Clinical Efficacy Comparison of Doxycycline versus Azithromycin Combined with Methylprednisolone in the Treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia in children

Clinical Efficacy Comparison of Doxycycline versus Azithromycin Combined with Methylprednisolone in the Treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia in children | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical Efficacy Comparison of Doxycycline versus Azithromycin Combined with Methylprednisolone in the Treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia in children Kui Zheng, Shu hong Zhou, Zhou Bo Han This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6821333/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background The escalating prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) in China has posed substantial challenges for pediatricians managing mycoplasma pneumoniae pneumonia (MPP). This study aimed to compare the clinical efficacy and prognostic outcomes between two treatment strategies for pediatric patients with macrolide-unresponsive mycoplasma pneumoniae pneumonia (MUMPP) following initial 72-hour intravenous azithromycin therapy: 1) continuation of intravenous azithromycin combined with methylprednisolone, versus 2) switch to oral doxycycline monotherapy. Methods We performed a retrospective analysis of children hospitalized for MPP at our institution between November 2023 and October 2024. Children with MPP who showed no clinical response to an initial 72-hour course of intravenous azithromycin were assigned to two groups: 1) intravenous azithromycin combined with methylprednisolone (AZM + methylprednisolone group), and 2) doxycycline monotherapy (DXC group). Clinical efficacy and prognosis were compared between groups using 1:1 propensity score matching (PSM) to adjust for baseline confounding, followed by calculation of statistical power for the primary outcomes. Results A total of 1,112 children with MPP were screened, of whom 493 (44.33%) met the criteria for MUMPP, and 382 were included in the final analysis. The DXC group showed a significantly higher rate of pulmonary imaging improvement at discharge compared to the AZM + methylprednisolone group (94.29%vs.77.14%, P 0.05). The AZM + methylprednisolone group had a significantly longer hospital stay than the DXC group [8 (7, 9) days vs. 6 (5, 7) days, P < 0.05]. Additionally, the refractory rate was higher in the AZM + methylprednisolone group (14.29% vs. 4.29%, P < 0.05). At 3-month follow-up, the incidence of new infections or diseases was significantly higher in the AZM + methylprednisolone group (32.86% vs. 4.29%, P 0.05). Notably, no cases of tooth discoloration-related adverse reactions were observed in the DXC group. Conclusion DXC demonstrated significantly greater efficacy than AZM + methylprednisolone in resolving radiographic abnormalities at discharge among MUMPP patients. AZM + methylprednisolone combination therapy correlated with longer hospital stays, higher rates of refractory MPP, and increased post-discharge risks of new infections or diseases. Azithromycin doxycycline macrolide-unresponsive Mycoplasma pneumoniae pneumonia children Figures Figure 1 Background Mycoplasma pneumoniae pneumonia (MPP) is a leading cause of community-acquired pneumonia (CAP) in children, accounting for 20–40% of cases [ 1 ]. Globally, MPP epidemics occur in 3-7-year cycles, with each outbreak typically lasting 1–2 years [ 2 ]. Notably, during 2023–2024, China experienced a large-scale Mycoplasma pneumoniae epidemic in pediatric populations, leading to a marked increase in the incidence of refractory Mycoplasma pneumoniae pneumonia (RMPP) and severe Mycoplasma pneumoniae pneumonia (SMPP) compared to previous years [ 1 ].Macrolides have long been the first-line therapy for MPP. However, the escalating prevalence of macrolide resistance—particularly in East Asian countries like Japan, China, and South Korea—has posed a critical clinical challenge. In certain regions, macrolide resistance rates have reached up to 90% [ 1 , 3 – 4 ]. As emphasized by Tong et al. [ 3 ], vigilant identification of macrolide-resistant MPP (MRMPP) is essential in pediatric patients who show no clinical response to macrolide therapy within 72 hours. Doxycycline is recommended as the first-line alternative antibiotic for MRMPP, especially in areas with high macrolide resistance[ 3 ]. However, the potential toxicity of tetracyclines and fluoroquinolones in children necessitates cautious use in pediatric practice[ 3 ]. Concurrently, Yang et al. [ 5 ] suggested that glucocorticoids may reduce and prevent MPP progression by suppressing aberrant immune responses, inhibiting excessive inflammatory factor release, and mitigating organ damage. This has led to recommendations for glucocorticoid use in severe or refractory MPP [ 5 – 6 ].Notably, the efficacy of glucocorticoids in pediatric MPP remains controversial. Zhang et al. [ 7 ] found Low-dose corticosteroids may not be beneficial in children inpatients with MPP, while Tashiro et al.[ 8 ] also found that adjunctive treatment with either low-dose or high-dose corticosteroids may not be beneficial for MPP. Additionally, systemic glucocorticoids can lead to various side effects, such as immunosuppression, impacts on growth and development, and neuropsychological effects[ 8 ]. Moreover, the side effects of glucocorticoid therapy in children with MPP remain underexplored, and longitudinal follow-up data regarding disease recurrence after methylprednisolone treatment are still limited. Currently, evidence is lacking on whether second-line antibiotics or combinations of azithromycin and glucocorticoids are superior in macrolide-unresponsive MPP (MUMPP). Therefore, this study aims to evaluate the clinical efficacy of doxycycline versus azithromycin combined with methylprednisolone in children with macrolide-unresponsive MPP, providing evidence-based guidance for clinical practice. Data and methods Patient data collection Herein, a retrospective analysis was conducted on 1,112 children with MPP and 493 children with MUMPP hospitalized at Bishan Hospital Affiliated to Chongqing Medical University between November 2023 and October 2024. A total of 382 children were finally enrolled in the study. All MPP cases underwent Mycoplasma pneumoniae PCR testing, while mycoplasma culture, drug sensitivity testing, and drug resistance gene analysis were not performed. Diagnoses of MPP, RMPP, and MUMPP were made in accordance with the Guidelines for the Diagnosis and Treatment of Mycoplasma pneumoniae Pneumonia in Children (2023 Edition) [ 9 ]. Data were extracted from the electronic medical record system, including gender, age, clinical manifestations, laboratory parameters,complete blood count, C-reactive protein(CRP) interleukin-6, aspartate aminotransferase(AST), alanine aminotransferase(ALT), lactate dehydrogenase(LDH), etc, chest radiography or lung CT findings, and administered pharmacotherapies at admission. Additionally, information was documented on the resolution of clinical symptoms (e.g,fever and cough) following inpatient treatment, performance of bronchoscopic lavage, presence of mixed infections, and admission/discharge dates. Blood routine tests, CRP levels, and chest imaging results within 24 hours prior to discharge were also recorded. As previously reported, pulmonary imaging regression in children with RMPP or SMPP typically occurs within 4–12 weeks [ 10 – 11 ]. Outpatient follow-up data within 3 months post-discharge were collected, including new infections, incident illnesses, MPP-related rehospitalization, occurrences of rash and dental discoloration, and results of repeated chest radiography or lung CT scans. Inclusion criteria and exclusion criteria Patients were included according to the following criteria:(1) All cases of MPP were confirmed by positive Mycoplasma pneumoniae PCR testing at admission and met the diagnostic criteria for MPP as specified in the guidelines.(2) Patients received initial intravenous azithromycin treatment for 72 hours following MPP diagnosis. A total of 493 MPP cases with persistent fever, lack of clinical/radiographic improvement, or clinical deterioration after 72 hours of treatment were screened, with 382 cases meeting all inclusion criteria.(3) Complete clinical data were required for inclusion.