jurnal

SuppL 1 - 1998 Poster Session 253

Antibiotic resistance pattern of pediatric Tlphoid fever patients P-6at Harapan Kita Children and Maternity Hospital Jakarta, 1996Sri Kusumo Amdani

AbstrakSejak 1 Januari sampai 3l Desember 1996, telah dirawat 552 pasien anak di RS Harapan Kita dengan diagnosis klinik demam

tifuid. Dari jumlah tersebut, hanya 133 (24,lVo) yang dipastikan secara bakterioLogis, yaitu lI4 S. typhi, 18 S. paratyphi A dan I S.paratyphi B. Rendahnya hasil kultur positif mungkin disebabkan oleh pemberian terapi antibiotika sebelum pasien dirawat. Hasil ujisensitivitas dari S. typhi menunjukkan: 97,47o sensitif terhadap kloramfenikol dan kotrimol

a254 Typhoicl Feyer and other Salmonellosis Med J Indones

ble 2. Table 3 shows complication and other diseasesof typhoid fever patients, while the treatment resultsare depicted in Table 4.Tble 1. Age and sex distribution of typhoid fever parients

Number of cases Total(%)Male (Vo) Female (Vo)

re (16.1)29 (24.6)r 6 (13.6)

Total 64 (s4.2) 54 (45.8) 118 (100 )Tabel 2, Clinical and laboratory features of children with

phoid fever

METHODSA retrospective study was carried out on all typhoid fe-ver patients admitted to Harapan Kita children's andMatemity Hospital during the period of I January to 31December 1996 with bacteriological confirmation. Werecorded all of the positive blood culture results withS.typhi and S.paratyphi in that period, and then col-lectedThe adwhosefrom this study. Results of sensitivity test for Salmo-nella on several ant posi-tive culture results. storyof illness and clinic ationuntil the patient was discharged or died. Blood culturefor Salmonella was carried out by using bile media andthe determination of bacterilogical sens,itivity was car-ried out by using criteria established by The NationalCommittee for Clinical Laboratory Standards (NCCLS)in the USA+.

A patient was considered cured if fever and otherclinical manifestations disappeared, the general con-ditions was going better, and there was no complica-tions4. Anemia was defined as hemoglobin concen-tration of less than 11 g/dl for children 6 months 6years, or less than 12 gldl for children more than 6years old7. Leukopenia was defined if the leucocytecount was 10

14 (11.9)21 (17.8)re (r6.1)

28)42.4)29.7)

33(s0(35(

ty-

Clinical manifestation+ Fever before admission (day), mean * SD* Temperature ("C), mean + SD* Diarrhea* Constipation* Nausea / vomit* Abdominal pain* Coated tongue* Abdominal distension+ Hepatomegaly* Splenomegaly

Laboratory features*Anemia- 6 years

* Leukopenia+ Lymphocytosis* Thrombocytopenia

6.9 + 4.339.2 + 0.6

43.5 7o52.5 %69.5 Vo85.6 %60.2 Vo40.7 7o27.1 %

OVo

39.4 7036.5 Vo21.1 Vo

47 Vo21 .2 Vo

Tabel 3. Complications of pediatric typhoid fever patients* Bronchopneumoniae* Encephalopaty* Peritonitis* Cholecystitis

12 (10.27o)2 ( r.1Eo)1 ( 0.8Eo)1 ( 0.8Vo)

Tabel 4. Results of treatment of pediatric typhoid fever patientsAntibotic Defervescence of

temDerature(day), mean + SD91 (l00Ea) 5,7 +2.334 ( 35%) 5.1 + 2.132 ( 33Eo) 5.9 + 2.316 (l6.5Vo) 6.1 + 2.415 (15.57o) 6.5 + 2.4

* 2l patients still have fever when clischargecl

The sensitivity pattern of S.typhi on various antibio-tics were obtained from 114 isolates, 97.4Vo were

N(%)

All patients+ChloramphenicolChloramphenicol + Ampicillin /AmoxycillinChloramphenicol + Co-trimoxazoleOthers

ChloramphenicolAmpicillin / amoxycillinCo-trimoxazoleCefotaximeCeftriaxoneCefoperazoneCefmetazoleCiprofloxacin

