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Antibiotic treatment for Clostridium difficile-associated diarrhea in adults

  1. Richard L Nelson1,*,
  2. Philippa Kelsey2,
  3. Hayley Leeman2,
  4. Naomi Meardon2,
  5. Haymesh Patel2,
  6. Kim Paul2,
  7. Richard Rees2,
  8. Ben Taylor2,
  9. Elizabeth Wood2,
  10. Rexanna Malakun3

Editorial Group: Cochrane IBD Group

Published Online: 7 SEP 2011

Assessed as up-to-date: 12 OCT 2010

DOI: 10.1002/14651858.CD004610.pub4


How to Cite

Nelson RL, Kelsey P, Leeman H, Meardon N, Patel H, Paul K, Rees R, Taylor B, Wood E, Malakun R. Antibiotic treatment for Clostridium difficile-associated diarrhea in adults. Cochrane Database of Systematic Reviews 2011, Issue 9. Art. No.: CD004610. DOI: 10.1002/14651858.CD004610.pub4.

Author Information

  1. 1

    Northern General Hospital, Department of General Surgery, Sheffield, Yorkshire, UK

  2. 2

    University of Sheffield, The Medical School, Sheffield, UK

  3. 3

    University of Sheffield, School of Medicine and Biomedical Sciences, Sheffield, UK

*Richard L Nelson, Department of General Surgery, Northern General Hospital, Herries Road, Sheffield, Yorkshire, S5 7AU, UK. altohorn@btinternet.com. Rick.Nelson@sth.nhs.uk.

Publication History

  1. Publication Status: New search for studies and content updated (no change to conclusions)
  2. Published Online: 7 SEP 2011

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Characteristics of included studies [ordered by study ID]
Anonymous 1994

MethodsRCT


ParticipantsCDAD


Interventionsteicoplanin dose study 100 mg bid (n=49) versus qid (n = 43)


Outcomescure
bacteriologic resolution
relapse


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskAbstract reports randomized, but not how

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Unclear riskAbstract reports double blind

Incomplete outcome data (attrition bias)
All outcomes
High risk47% dropouts, 20/43 in 100 mg bid group and 25/49 in 100 mg qid group

Other biasUnclear riskCriteria for 'improved' outcome not described

Boero 1990

MethodsRCT


ParticipantsCDAD


Interventionsvancomycin (n = 10) versus rifaximin (n =10)


Outcomescombined symptomatic and bacteriologic resolution


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
High riskNo mention of blinding of patients or outcome assessors

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts

Other biasHigh riskDid not exclude other pathogens in the stool as causes of diarrhoea

Unclear inclusion criteria and unclear cure criteria

de Lalla 1992

MethodsRCT


ParticipantsCDAD


Interventionsvancomycin (n = 24) versus teicoplanin (n = 27)


Outcomescure
bacteriologic resolution
relapse


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo description given

Allocation concealment (selection bias)Unclear riskNo description given

Blinding (performance bias and detection bias)
All outcomes
High riskNo mention of blinding of patients or outcome assessors

Incomplete outcome data (attrition bias)
All outcomes
Low risk5/51 dropouts; 4/24 in vancomycin group and 1/27 in teicoplanin group

Other biasUnclear riskNot described

Dudley 1986

MethodsRCT


ParticipantsCDAD


Interventionsvancomycin (n = 31) versus bacitracin (n = 31)


Outcomescure
bacteriologic resolution
relapse


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer generated

Allocation concealment (selection bias)Low riskA - Adequate

Blinding (performance bias and detection bias)
All outcomes
Unclear riskUnclear whether assessor was blinded

Incomplete outcome data (attrition bias)
All outcomes
High risk52% dropouts, groups not specified

Other biasHigh riskDid not exclude other pathogens in the stool as causes of diarrhoea

Good randomisation technique, but did not test for C. difficile in stool until after randomisation

Fekety 1989

MethodsRCT


ParticipantsCDAD


Interventionsvancomycin dose study (125 (n = 28) versus 500 mg (n = 28) qid


Outcomescure
bacteriologic resolution
relapse


Noteshigh dropout rate


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandom numbers table

Allocation concealment (selection bias)High riskNot used

Blinding (performance bias and detection bias)
All outcomes
High riskOutcome assessor not blinded

