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bacterial cells
Overview
• Case reports • Changing
• Historical epidemiology
perspective • Disease
• Organism & key • Diagnosis
properties • Treatment
• Infection control
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
Case Study 1 (cont’d)
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
Case Study 1 (cont’d)
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 > 30K, albumin 2.3, creatinine 3.1
MMWR 54:(47);1201-1205.
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
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”
Pathogenesis
Historical 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
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
Antimicrobial Asymptomatic
C. difficile
colonization
C. difficile exposure
C. difficile
Hospitalization infection
From Johnson S, Gerding DN. Clin Infect Dis. 1998;26:1027-1036; with permission.
Pathogenesis
Changing Epidemiology
• Increasing morbidity and mortality noted
beginning in 2000
• Outbreaks in US & Canada (>200 deaths)
• Was this due to poor infection control,
emergence of antibiotic resistance, or
something else?
• A new, hypervirulent strain was detected
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
IV=intravenously; PO=orally.
Fekety R. Am J Gastroenterol. 1997;92:739-750.
Gerding DN, et al. Infect Control Hosp Epidemiol. 1995;16:459-477.
American Society of Health-System Pharmacists. Am J Health-Syst Pharm. 1998;55:1407-1411.
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)
Louie T, et al. The 47th Annual ICAAC Meeting, Sept. 17-20, 2007; Chicago, IL. Abstract k-425-a.
Metronidazole vs Vancomycin
vs Tolevamer
IVIG* Probiotics
Rifaximin
Nitazoximide
Chasers
Rifampin
* Patients who produce antibody to toxins A and B usually do well so IVIG has been
tried.
Unproven Adjunctive Therapies
for Recurrent CDI
Probiotics
Saccharomyces boulardii May reduce the likelihood of further recurrences in some
Lactobacillus GG patients when added to and continued after treatment
with metronidazole or vancomycin1-3
Rifampin Efficacy in one series (n=7) when added to vancomycin4
Nitazoxanide Response demonstrated in patients (n=35) who failed
prior metronidazole therapy5 and similar response and
recurrence rates when compared with metronidazole for
initial therapy (n=110)6
Rifaximin “chaser” Effective when used for 14 days after vancomycin therapy
(n=8)7
P=0.04
*Metronidazole or vancomycin for 10–14 days plus placebo or S. boulardii 1 g daily × 4 weeks.
1. McFarland. JAMA. 1994;271:1913-1918.
2. Surawicz et al. Clin Infect Dis. 2000;31:1012-1017.
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. 2007;44:846-848.
Recurrent CDI: Fecal
Transplantation
• Rationale: restoration of bacterial homeostasis
• Preparation of donor specimen
– Fresh (<6 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
antibacterial
1
1.8 1.8 AHW = alcohol
1.4
0.5 hand wipe
0 ** ** * *0.6 -0.1
AHR = alcohol
hand rub
-0.5
-1
WWS CWS WWA AH AHR
W
Hand hygiene method
CFU = colony forming units
* Different from AHR (P<0.05).
Oughton M, et al. The 47th Annual ICAAC Meeting, 2007. ** Different from AHR and AHW (P<0.05)
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.
Isolation and Barrier Precautions