Tres Difficile

1
Tres Difficile

• Stephen M. Brecher PhDDirector of Microbiology
  VA Boston Health Care SystemWest Roxbury,
  Massachusetts

2
The opinions expressed in this presentation are
those of the presenter and do not necessarily
represent the views of the Veterans Affairs
Health-Care System
3
The Dominant Species

• The human body has 1013 human cells and a
  minimum of 1014 bacterial cells

4
Overview

• Case reports
• Historical perspective
• Organism key properties

• Changing epidemiology
• Disease
• Diagnosis
• Treatment
• Infection control

5
Case Study 1

• 60 yo male admitted to hospital for community
  acquired pneumonia, treated with levofloxacin and
  discharged
• 7 days later, seen at another hospital because of
  12-15 pound weight gain over last few days (my
  abdomen has never been so big) and hypertension
  (213/106)
• Afebrile, WBC of 8.5, albumin 3.1, creatinine
  0.9, no diarrhea noted
• Admitted, treated for hypertension and
  ciprofloxacin given to complete treatment for
  CAP discharged 3 days later

6
Case Study 1 (contd)
Day 1 Presents to ER 3 days after discharge Fever (101), diarrhea, generally feeling ill, no abdominal pain WBC 27.8K, albumin 2.9, creatinine 1.2 Admitted with C. difficile colitis listed as a possible dx, but not treated (except for levofloxacin)
Day 2 10 stools/day, altered mental status C. difficile EIA positive put on metronidazole 500 mg TID
7
Case Study 1 (contd)
Day 3 Transferred to SICU, anuric, abdominal pain, distension, developed cardiac complications, ventilated, renal failure. Poor prognosis and colectomy ruled out following surgical consult Oral and rectal vancomycin added WBC gt 30K, albumin 2.3, creatinine 3.1
Day 4 WBC 59.6K, toxic megacolon
Day 5 WBC 88K, made DNI/DNR, died
8
Historical Perspective

• In the 1960s it was noted that patients on
  antibiotics developed diarrhea1
• staphylococcal colitis
• Originally thought to be caused by S. aureus and
  treated with oral bacitracin
• Stool cultures routinely ordered for S. aureus
• Early 1970s, a new explanation
• clindamycin colitis
• Severe diarrhea, pseudomembranous colitis, and
  occasional deaths documented in patients on
  clindamycin

1. Gorbach SL. NEJM. 19993411689-1691.
9
Antibiotic Associated Pseudomembranous Colitis
Due to Toxin-Producing Bacteria

• Bartlett and co-workers1 demonstrated
  cytotoxicity in tissue culture and enterocolitis
  in hamsters from stool isolates from patients
  with pseudomembranous colitis
• Isolate was C. difficile
• Bacillus difficilis (now confirmed as C.
  difficile) was cultured from healthy neonates
  (with difficulty, hence the name) in 19352

1. Bartlett JG, et al. NEJM. 1978298 531-534.
2. Hall JC and OToole E. Am J Dis Child.
193549390-402.
10
Quiz Time

• Q. Why did it take so long to associate the
  organism C. difficile with the disease?
• A. Organism was (is) found in healthy infants
• Q. Why do antibiotics sometimes cause diarrhea
  (unrelated to C. difficile)?
• A. Disrupt the intestinal flora which plays a
  major role in digestion of food

11
Clostridium difficile

• Gram-positive, anaerobic, spore-forming bacillus
• Vegetative cells die quickly in an aerobic
  environment
• Spores are a survival form and live for a very
  long time in the environment
• Grows on selective media in 2 days and smells
  like horse manure (p-cresol)

12
Importance of Spores

• Resistant to heat, drying, pressure, and many
  disinfectants
• Resistant to all antibiotics because antibiotics
  only kill or inhibit actively growing bacteria
• Spores survive well in hospital environment
• Spores are not a reproductive form, they
  represent a survival strategy

13
Source of Infections

• Spores in hospital, nursing home, or long-term
  care environment associated with ill patients
• Large numbers of spores on beds, bed-rails,
  chairs, curtains, medical instruments, ceiling,
  etc.
• Asymptomatic carriers in those same environments
• Low risk compared to patients with active disease
• False negative lab tests (low sensitivity)
• Unknown in community based infections, but food
  has been implicated1

