Objective To explore the inhibitory effects and mechanisms of benzodiazepines on Helicobacter pylori (Hp).Methods The Hp international standard strain ATCC43504 was treated with benzodiazepines diazepam,midazolam,and remimazolam,respectively.The treatments with amoxicillin and clarithromycin were taken as the positive controls,and that with water for injection as the negative control.The inhibition zone of each drug was measured by the disk diffusion method.The minimum inhibitory concentration(MIC)and minimum bactericidal concentration(MBC)of each drug against Hp were determined.Hp suspension was configured and treated with diazepam and midazolam,respectively.The bacterial suspension without drug added was used as the control group.The concentration of K⁺ in each bacterial suspension was measured by an automatic biochemical analyzer before drug intervention(T₀)and 1(T₁),2(T₂),3(T₃),4(T₄),5(T₅),6(T₆),and 7 h(T₇)after intervention.Hp urease was extracted and treated with 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,2 MIC midazolam,1 mg/ml acetohydroxamic acid,and water for injection,respectively.The time required for the rise from pH 6.8 to pH 7.7 in each group was determined by the phenol red coloring method.Results The inhibition zones of diazepam,midazolam,remimazolam,amoxicillin,clarithromycin,and water for injection against Hp were 52.3,42.7,6.0,72.3,60.8,and 6.0 mm,respectively.Diazepam and midazolam showed the MIC of 12.5 μg/ml and 25.0 μg/ml and the MBC of 25 μg/ml and 50 μg/ml,respectively,to Hp.The concentrations of K⁺ in the diazepam,midazolam,and control groups increased during T₁-T₇ compared with those at T₀(all P<0.01).The concentration of K⁺ in diazepam and midazolam groups during T₁-T₄ was higher than that in the control group(all P<0.01).The time of inhibiting urease activity in the 1/2 MIC diazepam,1 MIC diazepam,2 MIC diazepam,1/2 MIC midazolam,1 MIC midazolam,and 2 MIC midazolam groups was(39.86±5.11),(36.52±6.65),(38.58±4.83),(39.25±6.19),(36.36±4.61),and(35.81±6.18)min,respectively,which were shorter than that in the acetohydroxamic acid group(all P<0.01)and had no significance differences from that in the water for injection group(all P>0.05).Conclusion Diazepam and midazolam exerted inhibitory effects on Hp,which may be related to the cleavage of Hp cells rather than inhibiting urease.
Midazolam ; Helicobacter pylori ; Urease ; Clarithromycin/pharmacology* ; Benzodiazepines/pharmacology* ; Diazepam/pharmacology* ; Amoxicillin ; Water ; Anti-Bacterial Agents/pharmacology*

The prevalence of Helicobacter pylori infection in Korea shows a decreasing trend and has changed to that of developed country, especially for those below 30 years old. However, the primary antibiotic resistance rates are higher than those of developed countries. The reason for the decrease in the efficacy of standard triple therapy is mainly due to the increase in the resistance against clarithromycin. Sequential therapy seems to be more effective than the standard triple therapy, but the intention-to-treat eradication rate of sequential therapy in Korea, which is mostly under 80.0%, is still not satisfactory. Therefore, a promising regimen is needed. Recently, the Japanese health insurance system admitted 'H. pylori-infected gastritis' as an indication of eradication. Furthermore, the Kyoto Consensus Meeting on H. pylori Gastritis held from January 30th to February 1st, 2014, proposed that 'all H. pylori positive patients should be offered to receive H. pylori eradication'. This suggests that the concept of eradication has been changed from 'treatment' to 'prevention'. Various individualized tailored therapy based on the polymorphism, age and other demographic factors and antibiotic resistance has been attempted to maximize H. pylori eradication therapy. The aim of this article is to review the current epidemiology, H. pylori resistance state, treatment guideline, and to assess the possible future strategy and treatment for H. pylori infection in Korea.
Anti-Bacterial Agents/pharmacology/*therapeutic use ; Aryl Hydrocarbon Hydroxylases/genetics/metabolism ; Clarithromycin/pharmacology/therapeutic use ; Disease Eradication/trends ; Drug Resistance, Bacterial ; Drug Therapy, Combination ; Guidelines as Topic ; Helicobacter Infections/*drug therapy/epidemiology ; *Helicobacter pylori/drug effects ; Humans ; Quinolones/pharmacology/therapeutic use ; Republic of Korea ; Treatment Failure

