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Journal of Rawalpindi Medical College (JRMC); 2014;18(2):209-212

Original Article
Azithromycin Versus Ofloxacin in Treatment of Enteric
Fever in Children
Ammara Manzoor, Tariq Mahmood, Rubina Zulfiqar
Department of Paediatrics ,Holy Family Hospital and Rawalpindi Medical College, Rawalpindi

Abstract year 2000, about 22 million new cases of typhoid fever
were reported with 210,000 deaths due to typhoid
Background: To compare the clinical efficacy of fever and 5.4 million cases of paratyphoid fever1. A
Azithromycin versus Ofloxacin in the treatment of
study conducted in May 2004 showed that South East
typhoid fever in terms of the proportion of children
Asia and Central Asia are the regions in which
becoming afebrile on 5th day of treatment.
incidence of typhoid fever is high, 100/100,000
Methods: In this randomized controlled trail 230 cases/year. Rest of Asia, Africa, Caribbean, Latin
patients of Typhoid fever, age ranging from 2-12 America, part of Europe and North America are the
years, were included. One hundred and fifteen regions with medium incidence of typhoid fever, 10-
patients were given Azithromycin and 115 patients 100/100,000 cases/per year. The rest of the developed
were given Ofloxacin randomly. Patients were world have low incidence of typhoid fever,
randomly divided into two groups . Group A was
<10/100,000 cases/year2. Pakistan has a high incidence
given Azithromycin 10 mg/kg/day once daily orally
of typhoid fever. It is the 4th commonest cause of death
for 7 days.Group B was given Ofloxacin
. According to a report of WHO, the incidence of
15mg/kg/day in two divided doses orally for 7 days.
typhoid fever in Pakistan is 573.2 per 100,000 persons
Both the groups were observed for duration of
per year. 3,4
becoming afebrile on 5th day of treatment.
Risk factors for transmission of typhoid fever and
Investigation to be done during hospital stay was
paratyphoid fever include over crowding, poor hand
Typhidot (IgM antibodies) . Chi-square test was
washing and poor personal hygiene, eating street food,
used to compare efficacy (afebrile on day 5) of both
drugs.P-value < 0.05 was considered significant. using water without boiling, sharing food, consuming
iced drinks, lower socioeconomic group, and poor
Results: The age range was from 5 to 12 years with sanitory conditions in houses. Typhoid fever is
a mean age of 7.7 ±2.45. 125 (54.3 %) were males and
frequently transmitted in summer and during rainy
105 (45.7 %) were females. 59.1% patients became
season due to contamination of water used for
afebrile on 5th day of treatment while 40.9 % patients
drinking5
failed to become afebrile.In the Azithromycin group
The incubation period of typhoid fever is one to two
69.6 % patients became afebrile on day 5th . In the
weeks.6 After ingestion of contaminated food or water,
Ofloxacin group, 48.7% became afebrile on day 5 th .
the bacteria enters into the lamina properia of
Proportion of patients becoming afebrile on 5 th day
intestine, from where it is taken up by macrophages
of treatment was significantly higher in the
which then spread the organism via lymphatics to
azithromycin group as compared to Ofloxacin group
(p= 0.01) various organs of host causing disease manifestations.7
The clinical picture of the disease may be mild or
Conclusion: Azithromycin is more effective in severe enough to cause fatal complications and death
children with typhoid fever in terms of greater
of the patient. Patients may present with high grade
proportion of children becoming afebrile on day 5 th
fever, anorexia, nausea, vomiting and diarrhea or
of treatment
sometimes abdominal pain, pallor, constipation,
Key Words: Azithromycin, Ofloxacin, Enteric jaundice, myalgias, arthralgias and
fever hepatosplenomegaly or encephalopathy, or ileus
Introduction intestinal perforation. Factors that determine the
Typhoid fever is a major health problem .It is an severity of the disease include, the duration of illness
important cause of mortality and morbidity world before starting appropriate therapy, age of the patient,
wide but with high incidence in developing countries previous vaccination, immunity of the host, dose of
of Asia. It is endemic in Pakistan and India. A recent inoculating organism and choice of antibiotic being
estimate of disease burden worldwide showed that in used for treatment. 8

