Sitafloxacin activity against Helicobacter pylori isolates, including those with gyrA mutations.
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ABSTRACT:
SUBMITTER: Murakami K
PROVIDER: S-EPMC2704646 | biostudies-literature | 2009 Jul
REPOSITORIES: biostudies-literature
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Sitafloxacin activity against Helicobacter pylori isolates, including those with gyrA mutations.
Murakami Kazunari K Okimoto Tadayoshi T Kodama Masaaki M Tanahashi Jin J Fujioka Toshio T Ikeda Fumiaki F Muraoka Hiroe H Takigawa Motoko M Saika Takeshi T Hasegawa Miyuki M Kobayashi Intetsu I
Antimicrobial agents and chemotherapy 20090420 7
Sitafloxacin showed MICs of less than or equal to 0.5 microg/ml against 105 isolates of Helicobacter pylori, including 44 isolates with mutations in the gyrA gene. The highest MICs for garenoxacin and levofloxacin were 8 and 64 times, respectively, higher than the highest MICs observed for sitafloxacin. ...[more]
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Project description:Although sitafloxacin (STFX)-containing regimens are effective rescue treatments for Helicobacter pylori infection, prevalence of fluoroquinolone resistance in H. pylori has increased rapidly worldwide. The change in resistance levels and gyrA mutations, a major cause of fluoroquinolone resistance, after unsuccessful STFX-containing treatment has not been investigated.We conducted a retrospective, non-randomized study to compare the minimum inhibitory concentrations (MICs) of STFX and the location of gyrA mutations in H. pylori before and after unsuccessful eradication with STFX-containing regimens at Keio University Hospital between December 2011 and March 2015.A total of 266 patients treated with STFX-containing regimens for third-line H. pylori eradication were evaluated. Double mutations in gyrA were acquired by 20.8% of strains that exhibited seven-fold increased STFX MICs, compared to pre-treatment MICs. The STFX MICs did not increase, however, when the location of the gyrA mutations did not change after treatment. Double mutations in gyrA developed in 60.0% of the strains in which eradication failed, which exhibited a baseline mutation at position D91, and in 11.1% of strains with baseline mutations at position N87.Acquisition of double mutations in gyrA evoked high-level resistance to STFX in H. pylori after unsuccessful eradication with STFX-containing regimens.
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Project description:Resistance to fluoroquinolone (FQ) antibiotics in Streptococcus pneumoniae has been attributed primarily to specific mutations in the genes for DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE). Resistance to some FQs can result from a single mutation in one or more of the genes encoding these essential enzymes. A group of 160 clinical isolates of pneumococci was examined in this study, including 36 ofloxacin-resistant isolates (MICs, > or = 8 micrograms/ml) recovered from patients in North America, France, and Belgium. The susceptibilities of all isolates to clinafloxacin, grepafloxacin, levofloxacin, sparfloxacin, and trovafloxacin were examined by the National Committee for Clinical Laboratory Standards reference broth microdilution and disk diffusion susceptibility testing methods. Among the ofloxacin-resistant strains, 32 of 36 were also categorized as resistant to levofloxacin, 35 were resistant to sparfloxacin, 29 were resistant to grepafloxacin, and 19 were resistant to trovafloxacin. In vitro susceptibility to clinafloxacin appeared to be least affected by resistance to the other FQs. Eight isolates with high- and low-level resistance to the newer FQs were selected for DNA sequence analysis of the quinolone resistance-determining regions (QRDRs) of gyrA, gyrB, parC, and parE. The DNA and the inferred amino acid sequences of the resistant strains were compared with the analogous sequences of reference strain S. pneumoniae ATCC 49619 and FQ-susceptible laboratory strain R6. Reduced susceptibilities to grepafloxacin and sparfloxacin (MICs, 1 to 2 micrograms/ml) and trovafloxacin (MICs, 0.5 to 1 microgram/ml) were associated with either a mutation in parC that led to a single amino acid substitution (Ser-79 to Phe or Tyr) or double mutations that involved the genes for both GyrA (Ser-81 to Phe) and ParE (Asp-435 to Asn). High-level resistance to all of the compounds except clinafloxacin was associated with two or more amino acid substitutions involving both GyrA (Ser-81 to Phe) and ParC (Ser-79 to Phe or Ser-80 to Pro and Asp-83 to Tyr). No mutations were observed in the gyrB sequences of resistant strains. These data indicate that mutations in pneumococcal gyrA, parC, and parE genes all contribute to decreased susceptibility to the newer FQs, and genetic analysis of the QRDR of a single gene, either gyrA or parC, is not predictive of pneumococcal resistance to these agents.
