a comparison of vancomycin and metronidazole for the treatment of clostridium difficile-associated...

8/13/2019 A COMPARISON OF VANCOMYCIN AND METRONIDAZOLE FOR THE TREATMENT OF CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA, STRATIFIED BY DISEASE SEVERITY.pptx

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1

Oleh :

Martin Susanto

Gunachitra Devarajoo

Naanthini Dilly Kannan

Pembimbing :

dr. Yuki Yunanda

Departemen KesehatanMasyarakat FK USU

JOURNAL READING

A COMPARISON OF VANCOMYCIN ANDMETRONIDAZOLE FOR THE TREATMENT OF

CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA,STRATIFIED BY DISEASE SEVERITY


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BACKGROUND

Clostridium difficile associated diarrhea (CDAD) isthe most common infectious etiology of nasocomialdiarrhea in acute care settings. The incidence andseverity of CDAD has been increasing .

Metronidazole is commonly used as first- linetreatment for CDAD but recently there havebeen reports of metronidazole treatmentfailure.

This study is conducted to compare metronidazolewith vancomycin in a prospective, randomized, double-blind, placebo controlled trial to investigate whichmedicine is superior for treating either mild or severeCDAD.


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METHOD This study was conducted at Saint Francis Hospital in Chicago.

From October 1994 through June 2002

Patients with CDAD were stratified according to whether theyhad mild or severe disease based on clinical criteria.

INCLUSION EXCLUSION

1. Patients having diarrhea ( 3nonformed stools in 24 hours)

1. Presence of suspected / proven life-

threathening intraabdominal

complications including perforated

viscus / bowel obstruction

2. C.difficile toxin A demonstrated in

the stool within 48 hours after

study entry/ pseudomembranouscolitis found on endoscopic

examination

2. Prior failure of CDAD to respond toeither study drugs

3. Patients have the ability to receiveoral medications

3. Pregnancy and history of allergy to

either study drug during the previous

14 days


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RESULTS

One hundred seventy-two patients were enrolled, and 150 ofthese patients successfully completed the trial.

The overall rate of cure was 84% (66 of 79 patients) in themetronidazole group and 97% (69 of 71 patients) in thevancomycin group (P = .006)

Among the patients with mild CDAD, treatment withmetronidazole or vancomycin resulted in clinical cure in 90% and98% of the patients, respectively (P = .36).

Among the patients with severe CDAD, treatment withmetronidazole or vancomycin resulted in clinical cure in 76% and

97% of the patients, respectively (P = .02). Clinical symptoms recurred in 14% of the patients treated with

metronidazole and 7% of those treated with vancomycin.


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DISEASESEVERITY

NO. OF PATIENTS CURED/ NO. OF PATIENTSTREATED (%)

MTZ GROUP VM GROUP TOTAL P VALUE

MILD 37 / 41 (90) 39 / 40 (98) 76 / 81 (94) .36

SEVERE 29 / 38 (76) 30 / 31 (97) 59 / 69 (86) .02

ALL 66 / 79 (84) 69 / 71 (97) 135 / 150 (90) .006

Rate of Cure of Clostridium DifficileAssociatedDiarrhea by Disease Severity and Treatment


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THERAPY WORKSHEET

Was the assignment of patients totreatments randomized?

Yes. The patients were randomly assignedto receive oral Metronidazole or oralVancomycin for 10 days[ pg 1; Abstract or pg 2; study design]

Was the randomization list concealed? Yes. A member of the pharmacy staffrandomized participants by selecting acard from a sealed envelope that had 1 ofthe active study drugs listed on it.[ pg 2; Treatment regimen]

Was follow-up of patients sufficientlylong and complete?

Yes. The study were conducted fromOctober 1994 through June 2002. From172 patients, 150 patients successfullycompleted the trial ( loss to follow up 20%) [ pg 1; methods and pg 3; Results]

Are the results of this single preventive or therapeutictrial valid?


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Were all patients analyzed in the groupsto which they were randomized?

Yes. The patients were randomized intometronidazole group and vancomycingroup and both groups were analyzed intomild and severe disease groups based on

severity assessment score developed forthis study.[ pg 2; Study design]

Were patients, clinicians, and studypersonnel kept blind to treatment?

Yes. This study is double-blind[ pg 2; Study design]

Were the groups treated equally, apartfrom the experimental treatment?

Yes. Patients frm both groups weremonitored daily to determine thefrequency of stools and the first day onwhich the diarrhea resolved, daily vitalsigns and abdominal symptoms wererecorded. [ pg 2 ; Study design ]

Were the groups similar at the start ofthe trial apart from the experimentaltherapy?

Yes. Both groups consist of patients whohad stool assay performed for C.difficiletoxin.[ pg 1 ; Methods ]


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Are the valid results of this randomized trialimportant?

What is the magnitude of thetreatment effect?

NNT, ARR, RRR, CER, EER

How precise is the estimate of thetreatment effect?

P value < 0.05 ( P value = 0.006 ), thetreatment effect is precise

YES( CURED)

NO( DIDNT CURE)

TOTAL

CONTROL( METRONIDAZOL )

66 13 79

EXPERIMENT( VANCOMYCIN )

69 2 71


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CALCULATIONS

Relative risk

reduction

(RRR)

Absolute risk

reduction

(ARR)

Number

needed

to treat

(NNT)

CER

= 66 / 79

= 0,84

= 84 %

EER

= 69 / 71

= 0,97

= 97 %

CER EERCER

= 0,840,97

0,84

= - 0,15

= -15 %

CER EER

= 0,840,97

= - 0,13

1/ARR

= 1 / 0,13

= 7,69

= 7

95% CI a -0,22 to -0,04 4 to 25


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Can you apply this valid, important evidence abouttherapy in caring for your patient?

Do these results apply to ourpatient?

Yes. Because CDAD is common inIndonesia

Is our patient so different from

those in the study that itsresults cannot apply?

No. Because the characteristics

of the patients in the study andthe patients in our country aresimilar, so the result can beapplied here.

Is the treatment feasible in our

setting?

Yes. Because both Metronidazole

and Vancomycin are available inIndonesia.


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What are our patients potential benefits and harmsfrom the therapy?

Risk of the outcome in our patient,relative to patients in the trial.

Expressed as a decimal:

NNT/ f = 7,69 / 1 = 7,69

(NNT for patients like ours)

Our patients expected event rateif they received

the control treatment (PEER) =______

1/(PEER RRR) = 1/________=______

(NNT for patients like ours)

Method I : f

Method II :1/(PEER RRR)


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Are our patients values and preferences satisfied bythe regimen and its consequences?

Do we and our patient have aclear assessment of their values

and preferences?

-

Are they met by this regimenand its consequences?

-


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CONCLUSIONS

This study have shown that metronidazole and vancomycin areequally effective for the treatment of mild CDAD, butvancomycin is superior for treating patients with severe CDAD.

This may require a modification of treatment guidelines for

CDAD, especially because of the increasing prevalence of anepidemic strain that is producing more-severe disease.


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TERIMA KASIH

a comparison of vancomycin and metronidazole for the treatment of clostridium difficile-associated...

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