Nifuroxazide (Ercefuryl) Plus Oral rehydration solution Versus Oral ...

Nifuroxazide (Ercefuryl) Plus Oral rehydration solution
Versus Oral Rehydration Alone in Hospitalized Pediatric
Gastroenteritis
Lourdes T. Santiago, M.D.,* Catherine P. Ranoa, M.D.,** Edmond G. Chan, M.D.*** and Ester
Tejada***
(*Medical Specialist II, San Lazaro Hospital; **Chief of Hospital V, San Lazaro Hospital; ***Resident Physician, San
Lazaro Hospital)
No Abstract Available [Phil J Microbiol Infect Dis 1985; 14(2):76-79]
Key Words: Nifuroxazide, gastroenteritis, diarrhea, oral rehydration solution
INTRODUCTION
Acute watery diarrhea due to infections is second only in incidence to infections of the
respiratory tract. In developing countries, however, acute diarrhea is the most common cause of
mortality in small children, maybe because they are easily affected by dehydration and/or acidbase
equilibrium disorders, especially if they are malnourished. 1,2 Oral glucose-electrolyte
solutions (oral rehydration solution or ORS) have been shown during the past 10 years to be
highly effective in the treatment of dehydration secondary to acute diarrhea in the developing
world. 3,4 Not only has it been successfully used in patients of all ages including newborns but it
has also been shown that ORS is usually sufficient by itself because in many cases, a satisfactory
water-electrolyte balance can be maintained and it allows hospitalization to be avoided. Even in
hospitals, it can replace intravenous infusions for the mild and moderately dehydrated patients.
But inspire of this knowledge, many researchers still claim that infectious diarrhea should
be treated with an anti-infectious agent because of the change in the etiological and
epidemiological situation of diarrhea recently. 5,6 They determined the usefulness of antibiotics in
these cases and concluded that systemic antibiotic therapy seemed useful for certain invasive
organisms, especially where there was danger of systemic propagation as in debilitated infants. 7,8
The use of oral antibiotics, on the other hand, is still debatable. In developing countries,
antibiotics are frequently used to shorten the course and positivity of specific infectious diarrhea
making the hospital stay short. 7,9,10 The disadvantage however, is the number of untoward
reactions recorded.
Nifuroxazide is a broad-spectrum intestinal anti-infectious agent with a strictly local
action suitable for the treatment of diarrhea. It is a synthetic derivative of the nitrofurans group. It
has the advantage of rapid action, stopping diarrhea of infectious origin within 24-48 hours at
most, and is active against the majority of organisms known to provoke diarrhea. Because of
these advantages, we decided to use this anti-infectious agent to test its clinical efficacy and
tolerance, and its eventual advantage when used with a concomitant rehydration therapy.
MATERIALS AND METHODS
The study was started last February, 1985 involving newly admitted pediatric cases, aged
11 months to 12 years of age, both male and female, with signs and symptoms of acute
gastroenteritis of abrupt onset and infectious in nature.
Excluded were newborns and infants younger than 9 months; patients who had been
treated with antibiotics during a period of one month prior to the study; patients in whom diarrhea
persisted for 7 days prior to treatment; and patients with any gastrointestinal tract anomaly.

Forty patients forming 2 groups of 20 each were included by randomization. Treatment
was done as follows:
1st group = received nifuroxazide suspension and ORS in relation to the dehydration
status of the child plus adequate diet (starting with diluted milk diet progressing until resumption
of normal diet. Breast-feeding was not disrupted),
2nd group = received ORS only in function to the dehydration status of the child.
The dosage of nifuroxazide suspension was 660 mg administered in 3 single doses of 220
mg (5 ml suspension) per day until disappearance of diarrheal symptoms and resumption of
normal diet. The rehydration therapy was adapted to the child's requirements. Diet was adapted
depending on the appearance of the stool. The first day of normal nutrition was considered as the
time of recovery. Stool or rectal swab culture was done before the start of the treatment and daily
thereafter until the patient was discharged.
The criteria for recovery included:
1. The total necessary quantity of rehydration solution in milliliters (total amount of
ORS),
2. The resumption of normal diet in days,
3. Shift from frequent watery stools to less frequent stool movements of a more normal
consistency.
Side effects were also noted, as well as the number and reasons for withdrawal, if any.
RESULTS
A total of 104 patients were examined for stool pathogens, out of which forty (40) were
positive for enteric pathogens and forty six (46) negative. Eighteen (18) absconded.
Of the twenty (20) cases from the nifuroxazide group, 13 were males and 7 females. In
the ORS group, 10 were males and 10 females.
Table 1 shows the age group of the patients. As seen, majority belonged to the 1-2 years
age group.
Table 1. Age Group and Sex of the Patients
Age Group M F Ercefuryl M F ORS
1 year 2 0 2 0 2 2
1 - 2 8 7 15 7 7 14
3 - 4 2 0 2 0 1 1
5 - 6 0 0 1 0 0 2
7 - 8 1 0 1 0 0 0
9 - 10 0 0 0 1 0 1
11- 12 0 0 0 0 0 0
Total patients 13 7 7 10 20
In many cases of gastroenteritis, the most important parameters in the analysis of results
are the duration of diarrhea, the consistency of the stools observed daily, and the amount of fluids
given. Table 2 shows the duration of diarrhea in days. It will be noticed that the difference
between the two groups is significant. Six patients from the nifuroxazide group had diarrhea for
one day only compared to the 3 patients in the ORS group. Four of the ORS patients still had
diarrhea up to the 4th day of hospitalization against the 3 in the nifuroxazide patients, and 2
patients in the ORS group against none in the treated group up to the 6th day.
During the episodes of diarrhea in children, the consistency of the stools was watery. The
stools gradually or abruptly became formed depending upon the response of the patient to the
treatment given. Table 3 showed the amount of fluids consumed by the two groups. In the treated
group the patients consumed a total amount of 36,600 ml ORS, whereas, in the ORS group the
patients had consumed 62,650 ml ORS or almost twice the nifuroxazide group.

