Infect Chemother.  2008 Oct;40(5):259-265. 10.3947/ic.2008.40.5.259.

Doxycycline Resistance in Orientia tsutsugamushi Isolated from Korean Patients

• Kim ES
• Kim MK
• Lee HM
• Kil SH
• Chung MH
• Lee JS
• Kang JS

• KMID: 2285049
• DOI: http://doi.org/10.3947/ic.2008.40.5.259

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 microg/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 microg/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.

Keyword

Orientia tsutsugamushi; Scrub typhus; Doxycycline; Resistance

MeSH Terms

Anti-Bacterial Agents
Doxycycline
Flow Cytometry
Fluorescence
Humans
Intensive Care Units
Korea
Membranes
Orientia tsutsugamushi
Pneumonia
Scrub Typhus
Sprains and Strains
Thailand
Treatment Failure
Anti-Bacterial Agents
Doxycycline

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