Infectious Diarrhea & CDI Flashcards
Define “acute infectious diarrhea”.
Acute: Increased frequency of defecation lasting < 14 days
Diarrhea: >= 3 loose or liquid stools OR more frequent than normal for an individual
Caused by one or more microorganisms
Describe the microbiology of acute infectious diarrhea.
Common pathogens include:
Bacteria: Campylobacter jejuni, Salmonella typhi, Shigella spp., E. coli, Vibrio cholera, Clostridioides difficile
Protozoal: Giardia intestinalis, Entamoeba histolytica, Cryptosporidium parvum
Viral: Norovirus, Rotavirus, Adenovirus
What are some diagnostic tests available to diagnose whether a patient has acute infectious diarrhea?
1) Fecal occult blood
- non-specific test that detects blood in diarrhea
- indicative of GIT damage
2) Ova & parasite test
3) Stool cultures
4) Polymerase chain reaction (PCR)
- more rapid turnover of results for identification of pathogens
Under what conditions will a diagnostic test be required to determine if a patient indeed experiencing acute infectious diarrhea?
Usually not indicated due to self-limiting nature.
Reserved for selected patients:
- Severe illness
- Persistent fever
- Bloody stools
- Immunosuppression
- Unresponsive to self-care Tx (e.g. fluid rehydration therapy, probiotics, adsorbents & antiperistaltics)
How can acute infectious diarrhea be prevented?
Good hand & food hygiene practices
Vaccinations
- Cholera & Typhoid prior to travel to endemic areas
- Rotavirus as part of childhood immunisation schedule
What are some non-pharmacological recommendations for the treatment of acute infectious diarrhea?
Early re-feeding as tolerated
Feed easily digestible food (e.g. crackers, toast, cereal, bananas)
When is Abx indicated for the Tx of acute infectious diarrhea?
Most cases are self-limiting & do not require antibiotics.
Indications for Abx:
- Severe disease: fever w/ bloody diarrhea OR mucoid stools (bacterial in nature) OR severe abdominal pain/cramps/tenderness
- Sepsis
- Immunocompromised
If Abx is indicated, what is the recommended Tx for pt experiencing acute infectious diarrhea?
1) IV Ceftriaxone 2g q24h x 3-5 days
- Pt. usually have severe symptoms requiring hospitalisation, thus IV Abx can be used.
2) PO Ciprofloxacin 500mg BD x 3-5 days
- ONLY for severe penicillin allergy
Tx duration may be extended to 10-14 days in pt w/ bacteremia, extra-intestinal infections or are immunocompromised.
What should we monitor for during Abx Tx of patients w/ acute infectious diarrhea?
Resolution of symptoms & clinical improvement
Further workup if persistent symptoms
Step down therapy if applicable.
Describe the morphological characteristics of Clostridioides difficile.
Gram-positive, spore-forming anaerobic bacillus that produces toxin A & B
Most common cause of nosocomial diarrhea
How is C. difficile transmitted?
Fecal-oral transmission
Contact with contaminated environmental surfaces (fomites)
Hand carriage by healthcare workers
Describe the pathogenesis of C. difficile infection (CDI).
1) C. difficile contains endospores that can survive acidity of stomach & reach large intestine.
2) Normal gut flora altered by broad-spectrum Abx
- most notably: clindamycin, fluoroquinolones, 2nd generation & higher cephalosporins, amoxicillin & ampicillin
3) Resulting in C. difficile flourishing w/in colon
4) Production of toxins A & B causes mucosal damage & subsequently pseudomembranous colitis if prolonged
- yellowish plaques formed over damaged epithelium
5) Results in fever, crampy abdominal pain & diarrhea
What are some risk factors associated with CDI?
1) Healthcare Exposure (highest risk)
- Prior hospitalisation
- Duration of hospitalisation
- Residence in nursing homes / long-term care facilities
2) Pharmacotherapy
- Systemic Abx -> no. of agents & duration used
- Use of high-risk Abx: clindamycin, 2nd or higher cephalosporins, FQ, ampicillin & amoxicillin
- Use of gastric acid suppressive therapy (i.e. antacids, H2RA & PPIs) -> decrease gastric pH increases CDI risk
3) Patient-Related Factors
- Multiple or severe comorbidities (DM, stroke, CHD etc)
- Immunosuppression
- > 65 y/o
- Hx of CDI
Explain the classification of CDI with respect to its clinical presentation.