Suppl I - 1998

sensitive to chloramphenicol and co-trimoxazole,96.5Vo to amoxicillin, 99.lVo to cefotaxime andceftriaxone, 96.9Vo to cefmetazole and l00%o tociprofloxacine. The pattern of sensitivity on antibiot-ics of S.paratyphi were obtained from 19 isolates andthe sensitivity test were l00%o toward all antibioticsmentioned above (Tble 5).Thbel 5. Sensitivity patternof Salmonellaftom 133 pediatric ty-

phoid fever patients for several antibiotics

Antibiotic S.typhi (7o) S.paratyphi (%)n=114 n=19

Poster Session 255

our series, the mean duration of fever before admis-sion was 6.9 + 4,3 days, lower than Nathin's study(9.1 t 5.4 days) and Rivai's series in pediatric pa-tients (9.2 days)a'e. The mean of temperature on ad-mission in present study was 39.2 + 0.6oC, similar toreport by Pape et al that all their patients had tempera-ture of more than 39'C in the beginning of hospitaliza-tion, but higher than Nathin's series (38.6 + 0.6"C)4.Gastrointestinal disorders are common in patientswith typhoid fever. Our series shows that diarrheawas less frequent than constipation (43.5Va vs52.57o). This finding is different with report byNathin et al which showed that diarrhea was morefrequent than constipation (42.0Vo vs 34.4Vo), blrttsimilar to the finding of other investigators in Jakartaand Surabaya in adult patients4,l. Coated tongue wasfound in 60.2Vo of patients, very similar to Nathin'sstudy (6I.lVo). Report of Hendarwanto showed thatcoated tongue in adult patients occured in 72-I007oof patients4'e.

Hepatomegaly and splenomegaly were subsequentlyfound in 27 .IVo and }Vo of patients in our series. Thisfinding is lower than Nathin's study which foundhepatomegaly in 40.5Vo and splenomegaly in 7.5Vo oftheir patients4. As reported by Hendarwanto, in adultpatients hepatomegaly was found in 35-82Vo andsplenomegaly in 23-36Vo of the patientse.

Periphera-l blood finding in typhoid fever patients arecharacterized by leucopenia with relative lymphocy-tosis. In this series, leucopenia was found only in21.27o of patients, while Nathin's series found in36.6Vo of patients and Rivai's series in children foundin 54Vo oftheir patients4,l0. In children below 6 yearsof age, anemia was found in 39.4Vo of patients, whilein children over 6 years of age anemia was found in36.5Vo of patients" These findings are very low com-pare to Nathin's study which found that anemia inchildren below and over 6 years of age were 54.8Voand 7 0.8Va of patients subsequently4. Anemia typhoidfever in general is of the normocytic-normochromictype, especially if intestinal blood loss occurs. Ane-mia is often found in severe acute infections which ischaracterized by inflammation and can be measuredby BSR+.

Typhoid fever is a systemic infectious disease, whichcan cause various complications in almost all organsystems of the host. In our series bronchopneumoniaewas the most frequent complication occured in pa-tients (10.2%o), while encephalopathy, peritonitis andcholecystitis were the other complications which oc-

9',7.496.597.499.t99.r96.99'7.1100

100100100100100100100100

DISCUSSIONThe diagnosis of typhoid fever is proven by cultureof the offending pathogen. In this present study, weonly found 24.IVo positive culture, similar toNathin's series (20.3%o)a. Hendarwanto reported thatpositive bone marrow cultures were more frequentlyobtained than positive blood cultures in adult patients(70-78 Vo vs 4O-50 Vo), but bone marrow punctionprocedure maybe to invasive for childreng.

The case fatality rate of all pediatric typhoid fever pa-tients in this series is 0.5Vo, whereas the overall mor-tality in Dr. Cipto Mangunkusumo Hospital Jakarta is3-7.3Voa and in Dr. Sutomo General Hospital Sura-baya is 0-0.95Eo4'to.

In this series, 50 (42.4Eo) patients were between 5-9years, and 33 (28Vo) patients were less than 5 yearsof age. Compared to Nathin's series which only hasl3.6Vo, our series has higher incidence of patientsless than 5 years, but lower incidence of cases morethan 10 years (29.7Vo vs37.5Vo)+. Reports from manyhospital in Indonesia indicated that the peak age inci-dence was in adolescents and young adults, whileJusuf et al reported that the highest attactrate was inchildren and adolescents between the ages of 5-15years3'g. According to Hendarwanto, there was nosignificant difference in sex distribution of typhoidfever patients in Indonesia, which was also in thispresent study, with 54.2Vo male and 45.87o femalee.

The clinical manifestation of typhoid fever in chil-dren are generally milder than in those of adults. In

256 Typhoid Fever and other Salmonellosis

cured only in a few patients (3.3Vo). In Hendar-wanto's report of adult patients, bronchopneumoniaeonly happened in 2.2 Vo - 7 .IVo of patientse. Compli-cations of pediatric typhoid patients at Dr. SutomoHospital Surabaya were intestinal hemorrhage, hepa-titis, febrile convulsion and septic shocklO.

