Clostridium difficile infection resident survival guide
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mugilan Poongkunran M.B.B.S [2]
Definition
Clostridium difficile infection (CDI) is defined as the acute onset of diarrhea (≥ 3 unformed stools in ≤24 hours) with either documented toxigenic Clostridium difficile (C. difficile) or its toxin, or colonoscopic or histopathological findings of pseudomembranous colitis in the absence of any other documented cause of diarrhea.[1]
- Health-care facility onset health-care facility associated (HO-HCFA): Onset of symptoms within 3 days of admission to a health-care facility
- Community onset health-care facility associated (CO-HCFA): Onset of symptoms within 4 weeks of discharge from a health-care facility
- Community onset (CA): Onset of symptoms outside health-care facility or <3 days after admission to a health-care facility and has not been discharged from health-care facility in the previous 12 weeks
- Indeterminate or unknown: Onset of symptoms after being discharged from a health-care facility 4-12 weeks previously
Causes
Life Threatening Causes
Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated. Clostridium difficile infection itself may present or complicate as a life-threatening condition and must be treated as such irrespective of the causes.
Common Causes
- Cephalosporins[2]
- Clindamycin[3]
- Fluoroquinolones[4]
- Histamine 2 receptor antagonists[5]
- Penicillins
- Proton-pump inhibitors (PPIs)[6]
Management
Characterize the symptoms: ❑ Diarrhea (Onset, duration, pattern, bloody or watery) ❑ Mental status change ❑ Fever ❑ Abdominal pain ❑ Abdominal distention ❑ Nausea ❑ Vomiting ❑ Loss of appetite | |||||||||||||||||||||||
Examine the patient:
1. Assess volume status: ❑ Extremities (Edema) ❑ Abdomen (Distension or tenderness) ❑ Anorectal (Bleeding) ❑ CVS ❑ RS | |||||||||||||||||||||||
Order tests: ❑ CBC | |||||||||||||||||||||||
Order tests for C. difficile | |||||||||||||||||||||||
Management plan | |||||||||||||||||||||||
❑ WBC ≤15,000 cells/µL, or ❑ Serum creatinine ≤1.5 times the premorbid level | ❑ WBC >15,000 cells/µL, or ❑ Serum creatinine >1.5 times the premorbid level | ❑ Hypotension or shock ❑ Ileus ❑ Megacolon | |||||||||||||||||||||
Mild or moderate initial episode | Severe initial episode | Complicated severe initial episode | |||||||||||||||||||||
❑ Metronidazole 500 mg 3 times/day, oral, for 10-14 days | ❑ Vancomycin 125 mg 4 times/day, oral, for 10-14 days | ❑ Vancomycin 500 mg 4 times/day, oral or by NG tube, PLUS ❑ Metronidazole 500 mg every 8 hours IV ❑ Consider administering rectal vancomycin in case of complete ileus | |||||||||||||||||||||
First recurrence? ❑ Repeat the treatment of the initial episode | |||||||||||||||||||||||
Second recurrence? ❑ Administer vancomycin in a tapered and/or pulsed way | |||||||||||||||||||||||
Yes | No | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
❑ Isolate the patient ❑ Discontinue non-C.Difficle treatment antibiotics ❑ Intravenous fluids OR Oral rehydration therapy based upon hydration status ❑ Appropriate attention to infection prevention and control ❑ Emperical antibiotic (Metronidazole OR vancomycin based on clinical severity) ❑ Hand hygiene and barrier precautions ❑ Single-use disposable equipment should be used | ❑ Intravenous fluids OR Oral rehydration therapy based upon hydration status ❑ Review further inciting antibiotic and other drug history and risk factors for CDI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Hospital approval/affordable for Nucleic acid amplification tests (NAATs) for C. difficile toxin | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Yes | No | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Fecal glutamate dehydrogenase (GDH) screening tests for C. difficile | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Positive | Negative | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Enzyme immunoassay (EIA) for toxins A + B | Evalute for other acute diarrhea causes | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Negative | Positive | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Fecal nucleic acid amplification tests:
❑ Polymerase chain reaction (PCR): Most preferred ❑ Isothermal amplification tests | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Negative | Positive | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Evalute for other acute diarrhea causes | No strong clinical suspicion of CDI | Strong clinical suspicion of CDI | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Rx for CDI | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
❑ Isolate the patient ❑ Discontinue non-C.Difficle treatment antibiotics ❑ Stop all anti-peristaltic agents ❑ Intravenous fluids OR Oral rehydration therapy based upon hydration status ❑ Appropriate attention to infection prevention and control ❑ Hand hygiene and barrier precautions ❑ Single-use disposable equipment should be used | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment of severity | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Any of the following:
❑ Admission to intensive care unit for CDI ❑ Hypotension with or without required use of vasopressors ❑ Fever ≥20.5 °C ❑ Ileus or significant abdominal distention ❑ Mental status changes ❑ Serum lactate levels >2.2 mmol/l ❑ WBC ≥35,000 cells/mm3 or <2,000 cells/mm3 ❑ End organ failure (mechanical ventilation, renal failure, etc.) | ❑Serum albumin <3g/dl
