7.7Treatment without prior identification of a pathogen

Bibliographic informationStudy type and evidence levelStudy detailsPatient characteristicsIntervention and comparisonOutcome measures, follow-up and effect sizeComments
Wolfsdorf 1973151

Location : South Africa
Study Type
RCT

Evidence Level 1−
Total number of participants
n = 34

Randomised into two treatment arms

Group 1
n = 18

Group 2
n = 26
Inclusion criteria:
Children aged 5–30 months admitted to hospital for gastroenteritis

Exclusion criteria :
Not stated

Withdrawal criteria :

Not stated
Comparison

Trimethoprim/sulphonamide vs placebo

No further details
Follow up

Outcome measures:

Mean duration of diarrhoea (days)

Group 1 = 5.250+−3.118
Group 2 = 6.607+−9.765
P = NS

Mean duration of vomiting (days)

Group 1 = 1.812+−3.505
Group 2 = 1.607+−2.998
P = NS

Mean duration of pyrexia (days)
Group 1 = 0.437+−0.6549
Group 2 =0.642+−0.9109
P = NS

Mean duration of hospital stay (hours)

Group 1 = 156.687+−93.672
Group 2 = 177071+−99.76
P = NS
Funding :
Burroughs Wellcome

Applicable to UK

Baseline comparability
Similar for age

Allocation concealment :
Code used

Sequence generation :
Code used

Blinding of outcome assessors :
Yes

Loss to follow up
None
Intention to treat analysis :
Not stated

Power calculation :
Not stated
Robins-Browne 1983152

Location : South Africa
Study Type
RCT

Evidence Level 1+
Total number of participants
n = 78

Randomised into two treatment arms

Group 1
Intervention :
Erythromycin
n = 39
Data presented for 32 participants

Group 2
Intervention :
Placebo
n = 39
Data presented for 33 participants
Inclusion criteria:
Children aged 1 months-2 years admitted to hospital with a history of diarrhoea not exceeding 96 hours and who had received no antimicrobial therapy for the current illness

Exclusion criteria :
Not stated

Withdrawal criteria :
Not stated
Comparison

Erythromycin vs placebo

Intervention details:

Group 1:
Erythromycin ethylsuccinate oral suspension, 40 mg/kg per day in divided doses for 5 days

Group 2:
Placebo oral suspension
Follow up
Daily examination for 7 days

Distribution of pathogens similar between groups

Outcome measures:

Mean duration of abnormal stool frequency

Group 1 = 1.4+−1.7 days
Group 2 = 1.8+−2.1 days
P = 0.37

Mean duration of abnormal stool consistency

Group 1 = 5.0+−1.4 days
Group 2 = 5.8+−1.3 days
WMD −0.80 [95% CI −1.46 to −0.14]
P = 0.02

Mean duration of vomiting

Group 1 = 3.4+−1.4 days
Group 2 = 3.7+−1.2 days
P = 0.35

Mean duration of dehydration

Group 1 = 3.3+−1.8 days
Group 2 = 3.3+−2.1 days
P = 1.00

Fever

Group 1 = 3.8+−1.6 days
Group 2 = 3.3+−1.5 days
P = 0.19
Funding :
South African MRC
University of Natal, Abbott Laboratories

Applicable to UK
No

Baseline comparability
Similar for age, sex, nutritional status, dehydration status, duration of current illness and severity of diarrhoea.

Allocation concealment :
Yes, pharmacy controlled

Sequence generation :
Code used

Blinding of outcome assessors :
Yes

Loss to follow up :
13/78
2 deaths (1 in each gp)
6 infective complications requiring antibiotics(3 in each gp)
5 voluntary withdrawals (Gp 1=3, Gp 2 =2)

Intention to treat analysis :
No

Power calculation :
None stated
Rodriguez 1989154

Location : Mexico
Study Type
RCT

Evidence Level 1+
Total number of participants
n = 125

Randomised into three treatment arms

Group 1
Intervention :
Furazolidone
n = 49

Group 2
Intervention :
Trimethoprim/sulfamethoxazole
n = 52

Group 3
Intervention :
No treatment
n = 24
Data presented for 22 participants
Inclusion criteria:
Patients aged 2–59 months brought to hospital with three or more watery stools in previous 24 hours, up to 5 days diarrhoea prior to admission, and presence of PMN leucocytes d blood in stool

Exclusion criteria :

Presence of amoeba in stools, severe concomitant disease, intolerance of or allergy to study drugs, receipt of antimicrobials, antidiahorroeals, or other drugs affecting the disease course, within 48 hours prior to admission.

Withdrawal criteria :

Poor clinical response to treatment (treatment failures)
Comparison

Intervention details:

Group 1:
7.5 mg/kg per day furazolidone in four equal doses a day for 5 days

Group 2:
8 mg/kg per day trimethoprim + 40 mg/kg per day sulfamethoxazole in two equal doses a day for 5 days

Group 3:
No treatment

Oral rehydration, antipyretics and nutritional support given as needed to all groups

Treatment success = clinical cure (absence of diarrhoea and alleviation of all symptoms) at day 3 and bacteriologic cure (negative stool culture) at day 6

For patients with negative culture:
Treatment success = clinical cure (absence of diarrhoea and alleviation of symptoms) at day 3

Distribution of pathogens similar between groups.

48/125 had negative stool culture
Follow up

Daily visits as outpatients to hospital. Clinical assessment at day 3, stool sample taken at days 1 and 6.

