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中华妇幼临床医学杂志(电子版)

Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition) ›› 2014, Vol. 10 ›› Issue (01): 29 -40. doi: 10.3877/cma.j.issn.1673-5250.2014.01.008

Special Issue: ；

Original Article

Correlation Between Drug-Resistance and Clinical Treatment of Mycoplasma Pneumoniae

Tao Zhang1, Bo Wang1, Suiqiong Wang1, Yuanping Tang1, Miaoling Liu1, Shumei Peng1, Ying Lin1, Ronghan Li1, Wenyu Deng1, Tianwen He1, Linlin Yang1()   

  1. 1. Guangdong Women and Children Hospital Affiliated Guangzhou Medical University, Guangzhou 510010, Guangdong Province, China
  • Received:2013-11-30 Revised:2014-01-15 Published:2014-02-01
  • Corresponding author: Linlin Yang
  • About author:
    (Corresponding author: Yang Linlin, Email: )
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Objective

To explore the effectiveness and safety of azithromycin sequential therapy for children with Mycoplasma pneumoniae (MP) infection, and analysis correlation of drug-resistance with indisciplined used of macrolide antibiotics application.

Methods

According to MP antibody titers 1: 320 for MP infection as standard to clinical diagnosis MP-IgM positive. From March 2011 to February 2013, a total of 792 children(screened 5-13 years old) with upper respiratory infection complicating cough or(and) fever who suspected MP infected were recruited. Among them 431 cases MP-IgM positive were as subjects. According to differences frequency of macrolide antibiotics application and frequency of MP infection in one year, 431 children with MP positive were divided into experimental group (n=217) and control group (n=214) . Patients in experimental group were preliminary screening subjects who without MP infection and macrolide antibiotics applied history in half of a year. Patients in control group were repeated MP infected and indisciplined used of macrolide antibiotics≥2 times in one year. MP cultures of children in both groups were detected twice times when they admitted. If their culture MP positive, 23S rRNA V PCR product were synthesis, and drug sensitivity test to 9 kinds of antibiotics were detected. Children in experimental group whose positive culture MP antibiotics sensitivity and 23S rRNA V had no mutation were gave macrolides sequential therapy. In the end of 2 weeks after macrolides sequential therapy, detection MP cuture again. If their culture MP positive, analysed drug sensitivity and screened the 23S rRNA V mutation or not. At those two time points, the curative effects of azithromycin sequential therapy were judged . Analysed whether it had correlation between frequency of macrolide antibiotics irregular application and drug resistant in control group. Drug resistance, extrapulmonary complications and hospitalization time between two groups were analysis by statistics methods. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Guangdong Women and Children Hospital Affiliated Guangzhou Medical University. Informed consent was obtained from the parents of each participating participant.

Results

In this study the MP infection rate was 54.4%(431/ 792) . MP culture positive rate was 26.6% (115/ 431) in MP-IgM positive children. There had significance difference between experimental group and control group in MP resistant strain rates, and MP-resistant strain rate in experimental group were much lower than that in control group (χ2 =4.651 , P=0.041) . There had significance difference of frequency of indisciplined used of macrolide antibiotics in control group among 214 cases, and the higher frequency of indisciplined used of macrolide antibiotics, the higher rate of MP-resistant strain (χ2/χ2 trend value=22.056, 21.932; P<0.05) . A total of 14 children in experimental group whose positive culture MP antibiotics sensitivity and 23S rRNA V had no mutation were gave macrolides sequential therapy. There were 4 cases after treatment of 2 and 4 weeks, their MP acute detection results also positive. In the end of 2 and 4 weeks after macrolides sequential therapy, the curative effect was 71.42 %(10/ 14) . among of 4 cases, only one case sequencing result and shew 23S rRNA V had no mutation. Those 4 cases were gaven macrolides sequential therapy again. There were only one case after treatment of another 2 weeks MP acute detection results also positive. In the end of 4 weeks after macrolides sequential therapy, the curative effects of azithromycin sequential therapy was 92.85%(13/ 14) . There had significance difference between 14 cases positive culture MP of antibiotics sensitivity in experimental group and 37 cases MP-resistant strain in control group in incidence of extrapulmonary complications, and those incidence in experimental group was much lower than those in contral group (χ2 =4.443, P<0.05) . There had significance difference between two groups in hospitalization time, and hospitalization time in experimental group was much shorter than that in control group (χ2 =7.305, P<0.05) .