​ Exclusion criteria were as follows:(1)Patients with underlying immunocompromising conditions (e.g., congenital heart disease, congenital pulmonary dysplasia) (n = 17);​(2) Cases with mixed infections (n = 36);​(4)Non-compliance with treatment protocols or voluntary discharge (n = 4);​(5)Loss to follow-up during the study period (n = 50);​(5)The second-line treatment was changed to levofloxacin (n = 4).Ultimately, 382 cases were included in the final analysis. Study Design and Definitions Macrolide-unresponsive MUMPP was defined as MPP cases in which persistent fever, lack of clinical/radiographic improvement, or deterioration occurred after 72 hours of standard macrolide antibiotic therapy. Patients were grouped according to the second - stage treatment regimen into either the azithromycin plus methylprednisolone (AZM + methylprednisolone group) or the oral doxycycline (DXC group). Of the 382 MUMPP cases, 269 were assigned to the oral DXC group and 113 to the intravenous AZM + methylprednisolone group. For the AZM + methylprednisolone group: intravenous azithromycin was administered at 10 mg/kg once daily for 5–7 days, followed by oral azithromycin for 1–2 weeks (10 mg/kg taken 3 days/week). Methylprednisolone was dosed at 2 mg/kg every 12 hours for 2–3 days, then reduced to 2 mg/kg daily for 1–2 days, with a total course of 3–5 days. The oral DXC group received doxycycline at 2 mg/kg every 12 hours; children over 45 kg were dosed as adults, with a total course of 10 days. Cases with persistent fever or clinical/radiographic deterioration 4 days after switching to second-line therapy were defined as refractory MPP: the DXC group received additional methylprednisolone or switched to intravenous levofloxacin, while the AZM + methylprednisolone group shifted to oral DXC or intravenous levofloxacin. Evaluation of efficacy At discharge, treatment efficacy was evaluated as follows: complete resolution of clinical symptoms (e.g., fever, cough) and significant absorption of pulmonary inflammation on imaging was defined as "markedly effective"; partial absorption as "effective"; and no absorption or progression as "ineffective" (effective/markedly effective = 1; ineffective = 0). Refractory mycoplasma pneumoniae pneumonia (RMPP) was defined as persistent fever 4 days after treatment adjustment, exacerbation of clinical signs or imaging findings, or development of extrapulmonary complications (yes = 1; no = 0). During the 3 - month follow - up, outcomes included: complete resolution of pulmonary inflammation on imaging (yes = 1; no = 0), readmission due to MPP (yes = 1; no = 0), and occurrence of new infections or diseases (yes = 1; no = 0). Sample size calculation method The primary outcome measure of this study was the incidence rate of new infections or diseases within 3 months post-intervention. The required sample size for this study was calculated using a formula designed to compare rate differences between groups, as outlined below: $$\:{N}_{B}=\left(\frac{{p}_{A}\left(1-{p}_{A}\right)}{k}+{p}_{B}\left(1-{p}_{B}\right)\right)\frac{{\left({Z}_{1-\alpha\:/2}+{Z}_{1-\beta\:}\right)}^{2}}{{\left({p}_{A}-{p}_{B}\right)}^{2}}$$ In the preliminary experiment, 20 cases were recruited in each of the two groups. The incidence of new infections or diseases within 3 months was 10% in the DXC group and 40% in the AZM + methylprednisolone group. Based on a Type I error (α) of 0.05, a statistical power (1-β) of 0.9, and a 1:1 allocation ratio between the two groups, a sample size of 39 cases per group was calculated. Accounting for a 5% dropout rate during follow-up, at least 41 cases were required in both the DXC group and the AZM + methylprednisolone group. $$\:{N}_{B}=\left({p}_{A}\left(1-{p}_{A}\right)+{p}_{B}\left(1-{p}_{B}\right)\right)\frac{{\left({Z}_{1-\alpha\:/2}+{Z}_{1-\beta\:}\right)}^{2}}{{\left({p}_{A}-{p}_{B}\right)}^{2}}$$ Statistical analysis For normally distributed continuous variables, data were presented as mean ± standard deviation (x ± s), and comparisons between groups were performed using the independent samples t - test. For skewed continuous variables, data were presented as median (interquartile range) [M(P25, P75)], and comparisons between groups were carried out using the Mann - Whitney U test. Categorical variables were described by counts and percentages, and comparisons between groups were analyzed using the chi - square test or Fisher's exact test. Propensity score matching (PSM) was used to balance potential confounding factors between the DXC group and the AZM + methylprednisolone group at a 1:1 ratio, employing the greedy nearest neighbor matching algorithm. After matching, the standardized mean differences (SMD) of covariates were calculated to assess the balance of baseline characteristics, with SMD < 0.2 indicating adequate balance. Statistical power was calculated using PASS 2021 software. All statistical tests were two - sided, and statistical significance was set at P < 0.05. Data analysis was performed using SAS 9.4 software (Copyright ©2016 SAS Institute Inc., Cary, NC, USA). Results Study Population and clinical characteristics Among 1112 children with MPP, 493 were diagnosed with MUMPP, giving an incidence of 44.33% (493/1112). After excluding cases with mixed infections [incidence 7.30% (36/493)], a total of 382 patients were included in the study (Fig. 1 ). Sputum culture and respiratory pathogen nucleic acid testing confirmed no co-infections in either group, and none of the included patients received human immunoglobulin or other immunotherapies during treatment. The 382 patients had a mean age of 7.01 ± 2.33 years, including 188 males and 194 females. Refractory MPP occurred in 20 cases (5.24%, 20/382): 8 cases (2.97%, 8/269) in the DXC group, of which 6 were treated with combined methylprednisolone and 2 were switched to levofloxacin plus methylprednisolone; 12 cases (10.62%, 12/113) in the AZM + methylprednisolone group, of which 10 were switched to doxycycline and 2 to levofloxacin. All patients were discharged after effective treatment, and none required admission to the ICU. 2.2 Baseline data comparison Before PSM, significant differences were observed between the AZM + methylprednisolone group and the DXC group in terms of age, hypoxemia, white blood cell count, lymphocyte count, LDH, AST, and ferritin levels (all P < 0.05). One-to-one Greedy Nearest Neighbor Matching was performed using propensity score matching (PSM) to balance baseline characteristics between the two groups. After matching, no significant differences were found in any baseline variables, and all standardized mean differences (SMDs) were < 0.2, indicating adequate balance of covariates between the two groups (Table 1 ). Table 1 Comparison of Baseline Data Before and After Matching Between the DXC Group and the AZM + Methylprednisolone Variables Before matching After Match DXC (n = 269) AZM + methylprednisolone (n = 113) P SMD DXC (n = 70) AZM + methylprednisolone (n = 70) P SMD Age (y), mean ± SD 8.67 ± 2.40 5.36 ± 2.26 < 0.001 1.420 6.33 ± 1.88 6.38 ± 2.01 0.871 0.028 Male, no. (%) 137 (50.93%) 51 (45.13%) 0.301 0.116 34 (48.57%) 32 (45.71%) 0.735 0.057 Days of onset, mean ± SD 5.97 ± 2.69 5.40 ± 2.57 0.054 0.219 5.40 ± 2.05 5.47 ± 2.96 0.868 0.028 Bronchoscopy lavage no. (%) 59 (21.93%) 28 (24.78%) 0.545 0.067 19 (27.14%) 18 (25.71%) 0.848 0.032 Hypoxemia no. (%) 17 (6.32%) 16 (14.16%) 0.013 0.261 7 (10.00%) 5 (7.14%) 0.546 0.102 Atelectasis no. (%) 6 (2.23%) 4 (3.54%) 0.704 0.078 2 (2.86%) 2 (2.86%) > 0.999 0.999 0.999 < 0.001 Lung consolidation no. (%) 173 (64.31%) 71 (62.83%) 0.783 0.031 49 (70.00%) 47 (67.14%) 0.716 0.062 Extrapulmonary complications no. (%) 8 (2.97%) 4 (3.54%) 0.999 0.032 1 (1.43%) 3 (4.29%) 0.620 0.172 WBC (×10 9 /L), mean ± SD 7.10 ± 2 7.70 ± 2.60 0.029 0.259 7.06 ± 2.00 7.36 ± 2.14 0.388 0.146 Mesogranulocytes (×10 9 /L), mean ± SD 4.57 ± 1.63 4.90 ± 2.23 0.158 0.169 4.45 ± 1.69 4.61 ± 1.58 0.564 0.098 Lymphocytes (×10 9 /L), mean ± SD 1.90 ± 0.68 2.18 ± 0.97 0.007 0.330 1.96 ± 0.68 2.10 ± 1.00 0.355 0.157 Platelet count (×10 9 /L), mean ± SD 267.20 ± 82.87 269.65 ± 75.66 0.787 0.031 258.20 ± 69.87 264.61 ± 78.87 0.611 0.086 CRP (mg/L), median (IQR) 12.50 (6.20, 23.51) 10.60 (6.37, 19.43) 0.460 0.083 12.14 (5.70, 24.70) 10.37 (6.88, 28.02) 0.796 0.044 LDH (U/L)median (IQR) 280 (246319). 