Update on fluoroquinolone resistance in Helicobacter pylori: new mutations leading to resistance and first description of a gyrA polymorphism associated with hypersusceptibility.
Helicobacter pylori eradication by standard therapy is decreasing due to clarithromycin and metronidazole resistance. Fluoroquinolones are valuable drugs for alternative therapy, but their activity needs to be updated. We determined minimum inhibitory concentrations (MICs) of the newly marketed fluoroquinolones (levofloxacin, moxifloxacin and gatifloxacin) and assessed the prevalence of resistance in 128 H. pylori strains isolated in 2004-2005. The quinolone resistance-determining region (QRDR) of gyrA was sequenced for all strains. Gatifloxacin MICs (MIC(50) = 0.25 mg/L) were two- to four-fold lower than those of the other fluoroquinolones. The prevalence of resistance (ciprofloxacin MIC > 1 mg/L) was 17.2% (22 strains). All resistant strains harboured one gyrA mutation at codons 86, 87 or 91, including three new mutations (Asp86Asn, Thr87Ile and Asn87Tyr). Ciprofloxacin-susceptible strains were devoid of such gyrA mutations, but harboured a polymorphism at codon 87 that distinguished 18 isolates (17%) with a Thr87 like the reference strain J99 from 88 strains with Asn87 like the reference strain 26695. Strains with Thr87 were four-fold more susceptible to nalidixic acid, pefloxacin, ciprofloxacin and levofloxacin and were equally susceptible to moxifloxacin and gatifloxacin. The high rate of quinolone resistance in H. pylori requires the use/implication of a 'test and treat' strategy that can confidently rely on QRDR gyrA sequencing.
Cattoir
Vincent
V
Laboratoire de Bactériologie-Virologie-Hygiène, Centre Hospitalier, Universitaire Henri Mondor, Assistance Publique-Hôpitaux de Paris, Université Paris XII, Créteil, France.
Nectoux
Juliette
J
Lascols
Christine
C
Deforges
Lionel
L
Delchier
Jean-Charles
JC
Megraud
Francis
F
Soussy
Claude-James
CJ
Cambau
Emmanuelle
E
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D002939:Ciprofloxacin / Q000494:pharmacology; D027081:DNA Gyrase / Q000187:drug effects / Q000235:genetics*; D024881:Drug Resistance, Bacterial / Q000235:genetics*; D024841:Fluoroquinolones / Q000494:pharmacology / Q000627:therapeutic use*; D016481:Helicobacter Infections / Q000188:drug therapy / Q000382:microbiology; D016480:Helicobacter pylori / Q000187:drug effects / Q000235:genetics*; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D009154:Mutation; D011110:Polymorphism, Genetic
D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D002939:Ciprofloxacin; D027081:DNA Gyrase