J Korean Med Sci.  2013 May;28(5):667-671. 10.3346/jkms.2013.28.5.667.

Inappropriateness of Quinolone in Scrub Typhus Treatment Due to gyrA Mutation in Orientia tsutsugamushi Boryong Strain

• Jang HC
• Choi SM
• Jang MO
• Ahn JH
• Kim UJ
• Kang SJ
• Shin JH
• Choy HE
• Jung SI
• Park KH

• KMID: 1777552
• DOI: http://doi.org/10.3346/jkms.2013.28.5.667

Abstract

The use of quinolone for treatment of rickettsial diseases remains controversial. Recent clinical studies suggest that quinolone is not as effective as others in patients with rickettsial diseases including scrub typhus, although the mechanism is not well understood. In this study, we evaluated the mutation in gyrA associated with quinolone resistance. We prospectively enrolled scrub typhus patients, collected blood samples and clinical data from October, 2010 to November, 2011. Among the 21 patients enrolled, one initially received ciprofloxacin for 3 days but was switched to doxycycline due to clinical deterioration. We obtained the gyrA gene of Orientia tsutsugamushi from 21 samples (20 Boryong strain, 1 Kato strain) and sequenced the quinolone resistance-determining region. All of 21 samples had the Ser83Leu mutation in the gyrA gene, which is known to be associated with quinolone resistance. This suggests that quinolones may be avoided for the treatment of serious scrub typhus.

Keyword

Scrub Typhus; Quinolone Resistance; Genotype; Rickettsia

MeSH Terms

Aged
Aged, 80 and over
Amino Acid Sequence
Anti-Bacterial Agents/*therapeutic use
Bacterial Proteins/*genetics
Ciprofloxacin/*therapeutic use
DNA Gyrase/*genetics
Doxycycline/therapeutic use
Drug Resistance, Bacterial
Female
Genotype
Humans
Male
Middle Aged
Molecular Sequence Data
Mutation
Orientia tsutsugamushi/classification/enzymology/*genetics
Phylogeny
Prospective Studies
Scrub Typhus/*drug therapy
Sequence Alignment
Sequence Analysis, DNA
Anti-Bacterial Agents
Bacterial Proteins
Ciprofloxacin
DNA Gyrase
Doxycycline

Figure

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  Fig. 1 Phylogenetic tree based on the nucleotide sequences of Orientia tsutsugamushi 56-kDa genes.

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  Fig. 2 DNA sequence alignment of the quinolone resistance-determining region (QRDR) domain of the gyrA genes of Orientia tsutsugamushi strains isolated from 21 patients. A comparison of the E. coli and O. tsutsugamushi QRDR regions containing the Ser83Leu mutation is shown. ECOLI, E. coli strain from the KEGG website; Boryong, Boryong strain of O. tsutsugamushi from the KEGG website.

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