​Kembara Xtra - Medicine - Clostridium Difficile Infection

​Kembara Xtra - Medicine - Clostridium Difficile Infection 
Introduction 

 A gram-positive anaerobic bacillus that forms spores and secretes toxins to cause clinical disease
Hospitalization, long-term care facility residency, usage of antibiotics, and age are frequently linked to Clostridioides difficile infection.
Transmission of spores is typically person-to-person via the fecal-oral channel but may also occur through exposure to contaminated surfaces or equipment. Severity of infection ranges from asymptomatic carrier to diarrhea, colitis, sepsis, perforation, and death. Spores of C. difficile can endure on dry surfaces for up to five months.
impacted system(s): gastrointestinal
Clostridium difficile infection, diarrhea caused by C. difficile or its associated disease (CDAD), colitis caused by C. difficile, and C. diff

Incidence and prevalence in Epidemiology

Incidence
C. difficile colonization was discovered in: 2-10% of the general population, 3-18% of inpatients, and 4-20% of long-term residents. 
Hospitalization rates are rising; the incidence of C. difficile infections is estimated to be 50/100,000 worldwide each year.
73/100,000 people nationwide have C. difficile infections related to healthcare.
52/100,000 people nationwide have C. difficile infection, according to data.
Prevalence

 In the United States, prevalence is rising in both the community and health care settings.
12% of illnesses related to healthcare were caused by C. difficile in 2010.
From 1993 to 2005, there were over 2 million cases of C. difficile-associated illness in hospitals in the United States.


Pathophysiology 

C. difficile is a gram-positive, anaerobic bacillus bacteria that can exist as spores or in vegetative form.
Spores can endure extreme circumstances and living outside of the body for months.
Spread via oral contact with feces. C. difficile is a noninvasive acid-resistant spore that primarily lives in the colon after passing through the stomach. Colonic colonization causes abnormalities in the normal microbiome's barrier functions. Disease is mediated by toxins:
- The hypervirulent strain BI/NAP1/027 of C. difficile is associated with increased rates of colectomy and death. - Toxins A (enterotoxin) and B (cytotoxin) attract neutrophils and monocytes, destroying colonic epithelial cells and generating clinical illness.
Genetics
unknown genetic components


Host risk factors are among the dangers.
- Hospitalization or long-term care facility - Age >65
- Comorbid conditions like end-stage renal disease, immunosuppression, chronic liver disease, and inflammatory bowel illness
feeding through an enteral tube; prior C. difficile infection
Factors that alter the regular colonic microbiome include:
Antibiotic exposure, especially perioperative prophylaxis; often implicated antibiotics, including cephalosporins, fluoroquinolones, ampicillin, amoxicillin, and clindamycin; and chronic acid suppression.
Recurrence rates from previous infections are 20%, and they become more frequent with each subsequent episode.

Patients without other risk factors (younger, no recent antibiotic exposure) are more likely to develop community-acquired C. difficile infections (no overnight stay in >12 weeks).
Longer hospital stays, longer antibiotic exposure times, and more frequent antibiotic use all raise risk.


Aspects of Geriatrics

The most typical cause of acute diarrheal disease in long-term care settings is C. difficile.
Child Safety Considerations
Neonates frequently act as carriers for infection in adults despite having a greater rate of C. difficile colonization (25–80%) and being less symptomatic than adults in general.

Prevention 

The prevalence of C. difficile infection is reduced by antibiotic stewardship programs. (6) The Society for Healthcare Epidemiology of America (SHEA)/Infectious Diseases Society of America (IDSA) preventative guidelines
- For patients, visitors, and healthcare professionals:
 When entering the room, wear gloves and a gown as part of the contact precautions
Hand sanitizers with alcohol in them are ineffective. It is advised to wash your hands with soap and water both before and after interacting with patients.
If at all possible, accommodate C. difficile patients in their own rooms.
- Disinfection and cleansing of the environment
Identify and lessen environmental sources; disinfect with hypochlorite or another spore-killing solution; and disinfect.
- Restrictions on antibiotic use
Reduce the frequency and length of antibiotic treatment. Use extra caution when giving antibiotics that are frequently cited as suspects.


