Original Article

A Prospective Study of Efficacy and Safety of Azithromycin and

Ofloxacin in the treatment of Typhoid Fever in Children at a Tertiary
Care Hospital
CM Kamaal1*, Vishal P Giri2, Imtiyaz Ahmad Shah2
1
Department, of Pharmacology, SMMH Government Medical College, Saharanpur, India
2
Department of Pharmacology, Teerthanker Mahaveer Medical College and Research Centre, Moradabad.

ABSTRACT

Introduction: Antimicrobial therapy is the mainstay for the treatment of Typhoid fever that shortens the
clinical course of typhoid fever and reduces the risk of death. For decades, chloramphenicol has been highly
effective against S. typhi, but multi-drug resistant (MDR) strains of S. typhi (resistant to chloramphenicol,
trimethoprim sulfamethoxazole, and ampicillin) has restricted its use in typhoid fever.
Objective: To compare the efficacy and safety of Azithromycin and Ofloxacin in children suffering from
uncomplicated typhoid fever.
Methods: Blood culture proven, uncomplicated typhoid fever patients admitted in the pediatric ward of J.
N. Medical college, Aligarh were treated with ofloxacin orally (15mg/kg/24 hrs BD for 5 days) and
azithromycin orally (10mg/kg/24 hrs OD on Day 1, then 5mg/kg OD for next 4 days). Patients were
clinically and bacteriologically evaluated during the study period and follow-up.
Results: 96.7 % cure rate was observed in azithromycin group. No relapse was recorded.
Conclusion: Both Ofloxacin as well as azithromycin may be considered as an empirical therapy for the
treatment of uncomplicated typhoid in children .

Keywords: Typhoid fever, Ofloxacin, Azithromycin.

INTRODUCTION ______________________________________________________

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Received: 17.02.16 | Revised: 18.02.16 | Accepted: 19.02.16
*Correspondence to: Dr. CM Kamaal
Assistant Professor, Department of Pharmacology,
SMMH Government Medical College, Saharanpur, India.
E-mail: doc_kam@hotmail.com
The term ‘enteric fever’ includes typhoid and paratyphoid
fevers. Typhoid fever is caused by a Gram negative
organism, Salmonella enterica subspecies entericaserovar
Typhi (Salmonella typhi), whereas paratyphoid fever is
caused by any of the three serovars of Salmonella enteric
subspecies enterica, namely S. paratyphiA, S. schottmuelleri
(also called S. paratyphiB), and S. hirschfeldii (also called S.
paratyphiC).[1]
The world sees approximately 22 million new typhoid cases
occur each year. The worst sufferers are young children in
poor, resource limited areas, who make up the majority of
the new cases and mortality figures (215,000 deaths
annually).[2]
Risk factors for transmission of typhoid fever and

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 Kamaal CM, et al.: Azithromycin and Ofloxacin in Typhoid Fever
paratyphoid fever include overcrowding, poor hand washing Exclusion Criteria
and poor personal hygiene, eating street food, using water (a) All cases with a history of treatment of fever with
without boiling, sharing food, consuming iced drinks, lower Macrolides / Fluoroquinolones within one week (b) A
socioeconomic group, and poor sanitary conditions in history of hypersensitivity to any of the trial drugs. (c)
houses. Diagnosis is made by blood, bone marrow, or stool Complicated cases of typhoid fever.
culture.[3-5]
Study Groups
Specific antimicrobial therapy shortens the clinical course of
The patients were divided into two treatment group by
typhoid fever and reduces the risk of death. For decades,
random allocation of treatment.
chloramphenicol has been highly effective against S. typhi,
but multi-drug resistant (MDR) strains of S. typhi (resistant
1) Azithromycin group (n 1= 61 patients): They were treated
to chloramphenicol, trimethoprim sulfamethoxazole, and
with Azithromycin 10mg/kg/24 hrs x OD x oral on Day
ampicillin) has restricted its use in typhoid fever.
1. Then 5mg/kg x OD for next 4 days.
Fluoroquinolones have proven to be effective for MDR cases
of typhoid fever. 3rd generation Cephalosporins like
2) Ofloxacin group (n2= 53 patients): They were treated
Ceftriaxone are now commonly being used for the treatment
with Ofloxacin 15mg/kg/24 hrs x BD x oral For total
of typhoid fever.[6]
duration of 5 days.

The current study goal is to examine the efficacy and safety

Symptomatic and supportive management was also given as
of ofloxacin and azithromycin therapy for the treatment of
needed.
uncomplicated typhoid fever in children .

