Publications (12)39.39 Total impact
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Article: Gemifloxacin can partially overcome quinolone resistance of H. pylori with gyrA mutation in Taiwan.
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ABSTRACT: The levofloxacin resistance caused by gyrA gene mutation is rising rapidly to limit wide application for Helicobacter pylori eradication. We investigated whether gemifloxacin has a superior antimicrobial activity to levofloxacin against H. pylori. Forty-four consecutive clinical H. pylori isolates with levofloxacin resistance and 80 randomly selected levofloxacin-sensitive controls were tested for gemifloxacin sensitivity by E-test. The resistance to levofloxacin or gemifloxacin was defined as minimal inhibitory concentration (MIC) > 1 mg/L. The clinical features and GyrA mutation patterns checked by direct sequencing were also analyzed to assess its association with the H. pylori gemifloxacin resistance. All levofloxacin-sensitive H. pylori isolates were sensitive to gemifloxacin. Eight strains (18.2%) resistant to levofloxacin could be still sensitive to gemifloxacin. Gemifloxacin achieved a 5-time lower in MIC levels against levofloxacin-resistant isolates. Nearly all levofloxacin-resistant isolates (97.7%, 43/44) had GyrA mutation at amino acid position 87 or 91. Double mutation sites may play dual roles in quinolone resistance, as N87K plus H57Y or D91N plus V77A mutations showed high-level resistance to both quinolones; whereas D91Y plus A97V or D91N plus A97V mutations showed low level levofloxacin resistance to become sensitive to gemifloxacin. In H. pylori isolates with single N87K, D91Y or D91N mutation, near 20% was gemifloxacin-sensitive and levofloxacin-resistant. The gemifloxacin-resistant rate of H. pylori was higher in patients with gastric ulcer than in those without (p <.05). Gemifloxacin is superior to levofloxacin in antimicrobial activity against clinical H. pylori isolates, and even overcome some levofloxacin resistance.Helicobacter 06/2012; 17(3):210-5. · 3.15 Impact Factor -
Article: Heteroresistance to cephalosporins and penicillins in Acinetobacter baumannii.
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ABSTRACT: Heteroresistance to antimicrobial agents may affect susceptibility test results and therapeutic success. In this study, we investigated heteroresistance to cephalosporins and penicillins in Acinetobacter baumannii, a major pathogen causing nosocomial infections. Two A. baumannii isolates exhibited heteroresistance to ampicillin-sulbactam, ticarcillin-clavulanic acid, cefepime, and cefpirome, showing a distinct colony morphology of circular rings within the inhibition halos. Pulsed-field gel electrophoresis (PFGE) and outer membrane protein (OMP) analysis demonstrated that subpopulations around the disks/Etest strips and the original strains all belonged to the same PFGE type and OMP profile. Population analysis profile (PAP) showed the presence of heteroresistant subpopulations with high cefepime resistance levels in two isolates (008 and 328). Interestingly, A. baumannii 008 contained two peaks: one was grown in the presence of up to 1 μg of cefepime/ml, the other apparently occurred when the concentration of cefepime was raised to 256 μg/ml. After serial passages without exposure to cefepime, the PAP curve maintained the same trend observed for the original strain of A. baumannii 008. However, the PAP curve showed a shift to relatively lower cefepime resistance (from 256 to 64 μg/ml) in A. baumannii 328 after 10 passages in antibiotic-free Mueller-Hinton agar plates. Convergence to a monotypic resistance phenotype did not occur. Growth rate analysis revealed that slower growth in resistant subpopulations may provide a strategy against antibiotic challenge. To our knowledge, this is the first report of heteroresistance to cephalosporins and penicillins in A. baumannii.Journal of clinical microbiology 12/2011; 50(3):721-6. · 4.16 Impact Factor -
Article: Clinical and microbiological characteristics of community-acquired Staphylococcus lugdunensis infections in Southern Taiwan.
