Changes

Diagnosis and Treatment or C.ostradaul der

Diagnosis and Treatment of C.difficil per

Natasha Bagdasarian et al.

Natasha Bagdasarian et al.

Published in JAMA 2019.

Published in JAMA 2019.

Systematic review of 116 included studies between 1978 and 2014.

Systematic review of 116 included studies between 1978 and 2014.

DIAGNOSIS

 

Laboratory testing cannot distinguish between asymptomatic colonization and

=DIAGNOSIS=

¿Eyed frat' cuitisten a forfindsfficile. The best test performance characteristics

* Laboratory testing cannot always distinguish between asymptomatic colonization and active infection.

-Diagnostic criteria

==Diagnostic criteria==

--Diarrhea

* Diarrhea

-Positive stool test for toxigenic C. diff or toxins or pseudomembranous colitis

* Positive stool test for toxigenic C. diff or toxins or visualization of pseudomembranous colitis

-Diagnostic approaches

==Diagnostic approaches==

-Toxigenic Culture (TC) and/or Cell Cytotoxicity Assay (CCA)

* Gold Standard: Toxigenic Culture (TC) and/or Cell Cytotoxicity Assay (CCA)

---Anaerobic culture for 24-48 hrs followed by colony selection and culture with

** Anaerobic culture for 24-48 hrs followed by colony selection and culture with human cells to test for cell cytotoxicity which takes an additional 24-48 hours.

human cells to test for cell cytotoxicity which takes an additional 24-48 hours.

** Time consuming and difficult, up to 5 days

** Detects a little as 3 picograms of toxin

--- Time consuming and difficult, up to 5 days

* Stool antigen looks for Glutamate dehydrogenase (GDH) via ELISA (EIA)

---Detects a little as 3 picograms of toxin

** Does not distinguish between toxigenic and non-toxigenic strains

-Stool antigen looks for Glutamate dehydrogenase (COH) via ELISA (SIA)

** Half of C. diff isolates are non-toxigenic

---Does not distinguish between toxigenic and non-toxigenic strains

* PCR / NAAT

---Half of C. diff isolates are non-toxigenic

** Detects tcdA/tcdB genes, mRNA for the toxins

--PCR / NAAT

** Detects presence of toxigenic strains of C. diff

--Detects tcdA/tcdB genes, mRNA for the toxins

** mRNA doesn't necessarily imply active infection

---Detects presence of toxigenic strains of C. diff

* EIA / ELISA

-mRNA doesn't necessarily imply active infection

** Detects toxin in stool

--EIA / ELISA

** Low sensitivity (0.73-0.87)

---Detects toxin in stool

* Multistep algorithms, there are dozens

---LOw sensitivity (0.73-0.87)

** EIA for GDH / Toxin A/B

-Multistep algorithms, there are dozens

*** Both positive = C. diff

--EIA for GDH / Toxin A/B

*** Both negative = NO C. diff

--Both positive = C. diff

*** Mixed results, use PCR for tcdB as tiebreaker

-Both negative = NO C. diff

** Toxin EIA 1 (Meridian), higher PPV, lower NPV

--Mixed results, use PCR for tedB as tiebreaker

** Toxin EIA 2 (TechLab), lower PPV, higher NPV

-Toxin EIA 1 (Meridian), higher PPV, lower NPV

** Highest NPV (99.8%) GDH EIA + NAAT

--Toxin EIA 2 (TechLab), lower PPV, higher NPV

** Highest PPV (93.5%) Toxin EIA 1 + NAAT

-Highest NPV (99.8%) GDH EIA + NAAT

 

---Highest PPV (93.5%) Toxin EIA 1 + NAAT

=TREATMENT=

TREATMENT

==First line treatment==

-First line treatment

*PO Vancomycin (78.5% success rate, 25,3% recurrence rate)

-PO Vancomycin (78.5% success rate, 25,3% recurrence rate)

*PO Metronidazole (66,3% success rate, 47% recurrence rate), recent strains have higher MIC

-PO Metronidazole (66,3% success rate, 47% recurrence rate), recent strains have

==Disease stratification==

higher MIC

*WBC (15), Cr (1.5% baseline), recurrence, hypotension, ileus, megacolon

-Disease stratification

*Mild = Metronidazole, preferred for cost and non-inferiority in mild disease

-WBC (15), Cr (1.5% baseline), recurrence, hypotension, ileus, megacolon

*Severe/Complicated = Vancomycin

-Mild = Metronidazole, preferred for cost and non-inferiority in mild disease

*Recurrent = Metro or Vanco for first recurrence, Vanco for subsequent

-Severe/Complicated = Vancomycin

==Newer treatments==

-Recurrent = Metro or Vanco for first recurrence, Vanco for subsequent

*Fidazomicin (87.7% success rate vs. 86.8% for vanco, 15.4% recurrence rate)

-Nener treatments

**Expensive

- -Fidazomicin (87.7% success rate vs. 86.8% for vanco, 15.4% recurrence rate)

*Fecal microbiota transplant (83-94% success rate for recurrent COL).

-=-Expensive

**Fecal microbiota transplantation restores gut microbiota diversity, with the instillation of donor stool into the gastrointestinal tract of an infected patient.

_-Fecal microbiota transplant (83-94% success rate for recurrent COL)

**This procedure has had good clinical response without reports of adverse events, for refractory or recurrent CDI.  

Fecal microbiota transplantation restores gut microbiota diversity, with the

**The first systematic review was published in 2011 and included 317 patients with recurrent CDI treated with fecal microbiota transplantation via enema, nasojejunal-tube/gastroscope or colonoscopy.  

instillation of donor stool into the gastrointestinal tract of an infected patient,

**Clinical resolution occurred in 92% of patients (89% after a single treatment), without serious adverse effects.

This procedure has had good clinical response without reports of adverse events, for

**A recent review of 536 patients reported a 27% clinical response rate.

refractory or recurrent COI. The first systematic revien was published in 2911 and

**A randomized trial of fecal microbiota transplantation demonstrated symptom resolution in 94% of patients who received vancomycin for 5 days followed by either one or two treatments with fecal microbiota transplantation, versus 31% in those receiving vancomycin alone for 14 days, and 23% for those receiving vanconycin for 14 days plus bowel lavage. This study was stopped early after interim analyses demonstrated superiority of fecal microbiota transplantation, Among 18 patients in the other treatment groups who received subsequent fecal microbiota transplantation 83% had symptom resolution

included 317 patients with recurrent COI treated with fecal microbiota

transplantation via enema, nasojejunal-tube/gastroscope or colonoscopy. Clinical

resolution occurred in 92% of patients (89% after a single treatment), without

serious adverse effects. A recent revien of 536 patients reported a 27% clinical

response rate.

A randomized trial of fecal microbiota transplantation demonstrated symptom

resolution in 94% of patients who received vancomycin for s days followed by either

one or two treatments with fecal microbiota transplantation, versus 31% in those

receiving vancomycin alone for 14 days, and 23% for those receiving vanconycin for

14 days plus bowel lavage. This study was stopped early after interim analyses

demonstrated superiority of fecal microbiota transplantation, Among 18 patients in

the other treatment groups who received subsequent fecal microbiota transplantation

83% had symptom resolution