Gastroenterology Subdivision

Journal Reading

Incidence of Antibiotic-Associated Diarrhea

in a Pediatric Ambulatory Care Setting

Alisara Damrongmanee MD*,Nuthapong Ukarapol MD

Abstract

Background
Although antibiotic-associated diarrhea (AAD) is
a common adverse event in children receiving
oral antibiotics, few epidemiological studies
have investigated this issue.

Objective
To determine the incidence of AAD in children
who received oral antibiotics at the Pediatric
Outpatient Department, Chiang Mai University
Hospital.
Material and Method
Children who were prescribed oral
antibiotics between September 2004
and June 2005 were randomly enrolled.
Subjects with immunodeficiencies,
acute/chronic diarrhea, and a history of
having taken antibiotics within two
weeks prior to this visit were excluded.
 Patients’ characteristics including age,
gender, principal diagnosis, and type of
antibiotics were recorded. Parents were
asked to observe stool frequency and
consistency until one week after discontinuing
antimicrobial agents and fill out an
appropriate questionnaire. AAD was defined if
there were at least three loose or liquid stools
per day for two consecutive days. Risk factors
including age, type, and dosage of the
antibiotics used, were analyzed.
Results
Two hundred and twenty-five children were
eligible for data analysis. The mean age was
4.1 years (0.3-14.5 years). Pharyngotonsillitis
was the most common diagnosis (53.8%), and
amoxicillin and cloxacillin comprised the most
common antibiotics prescribed in the present
cohort. The incidence of AAD was 6.2%. All
were presented while the patients were taking
antibiotics with a mean (+/- SD) onset and
duration of occurrence of 2.28 +/- 1.13 and 2.64
+/- 1.15 days, respectively.
Premature discontinuation of antimicrobial
agents was reported in nine patients (64.3%).
There was a trend towards a higher incidence
of AAD in the amoxicillin/clavulanate group
(16.7%) compared to amoxicillin (6.9%) and
erythromycin (11.1%) groups, although it was
not statistically significant. In addition, the
present study could not demonstrate an
association between younger age or the high
dosage of antibiotics used, and the
development of AAD
Conclusion
AAD was not uncommon in a
pediatric ambulatory care setting.
It tended to occur in youngerchildren
receiving amoxicillin/clavulanate
INTRODUCTION
Nephrotic Syndrome (NS) the most
frequent glomerular disease in childhood
minimal change disease (85% cases)

80-90% respond to initial corticosteroid

76-93% relapse Frequent Relapses

Nephrotic Syndrome (FRNS) or Steroid
Dependent Nephrotic Syndrome (SDNS)

FRNS or SDNS Cyclophosphamide

(CPA)
CPA effective in prolonging remission,
but potential carcinogenic & infertility
limited its use to only 1 or 2 courses of 8 –
12 weeks.

CPA has been evaluated as a second line

immunosupresive agent in Dept. of Child
Health, Cipto Mangunkusumo Hospital since
1975
AIM

To evaluate the efficacy of Cyclophosphamide

for inducing long term remission in FRNS or
SDNS
METHODS
Subjects : Pediatric patients who received initial
prednisone th/ for NS
Aged : 1-18 years
Place : Dept. of Child Health, Cipto
Mangunkusomo Hospital
Time : January 1985 – August 2000
Inclusion criteria :
Suffered from primary steroid-responsive
NS:
Who relapsed frequently
Who developed steroid dependence
Had been treated with CPA (as 2nd line
immunosuppresive th/)
Definition, criteria for NS, remission & relapse
same as those used by ISKDC
NS :
Heavy proteinuria (>40 mg/m2/h)
Hypoalbuminemia (<2.5 g/dl)
Edema
Hypercholesterolemia (>250 mg/dl)
Steroid-dependent patients : whom 2
consecutive relapses :
alternate-day prednisone treatment
regimen earlier relapse, or
within 14 days after the end of an
alternate-day prednisone regimen
Relapse :
Proteinuria > 4 mg/m2/h (++ or more by
Albustix), 3 consecutive days
remission
Frequent relapser experienced > 1
relapses (6 mo period) or > 3 relapses
(12 mo period)
Steroid resistance : no remission after a
min of 8 consecutive weeks of prednisone
theraphy
Complete remission : reduction of
proteinuria to  4 mg/m2/h for 3
consecutive days
FRNS or SDNS relapses :
Initial : Th/ prednisone 60 mg/m2/day (2
weeks)
Remission : Th/ CPA (2 mg/kg/d) 8-12
weeks (combination with prednisone 2/3
initial dose)
When CPA stopped, either prednisone
standard CPA th/ for FRNS & SDNS

Statistical analysis using SPSS 11.5 & Epi

Info
RESULTS
Total subjects : 190 NS patients
171 steroid responders :
64 patients frequent relapser or
steroid dependent :
26 frequent relapser
59%
12 steroid dependent
Th/ CPA & matched the inclusion
criteria
Table 1 & table 2 patient characteristics &
baseline clinical characteristics at the
beginning CPA th/
Table 3
Table 4
Figure 1
During R/ CPA :
Reversible leucopenia : 5 patients
Anemia : 1 patient
Hypertension : 2 patients
Trombocytopenia or hemorrhagic cystitis or
severe infection : none
Th/ for excessive vomiting : 1 patient
Renal failure : 4 patients (3 SDNS & 1
FRNS)
1st patient 70 days after remission
2nd patient 270 days
The rest patient suffered from
hypertension at the beginning of CPA
th/
2 patients death :
Chronic renal failure
Uncontrolled hypertension
DISCUSSION
A retrospective analysis study data was valid
study population representative
Treated patients were small number, but the
calculated power is sufficient (90%)
Study : FRNS & SDNS is higher than
Pulungan : 16,5% & 7,9%
Wilawirya : 18,9% & 1,6%
ISKDC, 1976 higher proportion of FRNS
(39%)
SDNS younger at the onset compared to
FRNS  Pennisi et al & Kemper et al
Other studies patient SDNS were older
when CPA started
Renal biopsy performed in 4 patients :
2 minimal changes NS
2 couldn’t be histopathologically
typed
Several factors correlated with favorable
outcome :
Duration of treatment
A cumulative dosage/body surface area
(BSA)  5040 mg/m2
Leucopenia during CPA theraphy
Frequent relapsing vs steroid dependent
status
Age at onset of the disease
Age when CPA therapy was started
Arbeitsgemeinschaft für Pädiatrische
Nephrologie (APN) response to 12-week
of CPA, better than 8 weeks
Ueda et al no difference between 8 week
& 12 week course
In our study 8 week course of CPA th/
Patients who got relapser after CPA
some had a marked reduction number
relapses 1 year (table 2)
FRNS significantly better response than
SDNS (table 3) ~ APA
Kemper et al : 70% SDNS relapsed &
86% SDNS after 2 years
FRNS significantly higher good
response than SDNS (85% vs 15% after
36 mo,P=0.0001,figure 2)
None patients any serious side
effect
Two patients died because chronic
renal failure & uncontrolled
hypertension
Conclusion

The efficacy of CPA better for th/ patients

with FRNS compared to SDNS
Table 1. Distribution of patient characteristics at the
beginning of CPA therapy

NS = Not significant
Table 2. Distribution of baseline clinical characteristics
Table 3. Relapse rate in patients with SDNS & FRNS after
CPA therapy
Table 4. Response to CPA in FRNS and SDNS
Figure 1. Sustained good response over a period of
5 years