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''This page is for <u>adult</u> patients; for pediatric patients see [[Special:MyLanguage/clostridium difficile (peds)|clostridium difficile (peds)]].''

==Background==

[[File:Pseudomembranous colitis 1.jpg|thumb|Pseudomembranous colitis with yellow pseudomembranes seen on the wall of the sigmoid colon.]]
*[[Special:MyLanguage/Clostridium|Clostridium]] is a genus of [[Special:MyLanguage/gram-positive bacteria|gram-positive bacteria]]
*Most common cause of infectious diarrhea in hospitalized patients
*Use contact isolation if suspect
*Alcohol-based hand sanitizers do not reduce spores, but good hand washing does<ref>Leffler DA and Lamont JT. Clostridium difficile Infection. N Engl J Med. 2015; 372:1539-1548.</ref>

===Risk factors for Pseudomembranous Colitis===

*Recent antibiotic use (any)
*GI surgery
*Severe underlying medical illness
*Chemo
*Elderly

==Clinical Features==

''Varies according to severity and intrinsic host factors (immunosuppression, etc.).''
*Profuse watery [[Special:MyLanguage/diarrhea|diarrhea]]
**Usually develops after 7-10 days of antibiotics use or within 2 weeks of discontinuation
*History of risk factor(s) (see Background)
*May report diffuse [[Special:MyLanguage/abdominal pain|abdominal pain]]/cramping
*At the extreme, may present with [[Special:MyLanguage/sepsis|sepsis]] secondary to intestinal perforation or [[Special:MyLanguage/toxic megacolon|toxic megacolon]]

==Differential Diagnosis==

{{Diarrhea DDX}}

==Evaluation==

[[File:MPX1834 synpic40781.png|thumb|Pseudomembranous colitis from ''C. difficile'' on abdominal CT demonstratin diffuse colonic wall thickening and a shaggy endoluminal contour.]]
[[File:PMC5137169 gr1.png|thumb|Pseudomembranous colitis with (A) Accordion sign in transverse colon (thin arrows). (B) Colonic wall thickness, target sign (thick arrow), peritoneal fluid (thin arrow) and pericolonic fat stranding (arrowhead).]]

===Workup===

*Consider testing patients with unexplained and new-onset ≥3 unformed stools within 24 hours<ref name="ISDA C. Diff 2017">Clinical Practice Guidelines for Clostridium difficile Infection in Adults and Children: 2017 Update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA) McDonald CL, et al. Clinical Infectious Diseases, Volume 66, Issue 7, 1 April 2018, Pages e1–e48, https://doi.org/10.1093/cid/cix1085</ref>
*Institutions should have an agreed protocol using a stool toxin test as part of a multistep algorithm (e.g. glutamate dehydrogenase [GDH] plus toxin; GDH plus toxin, arbitrated by nucleic acid amplification test [NAAT])
**or NAAT plus toxin) rather than a NAAT alone for all specimens received in the clinical laboratory when there are no preagreed institutional criteria for patient stool submission (Figure 2) (weak recommendation, low quality of evidence).

*C. diff toxin assay
**Sn 63-94%, Sp 75-100%
*Culture
**Positive culture only means C. diff present, not necessarily that it is causing disease

===Testing Algorithm===

''For patients with suspected Clostridium difficile associated diarrhea (CDAD)''
*'''Low''' suspicion
**Send stool for C. diff toxin assay
***Positive → treat (no further testing indicated)
***Negative → do not treat (no further testing indicated)
*'''High''' suspicion
**Send stool for C. diff toxin assay AND treat empirically
***Positive → treat (no further testing indicated)
***Negative → Consider discussion with ID (false negative tests may occur); eval for other causes of diarrhea

===Repeat testing===

*Never a need for repeat testing within 7 days of a previous test
*NO NEED to repeat positive tests as symptoms resolve as a “test of cure”
*NO NEED to repeat test soon after initial negative test (more likely to be a false positive test than a true positive test)

===Severe Criteria<ref name="IDSA">IDSA Guidelines [http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/cdiff2010a.pdf PDF]</ref><ref>ACG Guidelines for Diagnosis, Treatment, and Prevention of Clostridium difficile Infections http://gi.org/guideline/diagnosis-and-management-of-c-difficile-associated-diarrhea-and-colitis/</ref><ref>McDonald LC, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clinical Infectious Diseases. 2018;66:e1.</ref>===

