2012至2014年山西省儿童医院住院部肺炎链球菌分离株耐药性分析

Antibiotic resistance analysis of Streptococcus pneumoniae isolates from the hospitalized children in Shanxi Children＇s Hospital from 2012 to 2014

目的了解山西省儿童医院住院部肺炎链球菌分离株的耐药状况。方法收集2012年1月至2014年12月山西省儿童医院住院患儿各类体液标本中肺炎链球菌分离株，用E－test法和纸片扩散法进行药敏试验，分析肺炎链球菌对主要抗菌药物敏感率及最低抑菌浓度（MIC）等情况，比较非侵袭性肺炎链球菌耐药性的年度变化及不同标本来源肺炎链球菌的耐药性差异。率的比较采用Fisher确切概率法或χ^2检验。结果收集了671株肺炎链球菌，其中非侵袭性分离株607株，非脑脊液侵袭性分离株40株，脑脊液分离株24株。671株肺炎链球菌分离株对抗菌药物敏感性[株（%）]依次为：万古霉素671（100.0%），利奈唑胺671（100.0%），左氧氟沙星665（99.1%），青霉素595（88.7%），头孢曲松516（76.9%），头孢噻肟512（76.3%），磺胺甲基异噁唑－甲氧苄氨嘧啶（SMZ－TMP）103（15.4%），克林霉素28（4.2%），四环素26（3.9%），红霉素12（1.8%）。肺炎链球菌非侵袭性分离株对青霉素的敏感率2012—2014年分别为95.0%（96/101）、97.3%（110/113）、87.3%（343/393），3年间比较差异有统计学意义（χ^2＝13.266, P〈0.05），且2012年青霉素的MIC50、MIC90、最大MIC值（mg/L）分别为0.064、2.000、6.000，2014年上升至1.000、3.000、16.000；2012－2014年非侵袭性分离株对头孢曲松、头孢噻肟的敏感率3年间比较差异无统计学意义（χ^2＝1.172、1.198,均P〉0.05），但头孢曲松、头孢噻肟MIC50、MIC90、最大MIC值（mg/L）均由2012年的0.500、2.000、8.000上升至2014年的0.750、4.000、32.000；非侵袭性分离株对其余抗菌药物3年间的耐药状况的比较差异无统计学意义（P〉0.05）。统一按肺炎链球菌脑膜炎静脉注射给药折点判断，607株非侵袭性分离株对头孢曲松、头孢噻肟、SMZ－TMP的敏感株数分别为281（46.3%）、278（45.8%）、78（12.9%），低于非脑脊液侵袭性分离株（40株）的敏感株数[28（70%）、28（70%）、14（35%），χ^2＝8.453、8.817、15.094，均P〈0.012 5]，亦低于脑脊液分离株（24株）的敏感株数[18（75%）、18（75%），χ^2＝7.631、7.905，P〈0.012 5；11（45.8%），P＝0.001]；不同标本来源肺炎链球菌分离株对其余抗菌药物的耐药状况比较差异无统计学意义（P〉0.05）。结论2012—2014年山西省儿童医院住院患儿肺炎链球菌对万古霉素、利奈唑胺、左氧氟沙星等敏感率均超过95.0%，对青霉素、头孢曲松、头孢噻肟的敏感率分别为88.7%、76.9%、76.3%，对红霉素、克林霉素、SMZ－TMP、四环素等敏感率均低于20.0%；3年间非侵袭性分离株对青霉素的敏感率下降，对头孢曲松、头孢噻肟的敏感率无明显变化，但MIC50、MIC90、最大MIC水平上升；非侵袭性分离株对头孢曲松、头孢噻肟、SMZ－TMP的敏感率低于侵袭性分离株。

Objective To investigate the antibiotic resistance status of Streptococcus pneumoniae isolates from hospitalized children in Shanxi Children＇s Hospital. Method E-test and Kirby-Bauer methods were applied to determine drug sensitivity of the isolates collected from the body fluid specimens of hospitalized children in Shanxi Children~ Hospital from January 2012 to December 2014. The antimicrobial sensitivity and minimum inhibitory concentration （MIC） of Streptococcus pneumoniae to the conventional antibiotics were analyzed, in order to compare the annual trends of non-invasive isolates, while the differentiation of sensitivity from specimens. The comparison of rates was performed by Chi-squared test and Fisher~ exact test. Result A total of 671 isolates of streptococcus pneumoniae were obtained, which could be divided as non-invasive isolates （607）, invasive isolates from non-cerebrospinal fluid （non-CSF） （40） and invasive isolates from cerebrospinal fluid（CSF） （24）. The antimicrobial sensitivity（ isolates（ % ） ） of the 671 isolates were respectively vancomycin 671 （ 100. 0% ）, linezolid 671 （ 100. 0% ）, levofloxacin 665 （99. 1% ）, penicillin 595 （88.7%）, ceftriaxone 516 （76. 9% ）, cefotaxime 512 （76. 3 % ）, sulfamethoxazole-trimethoprin （SMZ-TMP） 103 （ 15.4% ）, clindamycin 28 （4. 2% ）, tetracycline 26 （ 3.9% ）, erythromyein 12 （ 1.8% ）. From 2012 to 2014, the susceptibility rates of non-invasive isolates to penicillin every year were 95.0% （96/101）, 97.3% （ 110/113）, 87. 3% （343/393）, respectively, and there was significant difference among the three years（ X2 = 13. 266, P 〈 0. 05 ） , and the values of MICs0, MICgo and the maximum values of MIC （mg/L） of penicillin were O. 064, 2. 000, 6. 000 in 2012, which grew up to 1. 000, 3. 000, 16. 000 in 2014. There was no significant difference in the susceptibility rate of non-invasive isolates to ceftriaxone and cefotaxime during these three years, （ X^2 = 1. 172, 1. 198, both P 〉 0. 05）. On the other hand, the values of MICs0, MICgo and the maximum value of MIC （mg/L） of ceftriaxone and eefotaxime both increased from 0. 500, 2. 000, 8. 000 in 2012 to 0. 750, 4. 000, 32. 000 in 2014. There was no significant difference in the susceptibility rate of non-invasive isolates to the rest antibiotic. Based on the same examining standard of CSF, the antimicrobial sensitivity （isolates （%）） of the non-invasive isolates to ceftriaxone, cefotaxime, SMZ-TMP were respectively 281 （46. 3% ）, 278（45.8% ）, 78（ 12. 9% ） , were significantly lower than the susceptibility rate of the invasive isolates from non-CSF （ 28 （70%） , 28 （70%） , 14 （ 35% ） , X^2 = 8. 453, 8. 817, 15. 094, all P 〈0. 012 5） , and lower than the invasive isolates from CSF （ 18（75% ） , 18（75% ）, X^2=7.631, 7. 905, P〈0.012 5; 11（45.8%）, P=0.001）. The sensitivity of the isolates to the rest antibiotics were similar（ P 〉 0. 05 ）. Couehmlon More than 95.0% strains of the streptococcus pneumoniae isolates from the hospitalized children in Shanxi Children~ Hospital were sensitive to vancomycin, linezolid, levofloxacin, and the susceptibility rate of penicillin, ceftriaxone, eefotaxime were 88.7%, 76.9%, 76.3%. However, less than 20.0% of streptococcus pneumoniae were sensitive to erythromycin, clindamycin, SMZ-TMP and tetracycline. The susceptibility rate of penicillin of non-invasive Streptococcus pneumoniae declined by these years, and the differences to ceftriaxone and cefotaxime can be neglected, but the values of MIC50, MIC90 and the maximum value of MIC of all were linearly rising. The susceptibility rate of antibiotics to ceflriaxone and cefotaxime of the non-invasive isolates was lower than the invasive isolates.