ANTIMICROBIAL RESISTANCE OF BACTERIAL PATHOGENS ASSOCIATED WITH DIARRHEAL PATIENTS ININDONESIA PERISKATJANIADI, MURADLESMANA, DECYSUBEKTI, NUNUNGMACHPUD, SHINTAKOMALARINI, WASISSANTOSO,CYRUSH.SIMANJUNTAK,NARAINPUNJABI,JAMESR.CAMPBELL,WILLIAMK.ALEXANDER, H.JAMESBEECHAMIII,ANDREWL.CORWIN, AND BUHARIA.OYOFO United States Naval Medical Research Unit No. 2, Jakarta, Indonesia; Sumber Waras Hospital, Jakarta, Indonesia; Friendship Hospital, Jakarta, Indonesia; National Institute of Health Research and Development, Ministry of Health, Jakarta, Indonesia; Medical Faculty, Trisakti University, Jakarta, Indonesia Abstract. The antimicrobial susceptibility patterns for 2,812 bacterial pathogens isolated from diarrheal patients admittedtohospitalsinseveralprovincesinthecitiesofJakarta,Padang,Medan,Denpasar,Pontianak,Makassar,and Batam,Indonesiawereanalyzedfrom1995to2001todeterminetheirchangingtrendsinresponsetoeightantibiotics: ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, tetracycline, cephalothin, ceftriaxone, norfloxacin, and ciprofloxacin. Vibrio cholerae O1(37.1%)wasthepathogenmostfrequentlydetected,followedby Shigella spp.(27.3%), Salmonella spp.(17.7%), V. parahaemolyticus (7.3%), Salmonella typhi (3.9%), Campylobacter jejuni (3.6%), V. cholerae non-O1 (2.4%), and Salmonella paratyphi A (0.7%). Of the 767 Shigella spp. isolated, 82.8% were S. flexneri, 15.0% were S. sonnei, and2.2%were S. dysenteriae (2.2%).There-emergenceof Shigella dysenteriae wasnotedin1998,after anabsenceof15years. Shigella spp.wereresistanttoampicillin,trimethoprim-sulfamethoxazole,chloramphenicol,and tetracycline. Salmonella typhi and Salmonella paratyphi Aweresusceptibletoallantibioticstested,while Salmonella spp. showed various resistance patterns according to species grouping. A small number of V. cholerae O1 were resistant to ampicillin, trimethoprim-sulfamethoxazole, chloramphenicol, and tetracycline; however, they were still sensitive to ceftriaxon, norfloxacin, and ciprofloxacin. Similar results were shown for V. cholerae non-O1. Campylobacter jejuni showed an increased frequency of resistance to ceftriaxone, norfloxacin, and ciprofloxacin, but was susceptible to erythromycin. This study shows that except for C. jejuni and V. parahaemolyticus, which appeared to be resistant to ciprofloxacin, the majority of the enteric pathogens tested were still susceptible to fluoroquinolones. INTRODUCTION Antimicrobial resistance in enteric pathogens is of great importance in the developing world, where the rate of diar- rheal diseases is highest. The progressive increase in antimi- crobial resistance among enteric pathogens in developing countries is becoming a critical area of concern. The acute diarrheal diseases for which antimicrobial therapy is clearly effective include shigellosis, cholera, and campylobacteriosis. However,forcampylobacteriosis,thediagnosisisusuallytoo late for antimicrobial therapy to be effective. 1,2 Among the bacteria causing diarrheal diseases, Salmonella spp. continue to be a major public health problem. Although most Salmo- nella infections are self-limiting, serious sequelae, including systemic infection and death, can occur. 3,4 In addition, since the 1960s various Salmonella spp. resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole have been reported with increasing frequency through out the world. 5 Strains of C. jejuni have also been reported as resis- tant to ampicillin, carbenicillin, clindamycin, gentamicin, to- bramycin, streptomycin, and metronidazole. 6 Theemergence of Campylobacter spp. that are resistant to ciprofloxacin has been reported in Thailand. 7,8 A similar emergence in Spain, where the isolation rate of ciprofloxacin-resistant Campylo- bacter increased from 0% in 1987 to 30% in 1991. 9 In Spain and elsewhere in Europe, the rate of Campylobacter resis- tance to fluoroquinolones appears to be increasing because fluoroquinolones are used in both human and veterinary medicine. 9 Overthepastseveraldecades,strainsof Shigella spp.have progressivelybecomeresistanttomostofthewidelyusedand inexpensive antimicrobials. 10 The re-emergence of Shigella dysenteriae after a 15-year absence was recently observed in Indonesia,andthisspecieswasshowntoberesistanttoampi- cillin, trimethoprim-sulfamethoxazole, and tetracycline. 11 Resistance (R) factor plasmids are extrachromosomal DNAelementsofbacteriathatconferdrugresistanceontheir hostbacteria.Theycantransferthemselvestootherbacteria by conjugation and by phage-mediated transduction. They can also integrate into the host chromosome. These factors canbetransferrednotonlyto Enterobacteriaceae,butalsoto a variety of gram-negative bacilli such as Pseudomonas, Vibrio cholerae,andothers.Infact,highlyvirulentstrainsof bacteria carrying R factors can cause infections in humans andanimals.AnimportantpointwithRfactorsisthatmany of them carry multiple drug resistance genes. 12 In Indonesia, most hospitals and clinics treat diarrheal- infected patients with antibiotics prior to receiving definitive laboratoryresults.Fortreatmentof Campylobacter infections inIndonesia,erythromycinismostoftenused.Forinfections with Salmonella spp. and Shigella spp., trimethoprim- sulfamethoxazole is used, while for cholera, tetracycline is used.Fluoroquinolonesarenotcommonlyusedforthetreat- mentofdiarrhealinfectionsbecausetheyareexpensive.Asa result of these concerns, this study sought to explore devel- opingtrendsandpatternsofresistancetoeightantimicrobial agentsusedforthetreatmentofpatientswithentericbacteria related diarrhea in Indonesia. MATERIALS AND METHODS Sample collection and bacteriologic isolation. A total of 2,812 strains of pathogenic bacteria were isolated from the stool samples of patients presenting with diarrhea from 1995 to2001.Therewere21,763rectalswabsamplescollectedfrom 11,823 males and 9,940 females. The median age of the pa- tients was three years (age range  1 month to 96 years). Fifty-four percent of the samples were collected from young children (0–4 years old). Rectal swab specimens were col- lectedonthedayofadmissionfrompatientsadmittedtothe Am. J. Trop. Med. Hyg., 68(6), 2003, pp. 666–670 Copyright © 2003 by The American Society of Tropical Medicine and Hygiene 666