Statistical analysis of data

MATERIALS AND METHODS
Study design
This randomized comparative prospective study was
conducted by Department of Pharmacology, J. N. Medical
College AMU Aligarh in association with Department of
Paediatrics and Department of Microbiology J. N. Medical
College on paediatric patients admitted in the Department of
Paediatrics, over a period of one year. A written consent was
obtained from the Parent/attendant of patient for inclusion in
the study.
All the data were calculated by SPSS software version 15.0.
The parametric variables were defined as mean ± standard
deviation.
RESULTS
71 out of the 114 patients were males (62.28%) with a male
to female ratio of 1.65:1. Age of all patients ranged between
08 months to 12 years. Mean age of patients was years7.73
± 3.14 years. The mean weight of all patients was 20.0 ± 8.43
kg. (Table 1)

In all cases, blood culture was positive for S. typhi.

Antimicrobial susceptibility test (AST) of isolates to Table 1: Base line characteristics of the cases
chloramphenicol, trimethoprim-sulfamethoxazole, between two groups
ampicillin, ciprofloxacin, ofloxacin, ceftriaxone, and Azithromycin Ofloxacin Total
azithromycin was also performed. Blood culture from Character
( n1=61) ( n2=53) (n= n2 +n2)
patients was processed by BACTEC 9240 blood culture
7.74±
automated system (Becton Dickinson). ID (identification) 7.71±3.07 7.73± 3.14
Age(yrs) 3.24[1
and AST were determined by BD Phoenix 100 automated [0.8-12] [0.8-12]
-12]
microbiology system.
Sex (M/F) 37/24 34/19 71/43
Laboratory Investigations
Investigations done in all cases were Complete blood count, 19.01± 21.3± 20.0±
Weight(kg)
blood culture for Salmonella typhi and drug susceptibility 9.15[6-42] 7.42[8-40] 8.43[6-42]
test (DST) with ofloxacin and azithromycin. Other tests (if
indicated) included were: Smear and serology for malarial mean ±SD [Range]
parasites, Urine analysis, Stool analysis, Liver function tests,
Renal function tests, Chest X-ray, USG Abdomen and ECG. Maximum incidence of disease was found in 5-10 year age
group and minimum incidence in < 1 year age group i.e
Inclusion Criteria 47.5% and 1.8% respectively. (Table 2).
(a) Children (b) uncomplicated typhoid fever, (c) blood Mean duration of fever before coming to the hospital was
culture positive for Salmonella typhi, (d) isolates 11.5 days in Azithromycin group and 11.4 days in Ofloxacin
(Salmonella typhi ) susceptible in vitro to ofloxacin and group. (P-value>0.05) (Table 3). Moderate grade was the
azithromycin, (e) signed informed consent to participate in most common as seen in 65.7% of cases whereas 23.2%
the study, (f) patient able to take oral medications. patients had mild grade of fever. Only 12.9% cases reported
high-grade fever (Table 4).
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 Kamaal CM, et al.: Azithromycin and Ofloxacin in Typhoid Fever
The most common pattern of fever observed was continuous
Table 2: Age distribution in treatment group 45.3% followed by remittent fever 31.5% and intermittent
fever 18.6% cases with rarely observed stepladder pattern in
4.6% cases. (p > 0.05) (Table 5).
Azithromycin
Age Ofloxacin group
group
Group(yrs) (n2=53)
(n1=61) Table 5: Pattern of fever

1(1.8%) 0 Azithromycin Ofloxacin Total

<1 Type of
Group((n1=5 Group(n2=5 (n= n2+
fever
8) 0) n2)
16(26.1%) 14(26.4%)
1-5 Continuou 49(45.3%
28(48.3%) 21(42%)
s )
29(47.5%)
5-10 24(45.3%) Remittent 18(31%) 16(32%) 34(31.5%

15(24.6%) 15(28.3%) Intermitte 20(18.6%

10-15 10(20%)
nt 10(17.2%) )

Stepladder 2(3.5%) 3(6%) 5(4.6%)

Continuous: Temperature remains throughout the day and at no time

touches the base line.
Table 3: Fever at presentation Remittent: Same as continuous fever but the diurnal variation is > 2°F.
Intermittent: Fever present only for some hours during the day and
Azithromyc Ofloxaci Total (%) remits to normal for the rest of the day.
Duration of Stepladder: Temperature shows an upward rising trend continuously for
in group n group (n=n1 +n2)
fever(days) 4-5 days.
(n1=58) (n2=50)

13(2 The minimum fever clearance time was 6 hrs in

1-7 14(24.1%) 27(25%)
6%)
Azithromycin group and 12 hrs in Ofloxacin group. The
mean fever clearance time was 53.55 hours in Azithromycin
8-14 33(56.9%) 26(52%) 59(54.6%) group while it was 73.08 hours in Ofloxacin group, showing
that Ofloxacin has taken more fever clearance time as
15-21 8(13.8%) 5(10%) 13(12%) compared to Azithromycin (P-value 0.01) (Table 6).