Drug of choice for typhoid fever at the moment is stillchloramphenicol, with the altemative drugs are am-picillin/amoxycillin, thiamphenicol and co-trimoxa-zole. The resistance of S.typhi to chloramphenicol, am-picillin, amoxycillin, co-trimoxazole and multidrugs re-sistant S.typhi (MDRST) is a problem now4. Thesensitivity pattern of S.typhi to some antibiotics isshown in Table 5. Small percentage of S.typhi was re-sistant to the following antibiotics: chloramphenicol(2.67o), ampicillin/amoxycillin (3.5Vo) and co-trimoxa-zole (2.67o). There were three isolates of S.ryphl resis-tant toward two or more drugs commonly used in thetreatment of pediatric typhoid fever (chloramphenicol,ampicillin/amoxycillin, co-trimoxazole), but the pa-tients were succesfuly treated with combination ofchloramphenicol and co-trimoxazole (two patients) andamoxycillin and co-trimoxazole (one patient), Thesedata indicate that there is resistance of S.typhi to com-monly used antibiotics, but the percentage is small. Thisfinding were very similar to a study from Dr. CiptoMangunkusumo Hospital l99l-I9944.

Other antibiotics clinically effective in the treatmentof pediatric typhoid fever are cefotaxime, ceftriax-one, cefoperazoe, cefmetazole and ciprofloxacin.The resistance rate of S.typhi to these antibiotics wasremarkably low, i.e. cefotaxime 0.9Vo, ceflriaxone0.9Vo, cefoperazone (3.l%o), cefmetazole (2.3Vo) andciprofloxacin ()Vo).

Since the prevalence of resistance of S.typhi tochloramphenicol is negligible, chloramphenicol isstill considered as a drug of choice for the treatmentof pediatric typhoid fever, followed by ampicillin/amoxycillin and co-trimoxazole.

In this study, 21 patients still had fever when they weredischarged in the 2nd - llth days after hospitalization asrequested by their parents. All97 patients left were suc-cesfully cured, 34 (35Vo) with chloramphenicol, 32(?3Vo) with combination of chloramphenicol and am-picillin/amoxycillin, 16 (16.5Vo) with combination ofchloramphenicol and co-trimoxazole and the rest withother antibiotics combination. In patients treated withchloramphenicol fever disappeared after 5.1 + 2.1 daysof treatment, not different with previous studies in de-fervescence of temperature point of viewa.

Med J Indones

CONCLUSIONSFrom 552 patients clinically suspected typhoid fever,I33 (24.IVo) were confirmed bacteriologically. Morethan one fourth of the patients were less than 5 yearsold, and the clinical manifestations of patients in thisseries were mild.

Resistance of S,typhi to commonly used antibioticsdid occur in small percentage. There were three iso-lates of S.typhi resistant toward two or more drugscommonly used in the treatment of pediatric typhoidfever, but the patients were succesfuly treated withcombination of that drugs. Chloramphenicol is stillconsidered as a drug of choice for the treatment of ty-poid fever in children.

REFERENCBS1. Soemarmo SP Opening remarks In: Nelwan RHH ed. Ty-

phoid fever: profle diagnosis and treatment in the1990's. Pa-pers presented at the first ISAC International Symposium;Bali (Balai Penerbit FKUI Jakarta, 1992) p. xvii-xviii.

2. Nathin MA, Hadinegoro SR. Ceftriaxone in the treatment oftyphoid fever in children. In: Nelwan RHH ed. Typhoid fe-ver: profle diagnosis and treatment in the 1990's. Papers pre-sented at the first ISAC International Symposium; Bali (BalaiPenerbit FKUI Jakarta, 1992) p. 133-9.

3. Jusuf H, Sudjana P. Cerebral complication of typhoid f'ever,Acta Med Indones 1996; XXVIII:179-83.

4. Nathin MA, Ringoringo HP, Tambunan T, Hadinegoro SR,Abdoerrachman HM, Tumbelaka AR, et al. Antibiotic resis-tance pattern of pediatric typhoid fever patients at the Depart-ment of child health, Cipto Mangunkusumo Hospital, Jakartain 1990-1994, Paediatr Indones 1996;36: 193-207.

5. Nicholson JF, Pesce MA. References ranges for laboratorytests. In: Behrman RE, Kliegman RM, Nelson WE, Vaughanlil VC eds. Nelson's textbook of pediatrics 14th ed. (WBSaunders Company Philadelphia, 1994): 1'7 99 -827 .

6. Utji R. Antimicrobial therapy of typhoid t'ever and suscepti-bility of Salmonella typhi To antimicrobials Acta Medlndones 1996; XXVIII: 185-8.

7. Markum AH, Abdulsalam M, Moeslichan Mz. Dampak ane-mia gizi den pencegahannya pada anak balita Presented at:Temu Karya Anemia Cizi, Semarang 1986.

8. Feigin RD. Typhoid fever- In: Behrman RE, Kliegrnan RM,Nelson WE, Vaughan lil VC, eds. Nelson's textbook of pedi-atrics l4th ed. (WB Saunders Company Philadelphia, 1994):731-4.

9. Soewandojo E. Typhoid fever: Management of complicationsand short overview of cases in Dr. Sutomo General HospitalSurabaya Indonesia, Acta Med lndones 1996; XXVIII: 159-66.

10. Hendarwanto. Clinical picture of typhoid fver. Acta Med In-donps 1996; XXVIII: 151-7.

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