M. Waqar Rabbani ( Department of Paediatrics, Nishtar Medical College, Multan. )
Imran Iqbal ( Department of Paediatrics, Nishtar Medical College, Multan. )
M. Suleman Malik ( Department of Paediatrics, Nishtar Medical College, Multan. )
We compared cefixime with chioramphenicol in a trial for treatment of children with culture positive typhoid fever. Twenty children were given cefixhne 10mg/kg/day oraiiy for 14 days and twenty received chioramphenicol 50 mg/kg/day orally for 14 days. On entry the clinical characteristics of the two groups were comparabIe. Clinical cure was observed in 18(90%) patients treated with cefixime and 9(45%) treated with chioramphenicol. Of 11 patients who did not respond to chloramphenicol, 10 were switched over to cefixime and all were cured. Overall 28 out of 30 cases (93.3%) were cured bycefixime (JPMA 48:163,1998).
WHO has estimated that every year more than 12.5 million case soft yphoid fever occur world wide1. Its incidence in developing countries is around 500/10000 annually. Our hospital data over 3 years (1994-96) shows that out of the total admissionof 11091 patients inPaediatric unit, 197 cases were of typhoid, thus constituting 1.7% of the total admissions (unpublished data) with maximum cases seen during the summer months. Resistant strains were reported from Mexico in 1972 againstchlommphenicol which was drug of choice for the treatment of entenc fever2. Later on in 1990, in UK, 19% of the Salmonella..typbi isolates were reported resistant to chloramphenicol3. Recently, strains resistant to more than one antibiotic have emerged, which have been labelled as multi-drug resistant (MDR) stzains4-7.
Different alternatives have been pioposed for the treatment of MDR typhoid but none is satisfactory and safe. Fluroquinolone derivatives are highly active agaisn( Salmonella lyphi in adults8 but potential cartilage and bone toxicity limits their use in children9-10. Third generation cephalosporins including cefotaxime, ceftriaxone and cefoperazone are reported to have a therapeutic success rate of greater than 90%11-14 but the need for parentemi administration and high cost are major limitations in their extensive use.
Cefixime is a third generation oral cephalosporin with a spectrum similarto otherthird generation cephalosporins15. A study conducted in Egypt found it useful in paediatnc entenc fever16. The drugwas also used in MDR typhoid in Pakistan17. We, in this study, have evaluated the safety and efficacy of cefixime in comparison to chioramphenicol in culture -positive typhoid fever.
Patients and Methods
This study was conducted in Department of Paediatric Medicine, Nishtar Hospital, Multan, between August 1994 and February 1995. Mter infonned consent, paediatric patients less than 15 years of age with a diagnosis of typhoid fever confirmed by isolation of Salmonella typhi from blood or bone marrow were recruited for the study. Patients having other concurrent infections, unconscious patients and culture-negative patients were excluded fmm the study.
Forty patients (20 each group) were randomized to receive either oral cefixime (10 mg/kg/day in two divided doses) or oral chloramphenicol (50 mg/kg/day in four divided doses). Both the groups were treated for 14 days.
Patients were initially admitted in the paediatric ward for supervision and daily clinical evaluation. Defervescence offever(indays fromstartof medication), and any side effects were recorded in all patients. Children with persistent pyrexia after 7 days of appmpnate therapy were diagnosed as non-responders and alternate medicine was started. Patients were followed up for four weeks after completion of treatment.
Patients ranged inagefrom2 to 12 years with a meanage of 6.2 years. There were 18 patients in 2-5 years age, 16 in age group 5-9 and 6 patients in >9 years age. There was a striking dominance of male children [males 31 (77.5%) and 9 females (22.5%)]. The mean temperature if patients at the times of admission was 102.4F. On initial examination, 65% of the patients had hepatomegaly and 15% had hepatosplenomegaly. Most of the chilren were anaemic with average haemoglobin 9.96 gm/dl.
The in vitro culture results of the 40 patients showed typhoid bacilli. The sensitivity to cefixime was 100% (40) and to chloramphenicol 92.5% (37).
Table I shows devervescence of fever on an average of 5.05 days in patients responding to cefixime and after an average of 5.5 days in those responding to chioramphenicol.
Table II compares cure rate of cefixime and chloramphenicol. Of the 20 patients who received cefixime, 18 (90%) were cured. Two patients did not respond to cefixime and were given I.V. cephalosporins. Twenty patients were given chioramphenicol and 9 (45%) were cured. Out of 11 non-responders to chloramphenicol, 10 were switched over to cefixime. All of them responded well to the changed treatment and their fever settled on an average of 4th day. Overall 28 cases out of 30 (93.3%) (P=0.0049) were cured by cefixime with fever settling afteran average of4.68 days. No significant adverse effects were noted in either group.
In this comparative study, we have evaluated cefixime in comparison to chioramphenicol, which was an established oral treatment for typhoid fever, before the emergence of resistant Salmonella typhi strains. Cefixime was effective clinically in 93.3% of paediatric patients with typhoid fever in our study as compared to chioramphenicol which was effective in 45%. This figure is comparable to other studies conducted previously in Egypt16 and Pakistan17. However, in vitro, sensitivity studies showed that Salmonella typhi isolates obtained fromthe 40 patients were sensitive to cefixime 100% while chioramphenicol was effective in 92.5%.
This study, on a limited scale, confirms that cefixime, in a dose of 10 mg/kg/day, is a safe and cost effective oral option for the treatment of typhoid fever in children.
The study was supported inpartby a research grant from Wellcome (Pakistan) Ltd.
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