Plus: Any ONE of the following: | Diarrhea plus any additional signs or symptoms not meeting severe or complicated criteria | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Severe and complicated | Severe | Mild-moderate | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Significant abdominal distention | No significant abdominal distention | Oral vancomycin 125 mg QID X 10 days | Oral metronidazole 500 mg TID X 10 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
❑ Oral vancomycin 125 mg QID Plus ❑ Intravenous metronidazole 500 mg TID ❑ CT ❑ Venous thromboembolism (VTE) prophylaxis | Any ONE of the following:
❑ Failure to respond to metronidazole therapy within 5–7 days | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
❑ Oral vancomycin 500 mg QID Plus ❑ Vancomycin per rectum (500 mg in a volume of 500 ml QID) Plus ❑ Intravenous metronidazole 500 mg TID ❑ Venous thromboembolism (VTE) prophylaxis | CT showing colon wall thickening, ascites, “megacolon”, ileus, or perforation | CT normal | ❑ Oral vancomycin 125 mg QID X 10 days OR ❑ Oral fidaxomicin 200 mg BD X 10 days) | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Surgical consultation and operative management in required cases | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
❑Monitor patient status ❑Complete the antibiotic course ❑ Discharge when completely recovered ❑Disinfection of environmental surfaces using an Environmental Protective Agency (EPA)-registered disinfectant | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
First recurrence
❑ Confirm diagnosis as above | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Severe | Mild-moderate | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Initial vancomycin regimen | Intial metronidazole regimen | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
❑Tapered and pulsed vancomycin regimen
Oral vancomycin 125 mg QID, followed by 125 mg daily pulsed every 3 days for ten doses X 10 days | ❑Tapered and pulsed vancomycin regimen
Oral vancomycin 125 mg QID, followed by 125 mg daily pulsed every 3 days for ten doses X 10 days | ❑ Oral metronidazole 500 mg TID X 10 days OR ❑ Oral vancomycin 125 mg QID X 10 days | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Second recurrence
❑ Confirm diagnosis as above | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Third recurrence
❑ Confirm diagnosis as above | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Do's
- Only stools from patients with diarrhea should be tested for C. difficile.[1]. Very occasionally, a patient with ileus and complicated disease will have a formed stool, in which case the laboratory should be made aware of this special clinical situation. Rectal swabs can be used for PCR and thus may be useful in timely diagnosis of patients with ileus.[7]
- Vancomycin therapy delivered via enema should be added to treatments in patients in whom oral antibiotics cannot reach a segment of the colon, such as with Hartman’s pouch, ileostomy, or colon diversion.
- Do C. difficile testing in all patients with IBD who develop diarrhea in the setting of previously quiescent disease or with a disease flare.[8] Initiate empirical therapy directed against CDI in inflammatory bowel disease IBD patients with severe colitis.[9]
- Do C. difficile testing in patients with underlying immunosuppression (including malignancy, chemotherapy, corticosteroid therapy, organ transplantation, and cirrhosis), with any diarrheal illness.
- Do C. difficile testing in women who are pregnant or periparturient with any diarrheal illness because of increased rate of maternal and fetal mortality.[10]
- Until the resolution of diarrhea, a patient with CDI should be placed in a private room or in a room with another patient with documented CDI as C.Difficle can be cultured from the skin surface of patients and from the surfaces in rooms of infected patients.[7] The ideal recommendation is to maintain contact precautions for 48hr after diarrhea ceases.[11]
- The evidence for the use of probiotics, Lactobacillus casei, Lactobacillus bulgaricus, and Streptococcus thermophilus to decrease the incidence of antibiotic-associated diarrhea is insufficient.[12]
Don't s
- Don't screen for clostridium difficle among patients without diarrhea.
- Don't repeat testing for negative tests.
- Dont use anti-peristaltic agents to control diarrhea for confirmed or suspected CDI patients, as they may obscure symptoms and precipitate complicated disease.[13]
- Repeat testing should be discouraged as it increases the likelihood of false positives and if requested, the physician should confer with the laboratory to explain the clinical rationale.[14][15]
- Empiric therapy for CDI should not be discontinued or withheld in patients with a high pre-test suspicion for CDI.
- Dont treat asymptomatic C.Difficle carriers as treating such patients may increase the shedding of spores and growth of new resistant strains.[16]
- Don't test for cure following an episode of clostridium difficile diarrhea.
References
- ↑ 1.0 1.1 Cohen SH, Gerding DN, Johnson S, Kelly CP, Loo VG, McDonald LC; et al. (2010). "Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA)". Infect Control Hosp Epidemiol. 31 (5): 431–55. doi:10.1086/651706. PMID 20307191.