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ABSTRACT: Most Staphylococcus lugdunensis strains (49/59, 83%) were related to clinical infections, were susceptible to most antimicrobial agents with an overall oxacillin-resistant rate of 5% (3/58), and carried relatively great genetic diversity. Community-acquired infections (41/49, 84%) were dominant, often developed in patients with comorbidity, and had rather benign clinical courses without mortality.Journal of clinical microbiology 06/2011; 49(8):3015-8. · 4.16 Impact Factor -
Article: Identification of clinically important anaerobic bacteria by an oligonucleotide array.
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ABSTRACT: Anaerobic bacteria can cause a wide variety of infections, and some of these infections can be serious. Conventional identification methods based on biochemical tests are often lengthy and can produce inconclusive results. An oligonucleotide array based on the 16S-23S rRNA intergenic spacer (ITS) sequences was developed to identify 28 species of anaerobic bacteria and Veillonella. The method consisted of PCR amplification of the ITS regions with universal primers, followed by hybridization of the digoxigenin-labeled PCR products to a panel of 35 oligonucleotide probes (17- to 30-mers) immobilized on a nylon membrane. The performance of the array was determined by testing 310 target strains (strains which we aimed to identify), including 122 reference strains and 188 clinical isolates. In addition, 98 nontarget strains were used for specificity testing. The sensitivity and the specificity of the array for the identification of pure cultures were 99.7 and 97.1%, respectively. The array was further assessed for its ability to detect anaerobic bacteria in 49 clinical specimens. Two species (Finegoldia magna and Bacteroides vulgatus) were detected in two specimens by the array, and the results were in accordance with those obtained by culture. The whole procedure of array hybridization took about 8 h, starting with the isolated colonies. The array can be used as an accurate alternative to conventional methods for the identification of clinically important anaerobes.Journal of clinical microbiology 04/2010; 48(4):1283-90. · 4.16 Impact Factor -
Article: Inducible clindamycin resistance in Staphylococcus aureus isolates causing bacteremia at a university hospital in southern Taiwan.
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ABSTRACT: A major concern while prescribing clindamycin to treat infections caused by inducible macrolide, lincosamide, and group B streptogramin (iMLS(B))-resistant strains is clinical therapy failure. In this study, we determined the prevalence, mechanism, and clonality of the iMLS(B) phenotype in oxacillin-resistant Staphylococcus aureus (ORSA) and oxacillin-susceptible S. aureus (OSSA). Among the 729 OSSA isolates collected from July 1995 to March 2006, 72 (10%) were clindamycin sensitive (Cli(s)) and erythromycin resistant (Erm(r)), and 55 (8%) had the iMLS(B) phenotype. In the 709 ORSA isolates collected from January 1997 to March 2006, 31 (4%) were Cli(s) and Erm(r), and 29 (4%) isolates demonstrated the iMLS(B) phenotype. In OSSA, ermC was the predominant (51 of 55 isolates) genetic determinant responsible for the iMLS(B) phenotype, whereas in ORSA, ermA was predominant (27 of 29). Pulsed-field gel electrophoresis showed that 8 pulsed types (RA to RH) were present in ORSA isolates (n = 27), and pulsed type RC was predominant in 17 isolates with 5 identifiable subtypes (RC1 to RC5); this type was prevalent from November 1997 to June 2004. In the OSSA (n = 24) isolates, 14 different pulsed types (SA to SN) were identified, but none was predominant. These results indicate that the incidence of iMLS(B) resistance phenotype is higher in OSSA than ORSA in Taiwan, and the genetic determinants responsible for the iMLS(B) phenotype vary in OSSA and ORSA.Diagnostic Microbiology and Infectious Disease 07/2007; 58(2):203-9. · 2.53 Impact Factor -
Article: Characterization of flgK gene and FlgK protein required for H. pylori colonization--from cloning to clinical relevance.