Incomplete outcome data (attrition bias)
All outcomes
High risk18% dropouts, groups not specified

Other biasHigh riskDid not exclude other pathogens in the stool as causes of diarrhoea

Wide range of treatment duration

Keighley 1978

MethodsRCT


ParticipantsCDAD


Interventionsvancomycin (n = 22) versus placebo (n = 22)


Outcomescure
bacteriologic resolution


Notes60% dropouts


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Low riskCentralized randomization by pharmacy

Blinding (performance bias and detection bias)
All outcomes
Unclear riskPatients were blinded, but it was unclear whether the outcome assessor was too

Incomplete outcome data (attrition bias)
All outcomes
High risk52% dropouts; 10/22 in vancomycin group and 13 of 22 in placebo, with additional lost data

Other biasHigh riskDid not exclude other pathogens in the stool as causes of diarrhoea

Good grouping of patients according to stool testing.

Poor follow up procedures leading to only 4/12 patients having follow up data in treatment arm

Lagrotteria 2006

MethodsRCT


ParticipantsCDAD


Interventionsmetronidazole (n = 20) versus metronidazole plus rifampin (n = 19)
39 randomized


Outcomesresolution of diarrhea within 10 days and relapse within 40 days


Notes0 dropouts


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "Randomization was computer generated, and blinded study staff enrolled patients using numbered packages."

Allocation concealment (selection bias)Low riskQuote: "The sequence of randomization numbers was concealed until the end of the study"

Comment: As study staff were blinded before enrollment, there does not seem to be a source of bias

Blinding (performance bias and detection bias)
All outcomes
High riskSingle-blinded

Quote: "A placebo was not used"

Comment: This could have been placebo controlled although good justification was given"

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo dropouts

Other biasHigh riskDid not exclude other pathogens in the stool as causes of diarrhoea

Louie 2009

MethodsRCT


ParticipantsCDAD


InterventionsOPT 80 at 3 doses (100 mg, 200 mg and 400 mg) n = 16 in each group


OutcomesResolution of diarrhoea and abdominal discomfort within the 10 day treatment period without requiring any additional therapy and relapse within 6 weeks of end of treatment


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskThe trial used "interactive voice randomization system"

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
High risk"the study was a dose-finding, randomized, open-label study"

Incomplete outcome data (attrition bias)
All outcomes
Low risk4% dropouts not included in analysis

Other biasUnclear riskPatients with severe disease were excluded and only patients with a primary episode or first relapse were included

Patients were excluded if they had > 24 hrs antibiotic (metronidazole or vancomycin) prior to enrolment

Musher 2006

MethodsRCT


ParticipantsCDAD


InterventionsNitazoxanide in two doses (n = 44) versus metronidazole (n = 98)


OutcomesResolution of diarrhea at 7 and 31 days and time to resolution


Notes32 dropouts


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskQuote: "patients were randomized to 1 of 3 groups, in double-blinded fashion"

Comment: No mention is made of how randomization was established

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble blind: tablets made to look identical

Incomplete outcome data (attrition bias)
All outcomes
High risk23% dropouts, groups not specified

Other biasHigh riskDid not exclude other pathogens in the stool as causes of diarrhoea

Musher 2009

MethodsRCT


ParticipantsCDAD


InterventionsVancomycin 125 mg 6 hourly (n = 27) versus nitazoxanide 500 mg 12 hourly (n = 22)


OutcomesComplete resolution of symptoms and signs attributable to C difficile within 3 days after completion of therapy

Relapse


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Low riskCentralized randomization (randomization codes held by study sponsor)

Blinding (performance bias and detection bias)
All outcomes
Low riskDouble-blind, double-dummy: all patients had active and placebo tablets for the duration of the study

Incomplete outcome data (attrition bias)
All outcomes
Low risk2% dropout not included in analysis

Other biasLow riskThe study appears to be free of other sources of bias

Teasley 1983

MethodsRCT


ParticipantsCDAD


Interventionsvancomycin (n = 56) versus metronidazole (n = 45)


Outcomescure
bacteriologic resolution


Notesno relapse data


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described

Incomplete outcome data (attrition bias)
All outcomes
Low risk7% dropouts; 4 from vancomycin group and 3 from metronidazole group

Other biasHigh riskDid not exclude other pathogens in the stool as causes of diarrhoea

Also unclear as to which patients had original antibiotic removed

Wenisch 1996

MethodsRCT


ParticipantsCDAD


Interventionsvancomycin versus metronidazole versus teicoplanin versus fusidic acid. N for each group a bit unclear as 126 randomized and 7 dropped out, leaving the specified numbers for analysis.


