Clostridium difficile infection (CDI)

fortnecessityusefulDéveloppement de logiciels

14 déc. 2013 (il y a 3 années et 10 mois)

259 vue(s)

Jorge A. Gilbert, MD, FACG,AGAF

Sanford GI Clinic

Associate Clinical Professor of Medicine

Sanford School of Medicine

University of South Dakota




Changing epidemiology of CDI


Diagnosis


Risk factors


Treatment


1935: G+, spore
-
forming anaerobic bacillus


1978:
Pseudomembranous

colitis


Leading
cuase

of diarrhea in healthcare
setting, common now in community


Greater incidence, morbidity, mortality


Hypervirulent

strains


Use and misuse of antibiotics


Increase of susceptible at
-
risk populations


USA National Hospital Discharge Survey:


31/100.000 in 1996


61/100.000 in 2003


2010:


Yearly incidence of 500.000


Mortality: 15000


20.000


1 Billion/yr




Ghantoji
. J Hosp Infect 2010



North American pulse
-
field
-
gel
electrophoresis, Type1, restriction
endonuclease

analysis group BI, PCR
ribotype

027, (NAP1/BI/027)


Highly resistant to
fluoroquinolones


Binary toxin genes


tcd

C gene deletion


Large quantities of toxin A &B


>80% of cases in Quebec outbreak (2003)


Confirmed in 40 states in US by 2008




Community acquired


No exposure to antibiotics


Severe course


Pregnant women


IBD


cirrhosis


Increase in rate: x2 in CD, x3 in CUC


More severe disease


No exposure to antibiotics


Colonic disease


Immunomodulators


No
pseudomembranes


Rx:
Vanco
.
Reassesment

of
immunosupression




Age > 65


Antibiotics


2 months


Hospitalization


Comorbid
/Multiple illness


Immunosuppression


Clinical
Dx
:


Diarrhea +/
-

abdominal pain,
n/v


Current or recent antibiotics


Fever


Leukocytosis


Febrile/Septic picture in a post
-
op patient



Stool tests


EIA for toxins A/B


Rapid


75% sensitive


Tissue
Cx

citotoxicity


>90% sensitive


Takes 24hrs, more expensive


PCR


Rapid, >95% sensitive


Dx

test at Sanford Health



Colonoscopy/
Sigmoidoscopy
:



Rarely required


To be done cautiously


Non
-
specific colitis to
pseudomembranous

colitis


Rectum and Sigmoid usually but not always
involved


Mild to moderate disease


Metronidazole
: 500mg
po

tid

x

10
-
14 days


Severe disease


Vancomycin
: 125mg
po

qid

x

10
-
14 days


No
antiperistaltics


Avoid/Minimize systemic
abx


Consider Rx before documentation of
Dx

if
clinical suspicion high


Fever, chills


Severe abdominal pain, rebound


Severe diarrhea. None if toxic
megacolon


Ileus


Shock


Wbc

>15k,
creatinine

>50%, low albumin,
high lactate


pseudomembranes



Treatment


Vancomycin
: 250mg or 500mg
po

QID


Vancomycin

enemas: 500mg iv
vanco

in 100 cc of
NS via Foley. Clamp. Q 6hrs


IV
Metronidazole
, 500mg
q

8hrs


Early surgical consultation

161 ICU pts with severe
C.diff
; 30d mortality

38/161
colectomy
: NR to
med.Rx
, shock,
megacolon
, perforation

Mortality: 58% with medical Rx, 34% surg. Rx

Predictors of 30d mortality:


-
Lactate >5


-
wbc

>20k


-
shock/
pressors


-
age > 75







Lamontagne
, Ann
Surg
, 2007




14 cases managed surgically


Overall mortality 36%


Subtotal
colectomy
: 11%


L.
Hemicolectomy
: 100%




Koss, CRD, 2006



First episode: 10
-
20%


Second episode: 40
-
60%, yrs


Vicious cycle of abnormal flora


Complex Rx options


No single effective Rx


Impaired immune response


Lower
IgG

to Toxin A


Vaccinated pts: lower levels of anti
-
toxin B abs
associated with recurrence


Altered fecal flora


Marked change in fecal
microbiota

in RCDI


Bacteroidetes
,
Firmicutes



Leav
, Vaccine, 2009


Chang, JID, 2008



Age >65


Severe /
Comorbid

underlying illness


Continued use of non
-
C diff antibiotics


Acid
-
antisecretory

agents (controversial)


Prior appendectomy


A curious connection………



Appendyx

may protect against
C.diff

recurrence


Retrospective study, 396 pts, 2005
-
2007


Presence or absence of
appendyx

by
Hx

or CT


Multivariate analysis of variables associated with
recurrence


Age >60


ARR of 2.44


Appendyx

present

ARR of 0.398



Im

et al.
Clin

Gast

Hep
. Dec 2011


Repeat antibiotics:
vanco
>metro


Pulse/taper
vanco



Rifaximin

chaser”