Outcome measures:

Clinical Cure at day 3

All participants
Group 1 = 43/49
Group 2 = 43/52
Group 3 = 10/22

Gp 1 vs Gp 3
RR 1.93 [95% CI 1.21–3.09]
Gp 2 vs Gp 3
RR 1.82 [95% CI 1.13–2.92]
Gps 1 + 2 vs Gp 3
RR 1.87 [95% CI 1.18–2.98]

Clinical Cure at day 3 pts with −ve stool cultures

Group 1 = 13/14
Group 2 = 20/23
Group 3 = 5/9

Gp 1 vs Gp 3
RR 1.67 [95% CI 0.92–3.05]
Gp 2 vs Gp 3
RR 1.57 [95% CI 0.85–2.87]
Gps 1 + 2 vs Gp 3
RR 1.61 [95% CI 0.89–2.91]

Bacteriologic cure at day 6 pts with +ve stool cultures

Group 1 = 20/34
Group 2 = 19/29
Group 3 = 4/12

Gp 1 vs Gp 3
RR 1.76 [95% CI 0.76–4.12]
Gp 2 vs Gp 3
RR 1.97 [95% CI 0.85–4.56]
Gps 1 + 2 vs Gp 3
RR 2.33 [95% CI 1.04–5.25]

Treatment cure at day 6

Group 1 = 31/49
Group 2 = 36/52
Group 3 = 5/22

Gp 1 vs Gp 3
RR 2.78 [95% CI 1.25–6.19]
Gp 2 vs Gp 3
RR 3.05 [95% CI 1.38–6.72]
Gps 1 + 2 vs Gp 3
RR 2.92 [95% CI 1.33–6.39]
Funding : Norwich Eaton Pharmaceuticals Inc, a Proctor & Gamble company

Applicable to UK
No

Baseline comparability
Similar for age, sex, height, weight, body temp and stools per day. Patients in Gp 1 had fewer days with diarrhoea compared to patients in either 2 treatment groups (P < 0.02)

Allocation concealment:
Not stated

Sequence generation :
Not stated

Blinding of outcome assessors:
No

Loss to follow up
2/24 in the control group voluntarily withdrawn

Intention to treat analysis:
No

Power calculation:
Not stated
Oberhelman 1987153

Location : Mexico
Study Type
RCT

Evidence
Level 1−
Total number of participants
n = 141

Randomised into two treatment arms

Group 1
Intervention :
Trimethoprim/sulfamethoxazole
n = 73

Group 2
Intervention :
placebo
n = 68
Inclusion criteria:
Children aged 3–84 months seen in hospital with diarrhoea as chief complaint.

Three or more unformed stools in previous 24 hours, <72 hours duration of diarrhoea, no antibiotic treatment in prior 7 days, absence of severe dehydration.

Exclusion criteria :
Not stated

Withdrawal criteria :
Not stated

74/141 had identifiable enteric pathogen

56/74 had a bacterial pathogen

6/31 ETEC mixed with others
25/31 ETEC only

7/10 patients had EPEC only
3/10 EPEC mixed with others

12 patients had Shigella
9 patients had Campylobacter
2 patients had Salmonella
4 patients had Cryptosporidium
6 patients had Giardia lablia
Comparison

Intervention details:

Group 1:
10 mg/kg per day trimethoprim + 50 mg/kg per day sulfamethoxazole oral suspension in two divided doses per day for 5 days

Group 2:
Placebo oral suspension in two doses per day for 5 days
Follow up

Daily assessments for 5 days except weight at day 5 and on assessment at 2 weeks post- treatment

Outcome measures:

Mean time to last illness stool :

All patients
Group 1 = 58.2
Group 2 = 75.5
P = 0.021

Patients with fever
Group 1 = 59.6
Group 2 = 94.6
P = 0.046

Patients with faecal leucocytes (>3/HPF)
Group 1 = 57.7
Group 2 = 106.5
P = 0.025

Mean no of unformed stools in 5 day period :

All patients
Group 1 = 9.8
Group 2 = 12.5
P = NS

Patients with fever
Group 1 = 9.1
Group 2 = 17.3
P = NS

Patients with faecal leucocytes (>3/HPF)
Group 1 = 10.1
Group 2 = 18.1
P = 0.041

Post treatment no of unformed stools in wk1 and wk2

All patients
Patients with fever
Patients with faecal leucocytes (>3/HPF)
Group 1
Group 2
P = NS
Funding :

Burroughs Wellcome Company
Grant AI 23049 National Institutes of Health

Applicable to UK

Baseline comparability
Similar for age, prior duration of illness, mean no stools in 24 hours prior to therapy, fever, dehydration, three faecal leucocytes per high- power field.

Allocation concealment :
Not stated

Sequence generation :
Not stated

Blinding of outcome assessors :
Daily assessments blinded – made by parents. Other assessments unclear

Loss to follow up :
None

Intention to treat analysis :
Not stated

Power calculation :
Not stated

50/141 partipants had body weight <3rd percentile for age (Mexican standards)

From: Evidence tables

Cover of Diarrhoea and Vomiting Caused by Gastroenteritis
Diarrhoea and Vomiting Caused by Gastroenteritis: Diagnosis, Assessment and Management in Children Younger than 5 Years.
NICE Clinical Guidelines, No. 84.
National Collaborating Centre for Women's and Children's Health (UK).
London: RCOG Press; 2009 Apr.
Copyright © 2009, National Collaborating Centre for Women’s and Children’s Health.

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