Outcomescure
bacteriologic resolution
relapse


Notescost data presented


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "patients were randomized according to a table of random numbers"

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
High riskNo mention of blinding of patients or outcome assessors

Incomplete outcome data (attrition bias)
All outcomes
Unclear risk5.5% dropouts, groups not specified

Other biasHigh riskDid not exclude other pathogens in the stool as causes of diarrhoea

Did exclude patients with no WBCs in stool sample "to insure inclusion of patients with significant disease due to C. difficile"

Did however explicitly report that original offending antibiotic had been stopped

Wullt 2004

MethodsRCT


ParticipantsCDAD


Interventionsfusidic acid (n = 67) versus metronidazole (n = 64)
131 randomized


Outcomescessation of diarrhea and conversion to toxin (-)


Notes17 dropouts


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "An independent statistician provided a computer-generated list of random set numbers"

Allocation concealment (selection bias)Low riskQuote: "the investigator teams were unaware of the treatment allocation"

Blinding (performance bias and detection bias)
All outcomes
Low riskAll medication packs were coded and contained identical-looking pills.

Incomplete outcome data (attrition bias)
All outcomes
High risk26% dropouts; 20/67 in fusidic acid group and 14/64 from metronidazole group

Other biasHigh riskDid not exclude other pathogens in the stool as causes of diarrhoea

Young 1985

MethodsRCT


ParticipantsCDAD


Interventionsvancomycin versus bacitracin; 21 in each group


Outcomescure
bacteriologic resolution
relapse


Notescost data presented


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot described

Allocation concealment (selection bias)Unclear riskNot described

Blinding (performance bias and detection bias)
All outcomes
Unclear riskPatients blinded but unclear whether assessors were too - although the abstract reports it was double-blind

Incomplete outcome data (attrition bias)
All outcomes
Low riskno dropouts

Other biasLow riskControls for diarrhoea resolution on removal of offending antibiotic

Zar 2007

MethodsRCT


ParticipantsCDAD


Interventionsvancomycin (n = 82) versus metronidazole (n = 90)


Outcomescessation of diarrhoea

conversion to C. difficile toxin A negative stool

relapse at 21 days post cure


Notes12.5% dropout, but achieved power


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskQuote: "a member of pharmacy staff randomized participants by selecting a card from a sealed envelope..."

Allocation concealment (selection bias)Low riskCentralized randomization by pharmacy using sealed envelope

Blinding (performance bias and detection bias)
All outcomes
Low riskQuote: "patients received either vancomycin liquid and a placebo tablet that was similar in appearance to metronidazole or a metronidazole tablet and an unpleasantly-flavored placebo liquid"

Incomplete outcome data (attrition bias)
All outcomes
Low risk13% dropouts, missing outcome data balanced in numbers across intervention groups with similar reasons for missing data across groups

Other biasUnclear riskNo patients with suspected or life-threatening intraabdominal complications (perforation or obstruction) were included

No patients in ITU or with pseudomembranous colitis were included

Unclear whether prior antibiotics had been stopped

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Johnson 1992Participants were asymptomatic carriers of Clostridium difficile without diarrhea

Louie 2006RCT with a non antibiotic arm (tolevamer)

Lowy 2010Does not compare two antibiotics and focuses on the recurrence of Clostridium difficile rather than treatment of the existing infection

Mattila 2008RCT with a non antibiotic arm (Clostridium difficile immune whey)

McFarland 2002Non-randomized study

Noren 2006Publication of antibiotic resistance development from a group previously reported by Wullt2004.