1. Jhung MA, et al. Emerg Infect Dis.
2008141039-1045.
14
Risk Factors for Infection

• Hospitalization or long-term care facility
• Antibiotics (some more than others)
• Increasing age (gt65, gtgt80)
• Co-morbidity
• Surgery
• ? Proton-pump inhibitors
• Community-associated cases
• Peri-partum
• Close contact of CDI (C. difficile infection)
  case
• Food

15
Case Study 2

• 31 yo pregnant female (14 weeks, twins) seen at a
  local ER with history of
• 3 weeks intermittent diarrhea
• 3 days cramping and watery diarrhea
• Stool for C. difficile toxin
• Received T/S for UTI 3 months prior to ER visit
• Admitted, treated with metronidazole and
  discharged
• Readmitted next day with severe colitis
• Treated in hospital for 18 days with
  metronidazole, oral vancomycin and
  cholestyramine, discharged

16
Case Study 2 (contd)

• Readmitted 4 days later
• Diarrhea and hypotension
• Spontaneously aborted her fetuses
• Subtotal colectomy, aggressive therapy
• Died on 3rd day
• Post-mortem showed toxic megacolon with evidence
  of pseudomembranous colitis

MMWR 54(47)1201-1205.
17
What Can We Learn From Case 2?

• We know nearly nothing about community based CDI
• Testing for C. difficile is now both an
  in-patient and out-patient test
• Risk factors other than colonic imbalance
  mediated by antibiotics must be considered

18
Role of Antibiotics

• All antibiotics (including metronidazole and
  vancomycin) are associated with CDI
• High-risk group
• Clindamycin
• Cephalosporins/penicillins/beta-lactams
• Fluoroquinolones
• Alteration of normal colonic flora thought to
  favor growth of C. difficile
• Antibiotics do not know they are suppose to
  kill/inhibit only the bad guys

19
PathogenesisHistorical Perspective

• Most CDI were mild
• Diarrhea was main symptom
• Pseudomembranous colitis and toxic megacolon were
  rare
• Discontinuing antibiotics worked in many cases
• High response rate to metronidazole and
  vancomycin

20
Incidence of CDI

• United States
• CDI is not a reportable disease so exact number
  of cases and deaths remain unknown
• Based on discharge diagnoses, CDI cases have
  tripled over last 5 years
• United Kingdom
• Deaths in UK 9,000/year

CDI C. difficile infection.
21
Pathogenesis

• Toxigenic strains produce 2 large protein
  exotoxins that are associated with virulence
• Toxins A and B
• Mutants strains that do not make toxins A and B
  are not virulent
• Some strains make a third toxin known as Binary
  Toxin
• By itself, not pathogenic
• May act synergistically with toxins A and B in
  severe colitis
• More common in animal strains

22
Pathogenesis of CDI
Asymptomatic C. difficile colonization
Antimicrobial
C. difficile exposure
C. difficile infection
Hospitalization
From Johnson S, Gerding DN. Clin Infect Dis.
1998261027-1036 with permission.
23
PathogenesisChanging Epidemiology

• Increasing morbidity and mortality noted
  beginning in 2000
• Outbreaks in US Canada (gt200 deaths)
• Was this due to poor infection control, emergence
  of antibiotic resistance, or something else?
• A new, hypervirulent strain was detected

24
Epidemic Strain

• Strain typed BI/NAP1/0271,2
• Is highly resistant to fluoroquinolones2,4
• Binary toxin genes are present
• Produces large quantities of toxins A and B1,3
• Has a tcdC gene deletion1

1. Warny M, et al. Lancet. 20053661079-1084.
2. Hubert B, et al. Clin Infect Dis.
   200744238-244.
3. CDC Fact Sheet. July 2005.
4. McDonald LC, et al. N Engl J Med.
   20053532433-2441.