Table 2. Duration of Diarrhea
Day Ercefuryl ORS
1 6 3
2 6 6
3 5 5
4 3 4
5 0 0
6 0 2
Total patients 20 20
Table 3. Amount of Fluids Given
Milliters of ORS Amount Used Ercefuryl Amount Used ORS
100 - 900 600 6 patients 3000 5 patients
1000 - 1900 5000 5 " 8400 7 "
2000 - 2900 8000 4 " 4000 2 "
3000 - 3900 6000 2 " - 0 "
4000 - 4900 - 0 " 9000 2 "
5000 -5900 10000 2 " 5500 1 "
6000 - 6900 - 0 " 6000 1 "
7000 - 7900 7000 1 " - 0 "
12250 - - 0 " 12250 1 "
Total 36600 ml 20 patients 62650 ml 20 patients
Resumption to normal diet is also an important parameter in gauging if the patient is
getting well. 11,12 Table 4 showed the day when the two groups resumed their normal diet. In the
treated group, all 20 cases resumed normal diet on their 3rd day of confinement. In the ORS
group, majority resumed normal diet on the 2nd day as in the nifuroxazide group; however, 4
resumed their normal diet on the 4th and 5th days.
Table 4. Day Normal Diet Was Resumed
Day Ercefuryl ORS
1st 1 2
2nd 12 10
3rd 7 4
4th 0 2
5th 0 2
6th 0 0
Total patients 20 20
As for the pathogens, Table 5 showed the different bacterial pathogens isolated. One ease
from the ORS group was positive for salmonella group B two times; before treatment and the
next day of confinement. In all other cases where a pathogen was isolated, the organisms were
isolated only once before treatment. The succeeding daily stool or rectal swab cultures were
negative until discharge.
During their treatment and stay in the hospital, no side effects or reactions were noted in
the nifuroxazide group. Some of the patients whose parents were insistent on shifting from ORS
to intravenous fluids were eliminated from evaluation. A few cases from the treated group went
home against medical advice but their diarrhea had improved and the stools were semisolid
already. We did not include these cases in our statistics.

Table 5. Bacterial Pathogens Isolated
Pathogens Ercefuryl ORS
Shigella 7 8
Salmonella 3 3
Vibrio cholerae 4 3
Toxigenic E. co1i 3 2
Enteropathogenic E. coli 1 2
Vibrio parahemolyticus 1 2
Vibrio fluvialis 1 0
Total patients 20 20
DISCUSSION
Since our intention in doing this study was to determine whether the addition of an oral
anti-infectious agent to the usual rehydration and diet therapy was of therapeutic value in the
diarrheas of infants and children, we were very careful and critical in our interpretations. We
know that many researchers consider ORS to be sufficient in combating dehydration to which we
agree but since we wanted to shorten the patient's stay in the hospital we think that an antiinfectious
agent is necessary, as seen in our results. The duration of illness is very important in
any government hospital. A decrease in the duration of the illness of the patient would mean a
shorter hospital stay which is advantageous psychologically and economically. Looking at our
results it is clear that the drug led to considerable improvement in the patient's symptomatology
and well-being. However, because the major problem is still the risk of dehydration, we think that
ORS should be a part of the drug treatment in infectious diarrhea.
In this study, we also put importance to the proper supervision of the patient's diet
because maintenance of adequate nutrition will prevent malnutrition, a condition that can hinder
early response of the patient. 11,12 Nutrition can be maintained because the gut remains able to
absorb a variety of nutrients. In fact, there is no physiological basis to the common belief that the
bowel should be "rested" during acute diarrhea.
Because we had done this study to hospitalized patients, we cannot say whether the
results would be the same for outpatients since usually only the mild and moderately dehydrated
cases are the ones treated in the Out-Patient Department, in which cases ORS alone is enough to
relieve the dehydration.
CONCLUSION
In conclusion, we think the drug has a therapeutic value especially when given
concomitant with an oral rehydration solution. In addition to the drug and flu id therapy, the diet
of the patient should be properly guided to reach maximum therapeutic level.
No side effects or reactions were noted from the nifuroxazide patients.
Acknowledgement
We wish to thank Laboratories Robert & Carriere for supplying the drugs used for this trial.
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