*Leukocytosis with a white blood cell count of ≥15000 cells/mL
*Serum creatinine level >1.5 mg/dL
*Serum [[Special:MyLanguage/lactate|lactate]] levels >2.2 mmol/l
*[[Special:MyLanguage/Mental status changes|Mental status changes]]
*[[Special:MyLanguage/leukocytosis|WBC]] ≥35,000 cells/mm3 or <2,000 cells/mm3
*Patient requiring ICU admission
*End organ failure ([[Special:MyLanguage/mechanical ventilation|mechanical ventilation]], [[Special:MyLanguage/renal failure|renal failure]], etc.)

===Severe Fulminant Criteria<ref>McDonald LC, et al. Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA). Clinical Infectious Diseases. 2018;66:e1.</ref>===

*[[Special:MyLanguage/Hypotension|Hypotension]] with or without required use of vasopressors
*[[Special:MyLanguage/Ileus|Ileus]] or significant abdominal distention
*Megacolon

==Management==

===Asymptomatic===

*No diagnostic testing or treatment required<ref>Bagdasarian, N, et al. Diagnosis and Treatment of Clostridium difficile in Adults. JAMA. 2015; 313(4):398-408.</ref>
*Consider discontinuing offending antibiotics

===Non-Severe===

Fidaxomicin first line per 2018 IDSA guidelines <ref>Stuart Johnson, Valéry Lavergne, Andrew M Skinner, Anne J Gonzales-Luna, Kevin W Garey, Ciaran P Kelly, Mark H Wilcox, Clinical Practice Guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 Focused Update Guidelines on Management of Clostridioides difficile Infection in Adults, Clinical Infectious Diseases, Volume 73, Issue 5, 1 September 2021, Pages e1029–e1044, https://doi.org/10.1093/cid/ciab549</ref>
{{Non-Severe Cdiff Antibiotics}}

===Severe===

{{Severe Cdiff Antibiotics}}

===Severe Fulminant===

''See criteria above (Evaluation section)''
*[[Special:MyLanguage/Vancomycin|Vancomycin]] 500 mg PO or NG four times daily for 10 days
*Considered rectal instillation of [[Special:MyLanguage/Vancomycin|Vancomycin]]
*[[Special:MyLanguage/Metronidazole|Metronidazole]] 500 mg IV every 8 hours, particularly if ileus is present.
*Consider emergency colectomy if:
**WBC >20K
**[[Special:MyLanguage/Lactate|Lactate]] >5
**Age >75
**Immunosuppression
**[[Special:MyLanguage/Toxic megacolon|Toxic megacolon]]
**Colonic perforation
**Multi-organ system failure

===Recurrent Infection===

''Relapse occurs in 10-25% of patients''
*Occurs <=4 weeks after the completion of therapy
**Otherwise consider other (more common) causes
*1st recurrence: Fidaxomicin first line therapy
*2nd recurrence: tapered [[Special:MyLanguage/vancomycin|vancomycin]] with pulse doses
*3rd recurrence: PO [[Special:MyLanguage/vancomycin|vancomycin]] 10-14 days followed immediately by [[Special:MyLanguage/rifaximin|rifaximin]] "chaser" 400mg TID x20 days <ref>Melville NA. Rifaximin 'Chaser' Reduces C difficile Recurrent Diarrhea. June 07, 2011. http://www.medscape.com/viewarticle/744157</ref>
*Other options:
**[[Special:MyLanguage/IVIG|IVIG]]
**Fecal transplant
**[[Special:MyLanguage/Fidaxomicin|Fidaxomicin]] 200mg BID x10 days noninferior to PO [[Special:MyLanguage/vancomycin|vancomycin]], and reduces recurrences at 4 weeks after treatment (~15% vs 25%) <ref>Louie TJ et al. Fidaxomicin versus [[Special:MyLanguage/Vancomycin|Vancomycin]] for Clostridium difficile Infection. N Engl J Med 2011; 364:422-431.</ref>

==Disposition==

*Admit:
**Severe diarrhea
**Outpatient antibiotic failure
**Systemic response (fever, leukocytosis, severe abdominal pain)

==[[Special:MyLanguage/Antibiotic Sensitivities|Antibiotic Sensitivities]]<ref>Sanford Guide to Antimicrobial Therapy 2014</ref>==

