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十年间智利比奥比奥地区幽门螺杆菌的抗生素耐药性监测

ANTIBIOTIC RESISTANCE SURVEILLANCE OF HELICOBACTER PYLORI AT THE BIOBÍO REGION (CHILE) IN A DECADE.

作者信息

Parra-Sepúlveda Cristian, Merino José S, Sáez-Carrillo Katia, González Carlos, García-Cancino Apolinaria

机构信息

Universidad de Concepción, Facultad de Ciencias Biológicas, Departamento de Microbiología, Concepción, Chile.

Universidad de las Américas, Facultad de Medicina Veterinaria y Agronomía, Concepción, Chile.

出版信息

Arq Gastroenterol. 2019 Oct-Dec;56(4):361-366. doi: 10.1590/S0004-2803.201900000-72.

Abstract

BACKGROUND

Helicobacter pylori infection in Chile remains as a public and private health-care system's challenge, with a prevalence of the infection over 70%. Nowadays, antibiotic treatment of the infection is mandatory to prevent the arising of severe associated diseases but failures in the eradication therapy mainly due to clarithromycin resistance has been observed worldwide and first line eradication therapy seems to be not effective anymore in several geographical areas. Thus, health-care systems are committed to maintain an epidemiological surveillance upon the evolution of the antibiotic resistance of this priority 2 pathogen.

OBJECTIVE

This work reports a 10 years surveillance of the primary antibiotic resistance of H. pylori clinical isolates at the Biobío region-Chile, and the evolution of resistance toward amoxicillin, clarithromycin, levofloxacin, metronidazole, and tetracycline among the species.

METHODS

H. pylori strains were investigated during the periods 2005-2007 (1435 patients analysed) and 2015-2017 (220 patients analysed) by inoculating a saline homogenate biopsy onto the surface of Columbia agar (Oxoid, Basingstoke, UK) - supplemented with 7% horse red blood cells plus DENT inhibitor (Oxoid, Basingstoke, UK) - following by incubation at 37ºC under 10% CO2 atmosphere for five days. Antibiotic resistance pattern of the isolates was assessed using the disk diffusion test in Müeller-Hinton agar supplemented with 7% horse red blood cells followed by incubation for further three days under 10% CO2 atmosphere. Statistical analysis was done using the SPSS v22 software and P values <0.05 were considered statistically significant.

RESULTS

A total of 41% of 1435 patients were detected to be infected with H. pylori by bacteriological culture in 2005-2007 period, meanwhile 32.7% from 220 patients were also infected in 2015-2017 period. The clinical isolates of H. pylori are mostly susceptible to amoxicillin and tetracycline (both over 98% of strains), but less susceptible to levofloxacin in both periods analysed (over 79% of the strains). On the other hand, metronidazole continuous showing the highest score of resistant isolates (over 40% of resistant strains), although an 18% fewer resistant strains were observed in 2015-2017 period. Clarithromycin, the key antibiotic in eradication therapies, has an increased frequency of resistant strain isolated in the decade (22.5% in 2005-2007 and 29.2% in 2015-2017). Multidrug resistant strains (two, three and four antibiotics) were also detected in both periods with the highest scores for simultaneous resistance to clarithromycin-metronidazole (18%) and clarithromycin-metronidazole-levofloxacin (12.5%) resistant strains. According to gender, the isolates resistant to amoxicillin, clarithromycin and metronidazole were more frequent in female, with a specific increment in amoxicillin and clarithromycin resistance.

CONCLUSION

The frequency of clarithromycin resistance (29.2%) detected in 2015-2017 suggests that conventional triple therapy is no longer effective in this region.

摘要

背景

幽门螺杆菌感染在智利仍是公共和私人医疗保健系统面临的一项挑战,其感染率超过70%。如今,必须对该感染进行抗生素治疗以预防严重相关疾病的发生,但在全球范围内已观察到根除治疗失败,主要原因是对克拉霉素耐药,并且在几个地理区域一线根除治疗似乎已不再有效。因此,医疗保健系统致力于对这种二级重点病原体的抗生素耐药性演变进行流行病学监测。

目的

本研究报告了智利比奥比奥地区对幽门螺杆菌临床分离株主要抗生素耐药性的十年监测,以及该菌种对阿莫西林、克拉霉素、左氧氟沙星、甲硝唑和四环素的耐药性演变情况。

方法

在2005 - 2007年期间(分析了1435例患者)和2015 - 2017年期间(分析了220例患者),将盐水匀浆活检标本接种到补充有7%马红细胞加DENT抑制剂(英国巴辛斯托克奥克托德公司)的哥伦比亚琼脂(英国巴辛斯托克奥克托德公司)表面,然后在37℃、10%二氧化碳气氛下孵育五天,对幽门螺杆菌菌株进行研究。使用在补充有7%马红细胞的Müeller - Hinton琼脂中进行纸片扩散试验评估分离株的抗生素耐药模式,然后在10%二氧化碳气氛下进一步孵育三天。使用SPSS v22软件进行统计分析,P值<0.05被认为具有统计学意义。

结果

在2005 - 2007年期间,通过细菌培养检测到1435例患者中有41%感染了幽门螺杆菌,同时在2015 - 2017年期间,220例患者中有32.7%也被感染。幽门螺杆菌的临床分离株大多对阿莫西林和四环素敏感(两种菌株均超过98%),但在两个分析时间段对左氧氟沙星的敏感性较低(超过79%的菌株)。另一方面,甲硝唑耐药分离株的比例持续最高(超过40%的耐药菌株),尽管在2015 - 2017年期间观察到耐药菌株减少了18%。根除治疗中的关键抗生素克拉霉素,在这十年中分离出的耐药菌株频率有所增加(2005 - 2007年为22.5%,2015 - 2017年为29.2%)。在两个时间段均检测到多重耐药菌株(对两种、三种和四种抗生素耐药),对克拉霉素 - 甲硝唑(18%)和克拉霉素 - 甲硝唑 - 左氧氟沙星(12.5%)同时耐药的菌株比例最高。按性别划分,对阿莫西林、克拉霉素和甲硝唑耐药的分离株在女性中更为常见,阿莫西林和克拉霉素耐药性有特定增加。

结论

2015 - 2017年检测到的克拉霉素耐药率(29.2%)表明传统三联疗法在该地区已不再有效。

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