Adapted from McDonald LC, et al. N Engl J Med.
20053532433-2441 with permission.
25
In Vitro Production of Toxins in Epidemic Strain
From Warny M, et al. Lancet. 20053661079-1084,
with permission.
26
Not So Fast

• 2 recent papers questioned whether this strain is
  more virulent
• NAP-1 strain was detected around 25 of time in
  their hospital (BID in Boston) but was not
  associated with increased severity of disease
  (non-epidemic setting)1
• 18 and 39 bp deletion containing strains were
  not associated with increased severity of CDI at
  the Mayo Clinic2
• Age gt65 and prior NH stay implicated
• 1. Cloud, J. et al. 2009. Cl Gastro and Hept.
  7868-873
• 2. Verdoorn, B. P. et al. Diag Micro and ID.
  10.1016/j.diagmicrobio.2009.0815

27
Should You Treat the Patient or Treat the Strain?

• Routine diagnostics laboratory tests do not
  provide strain type
• Routine tests not always reliable
• Always treat the patient based symptoms, history,
  risk factors and markers of severe disease

28
Symptoms of CDI

• Asymptomatic colonization
• Diarrhea
• mild ? moderate ? severe
• Abdominal pain and distension
• Fever
• Pseudomembranous colitis
• Toxic megacolon
• Perforated colon ? sepsis ? death

29
Markers of Severe Disease

• Leukocytosis
• Prominent feature of severe disease
• Rapidly elevating WBC
• Up to gt100 K
• gt10 BM/day
• Albumin lt 2.5
• Creatinine 2x baseline
• Hypertension
• Pseudomembranous colitis
• Toxic megacolon
• Severe distension and abdominal pain

30
Laboratory Diagnosis of C. difficile Infection
(CDI)
31
Which Test Should I Use?

• Considerations
• Accuracy
• Time to detection
• Prevalence in your population
• Screening tests followed by confirmatory tests
• In a low prevalence population, a screening test
  with a high sensitivity is useful (no/few false
  negatives)
• Cost
• Ease of use
• At this time, there is no perfect test for the
  diagnosis of CDI

32
What Should I do First?

• Make some rules
• Rule 1 Accept only liquid stools or soft stools
• Why? Any Exceptions?
• Rule 2 Limit repeat testing once a patient is
  positive
• Why? Any exceptions

33
The Specimen

• Fresh is best (test within 2 hours)
• Liquid or loose, not solid
• If unable to test within 2 hours, refrigerate at
  4C for up to 3 days
• Freeze at -70C (not -20C) if testing will be
  delayed
• Specimen quality will influence test results

In Manual Clin Micro. 9th ed. 2007p. 897.
34
Laboratory Diagnosis of CDI
Enzyme Immunoassay (EIA)
Glutamate Dehydrogenase (GDH)
Cell Culture Neutralization Assay (CCNA)
Laboratory Diagnosis
Toxigenic Culture (Culture and CCNA)
Stool Culture
Molecular Based (PCR Or LAMP)
35
Conflicting Results with EIA
Recently Published EIA Papers(1-6) Recently Published EIA Papers(1-6)
Parameter Range
Sensitivity 32 98.7
Specificity 92 100
PPV 76.4 96
NPV 88 100

1. Stamper PD, et al. J Clin Microbiol.
   200947373-378.
2. Musher DM, et al. J Clin Microbiol.
   2007452737-2739.
3. Sloan LM, et al. J Clin Microbiol.
   2008461996-2001.
4. Gilligan PH. J Clin Microbiol. 2008461523-1525.
5. Ticehurst JR. J Clin Microbiol.
   2006441145-1149.
6. Nice review by Planche T, et al. 2008.
   www.thelancet.com/infection

36
EIA Testing

• Advantages
• Rapid
• Inexpensive
• Relatively easy
• No costly equipment
• Batch or single test formats

• Disadvantages
• Great variations in published sensitivity and
  specificity
• Technologist error
• Contamination

37
Two-Step Tests1-3

• Screening Tests
• Glutamate dehydrogenase (GDH)
• Detects nearly all true positives as well as
  false positives
• Low PPV
• High sensitivity
• Very few false negatives
• Works best in a low-prevalence population
• EIA Is it accurate enough to use as a screening
  test? Confirmatory test?

