Objective  To evaluate the impact of different dosing times of doxycycline (DOX) on children with macrolide-resistant Mycoplasma pneumoniae pneumonia (MR-MPP).

Methods  Clinical data of children diagnosed with MR-MPP at Hangzhou Children's Hospital from January 2022 to December 2023 were analyzed. Children were divided into three groups based on treatment regimens: the doxycycline (DOX) group, the intravenous azithromycin converted to oral DOX (ATD) group, and the intravenous azithromycin alone (AZI) group.. The ATD group was further divided into ATD1 group (<3 days) and ATD2 group (≥3 days) according to the duration of azithromycin treatment. Clinical symptoms of each group were compared, and propensity score matching (PSM) analysis was used for adjustment.

Results  A total of 156 children with MR-MPP were included in the study, with 25 in the DOX group, 85 in the ATD group, and 46 in the AZI group. Compared with the ATD and AZI groups, the DOX group had a shorter hospital stay and fever duration, higher chest radiograph improvement rate, and lower glucocorticoid usage rate (P<0.05). The DOX group and ATD1 group had lower hospital stays, post-treatment fever durations, and glucocorticoid usage rates than the ATD2 group, and higher 96-hour fever resolution rates and chest X-ray improvement rates than the ATD2 group (P<0.05). The DOX group had a higher fever resolution rate within 72 hours compared to the ATD1 and ATD2 groups (P<0.05). PSM analysis showed that the DOX-ATD1 group had a lower hospital stay, post-treatment fever duration, and glucocorticoid usage rate than the ATD2 group, and a higher 72-hour fever resolution rate than the ATD2 group (all P<0.05). No adverse reactions related to DOX were observed during the treatment period.

Conclusion  Early oral administration of DOX within 72 hours can significantly improve the clinical efficacy in children with MR-MPP.

1.冯伟静, 陈建, 董泽伍. 痰热清联合甲泼尼龙治疗小儿重症支原体肺炎患者的疗效[J]. 西部医学, 2023, 35(12): 1813-1816. [Feng WJ, Chen J, Dong ZW. Efficacy of sputum reqing combined with methylprednisolone in pediatric patients with severe mycoplasma pneumonia[J]. Medical Journal of West China, 2023, 35(12): 1813-1816.] DOI: 10.3969/j.issn.1672-3511.2023.12.018.

2.孙小野. 许昌地区不同年龄段小儿肺炎支原体肺炎临床特点分析[J]. 数理医药学杂志, 2022, 35(4): 542-544. [Sun XY. Analysis of clinical characteristics of Mycoplasma pneumoniae in children of different ages in Xuchang[J]. Journal of Mathematical Medicine, 2022, 35(4): 542-544.] DOI: 10.3969/j.issn.1004-4337.2022.04.023.

3.Zhou Y, Zhang Y, Sheng Y, et al. More complications occur in macrolide-resistant than in macrolide-sensitive Mycoplasma pneumoniae pneumonia[J]. Antimicrob Agents Chemother, 2014, 58(2): 1034-1038. DOI: 10.1128/AAC.01806-13.

4.Izumikawa K, Izumikawa K, Takazono T, et al. Clinical features, risk factors and treatment of fulminant Mycoplasma pneumoniae pneumonia: a review of the Japanese literature[J]. J Infect Chemother, 2014, 20(3): 181-185. DOI: 10.1016/j.jiac.2013.09.009.

5.Kim K, Jung S, Kim M, et al. Global trends in the proportion of macrolide-resistant mycoplasma pneumoniae infections: a systematic review and Meta-analysis[J]. JAMA Netw Open, 2022, 5(7): e2220949. DOI: 10.1001/jamanetworkopen.2022.20949.

6.Okada T, Morozumi M, Tajima T, et al. Rapid effectiveness of minocycline or doxycycline against macrolide-resistant Mycoplasma pneumoniae infection in a 2011 outbreak among Japanese children[J]. Clin Infect Dis, 2012, 55(12): 1642-1649. DOI: 10.1093/cid/cis784.

7.陈燕芬, 余兴华, 杨帆. 阿奇霉素、多西环素静脉滴注治疗小儿肺炎支原体肺炎临床对比观察[J]. 山东医药, 2024, 64(24): 92-96. [Chen YF, Yu XH, Yang F. Clinical comparison of azithromycin and doxycycline for mycoplasma pneumoniae in children[J]. Shandong Medical Journal, 2024, 64(24): 92-96.] DOI: 10.3969/j.issn.1002-266X.2024.24.022.