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ABSTRACT: To characterize the role of flgK and its protein product in H. pylori colonization. The PCR cloning method identified the flgK gene. An isogenic flgK mutant was constructed by gene replacement and confirmed by Southern blot analysis and PCR analysis. The recombinant FlgK protein (r-FlgK) was purified. Electron microscopy (EM) was applied to demonstrate the flagella of H. pylori. An in vitro motility test was assessed in semisolid medium. The densities of H. pylori colonization with either the wild-type strain or its flgK mutant were compared among BALB/c mice with or without pre-immunization with r-FlgK. The serological responses to r-FlgK were analyzed for 70 clinical patients with different densities of H. pylori colonization. From a duodenal ulcer strain, the flgK gene was cloned and it contained 1821 bp, with a 95.7% identity to the published sequences. No flagella were observed under EM for the mutant strain, which had a loss of motility. H. pylori density was lower in the BALB/c mice inoculated by the mutant or with pre-immunization with r-FlgK compared to unimmunized mice or mice inoculated by the wild-type strain (P<0.05). In the H. pylori-infected patients, the serological responses to r-FlgK were uniformly low in titer. FlgK encoded by flgK is important for flagella formation and H. pylori motility. Deficiency in FlgK or an enhanced serological response to r-FlgK can interfere with H. pylori colonization. FlgK of H. pylori could be a novel target for vaccination.World Journal of Gastroenterology 08/2006; 12(25):3989-93. · 2.47 Impact Factor -
Article: Use of oligonucleotide array for identification of six foodborne pathogens and Pseudomonas aeruginosa grown on selective media.
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ABSTRACT: Identification of presumptive foodborne pathogens grown on selective media may take one to several days and requires a different battery of biochemical tests for each microorganism. A molecular identification method was developed in which universal primers were used to amplify the 16S to 23S rDNA intergenic spacer of target microorganisms, and PCR products were hybridized to a panel of species-specific oligonucleotides that were immobilized on a nylon membrane. The seven target microorganisms were Bacillus cereus, Escherichia coli, Listeria monocytogenes, Pseudomonas aeruginosa, Salmonella, Staphylococcus aureus, and Vibrio parahaemolyticus. After testing a large collection of target bacteria (29 to 51 strains) and nontarget bacteria (> 500 strains), the performances (sensitivity and specificity) of the oligonucleotide array were as follows: B. cereus (100 and 77%), E. coli (100 and 100%), L. monocytogenes (100 and 90%), P. aeruginosa (100 and 100%), Salmonella (100 and 100%), S. aureus (100 and 100%), and V. parahaemolyticus (100 and 94.2%). Other species in the B. cereus group cross-hybridized to the probes used for identification of B. cereus, and positive results should be confirmed by additional morphological observation of colonies. Listeria innocua cross-reacted with probes used to identify L. monocytogenes, but a simple hemolysis test was used to differentiate the two species. Some strains of Vibrio harveyi and Vibrio mimicus cross-hybridized with probes used for identification of V. parahaemolyticus and caused false-positive reactions. The advantage of the array is that a common protocol was used to identify the seven target microorganisms and multiple different microorganisms could be simultaneously identified on a single array.Journal of food protection 11/2005; 68(11):2278-86. · 1.94 Impact Factor -
Article: The rdxA gene plays a more major role than frxA gene mutation in high-level metronidazole resistance of Helicobacter pylori in Taiwan.
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ABSTRACT: Metronidazole-resistant H. pylori associating with mutations of rdxA or frxA is still a debated topic. This study investigates whether rdxA and frxA mutations of H. pylori accounted for the high MIC value (>/= 64 micro g/ml) of metronidazole (Mtz). From 126 clinical H. pylori isolates, we examined 14 Mtz-sensitive, 18 Mtz-resistant H. pylori, and eight pairs of Mtz-sensitive and Mtz-resistant colonies simultaneously present within a single gastric biopsy. The paired strains from one single biopsy were proven identical by PCR-RFLP. MICs of Mtz were checked by the E-test and agar dilution method. The mutations of rdxA and frxA sequencing were matched with the Mtz-susceptible ATCC 26695 and J99. There were 89% (16/18) of Mtz-resistant isolates with mutation of RdxA. Half of the 14 Mtz-sensitive strains, all without mutation of RdxA, still contained truncation of FrxA. Within the paired isolates from a single biopsy, rdxA mutation (86%) was more common than frxA mutation (43%) in those isolates with high-level Mtz-resistant H. pylori. RdxA truncation was more prevalent in Mtz-resistant strains with high MICs than in those with low to moderate MICs (75% vs. 20%, p =.01, OR: 12, 95% CI: 1.8-81.7). Mutations in the rdxA gene rather than the frxA gene generally determine a high MIC level of Mtz-resistant H. pylori in Taiwan.Helicobacter 11/2004; 9(5):400-7. · 3.15 Impact Factor -
Article: Higher gastric cycloxygenase-2 expression and precancerous change in Helicobacter pylori-infected relatives of gastric cancer patients.
