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Abstract
Background
Doxycycline has been the drug of choice for the treatment of scrub typhus. However, scrub typhus with poor response to doxycycline was first reported in Thailand in 1996. To date, it is not known whether doxycycline resistant scrub typhus is present in Korea. To investigate the doxycycline resistance of scrub typhus in Korea, we performed an experiment to evaluate the degree of growth inhibition of Orientia tsutsugamushi at the minimal inhibitory concentration (MIC) of doxycycline.
Materials and Methods
37 isolates of Orientia tsutsugamushi were collected from Korean patients with scrub typhus during 10 year period (from 1997 to 2007). 34 isolates consisted of Boryong serotype or related serotypes. These strains were stained with FS15, a monoclonal antibody against the linear epitope on the protein located at the outer membrane of O. tsutsugamushi. Three isolates were confirmed as serotype Gilliam, which was stained by anti-Gilliam antibody. The antibody-stainable 35 isolates were incubated in media containing 0.1 and 0.2 µg/mL of doxycycline for 3 days. Then the growth indices of Orientia were measured by flow cytometry. If the growth index was greater than 10%, the isolate was tentatively classified as an isolate resistant to doxycycline and its MIC was measured.
Results
Demographic and treatment data were similar to the results of previous reports. Infection was mainly observed in Inchon and the Chungcheongnam province. No patient showed delayed response to antibiotics. Of 35 hospitalized patients, 4 (11.4%) were managed at the intensive care unit, and 1 (2.9%) died of nosocomial pneumonia. All the 2 patients whose isolates were serotype Gilliam Yonchon/Ikeda-like strain were managed at the intensive care unit. Six of the 34 isolates from Korean patients exhibited growth indices greater than 10% at the MIC of doxycycline; however, the MICs of these isolates did not exceed 0.2 µg/mL. One isolate of serotype Gilliam showed an MIC of 0.0125 ug/mL, which seemed to be underestimated due to weak fluorescence of the anti-Gilliam antibody.
Conclusions
Although the number of tested isolates is small, insensitivity of scrub typhus to doxycycline is not a major reason for treatment failure in Korea. Serotype Gilliam, especially Yochon/Ikeda-like strain, may be associated with severe form of scrub typhus. More studies concerning the antibiotic susceptibility for serotype Gilliam are warranted.
Figures and Tables
Table 1
Demographic and Treatment Data of 37 Patients with Culture-Confirmed Scrub Typhus
*All except 3 isolates were FS15-reactive serotypes, i.e., serotype Boryong, Karp, Kato, Kuroki, or Kawasaki.
†referred from the ChungNam University hospital; NA - not available
‡2 strains were O. tsutsugamushi serotype Gilliam Yonchon/Ikeda-like strain
ICU, intensive care unit; SDH, subdural hematoma
References
1. Watt G, Chouriyagune C, Ruangweerayud R, Watcharapichat P, Phulsuksombati D, Jongsakul K, Teja-Isavadharm P, Bhodhidatta D, Corcoran KD, Dasch GA, Strickman D. Scrub typhus infections poorly responsive to antibiotics in northern Thailand. Lancet. 1996. 348:86–89.
2. Na DJ, Han SH, Moon KM, Kim DJ, Lee YD, Cho YS, Han MS, Yoon HJ. A case of possible doxycycline-resistant scrub typhus. Tuberc Respir Dis. 2007. 62:545–548.
3. Park JH, Shim SG. Upper gastrointestinal endoscopic features and predictable factors for clinical severity in the patients with tsutsugamushi disease. Korean J Med. 2005. 69:518–527.
4. Chanta C, Triratanapa K, Ratanasirichup P, Mahaprom W. Hepatic dysfunction in pediatric scrub typhus: role of liver function test in diagnosis and marker of disease severity. J Med Assoc Thai. 2007. 90:2366–2369.
5. Kantipong P, Watt G, Jongsakul K, Choenchitra C. Infection with human immunodeficiency virus does not influence the clinical severity of scrub typhus. Clin Infect Dis. 1996. 23:1168–1170.
6. Kim MJ, Kim MK, Kang JS. Improved antibiotic susceptibility test of Orientia tsutsugamushi by flow cytometry using monoclonal antibody. J Korean Med Sci. 2007. 22:1–6.
7. Kim ES, Kim MK, Lee HM, Chung MH, Lee JS, Park JE, Kang JS. In Vitro Antibiotic susceptibility of Orientia tsutsugamushi strain Boryong measured by flow cytometry. Infect Chemother. 2008. 40:212–217.
8. Kang JS, Chang WH. Antigenic relationship among the eight prototype and new serotype strains of Orientia tsutsugamushi revealed by monoclonal antibodies. Microbiol Immunol. 1999. 43:229–234.
9. Ree HI, Kim TE, Lee IY, Jeon SH, Hwang UW, Chang WH. Determination and geographical distribution of Orientia tsutsugamushi serotypes in Korea by nested polymerase chain reaction. Am J Trop Med Hyg. 2001. 65:528–534.
10. Tamura A, Yamamoto N, Koyama S, Makisaka Y, Takahashi M, Urabe K, Takaoka M, Nakazawa K, Urakami H, Fukuhara M. Epidemiological survey of Orientia tsutsugamushi distribution in field rodents in Saitama Prefecture, Japan, and discovery of a new type. Microbiol Immunol. 2001. 45:439–446.
11. Brown GW, Saunders JP, Singh S, Huxsoll DL, Shirai A. Single dose doxycycline therapy for scrub typhus. Trans R Soc Trop Med Hyg. 1978. 72:412–416.
12. Strickman D, Sheer T, Salata K, Hershey J, Dasch G, Kelly D, Kuschner R. In vitro effectiveness of azithromycin against doxycycline-resistant and -susceptible strains of Rickettsia tsutsugamushi, etiologic agent of scrub typhus. Antimicrob Agents Chemother. 1995. 39:2406–2410.
13. Kim MK, Odgerel Z, Kim MJ, Chung MH, Lim BU, Kang JS. Application of monoclonal antibody, specific for intracellular Orientia tsutsugamushi, to immunofluorescent antibody test for determining antibiotic susceptibility. Microbiol Immunol. 2004. 48:655–660.
14. Suchland RJ, Geisler WM, Stamm WE. Methodologies and cell lines used for antimicrobial susceptibility testing of Chlamydia spp. Antimicrob Agents Chemother. 2003. 47:636–642.
15. Hald T, Lo Fo Wong DM, Aarestrup FM. The attribution of human infections with antimicrobial resistant Salmonella bacteria in Denmark to sources of animal origin. Foodborne Pathog Dis. 2007. 4:313–326.
16. Stafford R, Kirk M, Selvey C, Staines D, Smith H, Towner C, Salter M. Outbreak Investigation Team. An outbreak of multi-resistant Shigella sonnei in Australia: possible link to the outbreak of shigellosis in Denmark associated with imported baby corn from Thailand. Euro Surveill. 2007. 12:E070913.1.
17. Lewis H, Ethelberg S, Lisby M, Madsen SB, Olsen KE, Rasmussen P, Kjelsø C, Vestergaard LS, Qureshi K, Howitz M, Mølbak K. Outbreak of shigellosis in Denmark associated with imported baby corn August 2007. Euro Surveill. 2007. 12:E070830.1.
18. Seong SY, Park SG, Kim HR, Han TH, Kang JS, Choi MS, Kim IS, Chang WH. Isolation of a new Orientia tsutsugamushi serotype. Microbiol Immunol. 1997. 41:437–443.
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