von Gottberg Anne, Klugman Keith P, Cohen Cheryl, Wolter Nicole, de Gouveia Linda, du Plessis Mignon, Mpembe Ruth, Quan Vanessa, Whitelaw Andrew, Hoffmann Rena, Govender Nelesh, Meiring Susan, Smith Anthony M, Schrag Stephanie
National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg, South Africa.
Lancet. 2008 Mar 29;371(9618):1108-13. doi: 10.1016/S0140-6736(08)60350-5. Epub 2008 Mar 21.
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.
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.
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.
Our data suggest that the use of fluoroquinolones to treat multidrug-resistant tuberculosis in children has led to the emergence of invasive pneumococcal disease caused by levofloxacin-non-susceptible S pneumoniae and its nosocomial spread.
使用氟喹诺酮类药物治疗儿童耐多药结核病可能会影响对这类药物耐药性的出现。我们的目的是评估南非儿童中由耐氟喹诺酮类肺炎链球菌引起的侵袭性肺炎球菌病的发病率及危险因素。
通过全国主动监测在2000年至2006年期间识别出21521例侵袭性肺炎球菌病病例，并于2003年在七个省份的15家哨点医院加强了监测。我们对19404株分离菌（占病例的90%）进行了氧氟沙星耐药性筛查，并对所有氧氟沙星耐药的分离菌测定了左氧氟沙星最低抑菌浓度（MIC）。对左氧氟沙星不敏感定义为MIC为4mg/L或更高。在两家检测到由对左氧氟沙星不敏感的肺炎链球菌引起侵袭性肺炎球菌病的结核病医院，对65名儿童进行了鼻咽部肺炎球菌携带情况评估。
12例侵袭性肺炎球菌病病例被确定为对左氧氟沙星不敏感，均为15岁以下儿童。所有分离菌均对利福平耐药。其中11名患者的结局已知；5例（45%）死亡。由对左氧氟沙星不敏感的肺炎链球菌引起的侵袭性疾病与结核病治疗史相关（9名分离菌不敏感的儿童中有8名[89%]有治疗史，而2202名分离菌敏感的儿童中有396名[18%]有治疗史；相对危险度[RR]为35.78，95%可信区间为4.49 - 285.30）以及医院获得性侵袭性肺炎球菌病相关（10名分离菌不敏感的儿童中有8名[80%]为医院获得性感染，而2709名分离菌敏感的儿童中有109名[4%]为医院获得性感染；RR为88.96，95%可信区间为19.10 - 414.29）。35名肺炎球菌携带者中有31名（89%）携带的细菌对左氧氟沙星不敏感。
我们的数据表明，使用氟喹诺酮类药物治疗儿童耐多药结核病已导致由对左氧氟沙星不敏感的肺炎链球菌引起的侵袭性肺炎球菌病的出现及其在医院内的传播。
