AbstractBackgroundCases of refractoryMycoplasma pneumoniaepneumonia have been increasing recently; however, whether viral coinfection or macrolide-resistantM.infection contribute to the development of refractoryM. pneumoniaepneumonia remains unclear. This study aimed to investigate the impacts of viral coinfection and macrolide-resistantM. pneumoniaeinfection onM. pneumoniaepneumonia in hospitalized children and build a model to predict a severe disease course.MethodsNasopharyngeal swabs or sputum specimens were collected from patients with community-acquired pneumonia meeting our protocol who were admitted to Shanghai Children’s Medical Center from December 1, 2016, to May 31, 2019. The specimens were tested with the FilmArray Respiratory Panel, a multiplex polymerase chain reaction assay that detects 16 viruses,Bordetella pertussis,M. pneumoniae, andChlamydophila pneumoniae. Univariate and multivariate logistic regression models were used to identify the risk factors for adenovirus coinfection and macrolide-resistant mycoplasma infection.ResultsAmong the 107 M. pneumoniaepneumonia patients, the coinfection rate was 56.07%, and 60 (60/107, 56.07%) patients were infected by drug-resistantM. pneumoniae. Adenovirus was the most prevalent coinfecting organism, accounting for 22.43% (24/107). The classification tree confirmed that viral coinfection was more common in patients younger than 3 years old. Adenovirus coinfection and drug-resistantM. pneumoniaeinfection occurred more commonly in patients with refractoryM. pneumoniaepneumonia (P = 0.019;P = 0.001). A prediction model including wheezing, lung consolidation and extrapulmonary complications was used to predict adenovirus coinfection. The area under the receiver operating characteristic curve of the prediction model was 0.795 (95% CI 0.679–0.893,P < 0.001). A prolonged fever duration after the application of macrolides for 48 h was found more commonly in patients infected by drug-resistantM. pneumoniae(P = 0.002). A fever duration longer than 7 days was an independent risk factor for drug-resistantMycoplasmainfection (OR = 3.500, 95% CI = 1.310–9.353,P = 0.012).ConclusionsThe occurrence of refractoryM. pneumoniaepneumonia is associated with adenovirus coinfection and infection by drug-resistantM. pneumoniae. A prediction model combining wheezing, extrapulmonary complications and lung consolidation can be used to predict adenovirus coinfection in children withM. pneumoniaepneumonia. A prolonged fever duration indicates drug-resistantM. pneumoniaeinfection, and a reasonable change in antibiotics is necessary.