• Confirmatory Tests
• CCNA
• Add 1-2 days
• CX followed by CCNA
• Add 3-4 days
• PCR
• Possibility of false positives due to
  colonization

1. Gilligan PH. J Clin Microbiol. 2008461523-1525.
   
2. Ticehurst JR. J Clin Microbiol.
   2006441145-1149.
3. Planche T, et al. 2008. www.thelancet.com/infectio
   n

38
Most Recent Studies

• Cdiff Quik Chek Complete (GDH and EIA on one test
  card)1
• Both
• Both - -
• 13.2 discrepant, re-test. Use PCR
• PCR had very high S,S, PPV and NPV2
• PCR resolved low false positive EIA3
• Quinn, C. D. 2010. J Clin Microbiol. 48 603-605
• Novak-Weekley, S. et al. 2010. J. Clin
  Microbiol.doi10.1128/JCM.01801-09
• Brecher, S. et al. 2009. ICAAC Abstract D-1422

39
Molecular-Based Assays

• Polymerase Chain Reaction (PCR)
• 3 FDA Approved test kits
• 2 of them are less expensive but more labor
  intensive
• 1 is easy enough to do that even I can do it,
  but is expensive
• I recently switched from an EIA to the expensive
  PCR
• The cost of a misdiagnosed patient is too great,
  especially for our Veterans

40
Treatment
41
Treatment ofMild to Moderate Disease

• Stop antibiotic(s) if medically reasonable
• Metronidazole
• Oral or IV, 500 mg TID for 10-14 days is standard
  therapy
• 520 failure rate
• 20 relapse rate
• Can use a full 2nd course for failure/relapse but
  beyond 2 courses, switch to vancomycin
• Failures not due to metronidazole resistance

42
Initial Treatment Options for CDI

• Historical response (96) and relapse rates (20)
  similar between metronidazole and vancomycin1
• More recently, efficacy of metronidazole for
  severe disease called into question2-4
• Recent prospective trials report vancomycin to be
  superior to metronidazole in severe CDI5-7

1. Aslam S, et al. Lancet Infect Dis.
20055549-557. 2. Fernandez A, et al. J Clin
Gastroenterol. 200438414-418. 3. Gerding DN.
Clin Infect Dis. 2005401598-1600. 4. Musher DM,
et al. Clin Infect Dis. 2005401586-1590. 5.
Lahue BJ, Davidson DM. The 17th ECCMID Meeting,
March 31 to April 4, 2007 Munich, Germany.
Abstract 1732_215. 6. Zar FA, et al. Clin Infect
Dis 200745302-307. 7. Louie T, et al. The 47th
Annual ICAAC Meeting, Sept. 17-20, 2007 Chicago,
IL. Abstract k-425-a.
43
Initial Treatment Options for CDI
Metronidazole 250 mg QID or 500 mg TID May be administered PO or IV Development of resistance rare Historical first-line agent
Vancomycin 125 mg QID Effective in enteral (oral or rectal) form only Typically reserved for severe disease, those failing to respond to metronidazole, or cases in which metronidazole is contraindicated
IVintravenously POorally. Fekety R. Am J
Gastroenterol. 199792739-750. Gerding DN, et
al. Infect Control Hosp Epidemiol.
199516459-477. American Society of
Health-System Pharmacists. Am J Health-Syst
Pharm. 1998551407-1411.
44
Metronidazole vs Vancomycin

• Zar et al1 classified patients as mild or severe
  CDI
• In mild disease, vancomycin was slightly better
  than metronidazole (98 vs 90)
• Not statistically significant
• In severe disease, vancomycin was significantly
  better than metronidazole (97 cure vs 76 cure)

1. Zar FA, et al. CID. 200745 302-307.
45
Clinical Success by Disease Severity Tolevamer
Phase III Results
Defining CDI Disease Severity
Mild CDI 35 BM/day WBC 15,000/mm3 Mild abdominal pain due to CDI
Moderate CDI 69 BM/day WBC 15,001 to 20,000/mm3 Moderate abdominal pain due to CDI
Severe CDI 10 BM/day WBC 20,001/mm3 Severe abdominal pain due to CDI
Any one of the 3 defining characteristics assigns
a patient to the more severe category.
Louie T, et al. The 47th Annual ICAAC Meeting,
Sept. 17-20, 2007 Chicago, IL. Abstract k-425-a.
46
Metronidazole vs Vancomycin vs Tolevamer

