结核病抗生素可能带来严重副作用

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科学家表示，一种用来治疗儿童耐多药结核病的抗生素可能导致患者产生对一种用于不相干病菌的药物的耐药性，这种病菌能引发肺炎链球菌疾病。

这项研究3月份发表于爱思唯尔期刊《柳叶刀》（The Lancet）上。作者们表示，试图预防耐药性肺炎链球菌扩散的卫生政策制定者应该考虑这个问题。

科学家们评估了21,521个入侵性肺炎链球菌疾病的病例——包括肺炎、毒血症和脑膜炎——这些病例来源于南非国家卫生实验室服务系统在2000年到2006年搜集的常规微生物监测数据。

他们发现12名被感染了肺炎链球菌的儿童对一种使用左旋氧氟沙星（levofloxacin）的治疗产生耐药性，左旋氧氟沙星属于氟喹诺酮类(fluoroquinolone)药物的一种，这种药物用来治疗耐多药结核病。

这些儿童中的89%过去曾经用氟喹诺酮治疗过结核病。大多数儿童在医院获得性感染了肺炎链球菌。

南非国立传染病研究所呼吸道和脑膜研究室联合主任Anne von Gottberg说，“这是一个大新闻。问题是接受过耐药结核病治疗的儿童能够传染肺炎链球菌到更广大的社区中，而这种链球菌现在也变得具有了耐药性。”

他还说：“如果这种细菌的耐药菌株传播，成年人，尤其是年长者或者免疫系统受损者将处于危险中，因为将会导致治疗肺炎失败。”

南非国家卫生实验室服务系统的病理学家、论文共同作者Nelesh Govender说，这项结果凸显了该系统经常性疾病监测的重要性。他说，“如果没有很好的基于实验室监测的系统可以让我们监督耐药性，我们将无法获得这个问题的蛛丝马迹。”

Govender说，作为一项短期措施，这一研究将促进生产更多链球菌疫苗的工作，大多数非洲国家很少获得这种疫苗，特别是对于那些入院治疗耐多药结核病的儿童。



（The Lancet），Volume 371, Issue 9618, 29 March 2008-4 April 2008, Pages 1108-1113，Anne von Gottberg，Stephanie Schrag

Emergence of levofloxacin-non-susceptible Streptococcus pneumoniae and treatment for multidrug-resistant tuberculosis in children in South Africa: a cohort observational surveillance study

Anne von Gottberg FCPath [SA] Microa, b, d, , , Prof Keith P Klugman FRCPatha, b, d, e, Cheryl Cohen FCPath [SA] Microa, c, Nicole Wolter PhDa, b, d, Linda de Gouveia MTa, d, Mignon du Plessis PhDa, b, d, Ruth Mpembe MTa, d, Vanessa Quan MBBCha, Andrew Whitelaw FCPath [SA] Microf, g, Rena Hoffmann MMedf, h, Nelesh Govender FCPath [SA] Microa, b, Susan Meiring MBChBa, Anthony M Smith PhDa, b, Stephanie Schrag DPhili and for the Group for Enteric, Respiratory and Meningeal Disease Surveillance in South Africa (GERMS-SA)


Summary
Background
Use of fluoroquinolones to treat paediatric cases of multidrug-resistant tuberculosis could affect the emergence of resistance to this class of drugs. Our aim was to estimate the incidence of, and risk factors for, invasive pneumococcal disease caused by fluoroquinolone-resistant Streptococcus pneumoniae in children in South Africa.

Methods
21 521 cases of invasive pneumococcal disease were identified by active national surveillance between 2000 and 2006, with enhanced surveillance at 15 sentinel hospitals in seven provinces introduced in 2003. We screened 19 404 isolates (90% of cases) for ofloxacin resistance and measured levofloxacin minimum inhibitory concentrations (MICs) for all isolates that were ofloxacin resistant. Non-susceptibility to levofloxacin was defined as an MIC of 4 mg/L or more. Nasopharyngeal pneumococcal carriage was assessed in 65 children in two tuberculosis hospitals where invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae had been detected.

Findings
12 cases of invasive pneumococcal disease were identified as being non-susceptible to levofloxacin, all in children aged under 15 years. All isolates were rifampicin resistant. Outcome was known for 11 of these patients; five (45%) died. Invasive disease caused by levofloxacin-non-susceptible S pneumoniae was associated with a history of tuberculosis treatment (eight [89%] of nine children with non-susceptible isolates had a history of treatment vs 396 [18%] of 2202 children with susceptible isolates; relative risk [RR] 35·78, 95% CI 4·49–285·30) and nosocomial invasive pneumococcal disease (eight [80%] of ten children with non-susceptible isolates had acquired infection nosocomially vs 109 [4%] of 2709 with susceptible isolates; RR 88·96, 19·10–414·29). 31 (89%) of 35 pneumococcal carriers had bacteria that were non-susceptible to levofloxacin.