The standard therapy for Helicobacter pylori infection in Korea is a triple-drug regimen consisting of a proton pump inhibitor with two antibiotics such as clarithromycin, amoxicillin, and metronidazole. However, as the eradication rate of this regimen has declined over the past decade, this prompted the formulation of new therapeutic regimens. New therapeutic strategies against H. pylori infection that had been tried all over the world include sequential therapy, concomitant therapy, and tailored therapy This article will review the basic concepts and the results of previous clinical trials on the aforementioned new therapeutic regiments.
Amoxicillin/pharmacology/therapeutic use ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Clarithromycin/pharmacology/therapeutic use ; Disease Eradication/trends ; Drug Therapy, Combination ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori/drug effects ; Humans ; Nitroimidazoles/pharmacology/therapeutic use ; Proton Pump Inhibitors/pharmacology/therapeutic use

Although, the prevalence of Helicobacter pylori infection in Korea has declined owing to the eradication therapy, recent seroprevalence of H. pylori infection is still reported to be as high as 54.4%. Until now, "standard regimen" for eradication of H. pylori has been conventional triple therapy consisting of proton pump inhibitor, amoxicillin, and clarithromycin. However, with the increase in antibiotic resistance, especially against clarithromycin, the eradication rate of conventional triple therapy has steadily declined during the past 13 years in Korea. Present eradication rate of standard triple therapy is reported to be less than 80%, which is the Maginot line of efficacy for the currently available regimen. Therefore, new first line eradication regimen is needed to enhance the eradication rate of H. pylori infection.
Amoxicillin/pharmacology/therapeutic use ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Asian Continental Ancestry Group ; Clarithromycin/pharmacology/therapeutic use ; Disease Eradication/trends ; Drug Administration Schedule ; Drug Therapy, Combination ; Helicobacter Infections/*drug therapy ; *Helicobacter pylori/drug effects ; Humans ; Proton Pump Inhibitors/therapeutic use ; Republic of Korea

We evaluated the antibiotic resistance rates and eradication rates of clarithromycin based triple therapy from 2005 to 2010 retrospectively. In addition, we investigated the mechanism of clarithromycin resistance in Helicobacter pylori strains isolated from Korean patients. Two hundred and twelve strains of H. pylori were isolated from 204 patients. H. pylori ATCC 43504 was used as the standard strain. The eradication rates of H. pylori from 2005 to 2010 were 89.3%, 82.6%, 86.3%, 87.7%, 81.8%, and 84.2%, respectively. Total eradication rate was 84.9%. DNA sequences of the 23S RNA gene in clarithromycin-resistant strains were determined. The resistance rates of H. pylori to amoxicillin, clarithromycin, metronidazole, tetracycline, ciprofloxacin, moxifloxacin, and levofloxacin were 9.0%, 8.5%, 36.3%, 0%, 14.2%, 14.2%, and 14.2%, respectively. The multidrug resistance rate of H. pylori was 16.5%. Sequence analysis of clarithromycin-resistant strains showed an A2144G mutation in 8 of 14 strains (57.1%), a T2183C mutation in 5 of 14 strains (35.7%), and double mutations of both A2144G and T2183C in 1 of 14 strains (7.1%). In the present study, triple therapy may still be an effective eradication therapy for H. pylori infections in Korea. The A2144G and T2183C mutations are mainly present in clarithromycin-resistant isolates.
Adult ; Aged ; Anti-Bacterial Agents/pharmacology/*therapeutic use ; Asian Continental Ancestry Group ; Clarithromycin/*therapeutic use ; DNA, Bacterial/analysis ; Drug Resistance, Bacterial/genetics ; Female ; Helicobacter Infections/*drug therapy/microbiology ; Helicobacter pylori/drug effects/genetics/*isolation & purification ; Humans ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Mutation ; Polymerase Chain Reaction ; RNA, Ribosomal, 23S/genetics ; Republic of Korea ; Retrospective Studies ; Sequence Analysis, DNA