Immune approaches


Probiotics


Fidaxomicin


Restoring normal flora: Fecal
Microbiota

Transplantation


First relapse: Second 14d course of
vanco

or
metro


Second relapse: Prolonged tapering & pulse dose
of
vanco

+/
-

probiotic


Third relapse: follow
vanco

Rx with
2wk of
rifaximin


INFECTION CONTROL



Kyne
. Gut 2001

























Wk1: 125mg
qid


Wk2: 125mg bid


Wk3: 125mg daily


Wk4: 125mg
qod


Wk5
-
6: 125mg q3d



Kyne
. Gut 2001


Tedesco. AJG 1985


7 pts with severe RCDI


5
-
7 episodes


Vanco
, then 2 wks of
rifaximin


6/7 no further relapses


Later series: 4/6 responded


Not FDA approved for CDI



Johnson.
Clin

Inf

Dis

2007


Johnson. Anaerobe 2009


Scattered reports of response to
IgG


Limitted

european

data in vaccines


Research on monoclonal antibodies to Toxin
A and B


VonDissel
. J Med Micro. 2006


McPherson.
Dis

Col Rect. 2006


Lowy. NEJM. 2010


Benefit of S.
boulardii


Metaanalyses
.
Pillai
. Cochrane Lib 2008


With antibiotics


Increasing dose of
vanco


L.
plantarum


Small trial, benefit (
Wullt
, SJID, 2003)


L. GG


No benefit in 2 small trials


Dificid


Approved by FDA in May 2011


Macrocyclic
,
macrolide

antibiotic


Inhibits bacterial RNA polymerase


Narrow spectrum, C. diff specific


Minimal absorption, high fecal concentration


2 phase III randomized studies against
vanco


>1000 patients


First bout of
C.Diff
, some with 1 prior bout


Similar rates of cure


Lower rates of recurrence with
fidaxomicin


No difference in recurrence in NAP1/BI/027


In SD area, 2 wk course of Rx


Metro: $40


Vanco

capsules: $1500


Vanco

liquid: $51


Fidaxomicin

(200mg bid): $4700


Fecal
Microbiota

transplantation (FMT)


Old practice in veterinary world


Trasfaunation


Equine diarrhea


1958: First human report of 4 pts with severe
pseudomembranous

colitis


1983: First documented case of
succesful

Rx
of RCDI with FMT


Scattered reports, different routes,
controversies and health concerns



Increasing clinical evidence of success


Greater acceptance by GI/ID communities


16S
rRNA
-
encoding gene clone libraries of
pts with CDI, RCDI, controls


Bacteroidetes

and
Firmicutes

dominant bacterial
phyla in the colon of controls and pts with first CDI


RCDI pts: marked decrease in normal phyla and rich
in others such as
Vellonella
, Clostridium,
Lactobacillus, Streptococcus,
Erysipelothrix
-
like
bacteria


Restoration of normal phyla after FMT



Chang.J

Inf

Ds. 2008.
Khorus
. J
Clin

Gast

2010


77 elderly pts,
colonoscopic

FMT


RCDI for 11 months


>90% success,
f
/up 17 months


>53% “would do it again” as first Rx option


Response in 6 days


8/30pts(27%) who needed an antibiotic had
recurrence



Mellow. ACG Meeting, Washington DC, Oct 2011



Sanford Clinic protocol


Approved by Clinical Practice Committee


Open
-
label


Colonoscopic

delivery


Patients with at least 3 bouts of C. diff. or 2
bouts with significant morbidity


May consider in acutely
ill patients (
fulminant

C.diff
)
deemed not surgical candidates


Clinical Presentation and
Diagnosis of Clostridium
difficile

Infection (CDI)

a

Clinical

Presentations
-
Mild to Moderate Disease

Clinical Presentations
-
Severe Disease


Mild to moderate diarrhea


May be associated with passage of blood in stool.


Fever, cramping, abdominal discomfort, and peripheral
leukocytosis

are
common, but found in fewer


than half of the patients


A history of treatment with antimicrobial or
antineoplastic

agents within
the previous 8 weeks is present


in the majority of patients


Fulminant

and sometime fatal
pseudomembranous

colitis


May develop severe colonic dilatation (toxic
megacolon
) and
present with


abdominal pain and distention but with minimal or no
diarrhea


Complications of severe C.
difficile

colitis include
dehydration, electrolyte


disturbances,
hypoalbuminemia
, toxic
megacolon
, bowel
perforation, hypotension,