Associated Conditions Sepsis, toxic megacolon, pseudomembranous colitis, colonic perforation

Presenting History Diarrhea and stomach discomfort or cramping are frequent presenting symptoms.
Recent antibiotic use (Risk of C. difficile infection may persist for 3 months after medication is ceased.) Age and underlying comorbidities.
Utilization of H2-receptor blockers or proton pump inhibitors
Recent hospitalization or stay at a nursing facility Diarrhea (defined as >3 stools in 24 hours) that is watery, foul-smelling, and occasionally bloody Fever (10%), anorexia, and nausea 
gastrointestinal interventions such as surgery, enemas, and tube feeding

clinical assessment 
Examine your abdomen for discomfort, a rise in distension, a decrease in bowel sounds, and peritoneal symptoms.
The initial manifestation might be fulminant and quickly deadly; the management strategy depends on the severity assessment.
Keep an eye out for symptoms of a systemic disease, such as fever, tachycardia, hypotension, and dehydration.

Infectious reasons are the differential diagnosis.
Shiga toxin-producing Escherichia coli infection - Shigella - Campylobacter - Noninfectious causes
Obstruction of the digestive tract and ischemic bowel disease
- Gastrointestinal cancer - Inflammatory bowel disease, including ulcerative colitis and Crohn's disease
Other antibiotic-associated diarrhea (75% of antibiotic diarrhea not linked to C. difficile) - Drug-associated diarrhea - Foodborne disease -


Diagnostic tests and laboratory results
Initial examinations (lab, imaging)
CBC, BMP, lactate, and serum creatinine to determine leukocytosis and the severity of the disease
There are various stool tests available to make a diagnosis.
- The Glutamate Dehydrogenase (GDH) Assay (Specificity: 89-99%; Sensitivity: 85-95%)
- Toxin A or B enzyme immunoassays with sensitivity ranging from 63% to 94%.
Tests for amplification of nucleic acids (NAATs)
- Gold-standard cytotoxicity tests performed on cell cultures
Stepwise testing methodology, frequently employed by may differ per facility - for instance, GED plus toxin assay with NAAT testing for inconsistent results
Repeat testing is not advised if experiencing the same episode of diarrhea. After a successful treatment, sluggish bowel movements continue for 3 to 6 weeks.
In the absence of symptoms of systemic disease or clinical suspicion of a complicated or severe disease, routine radiologic testing is not advised.
- Colonic distension and thumbprinting may be visible in plain films.
- In extreme situations (i.e., extraluminal air), a CT scan may reveal mucosal thickening, thickening of the colonic wall, pericolonic inflammation, or symptoms of a complex infection.
Endoscopy can test for the presence of pseudomembranes and rule out other disorders during diagnostic procedures.
Flexible sigmoidoscopy may miss 15-20% of pseudomembranes (from the proximal colon), despite the fact that not all patients with C. difficile infection have them.
Guidelines for Test Interpretation from SHEA/IDSA
Leukocytosis with a white blood cell (WBC) count of less than 15,000 cells per L and a serum creatinine level that is 1.5 times the premorbid level indicate a mild or severe condition.
Leukocytosis with a WBC count >15,000 cells/L or a serum creatinine level >1.5 times the premorbid level are two signs of a severe, simple disease.
Hypotension, sepsis, a noticeably high WBC count, and imaging signs indicate a severe, complicated disease

Treatment – Antimotility medications should not be used.
Refrain from using antibiotics carelessly.
Proton pump inhibitors have been linked to recurrent infections, although their causality has not been established.
Affected antibiotics should be stopped whenever possible.

