Intrinsic fluoroquinolone resistance in Orientia tsutsugamushi.
Scrub typhus is a public health concern for a population of over a billion humans, with an estimated incidence of one million cases/year in endemic areas. Although doxycycline remains the standard therapy, fluoroquinolones have been used successfully in a few patients. However, there is also clinical evidence that fluoroquinolones are ineffective in the treatment of scrub typhus. To clarify this matter, we determined the in vitro susceptibility of Orientia tsutsugamushi strain Kato to ciprofloxacin and ofloxacin and sequenced the quinolone resistance-determining region (QRDR) of the gyrA gene, the target of fluoroquinolones, of 18 fresh isolates from the Lao PDR. Orientia tsutsugamushi strain Kato was resistant to ciprofloxacin and ofloxacin in vitro (minimum inhibitory concentration=8 microg/mL). All sequences obtained, including those from the two available genomes of O. tsutsugamushi (strains Boryong and Ikeda), had a Ser83Leu mutation in their QRDR domain that is known to be associated with fluoroquinolone resistance. These findings re-emphasise the usefulness of in silico analysis for the prediction of antibiotic resistance and suggest that fluoroquinolones should not be used in the treatment of scrub typhus.
URMITE CNRS-IRD UMR 6236, Faculté de Médecine et de Pharmacie, Université de la Méditerranée, 27 Bd Jean Moulin, 13385 Marseille Cedex 05, France.
Wiwit
W
Tantibhedhyangkul
Emmanouil
E
Angelakis
Narongchai
N
Tongyoo
Paul N
PN
Newton
Catrin E
CE
Moore
Rattanaphone
R
Phetsouvanh
Didier
D
Raoult
Jean-Marc
JM
Rolain
D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D027081:DNA Gyrase / Q000235:genetics; D024881:Drug Resistance, Bacterial; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology*; D006801:Humans; D007812:Laos; D008297:Male; D008826:Microbial Sensitivity Tests; D020125:Mutation, Missense; D012285:Orientia tsutsugamushi / Q000187:drug effects*; D011247:Pregnancy; D012612:Scrub Typhus / Q000382:microbiology*; D017422:Sequence Analysis, DNA; D055815:Young Adult
D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D024841:Fluoroquinolones; D027081:DNA Gyrase