{| class="wikitable"
| align="center" style="background:#f0f0f0;"|'''Category'''
| align="center" style="background:#f0f0f0;"|'''Antibiotic'''
| align="center" style="background:#f0f0f0;"|'''Sensitivity'''
|-
| [[Special:MyLanguage/Penicillins|Penicillins]]||[[Special:MyLanguage/Penicillin G|Penicillin G]]||X2
|-
| ||[[Special:MyLanguage/Penicillin V|Penicillin V]]||X1
|-
| Anti-Staphylocccal [[Special:MyLanguage/Penicillins|Penicillins]]||[[Special:MyLanguage/Methicillin|Methicillin]]||X1
|-
| ||[[Special:MyLanguage/Nafcillin|Nafcillin]]/[[Special:MyLanguage/Oxacillin|Oxacillin]]||X1
|-
| ||[[Special:MyLanguage/Cloxacillin|Cloxacillin]]/[[Special:MyLanguage/Diclox.|Diclox.]]||X1
|-
| Amino-[[Special:MyLanguage/Penicillins|Penicillins]]||[[Special:MyLanguage/AMP|AMP]]/[[Special:MyLanguage/Amox|Amox]]||X1
|-
| ||[[Special:MyLanguage/Amox-Clav|Amox-Clav]]||X1
|-
| ||[[Special:MyLanguage/AMP-Sulb|AMP-Sulb]]||X2
|-
| Anti-Pseudomonal [[Special:MyLanguage/Penicillins|Penicillins]]||[[Special:MyLanguage/Ticarcillin|Ticarcillin]]||X1
|-
| ||[[Special:MyLanguage/Ticar-Clav|Ticar-Clav]]||X1
|-
| ||[[Special:MyLanguage/Pip-Tazo|Pip-Tazo]]||X1
|-
| ||[[Special:MyLanguage/Piperacillin|Piperacillin]]||X2
|-
| [[Special:MyLanguage/Carbapenems|Carbapenems]]||[[Special:MyLanguage/Doripenem|Doripenem]]||X2
|-
| ||[[Special:MyLanguage/Ertapenem|Ertapenem]]||X2
|-
| ||[[Special:MyLanguage/Imipenem|Imipenem]]||X2
|-
| ||[[Special:MyLanguage/Meropenem|Meropenem]]||X2
|-
| ||[[Special:MyLanguage/Aztreonam|Aztreonam]]||R
|-
| [[Special:MyLanguage/Fluroquinolones|Fluroquinolones]]||[[Special:MyLanguage/Ciprofloxacin|Ciprofloxacin]]||R
|-
| ||[[Special:MyLanguage/Ofloxacin|Ofloxacin]]||X1
|-
| ||[[Special:MyLanguage/Pefloxacin|Pefloxacin]]||X1
|-
| ||[[Special:MyLanguage/Levofloxacin|Levofloxacin]]||R
|-
| ||[[Special:MyLanguage/Moxifloxacin|Moxifloxacin]]||R
|-
| ||[[Special:MyLanguage/Gemifloxacin|Gemifloxacin]]||X1
|-
| ||[[Special:MyLanguage/Gatifloxacin|Gatifloxacin]]||R
|-
| 1st G [[Special:MyLanguage/Cephalo|Cephalo]]||[[Special:MyLanguage/Cefazolin|Cefazolin]]||X1
|-
| 2nd G. [[Special:MyLanguage/Cephalo|Cephalo]]||[[Special:MyLanguage/Cefotetan|Cefotetan]]||X1
|-
| ||[[Special:MyLanguage/Cefoxitin|Cefoxitin]]||R
|-
| ||[[Special:MyLanguage/Cefuroxime|Cefuroxime]]||X1
|-
| 3rd/4th G. [[Special:MyLanguage/Cephalo|Cephalo]]||[[Special:MyLanguage/Cefotaxime|Cefotaxime]]||R
|-
| ||[[Special:MyLanguage/Cefizoxime|Cefizoxime]]||R
|-
| ||[[Special:MyLanguage/CefTRIAXone|CefTRIAXone]]||X1
|-
| ||[[Special:MyLanguage/Ceftaroline|Ceftaroline]]||X1
|-
| ||[[Special:MyLanguage/CefTAZidime|CefTAZidime]]||X1
|-
| ||[[Special:MyLanguage/Cefepime|Cefepime]]||R
|-