• Patients stratified as mild, moderate, or severe
• Original goal of study was to evaluate tolevamer
  as a treatment for CDI

Drug Mild Moderate Severe
Tolevamer 59 46 37
Metronidazole 79 76 65
Vancomycin 85 80 85
Louie et al. ICAAC AbstractK-425-9 2007
47
C. difficile Infection Case 3

• 79-year-old woman with multiple medical problems
  admitted to hospital for treatment of
  community-acquired pneumonia
• Responds slowly to levofloxacin 750 mg daily
• After 6 days
• Develops diarrhea (9 loose BMs)
• WBC count 11,500/mm3
• Day 714 loose BMs, WBC count rises to 19,500/mm3
• Stool testing for C. difficile toxins A and B is
  requested
• Continued antibiotic therapy for pneumonia is
  deemed necessary
• How would you manage her care?
• Await stool test results and monitor her progress
• Empirically start metronidazole PO
• Empirically start metronidazole IV
• Empirically start vancomycin PO

48
C. difficile Infection Case 3

• 79-year-old woman with multiple medical problems
  admitted to hospital for treatment of
  community-acquired pneumonia
• Responds slowly to levofloxacin 750 mg daily
• After 6 days
• Develops diarrhea (9 loose BMs)
• WBC count 11,500/mm3
• Day 714 loose BMs, WBC count rises to
  19,500/mm3
• Stool testing for C. difficile toxins AB is
  requested
• Continued antibiotic therapy for pneumonia is
  deemed necessary
• How would you manage her care?
• Await stool test results and monitor her progress
• Empirically start metronidazole PO
• Empirically start metronidazole IV
• Empirically start vancomycin PO

49
Treatment of Severe Disease

• Follow definition of severe disease
• gt10 BM/day, high WBC, low albumin
• This is a life-threatening infection
• Surgical consultation recommended as patient may
  require a colectomy
• Oral vancomycin drug of choice
• Dose varies based on severity
• Can add metronidazole (oral or IV)

50
Management of Severe CDI

• Early recognition is critical
• Initiate therapy as soon as diagnosis is
  suspected
• Manage as for mild CDI plus
• Oral vancomycin (125 mg QID for 10 to 14 days) as
  initial treatment
• If patient is unable to tolerate oral medication,
  consider intracolonic vancomycin instillation (by
  enema)
• 0.51 g vancomycin (IV formulation) in 0.1 to 0.5
  L of normal saline via rectal (or Foley) catheter
• Clamp for 60 minutes
• Repeat every 412 hours

Gerding DN, et al. Infect Control Hosp Epidemiol.
199516459-477. Zar FA, et al. Clin Infect Dis.
200745302-307. Louie T, et al. The 47th Annual
ICAAC Meeting, Sept. 17-20, 2007 Chicago, IL.
Abstract k-425-a. Apisarnthanarak A, et al. Clin
Infect Dis. 200235690-696.
51
Management of Severe, Complicated CDI

• Potential role of intravenous immunoglobulin G
  (IVIG)1-6
• Antitoxin A IgG predicts clinical outcome of CDI
• Serum antibodies to toxins A and B are prevalent
  in healthy populations
• Recent studies in severe disease5,6
• Well tolerated in small numbers of patients
• Conflicting data regarding outcome improvement
  (mortality and need for colectomy)
• Often administered when surgery is considered
  imminent

1. Salcedo J, et al. Gut 199741366-370. 2.
Beales ILP. Gut. 200251456. 3. Kyne L, et al.
N Engl J Med. 2000342390-397.
4. Kyne L, et al. Lancet. 2001357189-193. 5.
McPherson S, et al. Dis Colon Rectum.
200649640-645. 6. Juang P, et al. Am J Infect
Control 200735131-137.
52
Multiple Recurrent CDI

