients with diabetes                           fluoroquinolone usage
   a. Toxin A
   b. Toxin B                                   7. The earliest cases of antibiotic-associated   10. Which antimicrobial use strategy is
                                                   pseudomembranous colitis were                     most likely to reduce the risk of CDI in
   c. Toxin E                                      reported around . . .                             the hospital setting?
   d. Binary toxin                                 a. 1960                                          a. Reduce overall fluoroquinolone use

4. Risk factors for CDI include all of the         b. 1984                                          b. Switch the preferred fluoroquinolone
   following except . . .                                                                              from ciprofloxacin to levofloxacin
                                                   c. 1992
   a. Antibiotic use                                                                                c. Switch the preferred fluoroquinolone
                                                   d. 1998
                                                                                                       from levofloxacin to moxifloxacin
   b. Advanced age
                                                                                                    d. Switch the preferred cephalosporin
   c. Use of statins                                                                                   from cefepime to ceftriaxone
   d. Hospitalization




                                                                                                                                                  11
IMPACT–CDAD
IMPACT– CDAD
Implementing Multidisciplinary Prevention Approaches and Containment Tactics–C. difficile-Associated Disease

About IMPACT–CDAD
IMPACT–CDAD, a year-long initiative, provides          Faculty Experts                                        On-demand Webcast:
a 360° approach to the threat posed by C. difficile.
                                                       Dale N. Gerding, MD, FACP, FIDSA                       Scientific Agenda
Available at www.impactcdad.com, this initiative       Professor of Medicine
offers educational activities to physicians,                                                                  Introduction
                                                       Loyola University Chicago Stritch School of Medicine
pharmacists, and nurses—the multidisciplinary          Maywood, Illinois                                      Dale N. Gerding, MD
team that spearheads infection prevention and                                                                 The Past, Present, and Future:
                                                       Carlene A. Muto, MD, MS
control and manages patients with CDAD.                Assistant Professor of Epidemiology and Medicine       Epidemiology of CDAD
A meeting held in Columbus, Ohio, on March 27,         University of Pittsburgh School of Medicine            Dale N. Gerding, MD
                                                       Pittsburgh, Pennsylvania
2008 was the cornerstone of this initiative.                                                                  Commentary from the Field
You can view on-demand webcast of this meeting         Ron E. Polk, PharmD, FIDSA                             L. Clifford McDonald, MD
by visiting www.impactcdad.com. Scientific             Professor of Pharmacy and Medicine
                                                       Virginia Commonwealth University                       Prevention: Patient Risk Factors
content presented at this meeting has formed the
                                                       Richmond, Virginia                                     and Infection Control
basis of these newsletters. You can expect the next
                                                                                                              Carlene A. Muto, MD, MS
issue in September 2008.                               Regional Faculty Experts                               Commentary from the Field
                                                       L. Clifford McDonald, MD, FACP                         Anne Pohlman, RN, MSN
                                                       Medical Epidemiologist
                                                       Centers for Disease Control and Prevention             Minimizing Risk through
                                                       Atlanta, Georgia                                       Antimicrobial Stewardship
                                                       Alla Paskovaty, PharmD                                 Ron E. Polk, PharmD
                                                       Clinical Coordinator in Antimicrobial Management       Addressing Today’s Crisis Through
                                                       Memorial Sloan-Kettering Cancer Center                 Modern Management Approaches
                                                       New York, New York
                                                                                                              Dale N. Gerding, MD
                                                       Anne Pohlman, RN, MSN
                                                       Critical Care Clinical Nurse Specialist
                                                                                                              Commentary from the Field
                                                       Chicago, Illinois                                      Alla Paskovaty, PharmD




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