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Majority (54.9% hepatomegaly.0 11.16 Treatment of 5 Std. Among newer fluoroquinolones. This is in contrast to a study which duration of becoming afebrile on 5th day of treatment. No 35 59 94 abdominal pain or discomfort.17 3. 2.0 8..0 5. proper treatment however it can be reduced to 1 % with proper treatment with antibiotics 10. Group A was given Azithromycin 10 Discussion mg/kg/day once daily orally for 7 days.15 25 This resistance again forced the physicians to search count 20 for newer antibiotics to which salmonella is sensitive.7% 59.13Increased use of fluoroquinolones 35 again created problem in treatment of typhoid fever 30 due to emergence of strains that were resistant to Fluoroquinolones.In the Ofloxacin group 48. The weight of the children ranged from 10 to for treatment of typhoid fever. 9 to compare efficacy (afebrile on day 5) of both drugs. age antibiotic given range from 2-12 years.00 0 down to 3rd and 4th generation cephalosporins.0 12. Patients were randomly divided into two groups.45 Mean = 7. Other tests which Typhidot (IgM antibodies) . were included.6 %) became afebrile describe the resistance to all first line antimicrobials on day 5th . The survivors used to have The age range was from 5 to 12 years with a mean prolonged disability and illness lasting for weeks or age of 7.001 and B .Age distribution of study groups Pediatric Department of Holy Family Hospital.P- Case fatality rate of typhoid fever is 10 % without value < 0. A p=0.The proportion of patients ampicillin. Antibiotic therapy is necessary males .7 ±2.0 7. About 15 % of infected patients with salmonella died in past in Results pre-antibiotic era.0 6. Patients had azithromycin ofloxacin Total fever >37°C in the presence of at least one or more of AFEBRILE yes 80 56 136 69.0 Azithromycin.18(2):209-212 Gold standard for diagnosis of typhoid fever is blood Investigation to be done during hospital stay was culture and bone marrow culture.0 10. Gatifloxacin is a 15 better alternative.4% 51. A study was group(p=0.from March 2012 to September on day 5th: Azithromycin versus Ofloxacin groups 2012. In the Multi Drug Resistance (MDR) is the term used to Azithromycin group majority (69.3 %) were even for many months.0% 100. Both the groups were observed for typhoid fever.6% 48. rose spots on skin and vomiting.0% 100.One Total 115 115 230 hundred and fifteen patients were given Azithromycin 100. Chi-square test was used are commonly used include Typhidot test and PCR. Dev = 2. persistent headache.11 40 kg with a mean weight of 237. azithromycin group as compared to Ofloxacin fluroquinolones are the drugs of choice 12.7% patients used for treatment of typhoid fever including became afebrile on day 5th.45 (Figure 1).0 4. Trimethoprim-Sulfamethoxazole and becoming afebrile on day 5th was higher in the chloramphenicol.e. splenomegaly / 30. Penams and Tigecycline. Due to these MDR strains. Table 1: Frequencies of patients becoming afebrile Rawalpindi . 3rd generation Cephalosporins like Ceftriaxone are now commonly being used for the 10 treatment of typhoid fever.0 9. showed that children less than 5 years of age are at 210 .1% the signs and symptoms .0 age in years Patients and Methods: This randomized controlled trail was conducted in Figure 1.0% and 115 patients were given Ofloxacin randomly.7 ciprofloxacin resistant typhoid fever now narrows N = 230.Group B was The results of present study revealed children given Ofloxacin 15mg/kg/day in two divided doses between age group 7-11 years. Total 230 diagnosed patients of Typhoid fever.Sample size was calculated by WHO calculator.3% 40.Journal of Rawalpindi Medical College (JRMC).05 was considered significant. mostly infected with orally for 7 days. i.48 kg.14. 2014.01)(Table 1) conducted in India in 2001 that showed 100% 40 susceptibility of all isolated Salmonella strains to Ciprofloxacin.

