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Primary Resistance (primary + resistance)

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Medical Sciences	87%

Selected Abstracts

Annual Change of Primary Resistance to Clarithromycin among Helicobacter pylori Isolates from 1996 through 2008 in Japan

HELICOBACTER, Issue 5 2009
Noriyuki Horiki
Abstract Background:, Recent studies have shown that the combination of proton pump inhibitor, amoxicillin and clarithromycin is one of the best choices for Helicobacter pylori eradication therapy. However, increasing number of cases of H. pylori infection showing resistance to clarithromycin therapy has been reported and this is currently the main cause of eradication failure. We investigated the annual changes of the antimicrobial susceptibility to clarithromycin, amoxicillin and minocycline during a period of 12 years in Japan. Methods:, This study comprised 3521 patients (mean age (SD), 55.4 (13.7) years-old, 2467 males and 1054 females) positive for H. pylori as assessed by microaerobic bacterial culture from 1996 through 2008. All patients were previously untreated for H. pylori and were enrolled in the study to assess primary resistance to the three antibiotics. Results:, The overall primary resistance to clarithromycin, amoxicillin and minocycline were 16.4%, (577/3521), 0.03% (1/3521) and 0.06% (2/3521), respectively. From1996 through 2004, the resistance rate to clarithromycin increased gradually to approximately 30% and then it remained without marked fluctuation since 2004. Analysis by gender showed a significant increase (p < .0001) in resistance rate to clarithromycin among females (217/1057, 20.6%) compared to males (360/2467, 14.6%). Analysis by age, disclosed significantly (p < .0001) higher resistance rate to clarithromycin in patients of more than 65-years-old compared to the younger population. Conclusions:, The resistance rate of H. pylori infection to clarithromycin in Japan has increased gradually to approximately 30% from 1996 through 2004, and remained unchanged since 2004. Elderly and females were at high risk of having resistance to clarithromycin. Our results suggested that the level of clarithromycin resistance in Japan has now risen to the point where it should no longer be used as empiric therapy. [source]

High Level of Antimicrobial Resistance in French Helicobacter pylori Isolates

HELICOBACTER, Issue 1 2010
Josette Raymond
Abstract Background: Helicobacter pylori is a human pathogen responsible for serious diseases including peptic ulcer disease and gastric cancer. The recommended triple therapy included clarithromycin but increasing resistance has undermined its effectiveness. It is therefore important to be aware of the local prevalence of antimicrobial resistance to adjust treatment strategy. Materials and Methods: Overall, 530 biopsies were collected between 2004 and 2007. The antimicrobial susceptibility of H. pylori was determined by E-test and molecular methods. Results: Among these, 138/530 (26%) strains were resistant to clarithromycin, 324/530 (61%) to metronidazole and 70/530 (13.2%) to ciprofloxacin. Whereas no resistance against amoxicillin and tetracycline was observed, only one strain was resistant to rifampicin. Compared to the patients never treated for H. pylori infection, the prevalence of resistance was significantly higher in patients previously treated (19.1% vs 68% for clarithromycin; 13.2% vs 53.3% for both clarithromycin and metronidazole). The trend analysis revealed an increase of primary resistance to ciprofloxacin between 2004 and 2005 (7.3%) vs 2006,2007 (14.1%) (p = .04) and the secondary resistance reached 22.7% in 2007. Interestingly, 27 biopsies (19.6%) contained a double population of clarithromycin-susceptible and -resistant strains. Conclusions: The reported high prevalence of clarithromycin and multiple resistances of H. pylori suggest that the empiric therapy with clarithromycin should be abandoned as no longer pretreatment susceptibility testing has assessed the susceptibility of the strain. As culture and antibiogram are not routinely performable in most clinical laboratories, the use of molecular test should be developed to allow a wide availability of pretreatment susceptibility testing. [source]

Annual Change of Primary Resistance to Clarithromycin among Helicobacter pylori Isolates from 1996 through 2008 in Japan

Prediction of the virological response to etravirine in clinical practice: Comparison of three genotype algorithms,,