316 (279361). < 0.001 0.549 292.50 (262.00, 326.00) 293.00 (263.00, 328.00) 0.846 0.033 ALT(U/L)median (IQR) 13 (10, 15) 13 (10 dec) 0.774 0.032 12.00 (10.00, 15.00) 12.00 (10.00, 15.00) 0.920 0.035 AST(U/L)median (IQR) 26 (22, 31) 31 (4) 27 < 0.001 0.770 29.00 (26.00, 34.00) 30.00 (26.00, 34.00) 0.645 0.024 Ferritin (U/L) median (IQR) 93.70 (72.30, 123.30) 81.40 (61.20, 111.40) 0.012 0.280 87.85 (66.40, 111.90) 79.60 (57.60, 111.60) 0.300 0.175 Comparison of blood routine and CRP indicators at discharge between the two groups. PSM analysis revealed that, compared with the DXC group, the AZM + methylprednisolone group exhibited significantly higher mean white blood cell count, mean granulocyte count, and mean platelet count, as well as lower CRP levels at discharge (P < 0.05). Following treatment, the white blood cell count and mean granulocyte count in the DXC group demonstrated a downward trend, whereas these parameters in the AZM + methylprednisolone group showed an upward trend. The intergroup differences were statistically significant (P < 0.05), as detailed in Table 2 . Table 2 Comparison of Blood Routine and CRP Indicators Before and After Matching in the DXC Group and the AZM + Methylprednisolone Group Variables Before matching After Match DXC (n = 269) AZM + methylprednisolone (n = 113) P DXC (n = 70) AZM + methylprednisolone (n = 70) P When discharged WBC (×10 9 /L), mean ± SD 6.50 ± 1.96 9.62 ± 3.47 < 0.001 6.91 ± 2.01 9.61 ± 3.63 < 0.001 Mesogranulocytes (×10 9 /L), mean ± SD 3.46 ± 1.53 5.90 ± 3.01 < 0.001 3.45 ± 1.59 6.14 ± 3.05 < 0.001 Lymphocytes (×10 9 /L), mean ± SD 2.61 ± 0.98 3.10 ± 1.54 0.004 2.82 ± 1.26 2.90 ± 1.48 0.755 Platelet count (×10 9 /L), mean ± SD 342.15 ± 105.90 429.33 ± 136.10 < 0.001 371.61 ± 124.31 421.63 ± 138.12 0.040 CRP (mg/L), median (IQR) 2.90 (1.15, 5.50) 1.99 (0.60, 4.42) 0.012 3.21 (1.60, 6.72) 2.10 (0.70, 4.42) 0.049 Difference (at discharge minus admission) WBC (×10 9 /L), mean ± SD -0.66 ± 2.43 1.93 ± 3.86 < 0.001 -0.28 ± 2.79 2.29 ± 3.80 < 0.001 Mesogranulocytes (×10 9 /L), mean ± SD -1.21 ± 2.04 0.97 ± 3.51 < 0.001 -1.14 ± 2.20 1.54 ± 3.15 < 0.001 Lymphocytes (×10 9 /L), mean ± SD 0.75 ± 0.99 0.96 ± 1.63 0.214 0.89 ± 1.23 0.83 ± 1.67 0.823 Platelet count (×10 9 /L), mean ± SD 78.76 ± 104.70 158.40 ± 123.82 < 0.001 113.80 ± 124.13 155.43 ± 131.69 0.078 CRP (mg/L), median (IQR) 10.26 (19.45, 4.69) 8.21 (13.19, 4.21) 0.173 10.60 (16.20, 5.41) 8.80 (13.62, 4.21) 0.330 Table 3 Comparison of Outcome Measures Before and After Matching Between the DXC Group and the AZM + Methylprednisolone Group Variables Before matching After Match DXC (n = 269) AZM + methylprednisolone (n = 113) P DXC (n = 70) AZM + methylprednisolone (n = 70) MD(95%CI)/ OR(95%CI) P Antipyretic time day,median (IQR) 2 (1, 2) 2 (1, 3) 0.240 2 (1, 2) 1 (1, 3) 1 (1, 0) 0.703 Cough relief time day,median (IQR) 3 (2, 5) 4 (3, 6) 0.048 3 (2, 5) 4 (2, 6) 1 (0, 1) 0.111 Days in hospital,median (IQR) 6 (5, 7) 8 (7, 9) < 0.001 6 (5, 7) 8 (7, 9) 2 (1, 2) < 0.001 Number of adverse reactions.(%) 10 (3.72%) 6 (5.31%) 0.668 4 (5.80%) 2 (2.90%) 4.18 (0.46, 38.39) 0.681 Number of cases of refractory MPP (%) 8 (2.97%) 12 (10.62%) < 0.001 3 (4.29%) 10 (14.29%) 3.72 (0.98, 14.16) 0.042 Number of cases with significantly effective discharge imaging (%) 155 (57.62%) 26 (23.01%) < 0.001 33 (47.14%) 19 (27.14%) 0.42 (0.21, 0.85) 0.014 Number of cases with ineffective discharge imaging (%) 12 (4.46%) 30 (26.55%) < 0.001 4 (5.71%) 16 (22.86%) 4.89 (1.54, 15.49) < 0.001 Number of effective cases shown by discharge imaging no. (%) 257 (95.54%) 83 (73.45%) < 0.001 66 (94.29%) 54 (77.14%) 4.89 (1.54, 15.49) 0.999 Number of new infections or diseases within 3 months (%) 23 (8.55%) 42 (37.17%) < 0.001 3 (4.29%) 23 (32.86%) 10.93 (3.10, 38.51) < 0.001 The number of cases with complete imaging absorption within 3 months no. (%) 264 (98.14%) 107 (94.69%) 0.132 69 (98.57%) 66 (94.29%) 0.24 (0.03, 2.20) 0.366 Comparison of Therapeutic Efficacy and Imaging Findings at Discharge Between the Two Groups Following PSM, the AZM + methylprednisolone group had a longer length of hospital stay [8 (7, 9) vs. 6 (5, 7) days, P < 0.05, statistical power = 0.999] and a higher refractory rate (14.29% vs. 4.29%, P < 0.05, statistical power = 0.543) compared with the DXC group. The DXC group exhibited higher rates of marked efficacy (47.14% vs. 27.14%, P < 0.05, statistical power = 0.849) and efficacy (94.29% vs. 77.14%, P < 0.05, statistical power = 0.706) in imaging findings at discharge than the AZM + methylprednisolone group. There were no significant differences between the two groups in the days to defervescence after medication, days to cough resolution after medication, or adverse reaction rate (all P > 0.05, Table 3 ). Comparison of 3-Month Follow-Up Outcomes and Prognosis Between the Two Groups During the 3-month follow-up, new infections or diseases occurred in 23 cases of the DXC group, including 2 cases of acute urticaria, 1 case of pertussis, 17 cases of upper respiratory tract infection, and 3 cases of lower respiratory tract infection. In the AZM + methylprednisolone group, 42 cases developed new infections or diseases, including 25 cases of upper respiratory tract infection, 7 cases of lower respiratory tract infection, 5 cases of acute urticaria, 3 cases of bronchial asthma, 1 case of acute enteritis, and 1 case of viral encephalitis. The incidence of new infections or diseases was significantly higher in the AZM + methylprednisolone group than in the DXC group (32.86% vs. 4.29%, P < 0.05, statistical power = 0.997). Two cases in the DXC group and two cases in the AZM + methylprednisolone group were readmitted due to MPP during the follow-up period, with no significant difference in the 3-month readmission rate between the two groups (0.00% vs. 1.43%, P > 0.05). There was also no significant difference in the rate of complete pulmonary imaging resolution between the two groups (98.57% vs. 94.29%, P > 0.05, Table 3 ). No adverse reactions such as tooth discoloration were observed in the 269 children of the doxycycline group during the 3-month follow-up. Discussion Mycoplasma pneumoniae (M. pneumoniae) is one of the most important pathogens of community-acquired pneumonia (CAP) in children. MPP is typically mild and even exhibits self-limiting characteristics [ 3 ]. During 2023–2024, China experienced a large-scale Mycoplasma pneumoniae (MP) outbreak, with notably increased reports of RMPP and SMPP compared to previous years [ 1 , 12 ]. Since 2000, the prevalence of Pneumonia Mycoplasma resistant to macrolide (MRMP) has been rising annually, particularly in East Asian countries such as Japan, China, and South Korea, with macrolide resistance rates reaching up to 90% in some regions [ 1 , 3 ]. MRMP infections inevitably lead to a series of clinical challenges, including prolonged fever, extended hospital stays, increased severe cases, and difficulties in antibiotic selection [ 12 ]. Early identification of MRMP is particularly critical. Tong et al. [ 3 ] recommended that if MPP children show no response to macrolide therapy within the initial 3 days, MRMPP should be suspected, and further treatment initiated.In this study, the prevalence of MUMPP was 44.33%, higher than the 16.3% reported by Ha et al. [ 13 ] during January 2015 to April 2017 in South Korea. Due to the lack of facilities for MP resistance testing in our hospital, we could not determine the proportion of MRMP. RMPP cases numbered 20 (5.19%, 20/385), lower than the 21.17% (47/173) reported by Ma et al. [ 14 ] in 173 MUMPP children from Baoji, China, during 2023. This discrepancy might relate to over two-thirds of children in our study being switched to doxycycline treatment. It is currently recognized that abnormal host immune responses, mixed infections, or macrolide resistance may be associated with MUMPP [ 3 , 9 ]. In this study, 36 cases of mixed infections were excluded, accounting for 7.30% (36/493), which was slightly lower than the 8%-60% incidence of viral/bacterial co-infections with MP reported in previous pediatric studies [ 3 , 15 ]. Macrolide antibiotics have long been the first-line treatment for MPP, though the clinical relevance of macrolide-resistant strains in refractory MPP remains controversial [ 1 ]. Tong et al. [ 3 ] recommended suspecting MRMP in MPP children unresponsive to macrolides within 3 days, with doxycycline suggested as the preferred alternative antibiotic for macrolide-resistant MPP. However, Ha et al. [ 13 ] reported that second-line therapy showed no better efficacy than prolonged macrolide treatment in MUMPP. Additionally, concerns exist regarding the use of tetracyclines or fluoroquinolones in children due to potential toxicities, such as tooth discoloration and enamel hypoplasia in children under 8 years with tetracyclines, and irreversible arthropathy with fluoroquinolones [ 1 ].This study found that compared with the AZM + methylprednisolone group, the DXC group had shorter hospital stays [8 (7,9) vs. 6 (5,7) days, P < 0.05], fewer refractory MPP cases (14.29% vs. 4.29%, P < 0.05), and higher imaging improvement rates at discharge (77.14% vs. 94.29%, P < 0.05), consistent with Ahn et al. [ 16 ] who reported that tetracyclines shorten fever duration and hospital stays in MRMP-infected patients. No tooth discoloration was observed in DXC group children during the 3-month follow-up, suggesting that switching to doxycycline is more effective and relatively safe for short-term use in MUMPP compared with azithromycin plus methylprednisolone. Todd et al. [ 17 ] reported that short-course doxycycline (≤ 10 days) in children < 8 years for MPP treatment does not cause tooth darkening, visible staining, or increased enamel hypoplasia risk. Furthermore, Lee et al.suggest in countries where macrolide-resistance rates are high, a second-line antibiotic such as doxycycline should be used for severe MPP early, even in children younger than 2 