that male children have easy access to street foods.2 to 9. 2004. 94% (30/32) were cured of the 2012 . and consequently may not be an caution. 211 . Fontana J. for children.Journal of Rawalpindi Medical College (JRMC). Foodborne Pathog Dis. is a clinical as well as a public health challenge due to The clinical cure rate was 64% with ofloxacin. 26 The Similar results were also obtained in Bangladesh in slightly lower cure rate in our study as compared to which male patients were more in number than the these studies may be due to higher doses of female patients infected with typhoid fever. Abed N. Ofloxacin (20mg/kg effective as an initial oral treatment for uncomplicated of body weight/day for 7 days). Vietnamese children and adults with mean fever clearance time. van Asten HA. azithromycin is an effective alternative in conditions when ofloxacin is contraindicated. Microbiologyopen. 96% (42 out of 44) were cured. Indonesia. Typhoid fever and Para Typhoid fever In: Current Diagnoses and Treatment 10mg/kg/day once daily for 7 days had an average Pediatrics.8 days [5.82(5):346-53.2 days]) (p < 0. particularly azithromycin .20. clearance time for patients treated with Conclusions azithromycin (5. Clinical burden of typhoid fever . Egyptian children. The global burden of typhoid fever. a new children or 1 g/day in adults given for 5 days. Rosselin M. (8. Azithromycin can Azithromycin group 69.2 days [7. However exploration of more antibiotic therapies .Azithromycin is a better choice than Ofloxacin in azithromycin (7. needs typhoid fever with no major side effects. 23 Salmonella serotype Typhimurium infections with an unusually long incubation period.1(3):243-58. Black RE. fever. Wiedemann A. Some antimicrobial regimens for the treatment of MDR investigators also did not specify whether clinical (multidrug resistant) (nalidixic acid resistant) Na (r) failures were excluded or included in calculations of typhoid fever. 2014. 21 In the azithromycin used in these studies. The mean (95% confidence interval.19 Males were reported more than females disease. p= 0. Luby SP.27 on day 5 was significantly higher in the Azithromycin The persistence of fever in some patients of our group as compared to Ofloxacin group. 23 3 World Health Organization.1 days]) and ofloxacin terms of shorter time of fever clearance. Widjaja S. Matyas BT. 23 According to 2.5 days]) was shorter than that for patients treated with ofloxacin. 76% rising levels of drug resistance and limited evidence with ofloxacin-azithromycin. and 82% (51/62) with for use of newer agents like Azithromycin.1 to 6.291(21):2607-15. The proportion of patients becoming afebrile children. Studies have examined a regimen of azithromycin 2012 . azithromycin was compared in terms of fever 2004 2.18(2):209-212 high risk. morbidity and mortality for 2010.6 % patients became afebrile be used safely for the treatment of typhoid fever in on day 5. in our study groups and it may be due to the reason Of Vietnamese adults. Appropriate treatment of typhoid fever (10mg/kg/day for the first 3 days) were compared. Sondheimer JM.A study may be due to the continued production of case series reported from south India showed that pyrogenic cytokines.01). Levin MJ. typhi among the family and close contacts. 2009. Of the paradigm for Salmonella pathogenesis. Bull World Health Organ. pp1154-56 fever clearance time on day 5 of treatment and this 5 Vollaard AM.4 days. WHO Geneva 2006 who were treated with Azithromycin in a dose of 4 Hay WW. 1 g/day) in 7 Velge P. 2 Crump JA.along with another study conducted in Amirtasir India.18. azithromycin typhoid fever. Boumart Z. with a mean fever clearance time of 4.9(3):245-48 at a dose of 20 mg/kg/day (maximum. the safety emergence of resistance to antibiotics which were of ofloxacin and azithromycin is equal in treatment of considered appropriate for its treatment . 24 In a study it was shown that about 20 % of patients of References 1 Buckle GC.28 This shows that time taken to fluoroquinolone use in fluoroquinolone reduced clear fever may not be an adequate measure of susceptibility strains should be done with great antibiotic efficacy. a 7-day course of azithromycin was more open randomized controlled trial. with a mean duration of fever of 5.5 days25. Multiplicity of Salmonella entry mechanisms.2 to 8. 6th International Conference on About 80% of the patients among this study group typhoid Fever and other salmonellosis.1 days [6. J Glob Health.2(1):10401-05. Risk factors for was comparable to results of another study in which typhoid and paratyphoid fever in Jakarta. has the potential to allow further transmission of S. 19th edition. Ali S. uncomplicated typhoid fever were entered into an In this study. Mintz ED. JAMA. DeGroot MA. Typhoid fever and typhoid fever treated with Ofloxacin had positive fecal paratyphoid fever: Systematic review to estimate global cultures immediately in their post treatment period.001). 6 Brooks JT. Walker CL. 1.An outbreak of clearance time. 22 Another study compared different appropriate end point in typhoid therapy trials. This transient fecal carriage in post treatment period 2012.

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