Allergy Asthma Respir Dis.  2018 Jan;6(1):62-67. 10.4168/aard.2018.6.1.62.

Clinical analysis of risk factors in refractory mycoplasma pneumonia in children

• Choi SY
• Seo JH
• Lee K
• Choi Q

• KMID: 2403187
• DOI: http://doi.org/10.4168/aard.2018.6.1.62

Abstract

PURPOSE
Refractory Mycoplasma pneumonia (RMP) has been increasing not only in Korea but worldwide. We investigated the incidence of M. pneumonia resistant to macrolides and risk factors for RMP.
METHODS
From October 2015 to May 2016, 62 pediatric patients who were admitted due to pneumonia diagnosed on the basis of chest x-ray with respiratory symptoms and positive for M. pneumoniae in polymerase chain reaction with no evidence of other bacterial or viral infections were included. Sequence analysis of the 23S rRNA gene in M. pneumoniae was performed to identify macrolide resistance. Patients with congenital anomalies, history of pulmonary disease, and unclear information on antibiotic use were excluded.
RESULTS
Mutations in the 23S rRNA gene were detected in 50 of 62 patients (80.6%). Risk factors were analyzed in only 45 patients. The RMP group consisted of 26 patients (57.8%) who had fever lasting more than 5 days and deteriorating chest x-ray findings. The lactate dehydrogenase (LDH) and C-reactive protein (CRP) levels were significantly higher in the RMP group than in the non-RMP group (LDH: 300±79 U/L vs. 469±206 U/L, CRP: 4.9±4.3 mg/dL vs. 2.5±1.7 mg/dL; P = 0.04 vs. P = 0.026). In univariate analysis, the RMP group was significantly associated with 23S rRNA gene mutation, lobar pneumonia, and pleural effusion (odds ration [OR]: 10.8, 4.1, 5.3; P = 0.004, P = 0.036, P = 0.046). The presence of macrolide resistance was found to be only a significant risk factor in logistic regression (OR; 8.827; 95% confidence interval, 1.376-56.622; P = 0.022).
CONCLUSION
Macrolide resistance was a significant risk factor in patients with RMP and identification of macrolide resistance might be helpful in predicting RMP and establishing target therapy for RMP.

Keyword

Mycoplasma; Refractory; Mutation; Resistant; Child

MeSH Terms

C-Reactive Protein
Child*
Fever
Genes, rRNA
Humans
Incidence
Korea
L-Lactate Dehydrogenase
Logistic Models
Lung Diseases
Macrolides
Mycoplasma*
Pleural Effusion
Pneumonia
Pneumonia, Mycoplasma*
Polymerase Chain Reaction
Risk Factors*
Sequence Analysis
Thorax
C-Reactive Protein
L-Lactate Dehydrogenase
Macrolides

Figure

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  Fig. 1. The schematic outline of study. PCR, polymerase chain reaction.

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  Fig. 2. Electropherogram shows the point mutation A2063G in domain V of 23S rRNA.

Reference

1. 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.

2. Kim JW, Seo HK, Yoo EG, Park SJ, Yoon SH, Jung HY, et al. Mycoplasma pneumoniae pneumonia in Korean children, from 1979 to 2006: a metaanalysis. Korean J Pediatr. 2009; 52:315–23.

3. Shin JE, Cheon BR, Shim JW, Kim DS, Jung HL, Park MS, et al. Increased risk of refractory Mycoplasma pneumoniae pneumonia in children with atopic sensitization and asthma. Korean J Pediatr. 2014; 57:271–7.

4. You SY, Jwa HJ, Yang EA, Kil HR, Lee JH. Effects of methylprednisolone pulse therapy on refractory Mycoplasma pneumoniae pneumonia in children. Allergy Asthma Immunol Res. 2014; 6:22–6.

5. Shah SS, Test M, Sheffler-Collins S, Weiss AK, Hall M. Macrolide therapy and outcomes in a multicenter cohort of children hospitalized with Mycoplasma pneumoniae pneumonia. J Hosp Med. 2012; 7:311–7.

6. Kawai Y, Miyashita N, Yamaguchi T, Saitoh A, Kondoh E, Fujimoto H, et al. Clinical efficacy of macrolide antibiotics against genetically determined macrolide-resistant Mycoplasma pneumoniae pneumonia in paediatric patients. Respirology. 2012; 17:354–62.

7. Wang M, Wang Y, Yan Y, Zhu C, Huang L, Shao X, et al. Clinical and laboratory profiles of refractory Mycoplasma pneumoniae pneumonia in children. Int J Infect Dis. 2014; 29:18–23.

8. Zhang Y, Zhou Y, Li S, Yang D, Wu X, Chen Z. The clinical characteristics and predictors of refractory Mycoplasma pneumoniae pneumonia in children. PLoS One. 2016; 11:e0156465.

9. Principi N, Esposito S. Macrolide-resistant Mycoplasma pneumoniae: its role in respiratory infection. J Antimicrob Chemother. 2013; 68:506–11.

10. Xin D, Mi Z, Han X, Qin L, Li J, Wei T, et al. Molecular mechanisms of macrolide resistance in clinical isolates of Mycoplasma pneumoniae from China. Antimicrob Agents Chemother. 2009; 53:2158–9.

11. 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.

12. 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.

13. 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.

14. Lu A, Wang C, Zhang X, Wang L, Qian L. Lactate dehydrogenase as a biomarker for prediction of refractory Mycoplasma pneumoniae pneumonia in children. Respir Care. 2015; 60:1469–75.

15. Matsuoka M, Narita M, Okazaki N, Ohya H, Yamazaki T, Ouchi K, et al. Characterization and molecular analysis of macrolide-resistant Mycoplasma pneumoniae clinical isolates obtained in Japan. Antimicrob Agents Chemother. 2004; 48:4624–30.

16. Oh CE, Choi EH, Lee HJ. Detection of genetic mutations associated with macrolide resistance of Mycoplasma pneumoniae. Korean J Pediatr. 2010; 53:178–83.

17. Kim JH, Kim JY, Yoo CH, Seo WH, Yoo Y, Song DJ, et al. Macrolide resistance and its impacts on M. peumoniae pneumonia in children: comparison of two recent epidemics in Korea. Allergy Asthma Immunol Res. 2017; 9:340–6.

18. Yu J. Clinical issues regarding increased macrolide-resistant Mycoplasma pneumoniae in children. Allergy Asthma Respir Dis. 2017; 5:1–2.

19. Morozumi M, Okada T, Tajima T, Ubukata K, Iwata S. Killing kinetics of minocycline, doxycycline and tosufloxacin against macrolide-resistant Mycoplasma pneumoniae. Int J Antimicrob Agents. 2017; 50:255–7.

20. Shan LS, Liu X, Kang XY, Wang F, Han XH, Shang YX. Effects of methylprednisolone or immunoglobulin when added to standard treatment with intravenous azithromycin for refractory Mycoplasma pneumoniae pneumonia in children. World J Pediatr. 2017; 13:321–7.