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ABSTRACT: This study was conducted to determine whether relatives of gastric cancer patients (GCF) showed greater gastric cycloxygenase-2 (COX-2) expression or a greater incidence of precancerous lesions after Helicobacter pylori infection and whether H. pylori eradication could reduce COX-2 expression. Three hundred subjects were enrolled in this study: half were relatives of 50 H. pylori-infected gastric cancer patients, and half were relatives of 50 H. pylori-infected duodenal ulcer (DU) patients (controls). Each relative underwent endoscopy to detect H. pylori infection and related gastric histology. One hundred and twenty GCFs were found to have H. pylori infection. After H. pylori eradication, 90 of the 120 GCFs were followed up with annual endoscopy examinations over the next 2 years. Gastric COX-2 intensity in all of the specimens collected from these patients was immunochemically stained and graded from 0 to 4. H. pylori infection, gastric atrophy, and intestinal metaplasia (IM) were more prevalent in GCFs than in relatives of H. pylori-infected patients with DUs (P < 0.05). H. pylori-infected GCFs also showed a greater COX-2 intensity than H. pylori-infected relatives of patients with DUs (89.1% versus 62.7%, P < 0.001; relative risk: 4.9; 95% confidence interval: approximately 2.34-10.29). Among the H. pylori-infected GCFs, COX-2 intensity correlated with atrophy and IM (P < 0.001). After H. pylori eradication, gastric COX-2 expression disappeared only in those relatives without IM (P < 0.001). GCFs are more likely to show greater gastric COX-2 expression and a higher incidence of precancerous lesions after H. pylori infection than the relatives of H. pylori-infected patients with only DUs. H. pylori eradication can reverse gastric COX-2 expression in patients without IM but not in patients with IM.Clinical Cancer Research 11/2003; 9(14):5245-51. · 7.74 Impact Factor -
Article: Vitamin C and E supplements to lansoprazole-amoxicillin-metronidazole triple therapy may reduce the eradication rate of metronidazole-susceptible Helicobacter pylori infection.
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ABSTRACT: To test whether vitamin C and E supplements to triple therapy can improve the Helicobacter pylori eradication rate and gastric inflammation. A total of 104 H. pylori-infected patients were randomized to receive: either lansoprazole, amoxicillin, and metronidazole twice daily for 1 week (triple-only group) or lansoprazole, amoxicillin, metronidazole plus vitamin C (250 mg) and vitamin E (200 mg) twice daily for 1 week, followed immediately by vitamin C and E once daily for 6 consecutive weeks (triple-plus-vitamin group). Eight weeks after the completion of triple therapy, patients were assessed for the effectiveness of H. pylori eradication. The severity of gastric inflammation in histology was assessed for the acute and chronic inflammation scores. Intention-to-treat and per-protocol eradication rates were 59.1% and 64.4% in the triple-only group, and 40% and 44% in the triple-plus-vitamin group. In the patients infected with metronidazole susceptible isolates, the triple-only group had a higher intention-to-treat eradication rate than those in the triple-plus-vitamin group (80% vs. 53.1%, p <.01). However, for the metronidazole resistance isolates, the intention-to-treat eradication rates between the two groups were not different (26.3% vs. 21.7%, p = NS). The improvements of both acute and chronic inflammation scores in histology were not different between the two groups. Adding vitamin C and E to triple therapy cannot improve the H. pylori eradication rate and gastric inflammation. For patients with metronidazole susceptible strain infection, adding these vitamins may even reduce the eradication rate of triple therapy.Helicobacter 10/2002; 7(5):310-6. · 3.15 Impact Factor -
Article: Pretreatment Gastric Histology Is Helpful to Predict the Symptomatic Response After H. pylori Eradication in Patients with Nonulcer Dyspepsia