Conclusions

Azithromycin sequential therapy for children infected with MP is safe, effective, and does not induce drug resistant strains. Resistant strains can be induced by irregular application of macrolide antibiotics application, and resistance rate is positively correlated with the frequency of irregular applications them.

Key words: Pneumoniae, Mycoplasma, Drug-resistance, Azithromycin, Sequential therapy, Child
表1 两组115例肺炎支原体培养结果呈阳性患儿的药敏试验结果比较[n（％）]
Table 1 Comparison of drug resistance rates among 115 cases children with mycoplasma cuture positive samples between two groups[n（%）]
组别 n 耐药率
实验组 56 31(55.4)
对照组 49 37(75.5)
χ2 　 4.651
P 　 0.041
表2 对照组214例患儿1年内不规律用药次数与耐药率关系比较[n（%）]
Table 2 Comparison of drug resistance rates among 214 cases with irregular treatment by azithromycin in one year in control group[n（%）]
1年内不规则用药次数(次) n 耐药率
4 68 22(32.3)
3 71 13(18.3)
2 75 2 (6.6)
χ2/χ2趋势值 　 22.056/21.932
P 　 <0.05
表3 115例肺炎支原体培养结果呈阳性患儿的药敏试验结果比较[n（％）]
Table 3 Comparison of drug sensitivity among 115 cases children with mycoplasma culture positive samples [n（%）]
药物名称 敏感率 中度敏感率 耐药率
红霉素 23(22.61) 19(17.39) 63(60.10)
阿奇霉素 62(54.10) 21(17.84) 32(28.06)
罗红霉素 23(20.00) 13(11.47) 79(68.53)
克拉霉素 45(38.90) 31(27.21) 39(33.89)
乙酰螺旋霉素 23(20.41) 30(25.78) 62(55.07)
克林霉素 27(23.54) 25(21.39) 63(55.07)
左氧氟沙星 112(97.39) 1 (0.87) 2 (1.74)
加替沙星 111(96.52) 3 (2.61) 1 (0.87)
司帕沙星 113(98.26) 2 (1.74) 0 (0.00)
图1 入院时实验组肺炎支原体培养呈阳性患儿23S rRNA V区PCR产物电泳结果（电泳样本编号。1: 2＃样本；2: 4＃样本；3: 11＃样本；4: 21＃样本；5: 35 ＃样本；6: 49＃样本；7: 55＃样本；8: 79＃样本；9: takara marker；10：140＃样本；11: 144＃样本；12: 180＃样本；13: 184＃样本；14: 199＃样本；15: 203＃样本）
Figure 1 Electrophoresis results of Mycoplasma pheumoniae culture positive patients in experimental group of 23S rRNA V PCR products （Number of sample．1：sample 2 ＃；2：sample 4 ＃; 3：sample 11＃；4 ：sample 21 ＃；5 ：sample 35＃；6：sample 49＃；7：sample 55 ＃；8：sample 79 ＃；9：takara marker; 10：sample 140 ＃；11：sample 144 ＃；12：sample 180 ＃；13：sample 184 ＃；14 ：sample 199 ＃；15：sample 203 ＃）
图2 入院时实验组患儿23S rRNA V区测序结果（图2A: 55＃样本；图2B: 184＃样本）
Figure 2 The 23S rRNA V sequencing results of experimental group （Figure 2A: sample 55 ＃；Figure 2B: sample 184 ＃）
图3 治疗2周后实验组肺炎支原体培养阳性的23S rRNA V PCR产物扩增后电泳结果（电泳样本编号。1: 2＃样本；2: takara marker; 3: 79＃样本；4: 140＃样本；5: 199＃样本）
Figure 3 The 23S rRNA V PCR electrophoresis results of Mycoplasma pneamoniae culture positive in experimental group after treatment 2 weeks （Number of sample．1 ：sample 2 ＃；2 ：takara marker；3：sample 79 ＃；4：sample 140 ＃；5 ：sample 199 ＃）
图4 治疗2周后实验组肺炎支原体培养阳性患儿的23S rRNA V区测序结果（图4A: 79＃样本；图4B: 199＃样本）
