Mycoplasma pneumoniae (MP), an atypical bacterium, is a prominent pathogen responsible for respiratory infections in children, contributing to up to 40% of community-acquired pneumonia (CAP) cases in this demographic globally (1, 2). In contrast to viral or typical bacterial pathogens, MP demonstrates distinctive epidemiological patterns, including cyclical epidemics occurring every 4–7 years and predilection for school-aged children (3). Although MP pneumonia (MPP) is generally self-limiting and rarely results in direct mortality (< 0.1%), its involvement in precipitating severe complications indirectly contributes to pneumonia-related fatalities (3, 4). The ongoing emergence of macrolide-resistant MP (MRMP), particularly due to mutations at positions 2063 (A2063G/C) and 2064 (A2064G/C) in the V domain of the 23S rRNA of MP, is associated with more severe pneumonia and a range of extrapulmonary complications, including pleuritis, pericarditis, and encephalitis (1, 3).

Due to the absence of a cell wall in MP, macrolides, such as azithromycin, clarithromycin and erythromycin, are considered the most effective and primary therapeutic agents for treating macrolide-susceptible or mild MPP (3, 5, 6). In cases of pneumonia induced by MRMP, newer tetracycline antibiotics, including doxycycline and minocycline, as well as fluoroquinolones, such as levofloxacin and moxifloxacin, are recommended as alternative treatments (3, 5, 7). Corticosteroids are advised for managing MPP with pronounced inflammatory responses (3). Beyond pharmacological interventions, the management of MPP necessitates radiological and laboratory assessments, bronchoscopy-guided examinations, interventional therapies, and adjunctive treatments, such as oxygen supplementation for hypoxia and humidified air (1, 5, 6). Consequently, the economic burden associated with MPP is significant and should not be overlooked. While there is existing research on the economic impact of CAP and infections caused by pneumococcal or respiratory syncytial virus (RSV) (8–11), there is a notable lack of studies addressing the direct medical costs of MPP in pediatric populations.

This study sought to quantify the direct hospitalization costs associated with pediatric MPP in China, with the aim of enhancing the efficiency of medical resource utilization, helping evaluate future prevention efforts and providing a foundation for government departments to formulate evidence-based health policies and public health intervention strategies.

With ongoing advancements in disease diagnosis and treatment methodologies, there is an increasing scholarly emphasis on the treatment burden associated with various diseases (8, 15). The pursuit of more effective therapeutic strategies at reduced costs has emerged as a central research priority. Nonetheless, research specifically addressing the economic aspects of MPP in pediatric populations remains notably limited. To address this gap, this retrospective study analyzed the direct medical costs associated with pediatric MPP hospitalizations at SCMC over a 13-year period. Our findings offer valuable insights for optimizing clinical decision-making, enhancing the efficiency of healthcare resource utilization, and alleviating the financial burden on affected families. Furthermore, this study provides quantitative evidence to inform governmental health resource allocation priorities and the development of policies aimed at mitigating the total disease burden.

Our study determined that the median age of patients with MPP was 6.50 years, aligning with the established epidemiological characteristics of MPP (3). The duration of hospital stay ranged from 4.00 to 7.00 days, which was in line with that reported in a prior Chinese study (16), suggesting that the condition of MPP typically improves after approximately 1 week of hospitalization. Furthermore, the median total cost per hospitalization in this study amounted to $1,250.52, surpassing the direct hospitalization cost of $851.48 reported in the prior study conducted in Shandong, which did not account for medical insurance reimbursement (16). This discrepancy is largely due to the variation in medical service prices across different provinces and cities. These prices are influenced by factors such as the level of local economic development, per capita income, public payment capacity, and the actual operational costs incurred by medical institutions (17). Additionally, pharmaceutical expenses constituted approximately 10% of the total direct hospitalization costs, indicating that controlling non-pharmaceutical expenditures, such as those related to radiological and laboratory examinations, is crucial for managing overall hospitalization costs.

Our research identified a notable rise in the incidence of MPP during the 2023–2024 period, which may be associated with the implementation of non-pharmaceutical interventions (NPIs) designed to curb the spread of COVID-19, a situation described as “immunity debt” (4, 18). The NPIs disrupted the transmission dynamics of MP, resulting in inadequate immune system stimulation, a reduction in herd immunity, and an increased vulnerability to infection. Following the relaxation of NPIs in late 2022, there was a widespread outbreak of SARS-CoV-2, which led to prolonged immune suppression or dysregulation, especially in children, thereby elevating their susceptibility to MPP (4). This post-COVID epidemiological transition has consequently contributed to an increase in MPP hospitalizations and severity within pediatric populations.