The First Line of Medicine

First episode of a mild or moderate illness (nonfulminant): Fidaxomicin 200 mg BID for 10 days; Vancomycin 125 mg QID for 10 days.
When none of the aforementioned treatments are available, it is reasonable to use metronidazole, 500 mg TID PO for 10 days.
Vancomycin or metronidazole can be administered intravenously (IV) if the patient is unable to take oral drugs.
First recurrence: Use vancomycin taper: 125 mg QID for 10 to 14 days, BID for a week, QD for a week, and then every 2 or 3 days for 2 to 8 weeks if a standard regimen was used during the original episode.
- If VAN was used to treat the initial episode, fidaxomicin 200 mg was administered BID for 10 days.
Vancomycin 125 mg PO QID for 10 to 14 days, followed by 125 mg PO BID for 7 days, 125 mg PO once daily for 7 days, and 125 mg PO every two to three days for 2 to 8 weeks:
Pulse dosing every two to three days enables spores to develop before being eliminated.
- Fecal microbiota transplantation should be considered with recurrence after 3 treatment courses. - Vancomycin 125 mg PO QID for 10 days followed by rifaximin 400 mg TID for 20 days.
In individuals with a severe C. difficile infection, enteral vancomycin is the first-line treatment:
125 mg QID PO for 10–14 days.
Vancomycin retention enema if unable to take PO or if there is indication of poor gastrointestinal motility. Fulminant infection: Consider surgical and critical care consultation. Fidaxomicin 200 mg given BID for 10 days.
- 500 mg of vancomycin PO or nasogastric tube per day. Consider administering 500 mg of vancomycin rectally if ileus or PO are not options.
- Metronidazole given intravenously (500 mg every 8 hours)

Caution 

Use oral or rectal versions of vancomycin to treat C. difficile infection. IV formulations that are not eliminated through the intestinal lumen are useless.

Next Line

Vancomycin: for patients who cannot tolerate or have failed metronidazole therapy and for pregnancy; Fecal transplant: feces from healthy, screened donor. Oral metronidazole: 500 mg PO TID for 10 to 14 days.
administered either orally or rectorily. Highly efficient for treating recurring infections (cure rates of 80–90% after stopping the offending drug); recipient gut flora changed in as little as 3 days after fecal transplantation.


Procedures involving surgery In the presence of a known infection, severe abdominal pain or indications of hemodynamic instability should result in surgical and critical care consultation.
The colon has been perforated.

Because of its frequent association with fulminant colitis, the Caution BI/NAP1/027 strain frequently necessitates surgical intervention in younger individuals with severe illness.


Further Treatments 
Probiotics Lactobacillus acidophilus and Saccharomyces boulardii have inhibitory effects on Clostridium difficile and can help prevent C. difficile infection. Adjunctive IV immunoglobulin (IVIG) has showed potential; additional data are needed before routine use.
Additional treatments under investigation:
- More recent antibiotics (such as rifabutin, tolevamer, and ramoplanin); - Monoclonal antibodies that control the effects of toxins
- C. difficile antitoxin antibody vaccine


Admission Initial stabilization Admission requirements
Reduced diarrhea severity and frequency - Tolerating oral diet and drugs - Hypovolemia - Inability to maintain enteric losses - Hematochezia - Electrolyte abnormalities - Discharge criterion

Take Action 

Because individuals may continue to release toxins for weeks after an acute infection, testing for them shouldn't be repeated.

patient observation
Relapses of colitis happen in 15-30% of cases, and they usually start 2–10 days after stopping antibiotics.


Other therapies and precautions include a regular diet and NPO if surgery is being considered for severe colitis.


Inform patients about C. difficile transmission, the necessity of proper hand washing with soap and water, the ineffectiveness of alcohol-based sanitizers, and the need to avoid overusing antibiotics in order to reduce the risk of C. difficile infection.

The majority of patients recover with oral antibiotics and conservative care; however, 1-3% of patients get severe/fulminant colitis that necessitates an urgent colectomy.