22-28 1(1.7%) 5(10%) 6(5.5%) A Total of 17-treatment failure, 2 in Azithromycin group and
15 in Ofloxacin group noted (Table 7).
>28 2(3.5%) 1(2%) 3(2.9%)
Only 2 (3.3%) participants in azithromycin group and
4(7.5%) in ofloxacin group developed complications (P-
value 0.309). Compliance was better in Azithromycin group
as compared with Ofloxacin group as only 2 patients (3.3%)
Table 4: Grades of fever missed the single dose in Azithromycin group and Ofloxacin
group 9 (17%) patients showed poor compliance (P value
Azithromycin Ofloxacin 0.01) (Table 8).
Grade of Total
group group
fever (n= n1+n1)
(n1=58) (n2 =50) Adverse drug events were observed in 99 (86.8%) patients
out of which 54 (88.5%) patients were from Azithromycin
Mild (up
13(22.4%) 12(24.0%) 25(23.2%)
group and 45 (84.9%) patients from Ofloxacin group. (Table
to 100°F) 9)
Moderate
(up to The most common adverse effects with Azithromycin were
38(65.5%) 33(66.0%) 71(65.7%)
100- loose stools 2(3.3%), abdominal pain 2 (3.3%) and skin
103°F)
rashes 1(1.6%), while in Ofloxacin group epigastric
High discomfort (3.8%), CNS disturbances (3.8%) were observed.
7(12.1%) 5(10.0%) 12(11.1%)
(104≥°F) The incidence of adverse drug effects in both groups were
statistically insignificant (P-value >0.05). (Table 10).

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 Kamaal CM, et al.: Azithromycin and Ofloxacin in Typhoid Fever

Table 6: Fever clearance time in two treatment group

Ofloxacin group
Azithromycin group Mann-Whitney-U
(n2=50) P-value
Fever Clearance time (n1=58) test

Maximum(hrs) 142 154

Minimum(hrs) 6 12 1041.00 0.01
Mean (hrs) 53.55 73.08

Table 7: Impact of drug on outcome of treatment

Result Azithromycin (n1=61) Ofloxacin (n2=53) Chi square P value
Clinical success

Clinical success 59(96.7%) 38(71.6%)

13.995 <0.01

Clinical failure 2(3.3%) 15(28.4%)

Table 8: Development of complications during treatment

Azithromycin group Ofloxacin group
Chi-Square P-value
Character (n1 =61) (n2 =53)
test
Complications developed 2(3.3%) 4(7.5%)
0.309
Complications not developed 59(96.7%) 49(92.5%) 1.03

Table 9: Adverse drug effects in both treatment groups

Total(%)
Azithromycin Ofloxacin
Adverse drug effects (n=n1+n2) Chi-square P-value
(n=61) (n=53)
Observed 54(88.5%) 45(84.9%) 99(86.8%)
0.32 0.569
Not observed 7(11.5%) 8(15.1%) 15(13.2%)

Table 10: Adverse effects during treatment

Azithromycin group Ofloxacin Group
ADE observed
(n1=61) (n2=53)
Nausea 1(1.6%) 1(1.9%)
Vomiting 1(1.9%)
Loose stools 2(3.3%)
Skin rashes 1(1.6%)
Abdominal pain 2(3.3%)
Epigastric discomfort 2(3.8%)
Photosensitivity 1(1.9%)
CNS disturbances 2(3.8%)
Others 1(1.6%) 1(1.9%)

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 Kamaal CM, et al.: Azithromycin and Ofloxacin in Typhoid Fever
Further trials for evaluation of efficacy profile of
Fig Fever clearance time in two groups
azithromycin and ofloxacin for the treatment of
180 uncomplicated typhoid fever are required in the Indian
Fever clearance time(hrs) 160
140 context, so that it might be recommended as empirical
120
100
80
Azithromycin therapy for treatment of typhoid fever in endemic areas.
Ofloxacin
60
40
20
0
1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 What this study adds
Patients no.
1. What is known about this subject?
Azalides, are another class of antibiotics which
Figure 1: Fever clearance time in two-treatment group
have shown promise in the treatment of typhoid
fever. But only few studies are exclusively
DISCUSSION reported in children.
The results of present study revealed children between age
group 8-12 years, mostly infected with typhoid fever. This is 2. What new information is offered in this
in contrast to a study, which showed that children less than study?
5 years of age are at higher risk.[7] Azithromycin as a single daily dose therapy for
5 days was effective in children for
In the Azithromycin group 69.6 % patients became afebrile uncomplicated typhoid fever.
on day 5. The proportion of patients becoming afebrile on
day 5 was significantly higher in the Azithromycin group as
compared to Ofloxacin group; p= 0.01).[8] In our study
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How to cite this article: Kamaal CM, Giri VP, Shah IA. A
Prospective Study of Efficacy and Safety of Azithromycin and
Ofloxacin in the treatment of Typhoid Fever in Children at a
Tertiary Care Hospital. Int Arch BioMed Clin Res. 2016
Feb;2(1):23-28
Source of Support: Nil, Conflict of Interest: None declared

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