• Rates of recurrent CDI
• 20 after first episode1
• 45 after first recurrence2
• 65 after two or more recurrences3
• Metronidazole or vancomycin resistance after
  treatment not reported
• Repeated, prolonged courses of metronidazole not
  recommended (risk for peripheral neuropathy)
• Several empirical approaches have been advocated
  but most have no controlled data

1. Aslam S, et al. Lancet Infect Dis.
20055549-557. 2. McFarland LV, et al. Am J
Gastroenterol. 2002971769-1775. 3. McFarland
LV, et al. JAMA. 19942711913-1918.
53
Treatment of Recurrent CDI

• First recurrence can be treated in the same way
  as a first episode according to disease severity1
• Metronidazole should not be used beyond first
  recurrence or for gt14 days2
• Concerns for hepatotoxicity and polyneuropathy
• Further recurrences can be treated with oral
  vancomycin taper and/or pulse dosing2,3

1. Gerding DN, et al. Infect Control Hosp
Epidemiol. 199516459-477. 2. McFarland LV, et
al. Am J Gastroenterol 2002971769-1775. 3.
Tedesco FJ, et al. Am J Gastroenterol.
198580867-868.

54
Other Treatments
Probiotics
IVIG
Rifaximin Chasers
Nitazoximide
Rifampin
Patients who produce antibody to toxins A and B
usually do well so IVIG has been tried.
55
Unproven Adjunctive Therapies for Recurrent CDI
Probiotics Saccharomyces boulardii Lactobacillus GG May reduce the likelihood of further recurrences in some patients when added to and continued after treatment with metronidazole or vancomycin1-3
Rifampin Efficacy in one series (n7) when added to vancomycin4
Nitazoxanide Response demonstrated in patients (n35) who failed prior metronidazole therapy5 and similar response and recurrence rates when compared with metronidazole for initial therapy (n110)6
Rifaximin chaser Effective when used for 14 days after vancomycin therapy (n8)7
1. McFarland LV, et al. JAMA. 19942711913-1918.
2. McFarland LV. J Med Microbiol.
200554101-111. 3. Surawicz CM, et al. Clin
Infect Dis. 2000311012-1017. 4. Buggy BP, et
al. J Clin Gastroenterol. 19879155-159. 5.
Musher DM, et al. J Antimicrob Chemother.
200759705-710. 6. Musher DM, et al. Clin Infect
Dis. 200643421-427. 7. Johnson S, et al. Clin
Infect Dis. 200744846-848.
56
Saccharomyces boulardii for CDI Prevention
S. boulardii
Recurrent CDI
P0.04
Metronidazole or vancomycin for 1014 days plus
placebo or S. boulardii 1 g daily 4 weeks.

• 1. McFarland. JAMA. 19942711913-1918.
• 2. Surawicz et al. Clin Infect Dis.
  2000311012-1017.

57
Recurrent CDI Rifaximin Chaser

• Eight women with multiple recurrences
• Rifaximin 400 mg BID for 2 weeks immediately
  after completing last course of vancomycin
• Seven of eight patients had no further diarrhea
  recurrence
• Single case of rifaximin resistance (identified
  after therapy) with recurrent CDI after a second
  course of rifaxmin
• Effective in interrupting recurrent episodes but
  resistance may become an issue

Johnson S, et al. Clin Infect Dis.
200744846-848.
58
Recurrent CDI Fecal Transplantation

• Rationale restoration of bacterial homeostasis
• Preparation of donor specimen
• Fresh (lt6 hours)
• 30 g or 2 cm3 volume
• Add 50 mL 0.9 normal saline, and homogenize with
  blender
• Filter suspension twice with paper coffee filter
• Delivered by nasogastric tube following
  vancomycin
• Results
• 1 of 16 survivors had a single subsequent
  recurrence

Aas J, et al. Clin Infect Dis. 200336580-585.
59
Infection Control

• Wash hands with warm soap and water
• Mechanical removal of spores
• Alcohol does not kill spores
• Stool is pre-treated with alcohol when growing C.
  difficile
• Contact and barrier precautions
• Private room
• Antibiotic stewardship

