In vivo selection of Pseudomonas Aeruginosa with decreased susceptibilities to fluoroquinolones during fluoroquinolone treatment of urinary tract infection.
OBJECTIVE
To present a case of fluoroquinolone treatment failure in urinary tract infection caused by Pseudomonas aeruginosa, accompanied by in vivo selection of the post-treatment isolate that showed decreased susceptibilities to fluoroquinolones, and to report fluoroquinolone resistance mechanisms in the post-treatment isolate.


METHODS
A patient with urinary tract infection was treated with a suboptimal dose of a fluorinated quinolone, gatifloxacin. P. aeruginosa strains were isolated before and after fluoroquinolone treatment. The pretreatment and post-treatment isolates were examined for relatedness by arbitrarily primed polymerase chain reaction. For these isolates, the minimum inhibitory concentration of antimicrobial agents was determined and mutations in the target genes (gyrA and parC) and regulatory genes (mexR and nfxB) for drug efflux pumps were analyzed.


RESULTS
Failure of fluoroquinolone treatment of urinary tract infection was observed. The post-treatment isolate, which was assumed to be isogenic to the pretreatment isolate, exhibited fourfold to 16-fold increases in the MIC of fluoroquinolones. In this isolate, a new mutation, not observed in the pretreatment isolate, was found only in the gyrA gene, resulting in an amino acid change of aspartic acid to asparagine in codon 87 of GyrA.


CONCLUSIONS
The P. aeruginosa isolate that was initially susceptible to fluoroquinolones showed decreased susceptibility to fluoroquinolones after treatment with a suboptimal dose of one fluoroquinolone. In the post-treatment isolate, the alteration of GyrA would be responsible for the decreased susceptibility to fluoroquinolones. We should be aware that inappropriate use of fluoroquinolones could select such a strain harboring a quinolone resistance-associated alteration of DNA gyrase.
Nakano
M
M
Department of Urology, Gifu University School of Medicine, Gifu, Japan.
Yasuda
M
M
Yokoi
S
S
Takahashi
Y
Y
Ishihara
S
S
Deguchi
T
T
D000368:Aged; D000890:Anti-Infective Agents / Q000008:administration & dosage*; D004269:DNA, Bacterial / Q000032:analysis; D004352:Drug Resistance, Microbial; D024841:Fluoroquinolones; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009154:Mutation; D011550:Pseudomonas aeruginosa / Q000145:classification* / Q000187:drug effects* / Q000235:genetics; D013045:Species Specificity; D017211:Treatment Failure; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology*
D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones