Pediatric Infection and Vaccine

The Korean Society of Pediatric Infectious Diseases (대한소아감염학회)
권호 표지
DOI QR코드

DOI QR Code

Clinical Features and Associated Factors of Macrolide-Unresponsive Mycoplasma pneumonia and Efficacy Comparison Between Doxycycline, Tosufloxacin and Corticostreoid as a Second-Line Treatment

마크로라이드 불응성 마이코플라즈마 폐렴의 임상 양상 및 연관 인자와 2차 치료제로서 doxycycline, tosufloxacin 및 corticosteroid의 효능 비교

  • Received : 2021.10.30
  • Accepted : 2024.04.04
  • Published : 2024.04.25
Download PDF
⟨ Previous Next ⟩

Abstract

Purpose: This study aimed to examine the clinical features and determinants of macrolide-unresponsive Mycoplasma pneumoniae pneumonia (MUMP) and to assess the differences in the time to fever resolution between doxycycline (DXC), tosufloxacin (TFX) and corticosteroid (CST) as second-line treatment. Methods: We retrospectively analyzed the medical records of patients under the age of 18 who were admitted to Nowon Eulji University Hospital between July 2018 and February 2020, diagnosed with mycoplasma pneumonia. Macrolide resistance was confirmed by detecting point mutations in the 23S rRNA gene. MUMP was clinically defined by persistent fever (≥38.0℃) lasting for 72 hours or more after the initiation of macrolide treatment. In cases of MUMP, patients were treated with an addition of CST, or the initial macrolide was replaced either DXC or TFX. Results: Out of 157 cases of mycoplasma pneumonia, 83 cases (52.9%) did not respond to macrolides. Patients with MUMP exhibited significantly higher C-reactive protein (CRP) levels (3.2±3.0 vs. 2.4±2.2 mg/dL, P=0.047), more frequent lobar/segmental infiltrations or pleural effusions (56.6% vs. 27.0%, P<0.001; 6.0% vs. 0.0%, P=0.032), and a higher prevalence of 23S rRNA gene mutations (96.4% vs. 64.6%, P<0.001) when compared to those with macrolide-susceptible M. pneumoniae pneumonia. In terms of second-line treatment, 15 patients (18.1%) responded to CST, 30 (36.1%) to DXC, and 38 (45.8%) to TFX. The time to defervescence (TTD) after initiation second-line treatment was significantly shorter in the CST group compared to the DXC (10.3±12.7 vs. 19.4±17.2 hours, P=0.003) and TFX groups (10.3±12.7 vs. 25.0±20.1 hours, P=0.043), with no significant difference observed between the DXC and TFX groups (19.4±17.2 vs. 25.0±20.1 hours, P=0.262). Conclusions: High CRP levels, the presence of positive 23S rRNA gene mutation, lobar or segmental lung infiltration, and pleural effusion observed in chest X-ray findings were significant factors associated with macrolide unresponsiveness. In this study, CST demonstrated a shorter TTD compared to DXC or TFX. Further, larger-scale prospective studies are needed to determine the optimal second-line treatment for MUMP.

목적: 본 연구는 마크로라이드 불응성 마이코플라즈마 폐렴(macrolide-unresponsive Mycoplasma pneumoniae pneumonia, MUMP)의 임상 양상 및 관련 인자와 2차 치료제로서 doxycycline (DXC), tosufloxacin (TFX) 및 corticosteroid (CST) 사용 후 해열되는 데까지 걸리는 시간의 차이를 평가하고자 하였다. 방법: 2018년 7월부터 2020년 2월까지 노원을지대학교병원에 발열 및 호흡기 증상과 함께 흉부 엑스선 상 폐렴 소견이 있어 입원하여 마이코플라즈마 폐렴으로 진단받은 18세 이하의 환자들의 의무기록을 후향적으로 분석하였다. M. pneumoniae의 23S 리보솜 RNA (23S rRNA) 유전자의 점 돌연변이 유무로 마크로라이드 내성을 확인하였다. MUMP는 마크로라이드계 항생제 치료 개시 후 72시간 이상 발열(≥38.0℃)이 지속된 경우로 임상적으로 정의하였다. MUMP의 경우, CST를 추가한 군과 이차 항생제인 DXC 또는 TFX로 변경한 군으로 구분하였다. 결과: 총 157명의 마이코플라즈마 폐렴 환자 중 MUMP 군은 83명(52.9%)이었으며, C-반응단백(C-reactive protein, CRP)의 상승(3.2±3.0 vs. 2.4±2.2 mg/dL, P=0.047), 흉부 X-선상 대엽/분절성 폐렴, 흉수(56.6% vs. 27.0%, P<0.001; 6.0% vs. 0.0%, P=0.032) 그리고 23S rRNA 유전자의 점 돌연변이(96.4% vs. 64.6%, P<0.001) 가 MUMP와 유의한 연관성을 보였다. MUMP 군 83명 중 30명(36.1%)은 DXC로, 38명(45.8%)은 TFX로 항생제를 변경하였고 15명(18.1%)은 CST를 추가하였다. 2차 치료로 변경 이후 발열 호전까지 걸린 평균 시간을 각 군별로 비교하였을 때 CST 군이 DXC, TFX 군보다 발열 호전까지의 시간이 유의하게 짧았고(10.3±12.7 vs. 19.4±17.2 시간, P=0.043; 10.3±12.7 vs. 25.0±20.1 시간, P=0.003), DXC 군과 TFX 군 사이에는 유의한 차이를 보이지 않았다(19.4±17.2 vs. 25.0±20.1 시간, P=0.262). 결론: CRP의 높은 상승과 흉부 X-선 상 대엽/분절성 폐렴 및 흉막 삼출, 그리고 23S rRNA A2063G 점 돌연변이가 마크로라이드 불응성과 유의한 연관이 있었다. CST 환자군에서 DXC나 TFX 환자군에 비하여 더 빠른 발열 호전을 보였다. 향후 MUMP에 대한 최적의 2차 치료제를 결정하기 위해 더 큰 규모의 전향적 연구가 필요하다.

Keywords

References

  1. Lee E, Cho HJ, Hong SJ, Lee J, Sung H, Yu J. Prevalence and clinical manifestations of macrolide resistant Mycoplasma pneumoniae pneumonia in Korean children. Korean J Pediatr 2017;60:151-7. https://doi.org/10.3345/kjp.2017.60.5.151
  2. Kim EK, Youn YS, Rhim JW, Shin MS, Kang JH, Lee KY. Epidemiological comparison of three Mycoplasma pneumoniae pneumonia epidemics in a single hospital over 10 years. Korean J Pediatr 2015;58:172-7.  https://doi.org/10.3345/kjp.2015.58.5.172
  3. Chan ED, Welsh CH. Fulminant Mycoplasma pneumoniae pneumonia. West J Med 1995;162:133-42.
  4. Principi N, Esposito S. Macrolide-resistant Mycoplasma pneumoniae: its role in respiratory infection. J Antimicrob Chemother 2013;68:506-11. https://doi.org/10.1093/jac/dks457
  5. Cheong KN, Chiu SS, Chan BW, To KK, Chan EL, Ho PL. Severe macrolide-resistant Mycoplasma pneumoniae pneumonia associated with macrolide failure. J Microbiol Immunol Infect 2016;49:127-30. https://doi.org/10.1016/j.jmii.2014.11.003
  6. Tong L, Huang S, Zheng C, Zhang Y, Chen Z. Refractory Mycoplasma pneumoniae pneumonia in children: early recognition and management. J Clin Med 2022;11:2824.
  7. Luo Z, Luo J, Liu E, Xu X, Liu Y, Zeng F, et al. Effects of prednisolone on refractory mycoplasma pneumoniae pneumonia in children. Pediatr Pulmonol 2014;49:377-80. https://doi.org/10.1002/ppul.22752
  8. Peuchant O, Menard A, Renaudin H, Morozumi M, Ubukata K, Bebear CM, et al. Increased macrolide resistance of Mycoplasma pneumoniae in France directly detected in clinical specimens by real-time PCR and melting curve analysis. J Antimicrob Chemother 2009;64:52-8. https://doi.org/10.1093/jac/dkp160
  9. The Korean Academy of Pediatric Allergy and Respiratory Disease; The Korean Society of Pediatric Infectious Diseases. Guidelines for treating macrolide refractory severe mycoplasma pneumonia in children -2019-. Seoul: The Korean Academy of Pediatric Allergy and Respiratory Disease, The Korean Society of Pediatric Infectious Diseases; 2020.
  10. Hong KB, Choi EH, Lee HJ, Lee SY, Cho EY, Choi JH, et al. Macrolide resistance of Mycoplasma pneumoniae, South Korea, 2000-2011. Emerg Infect Dis 2013;19:1281-4. https://doi.org/10.3201/eid1908.121455
  11. Yoo SJ, Kim HB, Choi SH, Lee SO, Kim SH, Hong SB, et al. Differences in the frequency of 23S rRNA gene mutations in Mycoplasma pneumoniae between children and adults with community-acquired pneumonia: clinical impact of mutations conferring macrolide resistance. Antimicrob Agents Chemother 2012;56:6393-6. https://doi.org/10.1128/AAC.01421-12
  12. Yen MH, Yan DC, Wang CJ, Tsao KC, Huang YC, Cheng SW, et al. The clinical significance of and the factors associated with macrolide resistance and poor macrolide response in pediatric Mycoplasma pneumoniae infection: a retrospective study. J Microbiol Immunol Infect 2023;56:634-40. https://doi.org/10.1016/j.jmii.2023.01.010
  13. Ha SG, Oh KJ, Ko KP, Sun YH, Ryoo E, Tchah H, et al. Therapeutic efficacy and safety of prolonged macrolide, corticosteroid, doxycycline, and levofloxacin against macrolide-unresponsive Mycoplasma pneumoniae pneumonia in children. J Korean Med Sci 2018;33:e268.
  14. Ahn JG, Cho HK, Li D, Choi M, Lee J, Eun BW, et al. Efficacy of tetracyclines and fluoroquinolones for the treatment of macrolide-refractory Mycoplasma pneumoniae pneumonia in children: a systematic review and meta-analysis. BMC Infect Dis 2021;21:1003.
  15. Zhou Y, Wang J, Chen W, Shen N, Tao Y, Zhao R, et al. Impact of viral coinfection and macrolide-resistant mycoplasma infection in children with refractory Mycoplasma pneumoniae pneumonia. BMC Infect Dis 2020;20:633.