BACKGROUND: Bacteria of the Mycobacterium abscessus group are the second most common pathogens responsible for lung disease caused by nontuberculous mycobacteria in Korea. There is still a lack of studies investigating the genetic mechanisms involved in M. abscessus resistance to antibiotics other than clarithromycin. This study investigated the characteristics of drug resistance exhibited by M. abscessus clinical isolates from Korea. METHODS: We performed drug susceptibility testing for a total of 404 M. abscessus clinical strains. Subspecies were differentiated by molecular biological methods and examined for mutations in drug resistance-related genes. RESULTS: Of the 404 strains examined, 202 (50.00%), 199 (49.26%), and 3 (0.74%) strains were identified as M. abscessus, M. massiliense, and M. bolletii, respectively. Of the 152 clarithromycin-resistant strains, 6 possessed rrl mutations, while 4 of the 30 amikacin-resistant strains contained rrs mutations, and 5 of the 114 quinolone-resistant strains had gyr mutations. All mutant strains had high minimal inhibitory concentration values for the antibiotics. CONCLUSIONS: Our results showed the distribution of the strains with mutations in drug resistance-related genes was low in the M. abscessus group. Furthermore, we performed drug susceptibility testing and sequence analyses to determine the characteristics of these genes in the M. abscessus group.
Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics ; Clarithromycin/pharmacology ; DNA Gyrase/genetics ; *Drug Resistance, Bacterial ; Humans ; Methyltransferases/genetics ; Microbial Sensitivity Tests ; Mutation ; Mycobacterium/drug effects/*isolation & purification ; Mycobacterium Infections, Nontuberculous/diagnosis/*microbiology ; Republic of Korea ; Sequence Analysis, DNA

OBJECTIVE: To investigate the expression of vascular endothelial growth factor in the nasal mucosa of chronic rhinosinusitis with nasal polys patients, and explored the regulation of clarithromycin on VEGF. METHOD: RT-PCR was used to detect the expression of VEGF in nasal mucosa from healthy control and CRSwNP. Nasal mucosal tissue explant culture measure and ELISA were used to explore the effect of clarithromycin on VEGF expression. RESULT: (1) VEGF mRNA expression level was significantly increased in CRSwNP compared with control and showed a statistic difference (P < 0.01). (2) There was a significant decrease in CRSwNP group undergo clarithromycin treatment on protein expression level of VEGF and showed a statistic difference (P < 0.05). CONCLUSION VEGF were overexpressed in CRSwNP group, which presume that play an important role in the pathogenesis of nasal polyps. Clarithromycin may play a therapeutical role on chronic rhinosinusitis through down-regulated the expression of VEGF.
Adult ; Chronic Disease ; Clarithromycin ; pharmacology ; Female ; Humans ; Male ; Nasal Mucosa ; metabolism ; Nasal Polyps ; complications ; Rhinitis ; complications ; metabolism ; Sinusitis ; complications ; metabolism ; Vascular Endothelial Growth Factor A ; metabolism ; Young Adult

BACKGROUNDMycobacterium abscessus (M. abscessus) can cause a variety of human infections, involving the lung, skin and soft tissues, and is generally believed to be acquired from environmental sources. The aim of this study was to investigate the molecular diversity and antibiotic susceptibility of M. abscessus isolates as the basis for strategies to improve control and management of infection.

METHODSSeventy M. abscessus isolates from patients attending the Guangzhou Thoracic Hospital were identified from 2003 to 2005 by biochemical tests, gas chromatography, polymerase chain reaction (PCR)-restriction analysis (PRA) of heat shock protein gene hsp65, and sequencing of the quinolone resistance determining regions (QRDRs) of gyrA. Susceptibilities to six antibiotics were determined by micro-broth dilution. Isolates were genotyped using randomly amplified polymorphic DNA (RAPD) analysis.

RESULTSMost isolates (63/70; 90%) were susceptible to amikacin but rates of susceptibility to other antibiotics varied from moderate, clarithromycin (60%) and imipenem (43%), to low for ciprofloxacin and ofloxacin (3%), and 87% of isolates had intermediate susceptibility to cefoxitin. RAPD analysis showed that the 70 clinical isolates displayed 69 unique RAPD patterns.