- ↑ Bartlett JG (2006). "Narrative review: the new epidemic of Clostridium difficile-associated enteric disease". Ann Intern Med. 145 (10): 758–64. PMID 17116920.
- ↑ Johnson S, Samore MH, Farrow KA, Killgore GE, Tenover FC, Lyras D; et al. (1999). "Epidemics of diarrhea caused by a clindamycin-resistant strain of Clostridium difficile in four hospitals". N Engl J Med. 341 (22): 1645–51. doi:10.1056/NEJM199911253412203. PMID 10572152.
- ↑ Pépin J, Saheb N, Coulombe MA, Alary ME, Corriveau MP, Authier S; et al. (2005). "Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: a cohort study during an epidemic in Quebec". Clin Infect Dis. 41 (9): 1254–60. doi:10.1086/496986. PMID 16206099.
- ↑ Kwok CS, Arthur AK, Anibueze CI, Singh S, Cavallazzi R, Loke YK (2012). "Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis". Am J Gastroenterol. 107 (7): 1011–9. doi:10.1038/ajg.2012.108. PMID 22525304. Review in: Ann Intern Med. 2012 Aug 21;157(4):JC2-13 Review in: Evid Based Med. 2013 Oct;18(5):193-4
- ↑ Janarthanan S, Ditah I, Adler DG, Ehrinpreis MN (2012). "Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis". Am J Gastroenterol. 107 (7): 1001–10. doi:10.1038/ajg.2012.179. PMID 22710578.
- ↑ 7.0 7.1 Kundrapu S, Sunkesula VC, Jury LA, Sethi AK, Donskey CJ (2012). "Utility of perirectal swab specimens for diagnosis of Clostridium difficile infection". Clin Infect Dis. 55 (11): 1527–30. doi:10.1093/cid/cis707. PMID 22911648.
- ↑ Jen MH, Saxena S, Bottle A, Aylin P, Pollok RC (2011). "Increased health burden associated with Clostridium difficile diarrhoea in patients with inflammatory bowel disease". Aliment Pharmacol Ther. 33 (12): 1322–31. doi:10.1111/j.1365-2036.2011.04661.x. PMID 21517920.
- ↑ Ben-Horin S, Margalit M, Bossuyt P, Maul J, Shapira Y, Bojic D; et al. (2009). "Combination immunomodulator and antibiotic treatment in patients with inflammatory bowel disease and clostridium difficile infection". Clin Gastroenterol Hepatol. 7 (9): 981–7. doi:10.1016/j.cgh.2009.05.031. PMID 19523534.
- ↑ Centers for Disease Control and Prevention (CDC) (2005). "Severe Clostridium difficile-associated disease in populations previously at low risk--four states, 2005". MMWR Morb Mortal Wkly Rep. 54 (47): 1201–5. PMID 16319813.
- ↑ Vonberg RP, Kuijper EJ, Wilcox MH, Barbut F, Tüll P, Gastmeier P; et al. (2008). "Infection control measures to limit the spread of Clostridium difficile". Clin Microbiol Infect. 14 Suppl 5: 2–20. doi:10.1111/j.1469-0691.2008.01992.x. PMID 18412710.
- ↑ Hickson M, D'Souza AL, Muthu N, Rogers TR, Want S, Rajkumar C; et al. (2007). "Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial". BMJ. 335 (7610): 80. doi:10.1136/bmj.39231.599815.55. PMC 1914504. PMID 17604300. Review in: Evid Based Med. 2008 Apr;13(2):46 Review in: Evid Based Nurs. 2008 Apr;11(2):57
- ↑ Koo HL, Koo DC, Musher DM, DuPont HL (2009). "Antimotility agents for the treatment of Clostridium difficile diarrhea and colitis". Clin Infect Dis. 48 (5): 598–605. doi:10.1086/596711. PMID 19191646.
- ↑ Deshpande A, Pasupuleti V, Pant C, Hall G, Jain A (2010). "Potential value of repeat stool testing for Clostridium difficile stool toxin using enzyme immunoassay?". Curr Med Res Opin. 26 (11): 2635–41. doi:10.1185/03007995.2010.522155. PMID 20923255.
- ↑ Luo RF, Banaei N (2010). "Is repeat PCR needed for diagnosis of Clostridium difficile infection?". J Clin Microbiol. 48 (10): 3738–41. doi:10.1128/JCM.00722-10. PMC 2953130. PMID 20686078.
- ↑ Johnson S, Homann SR, Bettin KM, Quick JN, Clabots CR, Peterson LR; et al. (1992). "Treatment of asymptomatic Clostridium difficile carriers (fecal excretors) with vancomycin or metronidazole. A randomized, placebo-controlled trial". Ann Intern Med. 117 (4): 297–302. PMID 1322075.