Resistance of Fluoroquinolone in Orientia tsutsugamushi Due to gyrA Mutation in Scrub typhus
Scrub typhus is a mite-borne rickettsial disease caused by Orientia tsutsugamushi in endemic areas, and a public health concern for a population of over a million new cases emerging and a billion people at risk of infection. Although doxycycline remains the standard therapy, some reported effectiveness of levofloxacin as alternative regimen when treatment with doxycycline fails. However, there are clinical studies that quinolone is not effective in patients with scrub typhus. To clarify these discrepant results, we evaluated the genotype and mutation in gyrA associated with quinolone resistances.
This prospective observational study enrolled patients admitted to a tertiary hospital with scrub typhus from 2008 to 2012. 27 patients enrolled, and we obtained the gyrA gene of Orientia tsutsugamushi from 27 samples. With blood samples, we sequenced the quinolone resistance-determining region (QRDR), the target of fluoroquinolones, by nested polymerase chain reaction targeting the 56-kDa antigen gene.
The genotype of samples were as followed; 7 Je-cheon strain, 5 Taguchi strain, 4 Boryoung strain, 3 Kanda strain, 3 Karp strain, 3 Pa-joo strain, 2 Ikeda strain. Irrespective of genotype, all 27 samples had the Ser83Leu mutation in the QRDR domain of gyrA gene, which is known to be associated with quinolone resistance.
Mutation of gyrA gene was identified in all DNA sample of O. tsutsugamushi, despite of genotype which enrolled for our study. These data provide evidence that O. tsutsugamushi has intrinsic resistance to fluoroquinolones, explaining treatment failures with such antibiotics in scrub typhus. Therefore fluoroquinolones should not be used for the treatment of scrub typhus, especially in severe cases.
S. K. CHO,
S. M. Choi, None
S. I. Jung, None
H. C. Jang, None
J. H. Ahn, None