Characterization of fluoroquinolone and carbapenem susceptibilities in clinical isolates of levofloxacin-resistant Pseudomonas aeruginosa.
BACKGROUND
Pseudomonas aeruginosa can rapidly acquire resistance to antibiotics, including fluoroquinolones and carbapenems.


METHODS
We characterized fluoroquinolone, carbapenem and other beta-lactam susceptibilities and analyzed fluoroquinolone and carbapenem resistance in 16 clinical isolates of levofloxacin-resistant P. aeruginosa.


RESULTS
All levofloxacin-resistant isolates showed high MICs (> or =32 microg/ml) for fluoroquinolones including norfloxacin, levofloxacin, sparfloxacin, gatifloxacin and pazufloxacin, whereas the MICs for sitafloxacin were between 2 and 16 microg/ml. These isolates had both a Thr83Ile mutation in GyrA and a Ser87Leu mutation in ParC. An additional mutation, Glu469Asp in GyrB, was detected in 3 isolates. Three of 16 isolates found during antibiotic therapy showed resistance to carbapenems (MIC, 16-32 microg/ml) because of a reduced production of OprD. Fluoroquinolones, beta-lactams and sulfamethoxazole-trimethoprim were used for 3 months before the isolation of levofloxacin-resistant P.aeruginosa.


CONCLUSIONS
Emergence of resistant isolates to both fluoroquinolones and carbapenems during antibiotic therapy is a serious clinical problem. Our results suggest that susceptibilities to fluoroquinolones as well as carbapenems should be monitored during a prolonged course of antibiotic therapy against P. aeruginosa infection.
Muramatsu
Hideaki
H
Division of Pharmacy, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Horii
Toshinobu
T
Takeshita
Akihiro
A
Hashimoto
Hisakuni
H
Maekawa
Masato
M
D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015780:Carbapenems / Q000494:pharmacology* / Q000627:therapeutic use; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000187:drug effects* / Q000235:genetics; D024841:Fluoroquinolones / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D064704:Levofloxacin; D008826:Microbial Sensitivity Tests; D009154:Mutation; D015242:Ofloxacin / Q000494:pharmacology / Q000627:therapeutic use; D018272:Porins / Q000096:biosynthesis; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D024841:Fluoroquinolones; D018272:Porins; C077157:OprD protein, Pseudomonas aeruginosa; D064704:Levofloxacin; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase