Karlowsky James A, Lagacé-Wiens Philippe R S, Low Donald E, Zhanel George G
Department of Medical Microbiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
Int J Antimicrob Agents. 2009 Oct;34(4):375-9. doi: 10.1016/j.ijantimicag.2009.05.008. Epub 2009 Jun 27.
Over the last 20 years, Canadian pneumococcal surveillance studies have documented a steady rise in macrolide resistance. In the current study, we probed the nature of associations between the emergence of macrolide-resistant Streptococcus pneumoniae in Canada and changes in macrolide (azithromycin, clarithromycin and erythromycin) prescription rates. Macrolide susceptibility testing data for respiratory tract isolates of S. pneumoniae (n=15109) were acquired from two published national Canadian surveillance databases, and dispensed outpatient macrolide prescription data were acquired from the proprietary Intercontinental Medical Statistics (IMS) Health Canada CompuScript database. Nationally, macrolide resistance increased from 3.7% in 1995 to 19.0% in 2005 (P=0.003) as the annual macrolide prescription rate increased from 106.7 to 123.2 prescriptions/1000 persons per year (P=0.003). From 1995 to 2005, azithromycin and clarithromycin prescriptions increased from 4.8 to 52.5 prescriptions/1000 persons per year (P<0.0001) and from 24.7 to 58.4 prescriptions/1000 persons per year (P=0.005), respectively, whilst erythromycin prescriptions decreased from 77.2 to 12.3 prescriptions/1000 persons per year (P<0.0001). By univariate regression analysis, increasing rates of azithromycin (R(2)=0.931; P<0.0001) and clarithromycin (R(2)=0.725; P=0.0009) prescriptions and a decreasing rate of erythromycin prescriptions (R(2)=-0.963; P<0.0001) were all associated with increasing macrolide resistance from 1995 to 2005. Multivariate regression analysis showed that a model including all three macrolide prescription rates provided the best fit to the trend of increasing macrolide resistance. When the data were analysed by provincial origin, no statistically significant associations were found between prescription rates of any macrolide and macrolide resistance rates by univariate and multivariate regression analyses. We conclude that increasing macrolide resistance among respiratory isolates of pneumococci in Canada from 1995 to 2005 was associated both with decreasing prescriptions for erythromycin and concurrent increases in prescriptions for azithromycin and clarithromycin (azithromycin>clarithromycin by univariate regression analysis). Resistance development is complex and factors other than macrolide use may also be associated with observed increases in macrolide resistance in Canada from 1995 to 2005.
在过去20年中，加拿大的肺炎球菌监测研究记录了大环内酯类耐药性的稳步上升。在本研究中，我们探究了加拿大耐大环内酯类肺炎链球菌的出现与大环内酯类（阿奇霉素、克拉霉素和红霉素）处方率变化之间的关联性质。从两个已发表的加拿大全国监测数据库中获取了肺炎链球菌呼吸道分离株（n = 15109）的大环内酯类药敏试验数据，并从专有的加拿大洲际医疗统计（IMS）健康CompuScript数据库中获取了门诊分发的大环内酯类处方数据。在全国范围内，随着大环内酯类年处方率从每年每1000人106.7张增加到123.2张（P = 0.003），大环内酯类耐药性从1995年的3.7%增加到2005年的19.0%（P = 0.003）。从1995年到2005年，阿奇霉素和克拉霉素的处方分别从每年每1000人4.8张增加到52.5张（P < 0.0001）和从24.7张增加到58.4张（P = 0.005），而红霉素处方从每年每1000人77.2张减少到12.3张（P < 0.0001）。通过单变量回归分析，阿奇霉素（R² = 0.931；P < 0.0001）和克拉霉素（R² = 0.725；P = 0.0009）处方率的增加以及红霉素处方率的下降（R² = -0.963；P < 0.0001）均与1995年至2005年大环内酯类耐药性的增加相关。多变量回归分析表明，包含所有三种大环内酯类处方率的模型最符合大环内酯类耐药性增加的趋势。当按省份来源分析数据时，通过单变量和多变量回归分析未发现任何大环内酯类的处方率与大环内酯类耐药率之间存在统计学上的显著关联。我们得出结论，1995年至2005年加拿大肺炎球菌呼吸道分离株中大环内酯类耐药性的增加与红霉素处方的减少以及阿奇霉素和克拉霉素处方的同时增加有关（单变量回归分析显示阿奇霉素>克拉霉素）。耐药性的发展是复杂的，1995年至2005年加拿大观察到的大环内酯类耐药性增加可能还与大环内酯类使用以外的因素有关。