years old. However, 8 cases in the DXC group developed refractory MPP, 6 of which required combined methylprednisolone treatment, indicating that abnormal host immune responses may contribute to some RMPP cases. The direct correlation between host immune responses and RMPP remains undefined. Evidence shows that children with MPP receiving immunosuppressive therapy exhibit significantly lower incidences of severe MPP and complications than those not receiving immunotherapy [ 16 ]. Some studies report that pulmonary neutrophil infiltration is widely recognized as a hallmark of MPP, with disease exacerbation linked to enhanced T-cell activation and neutrophil-mediated immune responses [ 19 ]. Researchers suggest that early glucocorticoid therapy in children with RMPP or SMPP can effectively suppress abnormal immune responses, mitigate excessive release of inflammatory cytokines, and prevent disease progression and organ damage [ 3 , 20 ]. A 2020 meta-analysis of 12 randomized controlled trials (RCTs) found that systemic glucocorticoids combined with azithromycin significantly improved total effective rate in children with RMPP compared to conventional therapy (OR = 6.37, 95% CI = 4.03–10.07, P < 0.001) [ 21 ]. However, the efficacy of glucocorticoids in MPP treatment remains controversial, prompting increasing calls for prudent use of these agents. Zhang et al. [ 22 ] suggested that low-dose corticosteroids may not benefit hospitalized children with MPP, while Bleecker et al. [ 23 ] reported no benefits of low-dose glucocorticoids even in severe or refractory pneumonia. Additionally, Wang et al. [ 12 ] recommended against routine use of systemic glucocorticoids in MRMP pneumonia.This study found that compared with the DXC group, the AZM + methylprednisolone group had longer hospital stays, a higher rate of refractory MPP, and lower imaging improvement rates at discharge. Twelve cases in the AZM + methylprednisolone group developed refractory MPP, of which 10 were switched to doxycycline and 2 to levofloxacin. Currently, there is limited literature on the follow-up of azithromycin combined with methylprednisolone therapy. Studies have shown that systemic intravenous glucocorticoids can induce multiple side effects, including immunosuppression, growth suppression, and neuropsychological impacts [ 22 – 23 ]. During the 3-month follow-up period of this study, new infections or diseases occurred in 23 cases of the doxycycline group and 42 cases of the AZM + methylprednisolone group. The AZM + methylprednisolone group exhibited a significantly higher incidence of post-discharge new infections or diseases than the DXC group (36.52% vs. 7.43%, P < 0.01). No significant intergroup difference was observed in the rate of drug-related adverse reactions. Additionally, Tashiro et al. [ 23 ] reported that adjunctive therapy with low-dose or high-dose corticosteroids was associated with prolonged hospital stays and higher medication costs during hospitalization. This study has several limitations that require acknowledgment. First, it was a retrospective, single-center study with a relatively small sample size, and findings should be validated by prospective, multicenter studies. Second, the follow-up period for adverse reactions of doxycycline (e.g., tooth discoloration) was short, precluding a comprehensive safety assessment of doxycycline in this population. Third, chest radiographs were the primary imaging modality used during follow-up, which may have underestimated pulmonary sequelae such as bronchiolitis obliterans in some children. Fourth, macrolide resistance testing was not performed, preventing us from determining the prevalence of macrolide-resistant strains in this cohort. Conclusion In summary, this study demonstrates that oral doxycycline more effectively improves pulmonary imaging findings at discharge and reduces the risk of refractory pneumonia in children with MUMPP compared with azithromycin plus methylprednisolone. Combination therapy with methylprednisolone may be necessary for severe or refractory cases but should be used judiciously. Patients treated with azithromycin plus methylprednisolone had prolonged hospital stays and a higher risk of developing new infections or diseases post-discharge. Abbreviations MP Mycoplasma pneumoniae MPP Mycoplasma pneumoniae pneumonia MUMPP Macrolide-unresponsive mycoplasma pneumoniae pneumonia MRMP Macrolide-resistant Mycoplasma pneumoniae RMPP Refractory Mycoplasma pneumoniae pneumonia SMPP Severe Mycoplasma pneumoniae pneumonia WBC White blood cell count CRP C-reactive protein AST Aspartate transaminase ALT Aalanine transaminase LDH Lactate dehydrogenase Declarations Ethics approval This study strictly adhered to the ethical principles outlined in the Declaration of Helsinki for human medical research and was approved by the Ethics Committee of the Bishan Hospital of Chongqing Medical University (approval number: Cqbykyll-29240918-79). Consent to participate As a retrospective study, consent and informed consent were obtained from all patients or the patient’s legal guardian(s) and/or their parents prior to study commencement. Clinical Trial Not applicable. Author contribution KZ.wrote the main text of the manuscript. S.h.Z.Sprepared all the fgures of the manuscript. Z.b.H. contributed to drafting and revising the article. All authors read and approved the fnal version of the manuscript. Availability of data and materials All cases source was the electronic medical records of Bishan Hospital of Chongqing Medical University from November 2023 to June 2024. We assure the accuracy and reliability of the data used, and the datasets used and/or analysed during the current study available from the corresponding author on reasonable request. Competing interests The authors declare that they have no conficts of interest. Funding This study was supported by Chongqing Bishan District Science and Technology Bureau(No. BSJ2024013,BSJ2024012). Acknowledgments The study would not have been possible without the excellent support from clinical staf from the Department of paediatrics,Bishan Hospital of Chongqing Medical University. Author details 1 Department of paediatrics,Bishan Hospital of Chongqing Medical University, Chongqing 402760, China (Chongqing Bishan District People's Hospital). 2 Department of Nursing, Chongqing Medical University, Chongqing 402760, China. References Ding G, Zhang X, Vinturache A, et al. Challenges in the treatment of pediatric Mycoplasma pneumoniae pneumonia. Eur J Pediatr. 2024;183(7):3001–11. 10.1007/s00431-024-05519-1 . Yamazaki T, Kenri T. Epidemiology of Mycoplasma pneumoniae Infections in Japan and Therapeutic Strategies for Macrolide-Resistant M. pneumoniae. Front Microbiol 2016; But 93. Doi: 10.3389 / fmicb. 2016.00693. Tong L, Huang S, Zheng C, et al. Refractory Mycoplasma pneumonia e Pneumonia in Children: Early Recognition and Management. J Clin Med. 2022;11(10):2824. 10.3390/jcm11102824 . Yan C, Xue GH, Zhao HQ, et al. Current status of Mycoplasma pneumoniae infection in China. World J Pediatr. 2024;20(1):1–4. 10.1007/s12519-023-00783-x . Yang EA, Kang HM, Rhim JW, et al. Early Corticosteroid Therapy for Mycoplasma pneumoniae Pneumonia Irrespective of Used Antibiotics in Children. J Clin Med. 2019;8(5):726. 10.3390/jcm8050726 . Liu J, He R, Zhang X et al. Clinical features and early corticosteroid treatment outcome of pediatric mycoplasma pneumoniae pneumonia. Front Cell Infect Microbiol 2023; Then 35228. Doi: 10.3389 / fcimb.2023.1135228. Zhang W, Huang L. Low-Dose Corticosteroid Treatment in Children With Mycoplasma pneumoniae Pneumonia: A Retrospective Cohort Study. Front Pediatr. 2020; But 6371. Doi: 10.3389 / fped. 2020.566371. Tashiro M, Fushimi K, Kawano K, et al. Adjunctive corticosteroid therapy for inpatients with Mycoplasma pneumoniae pneumonia. BMC Pulm Med. 2017;17(1):219. 10.1186/s12890-017-0566-4 . National Health Commission of the People’s Republic of China. Guidelines for diagnosis and treatment of mycoplasma pneumoniae pneumonia in children (2023 Edition). Intern J Epid Infec Dis. 2024; 50(2): 79-85.10.3760 / CMA.J.CN 331340-20230217-00023. Luo XQ, Luo J, Wang CJ, et al. Clinical features of severe Mycoplasma pneumoniae pneumonia with pulmonary complications in childhood: A retrospective study. Pediatr Pulmonol. 2023;58(10):2815–22. 10.1002/ ppl.26593. Huang L, Huang X, Jiang W, et al. Independent predictors for longer radiographic resolution in patients with refractory Mycoplasma pneumonia e pneumonia: a prospective cohort study. BMJ Open. 2018;8(12):e023719. 10.1136/bmjopen-2018-023719 . Wang YS, Zhou YL, Bai GN, et al. Expert consensus on the diagnosis and treatment of macrolide-resistant Mycoplasma pneumoniae pneumonia in children. World J Pediatr. 2024;20(9):901–14. 