8.崔雪琴, 韩国宏, 任启波. 多西环素治疗阿奇霉素耐药儿童肺炎支原体肺炎的效果[J]. 中华医院感染学杂志, 2024, (20): 3108-3112. [Cui XQ, Han GH, Ren QB. Effect of doxycycline in the treatment of Mycoplasma pneumoniae pneumonia in azithromycin-resistant children[J]. Chinese Journal of Hospital Infecology, 2024(20): 3108-3112.] http://kns.cnki.net/kcms/detail/11.3436.R.20240904.1030.026.html.

9.朱美君, 宋磊, 周峰, 等. 23S rRNA基因突变与儿童肺炎支原体耐药机制相关性[J]. 海南医学, 2018, 29(3): 365-368. [Zhu MJ, Song L, Zhou F, et al. 23 Association between S rRNA gene mutations and drug resistance mechanisms of M. pneumoniae in children[J]. Hainan Medical Journal, 2018, 29(3): 365-368.] DOI: 10.3969/j.issn.1003-6350.2018.03.020.

10.Li H, Li S, Yang H, et al. Resurgence of Mycoplasma pneumonia by macrolide-resistant epidemic clones in China[J]. Lancet Microbe, 2024, 5(6): e515. DOI: 10.1016/S2666-5247(23)00405-6.

11.陈锋, 张芙蓉. 儿童难治性肺炎支原体肺炎的早期临床特点及相关危险因素[J]. 中国热带医学, 2024, 24(7): 777-782. [Chen F, Zhang FR. Early clinical characteristics and associated risk factors of refractory M. pneumoniae pneumonia in children[J]. China Tropical Medicine, 2024, 24(7): 777-782.] DOI: 10.13604/j.cnki.46-1064/r.2024.07.04.

12.翟培珺, 许敏凡, 李悦铭, 等. 无锡地区2021-2023年肺炎支原体药敏分析[J]. 中国卫生标准管理, 2024, 15(11): 95-98. [Zhai PJ, Xu MF, Li YM, et al. Drug susceptibility analysis of M. pneumoniae in Wuxi region during 2021-2023[J]. China Health Standard Management, 2024, 15(11): 95-98.] DOI: 10.3969/j.issn.1674-9316. 2024.11.023.

13.周云连, 倪晨. 儿童肺炎支原体对大环内酯类抗菌药物的耐药现状及抗菌药物治疗的研究进展[J]. 浙江医学, 2024, 46(12): 1233-1238. [Zhou JL, Ni C. Current status of macrolide antimicrobial resistance against Mycoplasma pneumoniae and research progress of antimicrobial therapy in children[J]. Zhejiang Medical Journal, 2024, 46(12): 1233-1238.] DOI: 10.12056/j.issn.1006-2785. 2024.46.12.2024-918.

14.王晶, 李新民, 韩耀巍, 等. 肺炎支原体的致病机制及中药治疗儿童肺炎支原体感染的研究进展[J]. 天津中医药大学学报, 2022, 41(4): 513-520. [Wang J, Li XM, Han YW, et al. Progress on the pathogenic mechanism of M. pneumoniae and the treatment of traditional Chinese medicine for M. pneumoniae infection in children[J]. Journal of Tianjin University of Traditional Chinese Medicine, 2022, 41(4): 513-520.] DOI: 10.11656/j.issn.1673-9043.2022.04.20.

15.Lee H, Choi YY, Sohn YJ, et al. Clinical efficacy of doxycycline for treatment of macrolide-resistant mycoplasma pneumoniae pneumonia in children[J]. Antibiotics (Basel), 2021, 10(2): 192. DOI: 10.3390/antibiotics10020192.

16.Chen Y, Zhang Y, Tang QN, et al. Efficacy of doxycycline therapy for macrolide-resistant Mycoplasma pneumoniae pneumonia in children at different periods[J]. Ital J Pediatr, 2024, 50(1): 38. DOI: 10.1186/s13052-024-01615-y.

17.王兰, 吴良霞. 儿童大环内酯类耐药肺炎支原体感染研究进展[J]. 上海交通大学学报(医学版), 2015, 35(5): 780-784. [Wang L, Wu L.. Progress in macrolide-resistant Mycoplasma pneumoniae infection in children[J]. Journal of Shanghai Jiaotong University (Medical Science) , 2015, 35(5): 780-784.] DOI: 11.3969/j.issn. 1674-8115.2015.05.030.

18.Yang EA, Kang HM, Rhim JW, et al. Early corticosteroid therapy for mycoplasma pneumoniae pneumonia irrespective of used antibiotics in children[J]. J Clin Med, 2019, 8(5): 726. DOI: 10.3390/jcm8050726.

19.Gavrilovic S, Andrijevic A, Mujakovic A, et al. Adjunct corticosteroid treatment in patients with pneumonia: A precision medicine approach[J]. Bosn J Basic Med Sci, 2019, 19(4): 315-320. DOI: 10.17305/bjbms.2019.3977.