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Project description:AIM:To investigate the resistance of Helicobacter pylori (H. pylori) to ciprofloxacin (CIP), levofloxacin (LVX) and moxifloxacin (MOX) in the Beijing area and to elucidate the resistance mechanisms. METHODS:Seventy-nine H. pylori clinical strains, isolated from patients who had undergone upper gastrointestinal endoscopy in Peking University First Hospital from 2007 to 2009, were tested for their susceptibility to CIP, LVX and MOX using the E-test method. H. pylori strain 26695 was included in the susceptibility testing as a control strain. According to the minimal inhibitory concentration (MIC) values, a strain was classified as resistant to CIP, LVX or MOX when the MIC was > 1 microg/mL. We amplified by polymerase chain reaction (PCR) and sequenced the quinolone resistance-determining regions of the gyrA and gyrB genes from 29 quinolone-resistant and 16 quinolone-susceptible H. pylori strains selected at random. RESULTS:In this study, the resistance rates of H. pylori to CIP, LVX or MOX were 55.7% (44/79), and the primary resistance rates were 26.6% (21/79). Patients with secondary resistance had received LVX in previous eradication treatments, but not MOX or CIP. Forty-five strains, including 29 CIP, LVX or MOX-resistant strains (MIC: 1.5-32 microg/mL) and 16 susceptible strains, were selected randomly from the 79 strains and used in PCR analysis. Among these 45 strains, 27 resistant strains had mutations in the gyrA gene, including 11 strains with mutations corresponding to Asp-91 (MIC: 2-32 microg/mL), one of which also had a mutation corresponding to Val-150, and 16 strains had mutations at Asn-87 (MIC: 4-32 microg/mL), three of which also had mutations corresponding to Arg-140 or Val-150. In addition, Arg-140, Val-150 or Ala-97 mutations were separately detected in three susceptible strains. Analysis of the gyrB gene showed that one strain of low resistance had a mutation corresponding to Ser-457 that coexisted with an Asp-91 mutation. There was a significant difference in the occurrence of mutations in the gyrA gene between CIP, LVX and MOX-resistant and -susceptible strains (P < 0.05), but 2 resistant strains were found to possess no quinolone resistance-determining region mutations. CONCLUSION:Resistance is primarily mediated through point mutations in gyrA. Whether other mechanisms are responsible for resistance in strains without mutations in the QRDR should be detected.
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Project description:A high resistance rate (47.9%) to gatifloxacin (GAT; 8-methoxy fluoroquinolone) in Helicobacter pylori (H. pylori) strains from 48 Japanese patients is observed after unsuccessful H. pylori eradication. A significant association between MICs for GAT equal to or above 1 microg/ml and mutations of the gyrA gene of H. pylori was demonstrated.
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Project description:The treatment of Helicobacter pylori infection is complicated by antibiotic resistance. A high levofloxacin (LVX) resistance rate was previously demonstrated in H. pylori isolates from gastric mucosa (40%) and esophagus (19%) in individual hosts of a Venezuelan population. We aimed to assess the molecular mechanisms of LVX resistance and susceptibility in isolates from the gastroesophageal mucosa, by studying point mutations in the quinolone resistance-determining region of gyrA and gyrB genes. Sequencing of gyrA and gyrB genes (N = 120) helped to identify point mutations in 60 isolates (30 from antrum and 30 from esophagus) of five dyspeptic patients. Double (Asn87Thr and Asp91Asn) and single (Asn87Ile or Asn87Thr) mutations in the gyrA gene were identified in the esophageal mucosa. These mutations have been commonly found in the stomach. Occurrence of a single (Asn87Ile) mutation was associated with high resistance (minimum inhibitory concentration ≥ 32 μg/mL) to LVX. Only a single (Ser479Gly) mutation was found in the gyrB gene in both mucosae. One patient presented isolates with no mutations in the two genes studied. Isolates with the same mutation pattern in individual hosts revealed identical genetic profiles for these genes, confirming that isolates identified in the esophageal mucosa come from isolates colonizing the stomach. Helicobacter pylori resistance to LVX in the esophagus is related to double- and single-point mutations in gyrA and gyrB genes, such as those found in the stomach. Levofloxacin should be applied with caution, because its antibiotic effect on H. pylori is decreasing in Latin America, perhaps owing to high prescription rates.
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Project description:Helicobacter pylori strains with reduced susceptibility to fluoroquinolones have a mutation at either codon 87 Asn or 91 Asp of the gyrA gene. A rapid test based on an allele-specific PCR (AS-PCR) was designed to detect the gyrA mutations. Clinical H. pylori isolates were obtained from the stomachs of 51 patients with H. pylori infections who showed treatment failure. The MICs of gatifloxacin (GAT) were determined by the agar dilution method. Identical genotyping results were obtained with AS-PCR and conventional PCR. The gyrA mutations of H. pylori causing reduced susceptibility to fluoroquinolones could be detected successfully by this method. A significant association was observed between the presence of mutations, as detected by AS-PCR, and the resistance of the strains to GAT. Moreover, genotyping by AS-PCR took less than 3 to 4 h. The AS-PCR method for the detection of gyrA mutations in H. pylori is useful for easy identification of fluoroquinolone-resistant strains of H. pylori.
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