“SPINDLE DIFFICULT”

L.S.W /96/ FEMALEADL DEPENDENT/

CHAIR BOUND/ DUALLY INCONTINENT

SPICEFEVER AND DIARRHEA

HTN

AF

CCF

Osteoporosis

TIADementia

Depression

Iron deficiency anemia

Gout

Recent Hospitalizations

1/2014 : PneumoniaAugmentinChlarithromycin

24/ 3//2014: PneumoniaRocephine & DoxycyciineMoxifloxacin

10/4/2014 : GastroenteritisCeftriaxone Augmentin

Course in the Wards

Gastroenteritis with DehydrationIV fluidsIV Rocephine shifted to Augmentin

AKI and Hypernatremia

Deconditioning

Course in the Wards Gastroenteritis likely antibiotic related

Cd toxin not detectedAntibiotics discontinuedDiarrhea resolved

Delirium likely stroke disease

Poor Oral intake Depression – fluoxetine, mirtazipineWorsening DementiaNGT was inserted

Course in the Wards

Refeeding syndromeLow magnesium (0.57 )Low phosphate (0. 38)Low potassium ( 3.3)

PneumoniaIv tazocin

Course in the Wards

Recurrence of diarrhea

CD toxin : Negative CD PCR : Positive

Metronidazole 500 mg per NGT 6 hourly Vancomycin 250mg per NGT q6hourly

Epidemiology

Clostridium Difficile Anerobic gram positive

spore forming, toxin producing bacillus

Exists in spores and vegetative forms

causative pathogen for antibiotic associated diarrhea and colitis

NAP1/B1/027 – virulent strain

Clostridium difficile Pathonegesis

FROM THE FOLLOWING ARTICLE:Clostridium difficile infection: new developments in epidemiology and pathogenesis

Maja Rupnik, Mark H. Wilcox & Dale N. GerdingNature Reviews Microbiology 7, 526-536 (July 2009)

Risk factorsAntibiotics

Hospitalization

Advanced age

Severe illness

Gastric acid suppression

Enteral feeding

Gastroentrointestinal conditions & procedures

Obesity

Cancer chemotheray

Hematopoetic transplantation

Antidepressant

Antimicrobial agents that may induce Clostridium difficile diarrhea and colitis

Frequently associated

Occasionally associated

Rarely associated

Fluoquinolones Macrolides Aminoglycosides

Clindamycin Trimethoprim Tetracyclines

Penicillins sulfonamides Chloramphenicol

Cephalosphorins Metonidazole

Vancomycin

Clinical Manifestations and Diagnosis

Carrier state

Diarrhea and colitis

Pseudomembranous colitis

Recurrent disease :

relapse vs reinfection

Fulminant colitis

Clinical Manifestations

96% of patients with symptoms had received antimicrobials with 14 days before the onset of diarrhea

Symptoms begin soon after colonization ( median time onset 2-3 days )

Fever, cramping, abdominal discomfort and peripheral leukocytosis are common

Arthritis, bacteremia Unexplained Leukocytosis

Diagnosis

Presence of moderate to severe diarrhea or ileus

And either

A stool positive for C. Difficile toxins or toxigeneic c. Dificile

Endoscopic or histologic findings of pseudomembranous colitis

Diagnostics TestsOnly stools from patient with diarrhea should be tested for CD

• ( strong recommendation, High Quality evidence )

NAAT ( PCR are superior to toxins A & B EIA testing as a standard diagnostic test for CDI

• (strong recommedation, moderate quality evidence )

Glutamate Dehydrogenase can be used in 2 to 3 step screening algorithms with subsequent toxin A and B EIA testing, but the sensitivity of such is lower than NAATS

• ( strong recommendation, moderate quality evidence )Guidelines for diagnosis, treatment, and Prevention of clostridium difficle infections

American College of GastroenterologyPublished online 26 feb 2013

2010 UPDATE BY Society for Healthcare Epidemiology of America and infectious diseases Society of America

Diagnostic testing

Repeat testing should be discourage

• Strong recommendation, moderate quality evidence

Testing for cure should not be done

• ( strong recommendation, moderate quality evidence )

Stool culture is most sensitive and essential in epidemiologic studies • ( good evidence to support recommendation)

Guidelines for diagnosis, treatment, and Prevention of clostridium difficle infectionsAmerican College of Gastroenterology

Published online 26 feb 20132010 UPDATE BY Society for Healthcare Epidemiology of America and infectious diseases Society of America

