Background: Mycoplasma pneumoniae (M. pneumoniae) is a significant contributor to community-acquired pneumonia among children. Since 1968, when a strain of M. pneumoniae resistant to macrolide antibiotics was initially reported in Japan, macrolide-resistant M. pneumoniae (MRMP) has been documented in many countries worldwide, with varying incidence rates. MRMP infections lead to a poor response to macrolide antibiotics, frequently resulting in prolonged fever, extended antibiotic treatment, increased hospitalization, intensive care unit admissions, and a significantly higher proportion of patients receiving glucocorticoids or second-line antibiotics. Since 2000, the global incidence of MRMP has gradually increased, especially in East Asia, which has posed a serious challenge to the treatment of M. pneumoniae infections in children and attracted widespread attention from pediatricians. However, there is still no global consensus on the diagnosis and treatment of MRMP in children. Methods: We organized 29 Chinese experts majoring in pediatric pulmonology and epidemiology to write the world’s first consensus on the diagnosis and treatment of pediatric MRMP pneumonia, based on evidence collection. The evidence searches and reviews were conducted using electronic databases, including PubMed, Embase, Web of Science, CNKI, Medline, and the Cochrane Library. We used variations in terms for “macrolide-resistant”, “Mycoplasma pneumoniae”, “MP”, “M. pneumoniae”, “pneumonia”, “MRMP”, “lower respiratory tract infection”, “Mycoplasma pneumoniae infection”, “children”, and “pediatric”. Results: Epidemiology, pathogenesis, clinical manifestations, early identification, laboratory examination, principles of antibiotic use, application of glucocorticoids and intravenous immunoglobulin, and precautions for bronchoscopy are highlighted. Early and rapid identification of gene mutations associated with MRMP is now available by polymerase chain reaction and fluorescent probe techniques in respiratory specimens. Although the resistance rate to macrolide remains high, it is fortunate that M. pneumoniae still maintains good in vitro sensitivity to second-line antibiotics such as tetracyclines and quinolones, making them an effective treatment option for patients with initial treatment failure caused by macrolide antibiotics. Conclusions: This consensus, based on international and national scientific evidence, provides scientific guidance for the diagnosis and treatment of MRMP in children. Further studies on tetracycline and quinolone drugs in children are urgently needed to evaluate their effects on the growth and development. Additionally, developing an antibiotic rotation treatment strategy is necessary to reduce the prevalence of MRMP strains.

Refractory Mycoplasma pneumoniae pneumonia (RMPP) is a severe state of M. pneumoniae infection that has attracted increasing universal attention in recent years. The pathogenesis of RMPP remains unknown, but the excessive host immune responses as well as macrolide resistance of M. pneumoniae might play important roles in the development of RMPP. To improve the prognosis of RMPP, it is mandatory to recognize RMPP in the early stages, and the detection of macrolide-resistant MP, clinical unresponsiveness to macrolides and elevated proinflammatory cytokines might be clues. Timely and effective anti-mycoplasmal therapy and immunomodulating therapy are the main strategies for RMPP.

We sought to understand the situation of macrolide-resistant genotypes of Mycoplasma pneumoniae , and analyze the relationship between macrolide-resistant genotypes and clinical manifestations of Mycoplasma pneumoniae pneumonia (MPP). Full-length sequencing of the 23S rRNA gene of M. pneumoniae was performed in 235 nasopharyngeal aspirates (NPAs) from children with MPP. We also retrospectively compared the clinical characteristics of macrolide-resistant (MR) M. pneumoniae infections and macrolide-sensitive (MS) M. pneumoniae infections. A total of 206 patients had point mutations in the M. pneumoniae 23S rRNA gene, and these patients are referred to as MR patients. The remaining 29 patients without point mutations are referred to as MS patients. Among 206 MR patients, 199 (96.6%) had A2063G mutations, 6 had A2063T mutations, and the remaining patients had an A2064G mutation. Among the clinical manifestations, we found that the median fever durations were 8 days (range, 0 to 42 days) and 6 days (0 to 14 days) ( P < 0.01), the median hospitalization durations were 8 days (2 to 45 days) and 6 days (3 to 16 days) ( P < 0.01), and the median fever durations after macrolide therapy were 5 days (0 to 42 days) and 3 days (0 to 10 days) ( P < 0.01), respectively, in the MR and MS groups. We also found that the incidence of extrapulmonary complications in the MR group was significantly higher than that in the MS group ( P < 0.05). Moreover, the radiological findings were more serious in the MR group than in the MS group ( P < 0.05). The increasing prevalence of MR M. pneumoniae has become a significant clinical issue in the pediatric patients, which may lead to more extrapulmonary complications and severe clinical features and radiological manifestations.

To analyze the clinical characteristics of refracory Mycoplasma pneumoniae pneumonia (RMPP), and explore the related factors predicting RMPP. Retrospective analysis was performed on 634 children with Mycoplasma pneumoniae pneumonia (MPP) hospitalized in our hospital between January 1, 2011 and December 31, 2014. The clinical features, laboratory data, radiological findings between the RMPP group and the general Mycoplasma pneumoniae pneumonia (GMPP) group were compared and the predictive values of related factors were analyzed. The median age of the RMPP patients (n = 145) was much older than that of the GMPP patients (n = 489) (P<0.01). We also found more severe presentations, higher incidence of extra-pulmonary complications and more serious radiological findings in RMPP group, which needed oxygen more often, longer antibiotics administration and intensive care (P<0.05). Meanwhile, the levels of C-reactive protein (CRP), lactic dehydrogenase (LDH), immunoglobulin A (IgM), interleukin (IL)-6, IL-10, interferon gamma (IFN-γ) and the percentage of neutrophils, CD8+ in RMPP group were significantly higher than those in GMPP group (P<0.05); while the levels of prealbumin (PAB) were lower than that in GMPP group (P<0.01). In ROC curve analysis, the percentage of neutrophil, CRP, LDH, PAB, IL-6, IL-10 and IFN-γ were useful for differentiating patients with RMPP from those with GMPP. Multiple logistic regression analysis showed that the CRP≥16.5mg/L, LDH ≥417IU/L and IL-6 ≥14.75pg/ml were significant predictors regarding to RMPP. CRP≥16.5mg/L, LDH ≥417IU/L and IL-6 ≥14.75pg/ml might be the significant predictors of RMPP in children, which can aid in early recognition of RMPP.