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ABSTRACT: This study aimed to test whether pretreatment gastric pathology in H. pylori-infected nonulcer dyspepsia (HpNUD) patients is relevant to and predictive of the symptomatic response after H. pylori eradication. Anti-H. pylori triple therapy was administered to 250 HpNUD patients, enrolled as the therapy group. In addition, 60 patients were enrolled as the control group, in which omeprazole was an alternatives to the triple therapy. Pretreatment gastric histology was evaluated thoroughly by the updated Sydney system. A [13C] urea breath test was also performed to evaluate the H. pylori eradication two months and 12 months later. For each patient, the baseline, month 2, and month 12 symptom scores were assessed for the month 2 or month 12 residual symptom ratio (RSR-2m or RSR-12m), calculated from: 100% month 2 or month 12 score/baseline score. Based on either RSR-2m or RSR-12m, patients were categorized as good response (RSR < 50%),="" moderate="" response="" (50–70%),="" and="" poor="" response="" (="">70%) subgroups in both therapy and control groups to define the short-term and long-term symptomatic responses. Patients with successful H. pylori eradication in the therapy group showed a higher incidence of good symptomatic response (RSR < 50%)="" than="" those="" from="" the="" control="" group="" (month="" 2:="" 30.3="" vs="" 12%,="">P ; month 12: 34.7 vs 17.1%, P ). Univariate and multivariate analysis disclosed that patients with a higher acute inflammation score (AIS) and the lowest incidence of lymphoid follicles (LF) at pretreatment gastric histology are predisposed to having a good symptom response after H. pylori eradication (P . For HpNUD patients who have an AIS of more than three and an absence of LF at gastric histology, more than 85% had good short-term (month 2) and long-term (month 12) symptomatic relief after H. pylori eradication. In conclusion, nearly 30% of HpNUD patients can obtain symptomatic relief following H. pylori eradication. The pretreatment gastric histology of HpNUD can be helpful to monitor the symptomatic response after H. pylori eradication.Digestive Diseases and Sciences 11/2001; 46(12):2700-2707. · 2.12 Impact Factor -
Article: Adjuvant effect of vitamin C on omeprazole-amoxicillin-clarithromycin triple therapy for Helicobacter pylori eradication.
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ABSTRACT: To test the impact of vitamin C supplementation on triple therapy for H. pylori eradication. A total of 171 H. pylori-infected patients were randomized to receive different one-week triple therapies, including 20 mg omeprazole, 1 g amoxicillin, plus the following twice daily: (1) 250 mg clarithromycin (C250 group, n=55); (2) 250 mg clarithromycin and 500 mg vitamin C (V-C250 group, n=61); (3) 500 mg clarithromycin (C500 group, n=55). Six weeks after treatment, the success of H. pylori eradication was assessed by a 13C-urea breath test. Each collected H. pylori strain was defined as either clarithromycin susceptible or resistant by E-test. The demographic background, clarithromycin susceptibility of H. pylori, and drug compliance were similar among the three groups (p=NS). For clarithromycin susceptible infection, the V-C250 group had a higher eradication rate than the C250 group (ITT: 85% vs. 68% and PP: 90% vs. 73%, p = 0.03), but had an equivalent rate to the C500 group (p=NS). For clarithromycin resistant infection, all three groups had a similarly poor eradication rate of less than 34%. Adding vitamin C to one-week triple therapy can reduce the dosage of clarithromycin, but preserve the high eradication efficacy for clarithromycin susceptible H. pylori infection.Hepato-gastroenterology 54(73):320-4. · 0.66 Impact Factor
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2001–2011
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National Cheng Kung University
- • Department of Medical Laboratory Science and Biotechnology
- • Department of Pediatrics
- • Department of Internal Medicine
Tainan, Taiwan, Taiwan
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