10.1007/s12519-024-00831-0 . Ha SG, Oh KJ, Ko KP, et al. Therapeutic Efficacy and Safety of Prolonged Macrolide, Corticosteroid, Doxycycline, and Levofloxacin against Macrolide-Unresponsive Mycoplasma pneumoniae Pneumonia in Children. J Korean Med Sci. 2018;33(43):e268. Doi: 10.3346 / JKMS. 2018.33 e268. Ma YC, Zhou XH, Zhao XD, et al. [Efficacy of prolonged azithromycin versus switching to doxycycline in the treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia in children]. Zhongguo Dang Dai Er Ke Za Zhi. 2024;26(12):1294–300. 10.7499/j.issn.1008-8830.2406089 . Chinese. Shi S, Zhang X, Zhou Y, et al. Immunosuppression Reduces Lung Injury Caused by Mycoplasma pneumoniae Infection. Sci Rep. 2019;9(1):7147. 10.1038/s41598-019-43451-9 . Ahn JG, Cho HK, Li D, et al. Efficacy of tetracyclines and fluoroquinolones for the treatment of macrolide-refractory Mycoplasma pneumoniae pneumonia in children: a systematic review and meta-analysis. BMC Infect Dis. 2021;21(1):1003. 10.1186/s12879-021-06508-7 . Todd SR, Dahlgren FS, Traeger MS, et al. No visible dental staining in children treated with doxycycline for suspected Rocky Mountain Spotted Fever. J Pediatr. 2015;166(5):1246–51. 10.1016. / j.j peds. 2015.02.015. Lee KL, Lee CM, Yang TL, et al. Severe Mycoplasma pneumoniae pneumonia requiring intensive care in children, 2010–2019. J Formos Med Assoc. 2021;120(Pt 1):281–91. The doi: 10.1016 / j.j fma. 2020.08.018. Zhu Y, Luo Y, Li L et al. Immune response plays a role in Mycoplasma pneumoniae pneumonia. Front Immunol. 2023; When 89647. 10.3389/fimmu.2023.1189647 Yang EA, Kang HM, Rhim JW, et al. Early Corticosteroid Therapy for Mycoplasma pneumonia e Pneumonia Irrespective of Used Antibiotics in Children. J Clin Med. 2019;8(5):726. 10.3390/jcm8050726 . Qiu JL, Huang L, Shao MY, et al. Efficacy and safety of azithromycin combined with glucocorticoid on refractory Mycoplasma pneumoniae pneumonia in children: a PRISMA-compliant systematic review and meta-analysis. Medicine. 2020;99:e20121. Zhang L, Wang L, Xu S, et al. Low-Dose Corticosteroid Treatment in Children With Mycoplasma pneumonia e Pneumonia: A Retrospective Cohort Study. Front Pediatr. 2020. 10.3389/fped.2020.566371 . Bleecker ER, Menzies-Gow AN, Price DB, et al. Systematic Literature Review of Systemic Corticosteroid Use for Asthma Management. Am J Respir Crit Care Med. 2020;201(3):276–93. 10.1164/rccm.201904-0903SO . Tashiro M, Fushimi K, Kawano K, et al. Adjunctive corticosteroid therapy for inpatients with Mycoplasma pneumoniae pneumonia. BMC Pulm Med. 2017;17(1):219. 10.1186/s12890-017-0566-4 . Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6821333","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":471117335,"identity":"d085cd9f-c7c2-4fe8-8563-b553e80527c5","order_by":0,"name":"Kui Zheng","email":"","orcid":"","institution":"Bishan Hospital of Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Kui","middleName":"","lastName":"Zheng","suffix":""},{"id":471117336,"identity":"bb837cb3-ec50-48b9-8632-b8a2263d875f","order_by":1,"name":"Shu hong Zhou","email":"","orcid":"","institution":"Chongqing Medical University","correspondingAuthor":false,"prefix":"","firstName":"Shu","middleName":"hong","lastName":"Zhou","suffix":""},{"id":471117337,"identity":"cf672e1a-b5c7-4dbf-a904-7dfe4c456184","order_by":2,"name":"Zhou Bo Han","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYBACNv7mgw8/8NjI8bP3f3yQUFFDWAufxLFkYwmZNGPJngPGBg/OHCOsRY4hx0yCx+Zw4oYZCWaSD1uYiXAYw7FkA4mctMQNEglpFYkNbAz87d0J+LUwNx98UHDGxng7z4NjNxJ3yDBInDm7gbAtkj1psjvbE9tuJJ5hYzCQyCWkBegX3n+HGTccSGYrSGxjJlILD89hxQ0n0tgYiNMCDmQeUCCfYZZIOHOMh6Bf5PvhUdnD+PFHRY0cf3svfi0YgIc05aNgFIyCUTAKsAIALWBMSr1ekaEAAAAASUVORK5CYII=","orcid":"","institution":"Bishan Hospital of Chongqing Medical University","correspondingAuthor":true,"prefix":"","firstName":"Zhou","middleName":"Bo","lastName":"Han","suffix":""}],"badges":[],"createdAt":"2025-06-04 14:08:27","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6821333/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6821333/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":84817419,"identity":"b03e3204-3fd5-4d68-abbb-735568744743","added_by":"auto","created_at":"2025-06-17 15:49:15","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":68173,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of patients included as study participants.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-6821333/v1/96ca212f2ebeeecacb6a87db.png"},{"id":85718751,"identity":"fb291f5a-9ec6-4741-a9c0-679dab3bd012","added_by":"auto","created_at":"2025-07-01 04:53:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1177747,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6821333/v1/dd3d321a-52bf-4df2-b6c1-9a9dc3b4966d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical Efficacy Comparison of Doxycycline versus Azithromycin Combined with Methylprednisolone in the Treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia in children","fulltext":[{"header":"Background","content":"\u003cp\u003eMycoplasma pneumoniae pneumonia (MPP) is a leading cause of community-acquired pneumonia (CAP) in children, accounting for 20\u0026ndash;40% of cases [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Globally, MPP epidemics occur in 3-7-year cycles, with each outbreak typically lasting 1\u0026ndash;2 years [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Notably, during 2023\u0026ndash;2024, China experienced a large-scale Mycoplasma pneumoniae epidemic in pediatric populations, leading to a marked increase in the incidence of refractory Mycoplasma pneumoniae pneumonia (RMPP) and severe Mycoplasma pneumoniae pneumonia (SMPP) compared to previous years [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].Macrolides have long been the first-line therapy for MPP. However, the escalating prevalence of macrolide resistance\u0026mdash;particularly in East Asian countries like Japan, China, and South Korea\u0026mdash;has posed a critical clinical challenge. In certain regions, macrolide resistance rates have reached up to 90% [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. As emphasized by Tong et al. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], vigilant identification of macrolide-resistant MPP (MRMPP) is essential in pediatric patients who show no clinical response to macrolide therapy within 72 hours.\u003c/p\u003e \u003cp\u003eDoxycycline is recommended as the first-line alternative antibiotic for MRMPP, especially in areas with high macrolide resistance[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. However, the potential toxicity of tetracyclines and fluoroquinolones in children necessitates cautious use in pediatric practice[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Concurrently, Yang et al. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] suggested that glucocorticoids may reduce and prevent MPP progression by suppressing aberrant immune responses, inhibiting excessive inflammatory factor release, and mitigating organ damage. This has led to recommendations for glucocorticoid use in severe or refractory MPP [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].Notably, the efficacy of glucocorticoids in pediatric MPP remains controversial. Zhang et al. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e] found Low-dose corticosteroids may not be beneficial in children inpatients with MPP, while Tashiro et al.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] also found that adjunctive treatment with either low-dose or high-dose corticosteroids may not be beneficial for MPP. Additionally, systemic glucocorticoids can lead to various side effects, such as immunosuppression, impacts on growth and development, and neuropsychological effects[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Moreover, the side effects of glucocorticoid therapy in children with MPP remain underexplored, and longitudinal follow-up data regarding disease recurrence after methylprednisolone treatment are still limited.\u003c/p\u003e \u003cp\u003eCurrently, evidence is lacking on whether second-line antibiotics or combinations of azithromycin and glucocorticoids are superior in macrolide-unresponsive MPP (MUMPP). Therefore, this study aims to evaluate the clinical efficacy of doxycycline versus azithromycin combined with methylprednisolone in children with macrolide-unresponsive MPP, providing evidence-based guidance for clinical practice.