Numan 2007Assessment of immune whey efficacy

 
Comparison 1. Vancomycin versus Placebo

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptomatic Initial Response1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

 2 Bacteriologic Initial Response1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

 
Comparison 2. Metronidazole versus Vancomycin

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptomatic Initial Response3335Risk Ratio (M-H, Fixed, 95% CI)0.93 [0.86, 1.02]

 2 Bacteriologic Initial Cure162Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.70, 1.30]

 3 Bacteriologic Cure2163Risk Ratio (M-H, Fixed, 95% CI)0.85 [0.62, 1.17]

 4 Cure (symptomatic and bacteriologic cure)1172Risk Ratio (M-H, Fixed, 95% CI)0.88 [0.75, 1.02]

    4.1 Mild disease
190Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.76, 1.08]

    4.2 Severe disease
182Risk Ratio (M-H, Fixed, 95% CI)0.83 [0.64, 1.09]

 5 Symptomatic Cure minus recurrences including Zar with all exclusions treated as failures3335Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.81, 1.03]

 
Comparison 3. Bacitracin versus Vancomycin

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptomatic Initial Response2104Risk Ratio (M-H, Fixed, 95% CI)0.82 [0.60, 1.12]

 2 Symptomatic Cure2104Risk Ratio (M-H, Fixed, 95% CI)0.58 [0.34, 0.99]

 3 Bacteriologic Initial Response2104Risk Ratio (M-H, Fixed, 95% CI)0.52 [0.31, 0.86]

 4 Symptomatic Recurrence2104Risk Ratio (M-H, Fixed, 95% CI)1.11 [0.50, 2.48]

 
Comparison 4. Teicoplanin versus Vancomycin

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptomatic Initial Response2110Risk Ratio (M-H, Fixed, 95% CI)1.07 [0.95, 1.19]

 2 Symptomatic Cure2110Risk Ratio (M-H, Fixed, 95% CI)1.21 [1.00, 1.46]

 3 Bacteriologic Initial Response2110Risk Ratio (M-H, Fixed, 95% CI)1.43 [1.14, 1.81]

 4 Bacteriologic Cure159Risk Ratio (M-H, Fixed, 95% CI)1.82 [1.19, 2.78]

 5 Symptomatic Recurrence2110Risk Ratio (M-H, Fixed, 95% CI)0.44 [0.14, 1.36]

 6 Bacteriologic Recurrence159Risk Ratio (M-H, Fixed, 95% CI)0.37 [0.11, 1.23]

 
Comparison 5. Fusidic Acid versus Vancomycin

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptomatic Initial Response2191Risk Ratio (M-H, Fixed, 95% CI)0.94 [0.83, 1.08]

 2 Symptomatic Cure160Risk Ratio (M-H, Fixed, 95% CI)0.85 [0.61, 1.17]

 3 Bacteriologic Initial Response2191Risk Ratio (M-H, Fixed, 95% CI)0.96 [0.78, 1.18]

 4 Bacteriologic Cure160Risk Ratio (M-H, Fixed, 95% CI)0.68 [0.44, 1.06]

 5 Symptomatic Recurrence2191Risk Ratio (M-H, Fixed, 95% CI)1.09 [0.64, 1.86]

 6 Bacteriologic Recurrence160Risk Ratio (M-H, Fixed, 95% CI)1.87 [0.61, 5.73]

 
Comparison 6. Nitazoxanide versus Vancomycin

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptomatic Initial Response1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Nitazoxanide versus Vancomycin
149Risk Ratio (M-H, Fixed, 95% CI)1.04 [0.76, 1.43]

    1.2 Not severe disease
129Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.64, 1.49]

    1.3 Severe disease
120Risk Ratio (M-H, Fixed, 95% CI)1.14 [0.69, 1.90]

 2 Recurrence of diarrhea within 31 days1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Nitazoxanide versus Vancomycin
149Risk Ratio (M-H, Fixed, 95% CI)0.61 [0.06, 6.33]

    2.2 Not severe disease
129Risk Ratio (M-H, Fixed, 95% CI)0.46 [0.02, 10.45]

    2.3 Severe disease
120Risk Ratio (M-H, Fixed, 95% CI)1.0 [0.07, 13.87]

 3 Sustained response1Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 Nitazoxanide versus Vancomycin
149Risk Ratio (M-H, Fixed, 95% CI)1.09 [0.75, 1.58]