JOURNAL OF MEDICAL VIROLOGY, Issue 4 2009
Laurent Cotte
Abstract The current Agence Nationale de Recherche sur le SIDA (ANRS)/International AIDS Society (IAS) algorithm predicts resistance to etravirine for viruses harboring ,3 mutations from a list of 13 reverse transcriptase (RT) mutations. Two weighted algorithms, best correlated with fold changes to etravirine, have been described recently. A retrospective virological analysis of a major French city HIV sequences database was undertaken to assess the proportion of etravirine resistant viruses according to these three algorithms and the correlations between them. Two thousand six hundred eighty RT sequences were analyzed, including 749 from naive patients and 926 from patients previously treated with non-nucleoside reverse transcriptase inhibitor (NNRTI). Combinations of mutations associated with etravirine resistance according to the three algorithms were found in 0%, 2.3%, and 3.6% of naive patients, and in 2.4%, 20.4%, and 19.3% of patients previously treated with NNRTIs. Concordance between the algorithms was weak (2,×,2 Kendall's tau: 0.787, 0.395, and 0.584). Most of the discordance was due to the differential weights attributed to Y181C/V, L100I, and K101P in the two weighted algorithms. It is concluded that the current ANRS/ IAS algorithm probably underestimates the proportion of viruses partially resistant to etravirine in NNRTI-experienced patients. Improvements in algorithms are needed to take into account the partial resistance associated with some mutation patterns, and should include either additional mutations to the current list and/or differential weights for specific mutations. Surveys of naive patients should be conducted to estimate the risk of primary resistance to etravirine in a minority of cases. J. Med. Virol. 81:672,677, 2009 © 2009 Wiley-Liss, Inc. [source]

Prevalence of hepatitis B virus DNA polymerase mutations in treatment-naïve patients with chronic hepatitis B

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11-12 2009
M. H. NGUYEN
Summary Background, One of the most important factors in treatment failure using nucleos(t)ide analogues in chronic hepatitis B is anti-viral resistance. Primary drug resistance refers to amino acid changes in the hepatitis B virus polymerase/reverse transcriptase (rt) that result in reduced susceptibility to anti-viral agents. Pre-existing drug resistance mutations may occur in untreated patients and may affect their treatment outcomes. Aim, To determine the prevalence of hepatitis B DNA polymerase mutations in treatment-naïve patients. Methods, We used a direct PCR sequencing test to detect DNA polymerase mutations in 472 consecutive treatment-naïve patients at two community gastroenterology clinics in Northern California. Results, A majority of patients were Asians (>95%), had either genotype B or C (95%) and had no evidence of cirrhosis or liver cancer (94%). Mean age was 45 ± 13 and mean hepatitis B virus DNA was 5.3 ± 1.8 log10 IU/mL. Most patients did not have any detectable mutations (82.4%). Some (16.7%) had mutations of unknown clinical significance (rtV207M/L/I) and only 4 patients had rtA181A/S, rtA194S or M250I. Conclusions, No rtM204V/I or rtN236T mutations were observed in our study. Less than 1% of our patients had mutations that can be associated with primary resistance to existing anti-viral therapies for hepatitis B virus. [source]

Long-term efficacy of botulinum toxin A in treatment of various movement disorders over a 10-year period

MOVEMENT DISORDERS, Issue 6 2002
G-Y.R. Hsiung MD
Abstract Although botulinum toxin A (BTX) has been licensed in Canada for treatment of various movement disorders since 1990, few clinical studies regarding its long-term efficacy and side effects have been reported. We conducted a retrospective analysis of 235 patients who received BTX from our movement disorders clinic over a 10-year period (January 1990 to December 1999). A total of 2,616 treatment cycles (multiple injections) were administered to 235 patients with cervical dystonia (CD), hemifacial spasm (HS), blepharospasm (BP), and other movement disorders. Substantial benefit at 5 years was seen in most patients (90% in BP, 88% in HS, 63% in CD, 100% in jaw closing and lower limb dystonia, and 56% in writer's cramp). Benefit was maintained for up to 10 years in CD, HS, and BP data, with a 75.8% benefit reported. Twenty-eight percent of patients discontinued treatment during the follow-up period due to a variety of reasons. Of these, 9.1% of patients developed primary resistance, and 7.5% of patients secondary resistance. Adverse effects, mostly minor, developed in 27% of patients at any one time, occurring over 4.5% of treatment cycles. These were most frequently reported in blepharospasm (22 of 36 patients in 40 cycles), followed by hemifacial spasm (21 of 70 patients in 46 cycles), and cervical dystonia (17 of 106 in 28 cycles). Only 1.3% of patients discontinued therapy due intolerable adverse effects. The results show that BTX is a safe and effective treatment of various types of movement disorders, and most side effects are well tolerated. Discontinuation for any reason was also low after 5 years. Efficacy was maintained after long periods of treatment with high degree of patient satisfaction. © 2002 Movement Disorder Society [source]