\u003c/p\u003e"},{"header":"Data and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatient data collection\u003c/h2\u003e\u003cp\u003eHerein, a retrospective analysis was conducted on 1,112 children with MPP and 493 children with MUMPP hospitalized at Bishan Hospital Affiliated to Chongqing Medical University between November 2023 and October 2024. A total of 382 children were finally enrolled in the study. All MPP cases underwent Mycoplasma pneumoniae PCR testing, while mycoplasma culture, drug sensitivity testing, and drug resistance gene analysis were not performed. Diagnoses of MPP, RMPP, and MUMPP were made in accordance with the Guidelines for the Diagnosis and Treatment of Mycoplasma pneumoniae Pneumonia in Children (2023 Edition) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eData were extracted from the electronic medical record system, including gender, age, clinical manifestations, laboratory parameters,complete blood count, C-reactive protein(CRP) interleukin-6, aspartate aminotransferase(AST), alanine aminotransferase(ALT), lactate dehydrogenase(LDH), etc, chest radiography or lung CT findings, and administered pharmacotherapies at admission. Additionally, information was documented on the resolution of clinical symptoms (e.g,fever and cough) following inpatient treatment, performance of bronchoscopic lavage, presence of mixed infections, and admission/discharge dates. Blood routine tests, CRP levels, and chest imaging results within 24 hours prior to discharge were also recorded.\u003c/p\u003e \u003cp\u003eAs previously reported, pulmonary imaging regression in children with RMPP or SMPP typically occurs within 4\u0026ndash;12 weeks [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Outpatient follow-up data within 3 months post-discharge were collected, including new infections, incident illnesses, MPP-related rehospitalization, occurrences of rash and dental discoloration, and results of repeated chest radiography or lung CT scans.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eInclusion criteria and exclusion criteria\u003c/h3\u003e\n\u003cp\u003e Patients were included according to the following criteria:(1) All cases of MPP were confirmed by positive Mycoplasma pneumoniae PCR testing at admission and met the diagnostic criteria for MPP as specified in the guidelines.(2) Patients received initial intravenous azithromycin treatment for 72 hours following MPP diagnosis. A total of 493 MPP cases with persistent fever, lack of clinical/radiographic improvement, or clinical deterioration after 72 hours of treatment were screened, with 382 cases meeting all inclusion criteria.(3) Complete clinical data were required for inclusion.​\u003c/p\u003e \u003cp\u003eExclusion criteria were as follows:(1)Patients with underlying immunocompromising conditions (e.g., congenital heart disease, congenital pulmonary dysplasia) (n\u0026thinsp;=\u0026thinsp;17);​(2) Cases with mixed infections (n\u0026thinsp;=\u0026thinsp;36);​(4)Non-compliance with treatment protocols or voluntary discharge (n\u0026thinsp;=\u0026thinsp;4);​(5)Loss to follow-up during the study period (n\u0026thinsp;=\u0026thinsp;50);​(5)The second-line treatment was changed to levofloxacin (n\u0026thinsp;=\u0026thinsp;4).Ultimately, 382 cases were included in the final analysis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e\n\u003ch3\u003eStudy Design and Definitions\u003c/h3\u003e\n\u003cp\u003eMacrolide-unresponsive MUMPP was defined as MPP cases in which persistent fever, lack of clinical/radiographic improvement, or deterioration occurred after 72 hours of standard macrolide antibiotic therapy. Patients were grouped according to the second - stage treatment regimen into either the azithromycin plus methylprednisolone (AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group) or the oral doxycycline (DXC group).\u003c/p\u003e \u003cp\u003eOf the 382 MUMPP cases, 269 were assigned to the oral DXC group and 113 to the intravenous AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group. For the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group: intravenous azithromycin was administered at 10 mg/kg once daily for 5\u0026ndash;7 days, followed by oral azithromycin for 1\u0026ndash;2 weeks (10 mg/kg taken 3 days/week). Methylprednisolone was dosed at 2 mg/kg every 12 hours for 2\u0026ndash;3 days, then reduced to 2 mg/kg daily for 1\u0026ndash;2 days, with a total course of 3\u0026ndash;5 days. The oral DXC group received doxycycline at 2 mg/kg every 12 hours; children over 45 kg were dosed as adults, with a total course of 10 days.\u003c/p\u003e \u003cp\u003eCases with persistent fever or clinical/radiographic deterioration 4 days after switching to second-line therapy were defined as refractory MPP: the DXC group received additional methylprednisolone or switched to intravenous levofloxacin, while the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group shifted to oral DXC or intravenous levofloxacin.\u003c/p\u003e\n\u003ch3\u003eEvaluation of efficacy\u003c/h3\u003e\n\u003cp\u003eAt discharge, treatment efficacy was evaluated as follows: complete resolution of clinical symptoms (e.g., fever, cough) and significant absorption of pulmonary inflammation on imaging was defined as \"markedly effective\"; partial absorption as \"effective\"; and no absorption or progression as \"ineffective\" (effective/markedly effective\u0026thinsp;=\u0026thinsp;1; ineffective\u0026thinsp;=\u0026thinsp;0). Refractory mycoplasma pneumoniae pneumonia (RMPP) was defined as persistent fever 4 days after treatment adjustment, exacerbation of clinical signs or imaging findings, or development of extrapulmonary complications (yes\u0026thinsp;=\u0026thinsp;1; no\u0026thinsp;=\u0026thinsp;0).\u003c/p\u003e \u003cp\u003eDuring the 3 - month follow - up, outcomes included: complete resolution of pulmonary inflammation on imaging (yes\u0026thinsp;=\u0026thinsp;1; no\u0026thinsp;=\u0026thinsp;0), readmission due to MPP (yes\u0026thinsp;=\u0026thinsp;1; no\u0026thinsp;=\u0026thinsp;0), and occurrence of new infections or diseases (yes\u0026thinsp;=\u0026thinsp;1; no\u0026thinsp;=\u0026thinsp;0).\u003c/p\u003e\n\u003ch3\u003eSample size calculation method\u003c/h3\u003e\n\u003cp\u003eThe primary outcome measure of this study was the incidence rate of new infections or diseases within 3 months post-intervention. The required sample size for this study was calculated using a formula designed to compare rate differences between groups, as outlined below:\u003cdiv id=\"Equa\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equa\" name=\"EquationSource\"\u003e\n$$\\:{N}_{B}=\\left(\\frac{{p}_{A}\\left(1-{p}_{A}\\right)}{k}+{p}_{B}\\left(1-{p}_{B}\\right)\\right)\\frac{{\\left({Z}_{1-\\alpha\\:/2}+{Z}_{1-\\beta\\:}\\right)}^{2}}{{\\left({p}_{A}-{p}_{B}\\right)}^{2}}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cp\u003eIn the preliminary experiment, 20 cases were recruited in each of the two groups. The incidence of new infections or diseases within 3 months was 10% in the DXC group and 40% in the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group. Based on a Type I error (α) of 0.05, a statistical power (1-β) of 0.9, and a 1:1 allocation ratio between the two groups, a sample size of 39 cases per group was calculated. Accounting for a 5% dropout rate during follow-up, at least 41 cases were required in both the DXC group and the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group.\u003cdiv id=\"Equb\" class=\"Equation\"\u003e\u003cdiv format=\"TEX\" class=\"mathdisplay\" id=\"FileID_Equb\" name=\"EquationSource\"\u003e\n$$\\:{N}_{B}=\\left({p}_{A}\\left(1-{p}_{A}\\right)+{p}_{B}\\left(1-{p}_{B}\\right)\\right)\\frac{{\\left({Z}_{1-\\alpha\\:/2}+{Z}_{1-\\beta\\:}\\right)}^{2}}{{\\left({p}_{A}-{p}_{B}\\right)}^{2}}$$\u003c/div\u003e\u003c/div\u003e\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eFor normally distributed continuous variables, data were presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (x\u0026thinsp;\u0026plusmn;\u0026thinsp;s), and comparisons between groups were performed using the independent samples t - test. For skewed continuous variables, data were presented as median (interquartile range) [M(P25, P75)], and comparisons between groups were carried out using the Mann - Whitney U test. Categorical variables were described by counts and percentages, and comparisons between groups were analyzed using the chi - square test or Fisher's exact test. Propensity score matching (PSM) was used to balance potential confounding factors between the DXC group and the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group at a 1:1 ratio, employing the greedy nearest neighbor matching algorithm. After matching, the standardized mean differences (SMD) of covariates were calculated to assess the balance of baseline characteristics, with SMD\u0026thinsp;\u0026lt;\u0026thinsp;0.2 indicating adequate balance. Statistical power was calculated using PASS 2021 software. All statistical tests were two - sided, and statistical significance was set at P\u0026thinsp;\u0026lt;\u0026thinsp;0.05. Data analysis was performed using SAS 9.4 software (Copyright \u0026copy;2016 SAS Institute Inc., Cary, NC, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population and clinical characteristics\u003c/h2\u003e \u003cp\u003eAmong 1112 children with MPP, 493 were diagnosed with MUMPP, giving an incidence of 44.33% (493/1112). After excluding cases with mixed infections [incidence 7.30% (36/493)], a total of 382 patients were included in the study (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Sputum culture and respiratory pathogen nucleic acid testing confirmed no co-infections in either group, and none of the included patients received human immunoglobulin or other immunotherapies during treatment.