CONCLUSIONSThe high genetic diversity of isolates suggests that they are not transmitted from person to person but, presumably, are acquired independently from environmental sources. M. abscessus isolates displayed variable levels of susceptibility to all antibiotics tested, other than amikacin, indicating a need for routine susceptibility testing to guide treatment.

Amikacin ; pharmacology ; Anti-Bacterial Agents ; pharmacology ; Cefoxitin ; pharmacology ; China ; Chromatography, Gas ; Ciprofloxacin ; pharmacology ; Clarithromycin ; pharmacology ; Imipenem ; pharmacology ; Microbial Sensitivity Tests ; Mycobacterium ; drug effects ; genetics ; Polymerase Chain Reaction ; Random Amplified Polymorphic DNA Technique

BACKGROUND/AIMS: This study was performed to compare the prevalence rates of primary antibiotic resistance in Helicobacter pylori (H. pylori) isolates among different regions of Korea. METHODS: H. pylori were isolated from gastric mucosal biopsy specimens of 99 Koreans who lived in Gyeonggi (n=40), Kangwon province (n=40) and Busan (n=19) from April to August in 2008. All the patients had no history of H. pylori eradication therapy. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin were tested according to the agar dilution method. RESULTS: There was a difference in resistance to clarithromycin in three institutes located among Gyeonggi (32.5%), Kangwon province (12.5%) and Busan (42.1%) by One way ANOVA test (p=0.027) and nonparametric Kruskal Wallis test (p=0.027). However, by post-hoc analysis, there was no statistically significant difference among three regions. Similarly, the other 7 antibiotics (amoxicillin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin) did not show any significant difference. CONCLUSIONS: There was no significant regional difference of the primary antibiotic resistance of H. pylori. However, the included patient number might not be enough for this conclusion demanding further evaluations.
Amoxicillin/pharmacology ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Aza Compounds/pharmacology ; Azithromycin/pharmacology ; Ciprofloxacin/pharmacology ; Clarithromycin/pharmacology ; *Drug Resistance, Bacterial ; Female ; Helicobacter Infections/*epidemiology/microbiology ; Helicobacter pylori/*drug effects/isolation & purification ; Humans ; Male ; Metronidazole/pharmacology ; Microbial Sensitivity Tests ; Middle Aged ; Ofloxacin/pharmacology ; Quinolines/pharmacology ; Republic of Korea/epidemiology ; Tetracycline/pharmacology

BACKGROUND/AIMS: This study was performed to compare the prevalence rates of primary antibiotic resistance in Helicobacter pylori (H. pylori) isolates among different regions of Korea. METHODS: H. pylori were isolated from gastric mucosal biopsy specimens of 99 Koreans who lived in Gyeonggi (n=40), Kangwon province (n=40) and Busan (n=19) from April to August in 2008. All the patients had no history of H. pylori eradication therapy. The susceptibilities of the H. pylori isolates to amoxicillin, clarithromycin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin, and moxifloxacin were tested according to the agar dilution method. RESULTS: There was a difference in resistance to clarithromycin in three institutes located among Gyeonggi (32.5%), Kangwon province (12.5%) and Busan (42.1%) by One way ANOVA test (p=0.027) and nonparametric Kruskal Wallis test (p=0.027). However, by post-hoc analysis, there was no statistically significant difference among three regions. Similarly, the other 7 antibiotics (amoxicillin, metronidazole, tetracycline, azithromycin, ciprofloxacin, levofloxacin and moxifloxacin) did not show any significant difference. CONCLUSIONS: There was no significant regional difference of the primary antibiotic resistance of H. pylori. However, the included patient number might not be enough for this conclusion demanding further evaluations.
Amoxicillin/pharmacology ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Aza Compounds/pharmacology ; Azithromycin/pharmacology ; Ciprofloxacin/pharmacology ; Clarithromycin/pharmacology ; *Drug Resistance, Bacterial ; Female ; Helicobacter Infections/*epidemiology/microbiology ; Helicobacter pylori/*drug effects/isolation & purification ; Humans ; Male ; Metronidazole/pharmacology ; Microbial Sensitivity Tests ; Middle Aged ; Ofloxacin/pharmacology ; Quinolines/pharmacology ; Republic of Korea/epidemiology ; Tetracycline/pharmacology