    3.2 Not severe disease
129Risk Ratio (M-H, Fixed, 95% CI)1.06 [0.68, 1.66]

    3.3 Severe disease
120Risk Ratio (M-H, Fixed, 95% CI)1.17 [0.61, 2.23]

 
Comparison 7. Rifaximin versus Vancomycin

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptomatic Initial Response120Risk Ratio (M-H, Fixed, 95% CI)0.90 [0.69, 1.18]

 2 Bacteriologic Initial Response120Risk Ratio (M-H, Fixed, 95% CI)0.90 [0.69, 1.18]

 
Comparison 8. Metronidazole versus Nitazoxanide

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Initial resolution of diarrhea1142Risk Ratio (M-H, Fixed, 95% CI)0.92 [0.71, 1.19]

 2 Recurrence of Diarrhea at 31 d.1142Risk Ratio (M-H, Fixed, 95% CI)0.69 [0.24, 1.98]

 
Comparison 9. Metronidazole versus Metronidazole + Rifampin

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Resolution of Diarrhea139Risk Ratio (M-H, Fixed, 95% CI)1.03 [0.64, 1.65]

 2 Recurrence of diarrhea within 40 days139Risk Ratio (M-H, Fixed, 95% CI)0.95 [0.33, 2.77]

 
Comparison 10. Metronidazole versus Teicoplanin

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptomatic Initial Response159Risk Ratio (M-H, Fixed, 95% CI)0.97 [0.86, 1.09]

 2 Symptomatic Cure159Risk Ratio (M-H, Fixed, 95% CI)0.87 [0.69, 1.09]

 3 Bacteriologic Initial Cure159Risk Ratio (M-H, Fixed, 95% CI)0.76 [0.60, 0.98]

 4 Bacteriologic Cure159Risk Ratio (M-H, Fixed, 95% CI)0.76 [0.58, 1.00]

 5 Symptomatic Recurrence159Risk Ratio (M-H, Fixed, 95% CI)2.26 [0.48, 10.73]

 
Comparison 11. Metronidazole versus Fusidic Acid

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptomatic Initial Response2190Risk Ratio (M-H, Random, 95% CI)1.09 [0.60, 1.99]

 2 Symptomiatic Cure2190Risk Ratio (M-H, Fixed, 95% CI)1.00 [0.78, 1.30]

 3 Bacteriologic initial Cure2190Risk Ratio (M-H, Fixed, 95% CI)1.02 [0.83, 1.25]

 4 Bacteriologic Cure159Risk Ratio (M-H, Fixed, 95% CI)1.35 [0.87, 2.11]

 5 Symptomatic Recurrence2190Risk Ratio (M-H, Fixed, 95% CI)0.91 [0.53, 1.55]

 
Comparison 12. Teicoplanin versus Fusidic Acid

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptomatic Initial Response157Risk Ratio (M-H, Fixed, 95% CI)1.04 [0.92, 1.17]

 2 Symptomatic Cure157Risk Ratio (M-H, Fixed, 95% CI)1.36 [1.02, 1.83]

 3 Bacteriologic Initial Cure157Risk Ratio (M-H, Fixed, 95% CI)1.68 [1.19, 2.37]

 4 Bacteriologic Cure157Risk Ratio (M-H, Fixed, 95% CI)1.73 [1.19, 2.51]

 5 Symptomatic Recurrence157Risk Ratio (M-H, Fixed, 95% CI)0.26 [0.06, 1.11]

 
Comparison 13. Dose finding studies

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Symptomatic Initial Response2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    1.1 Vancomycin
156Risk Ratio (M-H, Fixed, 95% CI)0.92 [0.72, 1.17]

    1.2 Teicoplanin
192Risk Ratio (M-H, Fixed, 95% CI)0.79 [0.49, 1.29]

 2 Symptomatic Recurrence3Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    2.1 Vancomycin
156Risk Ratio (M-H, Fixed, 95% CI)0.8 [0.24, 2.67]

    2.2 Teicoplanin
192Risk Ratio (M-H, Fixed, 95% CI)1.14 [0.47, 2.78]

    2.3 OPT-80
148Risk Ratio (M-H, Fixed, 95% CI)0.2 [0.03, 1.43]

 3 Symptomatic Cure3Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    3.1 Vancomycin
156Risk Ratio (M-H, Fixed, 95% CI)0.95 [0.65, 1.38]