\u003c/p\u003e \u003cp\u003eThe 382 patients had a mean age of 7.01\u0026thinsp;\u0026plusmn;\u0026thinsp;2.33 years, including 188 males and 194 females. Refractory MPP occurred in 20 cases (5.24%, 20/382): 8 cases (2.97%, 8/269) in the DXC group, of which 6 were treated with combined methylprednisolone and 2 were switched to levofloxacin plus methylprednisolone; 12 cases (10.62%, 12/113) in the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group, of which 10 were switched to doxycycline and 2 to levofloxacin. All patients were discharged after effective treatment, and none required admission to the ICU.\u003c/p\u003e \u003cp\u003e2.2 Baseline data comparison\u003c/p\u003e \u003cp\u003eBefore PSM, significant differences were observed between the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group and the DXC group in terms of age, hypoxemia, white blood cell count, lymphocyte count, LDH, AST, and ferritin levels (all P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eOne-to-one Greedy Nearest Neighbor Matching was performed using propensity score matching (PSM) to balance baseline characteristics between the two groups. After matching, no significant differences were found in any baseline variables, and all standardized mean differences (SMDs) were \u0026lt;\u0026thinsp;0.2, indicating adequate balance of covariates between the two groups (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Baseline Data Before and After Matching Between the DXC Group and the AZM\u0026thinsp;+\u0026thinsp;Methylprednisolone\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c5\" namest=\"c2\"\u003e \u003cp\u003eBefore matching\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c10\" namest=\"c7\"\u003e \u003cp\u003eAfter Match\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDXC (n\u0026thinsp;=\u0026thinsp;269)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAZM\u0026thinsp;+\u0026thinsp;methylprednisolone\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;113)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSMD\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eDXC (n\u0026thinsp;=\u0026thinsp;70)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eAZM\u0026thinsp;+\u0026thinsp;methylprednisolone\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;70)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eSMD\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (y), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.67\u0026thinsp;\u0026plusmn;\u0026thinsp;2.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.36\u0026thinsp;\u0026plusmn;\u0026thinsp;2.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e1.420\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1.88\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e6.38\u0026thinsp;\u0026plusmn;\u0026thinsp;2.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.871\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e137 (50.93%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51 (45.13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.301\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.116\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e34 (48.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e32 (45.71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.735\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.057\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDays of onset, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.97\u0026thinsp;\u0026plusmn;\u0026thinsp;2.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.40\u0026thinsp;\u0026plusmn;\u0026thinsp;2.57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.054\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.219\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.40\u0026thinsp;\u0026plusmn;\u0026thinsp;2.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.47\u0026thinsp;\u0026plusmn;\u0026thinsp;2.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.868\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.028\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBronchoscopy lavage no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e59 (21.93%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (24.78%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.545\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.067\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e19 (27.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e18 (25.71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.848\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypoxemia no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17 (6.32%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (14.16%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.261\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7 (10.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5 (7.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.546\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.102\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtelectasis no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (2.23%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3.54%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.704\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 (2.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2 (2.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBronchiectasis no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (2.60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (2.65%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 (2.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2 (2.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePleural effusion no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (3.35%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3.54%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3 (4.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 (4.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung consolidation no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e173 (64.31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71 (62.83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.783\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e49 (70.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e47 (67.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.716\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.062\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtrapulmonary complications no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (2.97%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3.54%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.999\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 (1.43%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3 (4.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.620\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.172\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (\u0026times;10\u003csup\u003e9\u003c/sup\u003e /L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7.10\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.70\u0026thinsp;\u0026plusmn;\u0026thinsp;2.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.259\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.06\u0026thinsp;\u0026plusmn;\u0026thinsp;2.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.36\u0026thinsp;\u0026plusmn;\u0026thinsp;2.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.388\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.146\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMesogranulocytes (\u0026times;10\u003csup\u003e9\u003c/sup\u003e /L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.57\u0026thinsp;\u0026plusmn;\u0026thinsp;1.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.90\u0026thinsp;\u0026plusmn;\u0026thinsp;2.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.158\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.61\u0026thinsp;\u0026plusmn;\u0026thinsp;1.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.564\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.098\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes (\u0026times;10\u003csup\u003e9\u003c/sup\u003e /L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.18\u0026thinsp;\u0026plusmn;\u0026thinsp;0.97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.007\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.330\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.96\u0026thinsp;\u0026plusmn;\u0026thinsp;0.