Interestingly, there has been a notable decline in both the total cost per hospitalization and the drug cost per hospitalization over the past 5 years, a trend likely attributable to the national volume-based procurement policies initiated in December 2018 (19). These policies were designed to ensure the provision of high-quality and affordable pharmaceuticals and medical supplies by establishing a national drug public procurement market and a multi-party linkage procurement model (20). The national volume-based procurement policies mandated specific purchase volumes, required an upfront payment of 30%-50%, and employed a competitive bidding process. As a result, the average reduction in drug prices has exceeded 50%, leading to significant savings in drug expenditures (19, 21). Consequently, it is crucial to further refine these volume-based pharmaceutical procurement policies to effectively manage hospitalization costs.

Inflammatory response is a significant characteristic of MPP, particularly in pediatric cases of MRMPP and severe MPP (22–24). It is recommended that MPP cases exhibiting elevated levels of white blood cells, neutrophil percentage, C-reactive protein, procalcitonin, interferon-γ, and interleukin-6 be treated with corticosteroids (3). In our study, approximately three-quarters of hospitalized children received corticosteroid treatment. The findings indicated significant differences in the duration of hospital stay, total cost per hospitalization, and drug cost per hospitalization between the corticosteroid-treated group and the non-corticosteroid group. Due to the retrospective nature of this study, accurately distinguishing between severe and general MPP was not feasible. Previous research has demonstrated that the severe MPP group exhibits significantly higher levels of inflammatory cytokines compared to the general MPP group (24). It is plausible that the MPP cases in the corticosteroid group were more severe than those in the non-corticosteroid group, necessitating more intensive interventions, such as bronchoscopy-guided examination, which contributed to prolonged hospital stays and increased hospitalization costs.

As indicated in previous studies (25, 26), the detection rate of MRMP in this study was 81.89%. The findings demonstrated no significant differences in total cost or drug expenses per hospitalization between the groups with and without macrolide-resistant genes. The administration of newer tetracycline antibiotics or other effective drugs to children with MRMPP, upon detection of the macrolide-resistant gene, could significantly alleviate pneumonia symptoms and facilitate early recovery (27). Currently, pathogen diagnostic technologies are advancing rapidly. A variety of diagnostic methods, including molecular diagnostic techniques, targeted next-generation sequencing, and polymerase chain reaction for MP, have enhanced the capacity to detect MPP or MRMPP in children (6). Notably, targeted next-generation sequencing, which allows for the simultaneous and accurate identification of multiple pathogens, is increasingly being adopted (28). The outcomes of this study may support the implementation of rapid molecular diagnostics for precise pathogen targeting.

Our study also found that the hospitalization total cost was highest among children under 3 years of age, potentially due to the increased likelihood of mixed viral infections within this age group (29). Children with MPP who also have infections with viruses such as RSV, human rhinovirus, adenovirus, and human metapneumovirus may experience prolonged hospital stays and impose additional financial burdens on healthcare systems (29). To effectively manage medical expenses, the Diagnosis-Related Group (DRG) payment system has been implemented as a key cost-containment strategy in numerous countries worldwide (30–32). Based on our findings, it is recommended that the National Healthcare Security Administration consider age-based grouping when formulating DRG policies related to MPP. Specifically, the group of children under 3 years of age with MPP should receive increased medical reimbursement.

Nonetheless, there were some limitations of this study. Firstly, the research was conducted at a single hospital located in Shanghai, a region characterized by relatively rapid economic development in eastern China, which may introduce potential biases. Our research team intends to continuously monitor the medical burden of MPP in future studies to enhance the outcomes. Secondly, the study was unable to differentiate between severe and general MPP due to incomplete data, resulting in the inability to ascertain the hospitalization costs for children with severe MPP. Future prospective studies will be conducted to assess the medical burden of both severe and general MPP, thereby providing a foundation for refining DRG policies. Thirdly, a limitation of this 13-year retrospective study was the potential for inconsistent documentation and missing data, which hindered the identification of factors influencing the medical burden. To address these challenges, future prospective research should aim to accurately ascertain the determinants of medical burden. Fourthly, owing to technical constraints and challenges in data accessibility, the cost data spanning the 13-year period in this study utilized a consistent exchange rate, and adjustments for inflation were not incorporated. This methodological choice may impact the temporal comparability of the economic data.

In conclusion, the medical burden of MPP has remained relatively stable. It is recommended that children under the age of three with MPP be allocated higher medical reimbursement expenditures. Additionally, the immediate administration of susceptible medications is advised upon detection of the macrolide-resistant gene.