renal failure, systemic inflammatory response syndrome,
sepsis and death

Diagnostic Testing
b

1.
Polymerase chain reaction (PCR): rapid, sensitive and specific


Sanford recommended

test

2.
Enzyme immunoassay (EIA): variable sensitivity

and specificity

3.
Cell
cytotoxin

assay and stool culture: accurate, but not practical, slow turn around time

4.
Sigmoidoscopy

or Colonoscopy: detects

acute colitis with or without
pseudomembranes



Use

with caution in suspicious cases if negative stool results



Biopsies helpful

5.
C.
difficile

testing should not routinely be performed in children less than 1 year of age

Treatment Guidelines
c

Clinical Definition


Supportive Clinical Data

Recommended

Treatment

Initial episode, mild or moderate

Leukocytosis

with a white blood cell

count of
<15,000 cells/µL and a serum
creatinine

level <1.5 times the
premorbid

level

Metronidazole
: 500 mg 3 times per day by
mouth for 10
-
14 days.


Pediatric dose:
Metronidazole

7.5 mg/kg/dose
by mouth every 6 hours (maximum dose is 2
grams/day) for 7 to 10 days.

Initial episode, severe

Leukocytosis

with a white

blood cell count of
≥15,000 cells/µL or a serum
creatinine

level
≥ 1.5 times the
premorbid

level

Vancomycin
:

125 mg 4 times per day by mouth
for 10
-
14 days.

Pediatric dose: 10 mg/kg/dose by mouth every
6 hours (maximum dose is 2 grams/day) for
10
-
14 days.

Initial episode,

severe,
complicated

Hypotension or shock,
ileus
,
megacolon


Vancomycin
: 125
-
250 mg 4 times per day by
mouth or by
nasogastric

tube, plus

metronidazole
, 500 mg every 8 hours
intravenously. If complete
ileus
, consider adding
rectal instillation of
vancomycin
.

Consider GI and/or surgical consult

First recurrence

Same as initial episode; or
vancomycin

if first
episode treated with

metronidazole

Second recurrence

Prolonged course of
vancomycin

in a tapered
and/or pulsed regimen

Fidaxomicin

(
Dificid
):

200 mg by mouth 4 times
per day for 10 days (limited to patients 18 years
or older)

Consider

GI or ID consult

Table c: Additional Treatment Guidelines

Discontinue therapy

with the inciting antimicrobial agent(s) as soon as possible

When CDI is suspected, consider initiating empirical treatment before confirmation of diagnosis

If the stool

test result is negative, the decision to initiate, stop, or continue treatment must be individualized

Avoid use of
antiperistaltic

agents, as they may obscure symptoms and precipitate toxic
megacolon


Colectomy

may be required for severely ill patients: lactic acidosis, worsening
leukocytosis
, septic
-
like syndrome are
potential indications for surgery


If surgical management is necessary, subtotal
colectomy

with preservation of the rectum is treatment of choice

Do not use
metronidazole

beyond the first recurrence of CDI or for long
-
term chronic therapy because potential for
cumulative neurotoxicity

Treatment

of the second or later recurrence of CDI with
vancomycin

therapy using a tapered and/or pulse regimen is the
preferred next strategy

Table

b:
Specimen Collection


With PCR testing,

only one stool sample need be tested during the same episode of diarrhea


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Table

a: Clostridium
difficile

Infection (CDI) Definition


Must include presence of symptoms and a stool test result positive for the presence of
toxigenic

C.
difficile

or its toxins or endoscopic or
histopathologic

findings demonstrating


acute colitis with or without
pseudomembranes




Use the same criteria to diagnose recurrent CDI

Table e: Infection Control Measures for Prevention of Horizontal Transmission

of Clostridium


difficile

(for patients with known or suspected infection)

Hand

Hygiene (wash hands with soap or antimicrobial soap and water after caring for or contacting
patients)

NOTE
: Alcohol based hand sanitizers are not effective against C.
difficle

spores

IN
-
PATIENT

NURSE DRIVEN PROTOCOL: Patient tested for C.
difficile

by PCR and placed in isolation if 3
or more unformed stools in 24 or fewer consecutive hours.

Contact Precautions (don
gloves and gowns upon room entry). Maintain contact precautions for 48
hours after diarrhea is resolved.

1.
Glove
s

2.
Gowns

3.
Maintain contact precautions for the duration of diarrhea

Use

of private rooms or
cohorting

and private bathrooms

Environmental cleaning,

disinfection and equipment

1.
Disinfect patient rooms and high touch environmental surfaces twice daily

2.
Disinfect equipment between uses for patients

3.
Provide disposable thermometers

4.
Use of hypochlorite (1000
ppm

available chlorine) for disinfection

5.
Dedicate equipment to patient’s use as much as possible

Table d: CDI Risk
Factors



Advanced age


Extended

hospitalization


Exposure to antimicrobial


agents


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