Mild: loose stools, abdominal cramps Moderate: - Fever, nausea, malaise - Abdominal cramps & distension - Leukocytosis (increased WBC) - Hypovolemia Severe/Fulminant: - Ileus (intestinal paralysis due to immense inflammation; diarrhea is stopped) - Toxic megacolon (often hand-in-hand w/ ileus) - Pseudomembranous colitis - Perforation - Death
How is CDI clinically diagnosed?
Based on BOTH clinical suspicion based on signs & symptoms AND confirmatory test or finding.
1) Clinical Suspicion: EITHER/OR
- Unexplained & new-onset diarrhea (i.e. >= 3 unformed stools in 24h) OR
- Radiological evidence of ileus or toxic megacolon
+
2) Confirmatory Test/Finding: EITHER/OR
- Positive diagnostic test results for C. difficile or its toxins OR
- Histopathological findings of pseudomembranous colitis
Why is stool cultures not routinely performed to diagnose whether a patient has CDI?
Long turnaround time
What are some “don’ts” in the diagnosis of CDI?
DON’T test asymptomatic patients
DON’T repeat testing in < 7 days
DON’T perform test of cure
- > 60% of pt remain positive despite successful Tx
What are some infection control methods to minimise the risk of CDIs?
Healthcare:
- Practice hand hygiene
- Contact precautions recommended until 48h after diarrhea resolves
- Wear PPE & wash hands with SOAP & WATER (preferred) after pt care
Home:
- Wash hands w/ soap & water after using bathroom
- Use separate bathroom where possible
- Clean toilets, linens, towels, clothing w/ bleach
What are some diagnostic tests available, besides stool cultures, for the diagnosis of CDI?
1) Nucleic acid amplification tests (NAAT):
- Toxin enzyme immunoassay (EIA) -> presence of toxins A & B
- Glutamate dehydrogenase EIA -> enzyme present w/ C. difficile
2) Polymerase chain reaction (PCR)
What are some factors to consider for in the pharmacological treatment of CDI?
If possible, discontinue all other concurrent Abx
- increase clinical response & reduce recurrence
Empiric CDI Tx is recommended ONLY if:
- Substantial delay (> 48h) in diagnostics
- Fulminant CDI
Define the various types of CDI according to IDSA guidelines.
Non-Severe: WBC < 15x10^9 /L AND SCr < 133 umol/L
Severe: WBC >= 15 x 10^9 /L OR SCr >= 133 umol/L
Fulminant: same lab parameters as severe AND hypotension / ileus / toxic megacolon / psuedomembranous colitis
58 y/o male with PMH of T2DM and HTN is receiving a 4-week course of piperacillin/tazobactam for DFI caused by P. aeruginosa. 2 weeks into his antibiotic course, he complained of new-onset loose stools (5 episodes/day).
T 38.4 deg C, BP 126/86, HR 76, RR 22
WBC 11.8 x 10^9 /L, creatinine 117 umol/L
Allergies: no known drug allergies
C. difficile PCR: positive
Assuming that this is his first episode of CDI, recommend an appropriate management strategy.
For non-severe CDI:
Vancomycin 125mg PO QDS x 10 days OR
Fidaxomicin 200mg PO BD x 10 days
Alternative (less preferred):
Metronidazole 400mg PO TDS x 10 days
Extend to 14 days if symptoms are not completely resolved.
55 y/o male with PMH of T2DM and HTN is receiving a 4-week course of piperacillin/tazobactam for DFI caused by P. aeruginosa. 2 weeks into his antibiotic course, he complained of new-onset loose stools (5 episodes/day) and abdominal discomfort.
T 38.4 deg C, BP 126/86, HR 76, RR 22
WBC 11.8 x 10^9 /L, creatinine 140 umol/L
Allergies: no known drug allergies
C. difficile PCR: positive
Assuming that this is his first episode of CDI, recommend an appropriate management strategy.
For severe CDI:
Vancomycin 125mg PO QDS x 10 days OR
Fidaxomicin 200mg PO BD x 10 days
Extend to 14 days if symptoms are not completely resolved.
56 y/o female with PMH of T2DM and HTN is receiving a 4-week course of piperacillin/tazobactam for DFI caused by P. aeruginosa. 2 weeks into her antibiotic course, she complained of new-onset loose stools (5 episodes/day) and severe abdominal discomfort.