    3.2 Teicoplanin
192Risk Ratio (M-H, Fixed, 95% CI)0.61 [0.29, 1.29]

    3.3 OPT-80
148Risk Ratio (M-H, Fixed, 95% CI)1.26 [1.03, 1.54]

 4 Bacteriologic Cure2Risk Ratio (M-H, Fixed, 95% CI)Subtotals only

    4.1 Vancomycin
156Risk Ratio (M-H, Fixed, 95% CI)0.8 [0.24, 2.67]

    4.2 Teicoplanin
192Risk Ratio (M-H, Fixed, 95% CI)0.98 [0.51, 1.88]

 
Summary of findings for the main comparison. Metronidazole versus Vancomycin for Clostridium difficile-associated diarrhea in adults

Metronidazole versus Vancomycin for Clostridium difficile-associated diarrhea in adults

Patient or population: patients with Clostridium difficile-associated diarrhea in adults
Settings:
Intervention: Metronidazole versus Vancomycin

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlMetronidazole versus Vancomycin

Symptomatic Cure minus recurrences including Zar with all exclusions treated as failuresStudy populationRR 0.91
(0.81 to 1.03)
335
(3 studies)
⊕⊝⊝⊝
very low1,2,3

782 per 1000712 per 1000
(626 to 805)

Medium risk population

781 per 1000711 per 1000
(625 to 804)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Sparse data
2 The Wenisch 1996 study was not blinded
3 Both the Teasley 1983 and Wenisch 1996 studies did not exclude other pathogens in stool as causes of diarrhea
 
Summary of findings 2. Teicoplanin versus Vancomycin for Clostridium difficile-associated diarrhea in adults

Teicoplanin versus Vancomycin for Clostridium difficile-associated diarrhea in adults

Patient or population: patients with Clostridium difficile-associated diarrhea in adults
Settings:
Intervention: Teicoplanin versus Vancomycin

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlTeicoplanin versus Vancomycin

Symptomatic CureStudy populationRR 1.21
(1.00 to 1.46)
110
(2 studies)
⊕⊝⊝⊝
very low1

714 per 1000843 per 1000
(693 to 1000)

Medium risk population

708 per 1000835 per 1000
(687 to 1000)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Sparse data
2 The Wenisch 1996 and de Lalla 1992 studies were not blinded
3 The Wenisch 1996 study did not exclude other pathogens in stool as causes of diarrhea
 
Summary of findings 3. Metronidazole versus Teicoplanin for Clostridium difficile-associated diarrhea in adults

Metronidazole versus Teicoplanin for Clostridium difficile-associated diarrhea in adults

Patient or population: patients with Clostridium difficile-associated diarrhea in adults
Settings:
Intervention: Metronidazole versus Teicoplanin

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlMetronidazole versus Teicoplanin

Symptomatic CureStudy populationRR 0.87
(0.69 to 1.09)
59
(1 study)
⊕⊕⊝⊝
low1

833 per 1000750 per 1000
(583 to 966)

Medium risk population

833 per 1000750 per 1000
(583 to 966)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk ratio;

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Sparse data
2 The Wenisch 1996 study was not blinded
3 The Wenisch 1996 study did not exclude other pathogens in stool as causes of diarrhea
 
Table 1. Guidelines for Antibiotic Treatment of CDAD

HPA1ESCMID2SHEA & IDSA3

MILD CDADStop inciting antibiotic and observe, or metronidazole 500 mg po tid. Alternate dosing also recommended and change to vancomycin if no better in 4 days.Stop inciting antibiotic and observe, or Metronidazole 500 mg po tidStop inciting antibiotic, or metronidazole 500 mg po tid for 10 days.

SEVERE CDADVancomycin 500 mg po qid with taperingVancomycin 125 mg po qid for 10 daysVancomycin 125 mg po qid for 10 days

SEVERE AND CANNOT TOLERATE ORAL MEDSIntravenous metronidazole and vancomycin via nasogastric tube or enemas qid.samesame

SURGERYFor toxic megacolon or lactate > 5For perforation, toxic megacolon, Ileus, lactate > 5

RECURRENCEFirst as Primary

2nd: oral vancomycin with taper
same