| Oral 1st G. [[Special:MyLanguage/Cephalo|Cephalo]]||[[Special:MyLanguage/Cefadroxil|Cefadroxil]]||X1
|-
| ||[[Special:MyLanguage/Cephalexin|Cephalexin]]||X1
|-
| Oral 2nd G. [[Special:MyLanguage/Cephalo|Cephalo]]||[[Special:MyLanguage/Cefaclor|Cefaclor]]/[[Special:MyLanguage/Loracarbef|Loracarbef]]||X1
|-
| ||[[Special:MyLanguage/Cefproxil|Cefproxil]]||X1
|-
| ||[[Special:MyLanguage/Cefuroxime axetil|Cefuroxime axetil]]||X1
|-
| Oral 3rd G. [[Special:MyLanguage/Cephalo|Cephalo]]||[[Special:MyLanguage/Cefixime|Cefixime]]||X1
|-
| ||[[Special:MyLanguage/Ceftibuten|Ceftibuten]]||X1
|-
| ||[[Special:MyLanguage/Cefpodox|Cefpodox]]/[[Special:MyLanguage/Cefdinir|Cefdinir]]/[[Special:MyLanguage/Cefditoren|Cefditoren]]||X1
|-
| [[Special:MyLanguage/Aminoglycosides|Aminoglycosides]]||[[Special:MyLanguage/Gentamicin|Gentamicin]]||R
|-
| ||[[Special:MyLanguage/Tobramycin|Tobramycin]]||R
|-
| ||[[Special:MyLanguage/Amikacin|Amikacin]]||R
|-
| ||[[Special:MyLanguage/Chloramphenicol|Chloramphenicol]]||I
|-
| ||[[Special:MyLanguage/Clindamycin|Clindamycin]]||X1
|-
| [[Special:MyLanguage/Macrolides|Macrolides]]||[[Special:MyLanguage/Erythromycin|Erythromycin]]||X1
|-
| ||[[Special:MyLanguage/Azithromycin|Azithromycin]]||X1
|-
| ||[[Special:MyLanguage/Clarithromycin|Clarithromycin]]||X1
|-
| Ketolide||[[Special:MyLanguage/Telithromycin|Telithromycin]]||X1
|-
| Tetracyclines||[[Special:MyLanguage/Doxycycline|Doxycycline]]||X1
|-
| ||[[Special:MyLanguage/Minocycline|Minocycline]]||X1
|-
| Glycylcycline||[[Special:MyLanguage/Tigecycline|Tigecycline]]||X1
|-
| ||[[Special:MyLanguage/Daptomycin|Daptomycin]]||X1
|-
| Glyco/Lipoclycopeptides||[[Special:MyLanguage/Vancomycin|Vancomycin]]||'''S'''
|-
| ||[[Special:MyLanguage/Teicoplanin|Teicoplanin]]||'''S'''
|-
| ||[[Special:MyLanguage/Telavancin|Telavancin]]||'''S'''
|-
| ||[[Special:MyLanguage/Fusidic Acid|Fusidic Acid]]||X1
|-
| ||[[Special:MyLanguage/Trimethoprim|Trimethoprim]]||X1
|-
| ||[[Special:MyLanguage/TMP-SMX|TMP-SMX]]||X1
|-
| Urinary Agents||[[Special:MyLanguage/Nitrofurantoin|Nitrofurantoin]]||X1
|-
| ||[[Special:MyLanguage/Fosfomycin|Fosfomycin]]||X1
|-
| Other||[[Special:MyLanguage/Rifampin|Rifampin]]||X1
|-
| ||[[Special:MyLanguage/Metronidazole|Metronidazole]]||'''S'''
|-
| ||[[Special:MyLanguage/Quinupristin dalfoppristin|Quinupristin dalfoppristin]]||I
|-
| ||[[Special:MyLanguage/Linezolid|Linezolid]]||I
|-
| ||[[Special:MyLanguage/Colistimethate|Colistimethate]]||X1
|}

==See Also==

*[[Special:MyLanguage/Diarrhea|Diarrhea]]
*[[Special:MyLanguage/Clostridium|Clostridium]]

==References==

<references/>

[[Category:ID]]
[[Category:GI]]

Clostridium difficile/en - Revision history

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