T 38.4 deg C, BP 96/56, HR 76, RR 22
WBC 16.8 x 10^9 /L, creatinine 141 umol/L
Allergies: no known drug allergies
C. difficile PCR: positive
Assuming that this is her first episode of CDI, recommend an appropriate management strategy.
For fulminant CDI w/o ileus:
Vancomycin 500mg PO QDS + Metronidazole 500mg IV q8h x 10 days
Extend to 14 days if symptoms are not completely resolved.
54 y/o female with PMH of T2DM and HTN is receiving a 4-week course of piperacillin/tazobactam for DFI caused by P. aeruginosa. 2 weeks into her antibiotic course, she complained of severe abdominal discomfort at the A&E. She mentioned that she had new-onset loose stools (5 episodes/day) yesterday but her diarrhea has stopped suddenly today.
T 38.4 deg C, BP 96/56, HR 76, RR 22
WBC 16.8 x 10^9 /L, creatinine 141 umol/L
Allergies: no known drug allergies
C. difficile PCR: positive
Assuming that this is her first episode of CDI, recommend an appropriate management strategy.
For fulminant CDI w/ ileus:
Vancomycin 500mg PO QDS + Vancomycin 500mg PR QDS + Metronidazole 500mg IV q8h x 10 days
Extend to 14 days if symptoms are not completely resolved.
Postulate a reason why metronidazole may still be used as first-line Tx for CDI in some patients locally.
Cost & logistical considerations
- IV Vancomycin is the only formulation available in SG, thus it can be inconvenient to administer.
- However, avoid prolonged / repeated courses of metronidazole due to cumulative & potentially irreversible neurotoxicity.
What is the mechanism of action of fidaxomicin?
Narrow-spectrum macrocyclic (novel macrolide) Abx that inhibits transcription & protein synthesis of C. difficile by binding to RNA polymerase enzyme
What is the spectrum of activity of fidaxomicin?
Primarily gram-positive aerobes & anaerobes
Bactericidal against C. difficile
List some potential benefits of fidaxomicin.
Lower MIC than for metronidazole & vancomycin
Significant PAE (post-Abx effect) against C. difficile (5.5-12h)
Less effect on normal Bacteriodes spp. in gut
Postulate a reason why fidaxomicin is not widely used for the treatment of CDI despite being a first-line drug recommended in IDSA guidelines.
Very expensive
- $2k»_space; $30 when comparing fidaxomicin 200mg PO BD x 10 days vs vancomycin 125mg PO QDS x 10 days
Thus, clinical use is limited to severe and/or recurrent non-responsive cases to maximise standard therapy
58 y/o male with PMH of T2DM and HTN is receiving a 4-week course of piperacillin/tazobactam for DFI caused by P. aeruginosa. 2 weeks into his antibiotic course, he complained of new-onset loose stools (5 episodes/day).
T 38.4 deg C, BP 126/86, HR 76, RR 22
WBC 11.8 x 10^9 /L, creatinine 117 umol/L
Allergies: no known drug allergies
C. difficile PCR: positive
Assuming that this is his second episode of CDI, recommend an appropriate management strategy.
If metronidazole for initial episode:
Vancomycin 125 mg PO QDS x 10 days
If vancomycin/fidaxomicin for initial episode:
1) Fidaxomicin 200mg PO BD x 10 days OR
2) Vancomycin PO taper
- e.g. 125 mg QDS x 10 days, 125mg BD x 1 week, 125mg OD x 1 week, 125mg q2-3 daysx 2-8 weeks
What are some monitoring parameters we should look out for during Abx Tx of CDI?
Clinical improvement expected in 5-7 days
Additional diagnostics or consider escalation of pharmacological Tx if poor response
Do NOT continue CDI Tx for as long as Tx duration of concurrent Abx for an ongoing infection!!
- e.g. DFI, pressure ulcer infection
Probiotics can be recommended for routine use to prevent or treat CDI. True or false?
False
Antiperistaltics, such as loperamide, diphenoxylate & atropine has limited role in infectious diarrhea and should not be recommended as adjunctive Tx. True or false?
True.
Anti-motility agents reduces bowel input, which reduces ability to perform stool testing & are associated with poor outcomes esp. if diarrhea is not treated appropriately.
