In the present study, we investigated and compared the laboratory test results, imaging results from chest CT and treatment results between MMP patients caused by MRMP and MSMP. We found that MRMP patients could be more difficult to treat because of their longer hospitalization duration, greater frequency of second-line antibiotic use and bronchoscope use; additionally, MRMP could be more severe because of its greater inflammatory markers, including CRP and LDH levels and D-dimer levels, and greater rate of lung consolidation.
The tests for M. pneumoniae infection include culture, serologic tests and PCR; among these tests, RT–PCR is the most reliable because of its high accuracy and speed and because it can be used for current infection tests[16]. Therefore, we applied an RNA test for the detection of M. pneumoniae infection in our study. The macrolide resistance of M. pneumoniae was diagnosed by RT‒PCR tests targeting the A2063G and A2064G mutations, which account for nearly all macrolide resistance-associated mutations in China and are correlated with a high level of macrolide resistance[17-18]. Lung consolidation has predictive value in RMPP[19], and the rate of lung consolidation observed in patients with MPP caused by MRMP was greater than that in patients with MSMP, suggesting that MRMP was more likely to lead to RMPP.
The prevalence of MRMP has placed a serious burden on the health of children, which could cause prolonged fever and radiological progression. MRMP is the main cause of increased RMPP in children. Due to the decreased efficacy of conventional macrolide antibiotics and increased pathogen load, the body will experience an excessive immune response to pathogens, which results in damage[4]. The inflammatory markers CRP and LDH were increased in MRMP-infected patients, which could reflect the increased intensity of inflammation caused by MRMP. According to the study by Jeong JE et al.[20], the levels of CRP and LDH were greater in MPP patients with prolonged fever, which was similar to our findings in MRMP patients with longer disease courses. D-dimer levels are closely related to the inflammatory response and may reflect the coagulation status of infectious diseases[21]. D-dimer levels are usually greater in severe MMP patients than in mild patients, and elevated serum D-dimer levels might be used as an indicator of the severity of MPP[22]. The D-dimer levels in MRMP-infected MPP patients were greater than those in MPP patients caused by MSMP, suggesting that MRMP could cause more severe MPP than MSMP. We found no significant differences in WBC, NEUT or LYM counts between MRMP- and MSMP-infected MPP patients, suggesting that the WBC count and differentiation status were not correlated with the MRMP or the severity of MPP, which was in accordance with the findings of previous studies by Fan F et al.[19].
A bronchoscope was used for the treatment of the majority of the MPP patients in our study. Due to the self-limiting nature of MPP, bronchoscopy is an effective procedure for treating this disease, and it can aid in the relief of symptoms and recovery of patients. A bronchoscope was regularly used for the treatment of MPP patients in our study, especially for patients with MRMP-caused MPP, suggesting the important clinical value of bronchoscopy. There were more hospitalization days for MPP patients caused by MRMP than for MSMP patients; therefore, MRMP could increase the disease course during treatment, and these results are consistent with those of a previous study by Yang HJ et al.[23]. Corticosteroids are immune modulators used to treat MPP, and they can be used to control lung injuries caused by initial hyperactive immune reactions. Therefore, corticosteroids were used for most of the MPP patients (MRMP or MSMP) in our study. The effect of corticosteroids on immune cells is dose dependent, and the dose of corticosteroids can be adjusted according to the severity of disease[16]. Although the possibility of adverse effects in the future may exist, alternative antibiotics, including doxycycline and levofloxacin, were frequently used based on consideration of the disease severity and the agreement of the guardians of the patients in our study. The selection of second-line antibiotics was mainly based on the age of the patients in our study, but further studies are needed to compare the effects of these two kinds of alternative antibiotics. In our study, the frequency of second-line antibiotic use was greater in MRMP-caused MPP patients than in MSMP patients, supporting the reduced effect of macrolides in the treatment of MRMP infections. However, interestingly, no alternative antibiotics to azithromycin were used in 14 of the 50 MRMP-related MPP patients; similarly, 26 of the 55 MSMP patients were treated with alternative antibiotics. Macrolide has anti-inflammatory and immunoregulatory functions, suggesting that it is effective in the treatment of some MRMP-infected patients[16]. Alternative antibiotics were used in MSMP patients when macrolide use did not improve their condition or when the pneumonia worsened. The decrease in the effect of macrolides in the treatment of MSMP patients might be because macrolide resistance developed during macrolide treatment, which has been confirmed in previous studies[24]. However, the degree to which macrolide resistance develops and the duration of macrolide resistance development during macrolide treatment require additional studies.
There are several limitations to our study. Although A2063G and A2064G are the predominant mutations associated with macrolide resistance and almost no other mutations have been discovered in this district, the possibility that other macrolide resistance-associated mutations might exist during our study and might influence our diagnosis and treatment cannot be excluded.