Figure 4 The 23S rRNA V sequencing results of experimental groups Mycoplasma pneumoniae culture postive after treatment 2 weeks （Figure 4A：samples 79 ＃；Figure 4B：samples 199 ＃）
图5 治疗4周后实验组肺炎支原体培养阳性患儿23S rRNA V PCR产物电泳结果（电泳样本编号。1：2＃样本；2: takara marker）
Figure 5 The23S rRNA V PCR electrophoresis results of Mycoplasma pneumoniae culture positive in experimental group after treatment 4 weeks （Number of sample．1：sample 2＃；2：takara marker）
图6 治疗4周后实验组肺炎支原体培养阳性患儿的23S rRNA V区测序结果（2＃样本）
Figure 6 The 23S rRNA V sequencing result of experimental groups Mycoplasma pneumoniae culture postive after treatment 4 weeks （sample 2＃）
图7 对照组肺炎支原体培养阳性患儿23S rRNA V区PCR产物电泳结果（13, 34：takara marmer; 1~ 12, 14～27：共计26个样本23S出现A2063G突变；28～30: 3个样本23S出现A2064G突变；31～32：2个样本23S出现A2063C突变；33, 35：2个样本23S出现A2063T突变；36~ 38：3个样本23S出现G2062A突变；39: 1个样本23S出现C2617G突变）
Figure 7 The 23S rRNA V PCR electrophoresis results of Mycoplasma pneumoniae culture positive in control group （13, 34：takara marmer；1-12，14-27：a total of 26 samples A2063G mutation in 23S rRNA V zone；28-30: 3 samples A2064G mutation in 23S rRNA V zone；31-32：2 samples A2063C mutation in 23S rRNA V zone；33，35：2 samples A2063Tmutation in 23S rRNA V zone；36-38: 3samples G2062A mutation in 23S rRNA V zone; 39: 1 sample C2617G mutation in 23S rRNA V zone）
图8 对照组37个样本23S rRNA V区突变测序结果（图8A:1#样本；图8B:33#样本；图8C:56#样本；箭头所指为突变位点）
Figure 8 The sequencing result of A2063G mutation in 23S rRNA V zone of 37 samples in control group(Figure 8A：samples 1 # ；Figure 8B：samples 33 # ；Figure 8C： samples 56 # ； mutations showed by arrows)
图9 对照组3个样本23S rRNA V区突变测序结果（图9A: 7＃样本；图9B：174＃样本；箭头所指为突变位点）
Figure 9 The sequencing result of A2064G mutiation in 23S rRNA V zone of 3 samples in control group(Figure 9A：sample 7＃；Figure 9B：sample 174 ＃；mutations showed by arrows）
图10 对照组2个样本23S rRNA V区突变测序结果（197＃样本；箭头所指为突变位点）
Figure 10 The sequencing result A2064C mutiation in 23S rRNA V zone of 2 samples in control group(sample 197 ＃；mutations showed by arrows）
图11 对照组2个样本23S rRNA V区突变测序结果（243 ＃样本；箭头所指为突变位点）
Figure 11 The sequencing result A2063T mutiation in 23S rRNA V zone of 2 samples in control group(sample 243＃；mutations showed by arrows）
图12 对照组3个样本23S rRNA V区突变测序结果（图12a: 10＃样本；图12b: 175＃样本；箭头所指为突变位点）
Figure 12 The sequencing result G2062A mutiation in 23S rRNA V zone of 37 samples in control group(Figure 12a：sample 10＃；Figure 12b: sample 175 ＃；mutations showed by arrows）
图13 实验组2个样本23S rRNA V区突变测序结果（256＃样本；箭头所指为突变位点）
Figure 13 The sequencing result C2617G mutiation in 23S rRNA V zone of 1 sample in experimental group(sample 256＃；mutations showed by arrows）
表4 实验组25例MP药物敏感株与对照组37例MP耐药株患儿的肺外并发症发生率比较[n（%）]
Table 4 Comparison of the complication between 14 cases drug sensitivity samples in experimental group and 37 cases drug resistant samples in control group[n（%）]