Other Methodologies

Sigmoidoscopy or colonoscopy

• Detects pseudomembranous colitis in 51-55% of CDI cases

Histopathology

Abdominal CT SCAN – facilitate diagnosis, but not sensitive nor specific

Guidelines for diagnosis, treatment, and Prevention of clostridium difficle infectionsAmerican College of Gastroenterology

Published online 26 feb 20132010 UPDATE BY Society for Healthcare Epidemiology of America and infectious diseases Society of

America

MANAGEMENT OF MILD, MODERATE,

SEVERE CDI

CDI Severity Scoring System

Severity criteria

Mild to moderate Diarrhea + s/s not meeting severe or complicated criteria

Severe Disease <3g/dl + 1 of the ff:WBC >15,000 cells/mm3, abdominal tenderness

Severe and Complicated disease

Any of the following attributable to CDIAdmission to ICUHypotension +/- vasopressorsFever >38.5 CIleus or significant abdominal distentionMental status changes WBC >35,0000or <2,000

Recurrent CDI Recurrent within 8 weeks of completion of therapy

Factors to Consider Before Treating

AGE

Peak White cell

count

Peak serum

creatinine

Treatment

•Metronidazole 500mg TDS or 250mg QDS for 10-14 days THEN

•Vancomycin 125mg orally QDS 10-14 days. If no response

Mild disease

•Vancomycin500mg 4x/day + metronidazole 500mg every 8 hours IV

•If complete ileus : add rectal vancomycin

Severe disease

•If symptoms is mild, conservative management may be appropriate

•If antibiotics are needed, repeat treatment as in initial episode

•Alternative : Fidaxomicin 200mg BD x 10 days

First Relapse

UPTODATE

Treatment•Tapering and pulsed

vancomycin with or without probiotics

•125mg QDS for 7-14 days•125 BD x 7 days•125 once x 7 days•125mg orally every other

day for 7 days•125mg orally every 3 days

x 14 days•Alternative : Fidaxomicin

200mg orally BD x 10days

Second Relapse

UPTODATE

Treatment•Fidaxomicin

200mg Orally BD x 10 days

•Alternative : vancomycin 125mg QDS x 14 days followed by rifiximim 400mg BD x 14 days

Subsequent relapse

Fidaxomicin

Macrolide, bactericidal Narrower antimicrobial spectrum than

Metronidazole & Vancomycin

3RCT : in non severe C. Difficile , clinical cure rates with vacomycin were similar

Recurrence is less often among patients with non NAP1 strain ( 10 vs 28 % )

UPTODATE

Probiotics May be effective for prevention and treatment

Alteration of intestinal floraAntimicrobrial activityIntestinal barrier protectionimmunomodulation

Administration consist only of regimens with demonstrated efficacy

Dosage of >10 billion CFU per day A cocrane review: insufficient evidence to

recommend as adjunct in treatment

UPTODATE

RICE WATERThe advantage of using rice water is that rice is cooked daily in South East Asia.

WHO photograph by Dr Gramiccia In South East Asia, rice is prepared in two ways - to produce either dry, cooked rice or, with extra water, rice porridge. This leaves a fluid (rice water) on top of the cooked rice grains.

Professor Wong Hock Boon, a paediatrician working in Singapore, has been using rice water to rehydrate babies for several years. If the babies are bottle-fed rice water is given exclusively for the first 24 hours of treatment - breastfeeding can continue as normal (1).

Professor Wong and his colleagues have found that many babies who have not responded to other rehydration solutions respond well to rice water. If diarrhoea starts again with the re-introduction of milk, extra rice water is given with additional rice porridge. Older babies are sometimes given rice porridge alone.

Rice water and diarrhoea

Treatment

Antimotility Agents and OpoidsAssociated with increase risk of toxic

megacolon IVIG

No effective immunotherapy is currently available

Does not have a role as sole therapy for RCDI

May be helpful in patient with hypogammaglobulimenia

Colectomy

Consider in severely ill patients

Monitoring serum lactate and White cell may be helpful in prompting a decision to operate

FECAL MICROBIOTA TRANSPLANTATION IN

THE TREATMENT OF RECURRENT CDI

Fecal Microbiota Transplantation

Patient selectionSevere and Recurrent C. Difficile infection

Cure rates 81-94% in patients with recurrent disease

Response within 24h to 12 days Only method capable of providing

durable implantation of probiotics Route of administration :

Colonoscopy, nasogastric, enema

Infection Control, & Prevention

A hospital – based infection contol program can help decrease the incidence of CDI

Routine screening for C. Difficile in hospitalized patients without diarrhea is not recommended and asymptomatic carriers should not be treated