60
Efficacy of Hand Hygiene Methods for Removal of
C. difficile Contamination from Hands
WWS warm water and soap CWS cold water and
soap WWA warm water and antibacterial AHW
alcohol hand wipe AHR alcohol hand rub
Decrease in colony counts
compared with no wash
2.5
2
1.5
1
1.8
1.8
Decrease in colony counts
(log CFU/mL)
1.4
0.5




0.6
0
-0.1
-0.5
-1
Hand hygiene method
CFU colony forming units Different from AHR
(Plt0.05). Different from AHR and AHW (Plt0.05)
Oughton M, et al. The 47th Annual ICAAC Meeting,
2007.
61
Alcohol Gels and Hand Hygiene

• Alcohol-based gels appear to be less able to
  remove C. difficile spores
• However, in general they
• Provide an excellent method of hand hygiene
  effective against many common nosocomial
  pathogens
• Are convenient thereby increasing compliance
• Have not been implicated in CDI outbreaks
• In the setting of a CDI outbreak or increased
  rates, visitors and healthcare workers should
  wash hands with soap and water after caring for
  patients with C. difficile

CDC. Fact Sheet, August 2004 (updated 7/22/05).
Oughton M, et al. The 47th Annual ICAAC Meeting,
Sept. 17-20, 2007 Chicago, IL.
62
Isolation and Barrier Precautions

• Patients with CDI and incontinence should be in
  private rooms or cohorted if private rooms are
  not available
• Contact precautions and isolation
• Gloves and gowns required for direct contact and
  contact with environment
• Discontinuation of isolation when diarrhea
  resolves
• Dedicated equipment when possible

CDC Guideline for Isolation Precautions,
2007. Gerding DN, et al. Infect Control Hosp
Epidemiol. 199516459-477. Simor AE, et al.
Infect Control Hosp Epidemiol. 200223696-703.
63
Environmental Disinfection

• Removal/thorough cleaning of environmental
  sources can decrease incidence
• Use chlorine-containing agents (at least 5000
  ppm available chlorine 10 minutes contact time)
  for environmental contamination, especially in
  outbreak areas
• Fogging

Poutanen SM, Simor AE. Can Med Assoc J.
200417151-58. CDC. Fact Sheet, July
2005. McMullen KM, et al. Infect Control Hosp
Epidemiol. 200728205-207. Mayfield JL, et al.
Clin Infect Dis. 200031995-1000. Fawley WN, et
al. Infect Control Hosp Epidemiol.
200728920-925.
64
Antimicrobial Use Restrictions

• Practice antimicrobial stewardship
• Decrease duration of exposure and number of
  antimicrobial agents
• Best evidence for controlling C. difficile
  demonstrated with restriction of cephalosporin or
  clindamycin
• Recent reports of fluoroquinolone restriction
  helping to control outbreaks

McNulty C, et al. J Antimicrob Chemother.
199740707-711. Pear SM, et al. Ann Intern Med.
1994120272-277. Climo MW, et al. Ann Intern
Med. 1998128989-995. Kallen AJ, et al. Infect
Control Hosp Epidemiol. 200930264-72.
65
Summary

• CDI is increasing in incidence, severity and poor
  outcomes
• Laboratory diagnosis is challenging
• Carefully evaluate what works best in your
  setting
• No reasonable explanation for treatment failures
• Community based infections are not well
  understood
• Improved therapies are needed
• Extremely important to accurately detect and
  aggressively treat severe disease

66
Y Chromosome
Gitschier, J., Science, 1993 (261) p. 679

• Testis Determining Factor (TDF)
• Gadgetry (MAC- locus)
• Channel Flipping (FLP)
• Catching and Throwing (BLZ-1)
• Self-confidence (BLZ-2)
• (note unlinked to ability)
• Ability to remember and tell jokes (GOT-1)
• Sports Page (BUD-E)
• Addiction to death destruction
• movies (MOV-E)
• Air Guitar (RIF)
• Ability to identify aircraft (DC10)
• Pre-adolescent fascination with Arachnid
• and Reptilia (MOM-4U)
• Spitting (P2E)
• Sitting on the john reading (SIT)
• Inability to express emotion over the
• phone (ME-2)
• Selective hearing loss (HUH?)

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