Association of p53 codon 72 polymorphism and MDM2 SNP309 with clinical outcome of advanced nonsmall cell lung cancer

CANCER, Issue 4 2008
Ji-Youn Han MD
Abstract BACKGROUND. The purpose of the study was to investigate whether polymorphisms of p53 codon 72 (Arg72Pro) and MDM2 SNP309 (309T>G) affect p53 expression and the clinical outcome of patients with advanced nonsmall cell lung cancer (NSCLC). METHODS. A total of 148 NSCLC patients, previously enrolled in 2 different prospective clinical trials, were genotyped for the p53 Arg72Pro and MDM2 309T>G polymorphisms. Immunohistochemical staining of p53 protein was performed on 61 tumor samples. Genotypes were correlated with p53 expression, clinicopathologic factors, tumor response, and survival. Multivariate logistic or Cox regression analyses were used to adjust for possible confounding variables. RESULTS. The distribution of sex, age, performance status, stage, tumor histology, and smoking habit was not significantly different among polymorphism variants. However, a significant association was observed between p53 Arg72Pro polymorphism and primary resistance to chemotherapy. Patients with the Pro/Pro variant were more likely to be resistant to first-line chemotherapy, especially the irinotecan plus cisplatin regimen, than those with Arg/Arg or Arg/Pro variants (60% vs 27%, P = .014). In multivariate analysis, the Pro/Pro genotype was strongly predictive for shorter progression-free survival (PFS) (hazard ratio [HR] = 1.952, P = .01). The p53 overexpression was associated with MDM2 SNP309. The TT genotype showed more p53 overexpression than TG or GG genotypes (P = .036). In multivariate analysis, the MDM2 TT genotype was independently predictive for longer survival (HR = 1.742, P = .032). CONCLUSIONS. The p53 72Pro/Pro variant was predictive for primary resistance to chemotherapy and shorter progression-free survival. The MDM2 SNP309 was associated with less p53 overexpression and prognostic for worse survival. Genotyping these polymorphisms may be useful for predicting the clinical outcome of advanced NSCLC. Cancer 2008. © 2008 American Cancer Society. [source]

Evaluating budesonide efficacy in nasal polyposis and predicting the resistance to treatment

CLINICAL & EXPERIMENTAL ALLERGY, Issue 1 2009
F. C. P. Valera
Summary Background Cell resistance to glucocorticoids is a major problem in the treatment of nasal polyposis (NP). Objectives The objectives of this study were to observe the effect of budesonide on the expression of IL-1,, TNF-,, granulocyte macrophage-colony stimulating factor, intercellular adhesion molecule (ICAM)-1, basic fibroblast growth factor, eotaxin-2, glucocorticoid receptor (GR)-,, GR-,, c-Fos and p65 in nasal polyps and to correlate their expression to clinical response. Methods Biopsies from nasal polyps were obtained from 20 patients before and after treatment with topical budesonide. Clinical response to treatment was monitored by a questionnaire and nasal endoscopy. The mRNA levels of the studied genes were measured by real-time quantitative (RQ)-PCR. Results There was a significant decrease in the expression of TNF-, (P<0.05), eotaxin-2 (P<0.05) and p65 (P<0.05) in NP after treatment. Poor responders to glucocorticoids showed higher expression of IL-1, (3.74 vs. 0.14; P<0.005), ICAM-1 (1.91 vs. 0.29; P<0.05) and p65 (0.70 vs. 0.16; P<0.05) before treatment. Following treatment, IL-1, (4.18 vs. 0.42; P<0.005) and GR-, (0.95 vs. 0.28; P<0.05) mRNA expression was higher in this group. Conclusion Topical budesonide reduced the expression of TNF-,, eotaxin-2 and p65. Poor responders to topical budesonide exhibit higher levels of IL-1,, ICAM-1 and nuclear factor (NF)-,B at diagnosis and higher expression of both IL-1, and GR-, after treatment. These results emphasize the anti-inflammatory action of topical budesonide at the molecular level and its importance in the treatment of NP. Nevertheless, IL-1,, ICAM-1 and NF-,B may be associated with primary resistance to glucocorticoids in NP, whereas higher expression of GR-, in poor responders only after glucocorticoid treatment may represent a secondary drug resistance mechanism in this disease. [source]