Antibiotic stewardship is recommended to reduce the risk of CDI

Infection Control and Prevention

Gloves and gowns upon entry to a room Emphasize compliance with practice of

hand hygiene Hand wash with soap and water after

caring for or contacting patient with CDI Accommodate patients with CDI in

private room with contact precaution

Environmental Cleaning and Disinfection

Identification and removal of environmental sources of C. Dificille including replacement of electronic rectal thermometers

with disposable, can reduce the incidence of CDI

Use chlorine-containing cleaning agents or other sporicidal agents to address environmental contamination in area associated with increased rates CDI

Prognosis

Mild disease, may recover without specific therapy

Debilitating and can last for several weeks 20-27% treated for first episode , relapse

after successful completing the antibiotics , 3days -3week after treatment

65%- relapse rate with patient with 2 or more relapses

Prognosis Adverse outcomes

Treatment failureSevere or complicated infectionSepsisNeed for admission to ICUNeed for colectomyIncrease length of hospital stay Need for hospitalization for community acquired

CDIMortality 4.2-6.9%

THANK

YOU

Sources

UPTODATE American College of Gastroenterology 2010 Update by Society for Healthcare

Epidemiology of America (SHEA ) and the Infectious Diseases Society of America

Center for Infectious Disease CGH Guidelines http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2224300/figure/f1/ https://www.nuh.nhs.uk/media/1069241/

new_cdiff_testing_and_reporting.pdf

Proposed algorithm for detection of C. difficile in fecal specimens submitted for C. difficile testing. Tests used are C.DIFF CHEK-60 for C. difficile specific antigen (glutamate dehydrogenase) and TOX A/B QUIK CHEK for toxin A/B (both TechLab/Wampole). The percentage values refer to the total numbers of stool specimens analyzed (n = 1,468). Results for nine specimens (0.6%) which did not fit into the described categories are not included. J Clin Microbiol. Jan 2008; 46(1): 328–330

Differential Diagnosis

Osmotic diarrhea Antibiotics alter colonic microflora

Impaired carbohydrate fermentation

Increased osmotic concentration in colonic lumen

Prevention strategies

Early detection and isolationRapid implementation of contact precautionsVigilant screening for new onset diarrhea in

patients at risk and rapid and accurate testing

Contact precaution

Prevention and strategies Hand Hygiene

Healthcare personel should hand wash hands with soap and water

Alcohol based hand rub does NOT eradicate C. Difficile spores

Adherance to gloves is also important

Surawicz, C. M. & Alexander, J. (2011) Treatment of refractory and recurrent Clostridium difficile infectionNat. Rev. Gastroenterol. Hepatol. doi:10.1038/nrgastro.2011.59

Figure 1 Treatment algorithm for recurrent Clostridium difficile infection

Permission obtained from Nature Publishing Group ©Surawicz, C. M. Nat. Clin. Pract. Gastroenterol. Hepatol. 1, 32–38 (2004)

Factors contributing to the development of Clostridium difficile colonization and diarrhea [adapted, with permission, from Johnson S, Gerding DN. Clostridium difficile-associated

diarrhea. Clin Infect Dis 1998;26:1027-36, published by the University of Chicago Press, Infectious Diseases Society of America; 1998]. Photo: Lianne Friesen and Nicholas Woolridge

How C. Difficile Spreads

Few days later, persistence of diarrhea, retested for CD, which turns out to be positive. Was given proper antiobitiotics, with resolution of diarrhea

At Rehab facility – with no strict contact precaution. L.S.W. developed diarrhea, CD toxin was not tested at that time. health care worker attends to her, infects another patient

1 ½ month later : admitted to Pneumonia, given another course of antibiotics. A health care worker forgetting to wash hands /wear gloves after attending to a C. D. Infected

patient next to her bed, infecting patient

L.S.W . 96/female, went to doctor, diagnosed with Pneumonia, given antibiotics that put her at risk of developing antibiotic related diarrhea

Recurrent Disease

Complete abatement of CDI symptoms while on appropriate treatment

Followed by subsequent reappearance of diarrhea and other symptoms after treatment has been stopped

Risks factors : > 65 years old, severe underlying medical condition, need forongoing therapy with concomitant antiobiotics during treatment with CDI

Pathophysiology :not fully understood

FIGURE 1 | Treatment algorithm for recurrent Clostridium difficile infection

FROM THE FOLLOWING ARTICLE: Treatment of refractory and recurrent Clostridium difficile infection

Christina M. Surawicz & Jacob Alexander Nature Reviews Gastroenterology & Hepatology 8, 330-339 (June 2011)