组别 n 肺外并发症发生率
实验组 25 1 (4.0)
对照组 37 16(43.2)
χ2 　 4.443
P 　 <0.05
表5 实验组与对照组患儿的住院时间比较（±s）
Table 5 Comparison of the hospitalization time between two groups （±s）
组别 n 住院平均时间(d)
实验组 217 7.71±1.35
对照组 214 11.91±1.97
χ2 　 7.305
P 　 <0.05
[1]
Atkinson TP，Balish MF，Waites KB．Epidemiology，clinical manifestations，pathogenesis and laboratory detection of Mycoplasma pneumoniae infections[J]．FEMS Microbiol Rev，2008，32(6):956-973．
[2]
Spuesens EB，Meijer A，Bierschenk D，et al．Macrolide resistance determination and molecular typing of Mycoplasma pneumoniae in respiratory specimens collected between 1997 and 2008 in Netherlands[J]．J Clin Microbiol，2012，50(6):1999-2004．
[3]
Morozumi M，Takahashi T，Ubukata K．Macrolide-resistant Mycoplasma pneumoniae：characteristics of isolates and clinical aspects of community-acquired pneumonia [J]．J Infect Chemother，2010，16(2):78-86．
[4]
Liu Y，Ye X，Zhang H，et al．Antimicrobial susceptibility of Mycoplasma pneumoniae isolates and molecular analysis of macrolide-resistant strains from Shanghai，China[J]．Antimicrob Agent Chemother，2009，53(5):2160-2162．
[5]
Zhao F，Lyu M，Tao X，et al．Antibiotic sensitivity of 40 Mycoplasma pneumoniae isolates and molecular analysis of macrolide-resistant isolates from Beijing，China[J]．Antimicrob Agents Chemother，2012，56(2):1108-1109．
[6]
史大伟．阿奇霉素体外诱导肺炎支原体耐药的研究[M]．北京：首都医科大学出版社，2010, 1-49．
[7]
Matsuoka M，Narita M，Okazaki N，et al．Characterization and molecular analysis of macrolide resistant Mycoplasma pneumoniae clinical isolates obtained in Japan [J]．Antimicrib Agent Chemother，2004，45(8):617-620．
[8]
Hirai Y，Shiode J，Masayoshi T，et al．Application of an indirect immunofluorescence test for detection of Mycoplasma pneumoniae in respiratory exudates[J]．J Clin Microbiol，1991，29(9):2007-2012．
[9]
Matsuoka M，Narita M，Okazaki N，et al．Characterization and molecular analysis of macrolide resistant Mycoplasma pneumoniae clinical isolates obtained in Japan [J]．Antimicrib Agent Chemother，2004，45(8):617-620．
[10]
吴茜，温柏平，李杨方，等．1 402例小儿急性下呼吸道感染多病原学临床研究[J/CD]．中华妇幼临床医学杂志：电子版，2012，8(3):312-316．
[11]
舒兆秋，廖蕴宏，任风光．武汉市青山地区儿童肺炎支原体感染的流行病学分析[J/CD]．中华妇幼临床医学杂志：电子版，2008，4(3):221-224．
[12]
Peters J，Singh H，Brooks E G，et al．Persistence of community-acquired respiratory distress syndrome toxin-producing Mycoplasma pneumoniae in refractory asthma[J]．Chest，2011，140(2):401-407．
[13]
马红秋，付晓燕，刘禧杰，等．儿童肺炎支原体肺炎肺外并发症的发生与耐药的关系[J]．河北医药，2010，32(24):3445-3446．
[14]
成智．儿童重症肺炎支原体肺炎研究进展[J]．国际儿科学杂志，2012，39(1):92-95．
[15]
李昌崇　 林立．儿童肺炎常见细菌病原及耐药现状[J/CD]．中华妇幼临床医学杂志：电子版，2010，6(5):308-314．
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