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2.10\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.355\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.157\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count (\u0026times;10\u003csup\u003e9\u003c/sup\u003e /L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e267.20\u0026thinsp;\u0026plusmn;\u0026thinsp;82.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e269.65\u0026thinsp;\u0026plusmn;\u0026thinsp;75.66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.787\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e258.20\u0026thinsp;\u0026plusmn;\u0026thinsp;69.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e264.61\u0026thinsp;\u0026plusmn;\u0026thinsp;78.87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.611\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.086\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/L), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12.50 (6.20, 23.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.60 (6.37, 19.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.460\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.083\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12.14 (5.70, 24.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10.37 (6.88, 28.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.796\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLDH (U/L)median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e280 (246319).\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e316 (279361).\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.549\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e292.50 (262.00, 326.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e293.00 (263.00, 328.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.846\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.033\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eALT(U/L)median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (10, 15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (10 dec)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.774\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.032\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e12.00 (10.00, 15.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e12.00 (10.00, 15.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.920\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.035\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAST(U/L)median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (22, 31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (4) 27\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.770\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e29.00 (26.00, 34.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e30.00 (26.00, 34.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.645\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.024\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFerritin (U/L) median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e93.70 (72.30, 123.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e81.40 (61.20, 111.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e87.85 (66.40, 111.90)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e79.60 (57.60, 111.60)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.300\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c10\"\u003e \u003cp\u003e0.175\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eComparison of blood routine and CRP indicators at discharge between the two groups.\u003c/b\u003e \u003c/p\u003e \u003cp\u003ePSM analysis revealed that, compared with the DXC group, the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group exhibited significantly higher mean white blood cell count, mean granulocyte count, and mean platelet count, as well as lower CRP levels at discharge (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Following treatment, the white blood cell count and mean granulocyte count in the DXC group demonstrated a downward trend, whereas these parameters in the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group showed an upward trend. The intergroup differences were statistically significant (P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), as detailed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Blood Routine and CRP Indicators Before and After Matching in the DXC Group and the AZM\u0026thinsp;+\u0026thinsp;Methylprednisolone Group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"8\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eBefore matching\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eAfter Match\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDXC (n\u0026thinsp;=\u0026thinsp;269)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAZM\u0026thinsp;+\u0026thinsp;methylprednisolone\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;113)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDXC (n\u0026thinsp;=\u0026thinsp;70)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAZM\u0026thinsp;+\u0026thinsp;methylprednisolone\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;70)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWhen discharged\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (\u0026times;10\u003csup\u003e9\u003c/sup\u003e /L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.50\u0026thinsp;\u0026plusmn;\u0026thinsp;1.96\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.62\u0026thinsp;\u0026plusmn;\u0026thinsp;3.47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.91\u0026thinsp;\u0026plusmn;\u0026thinsp;2.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e9.61\u0026thinsp;\u0026plusmn;\u0026thinsp;3.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMesogranulocytes (\u0026times;10\u003csup\u003e9\u003c/sup\u003e /L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.90\u0026thinsp;\u0026plusmn;\u0026thinsp;3.01\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.45\u0026thinsp;\u0026plusmn;\u0026thinsp;1.59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.14\u0026thinsp;\u0026plusmn;\u0026thinsp;3.05\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes (\u0026times;10\u003csup\u003e9\u003c/sup\u003e /L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.61\u0026thinsp;\u0026plusmn;\u0026thinsp;0.98\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.10\u0026thinsp;\u0026plusmn;\u0026thinsp;1.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.82\u0026thinsp;\u0026plusmn;\u0026thinsp;1.26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.90\u0026thinsp;\u0026plusmn;\u0026thinsp;1.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.755\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count (\u0026times;10\u003csup\u003e9\u003c/sup\u003e /L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e342.15\u0026thinsp;\u0026plusmn;\u0026thinsp;105.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e429.33\u0026thinsp;\u0026plusmn;\u0026thinsp;136.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e371.61\u0026thinsp;\u0026plusmn;\u0026thinsp;124.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e421.63\u0026thinsp;\u0026plusmn;\u0026thinsp;138.12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.040\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/L), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.90 (1.15, 5.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.99 (0.60, 4.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.21 (1.60, 6.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.10 (0.70, 4.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.049\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDifference (at discharge minus admission)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (\u0026times;10\u003csup\u003e9\u003c/sup\u003e /L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-0.66\u0026thinsp;\u0026plusmn;\u0026thinsp;2.43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.93\u0026thinsp;\u0026plusmn;\u0026thinsp;3.86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-0.28\u0026thinsp;\u0026plusmn;\u0026thinsp;2.79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.29\u0026thinsp;\u0026plusmn;\u0026thinsp;3.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMesogranulocytes (\u0026times;10\u003csup\u003e9\u003c/sup\u003e /L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-1.21\u0026thinsp;\u0026plusmn;\u0026thinsp;2.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.97\u0026thinsp;\u0026plusmn;\u0026thinsp;3.51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-1.14\u0026thinsp;\u0026plusmn;\u0026thinsp;2.20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.54\u0026thinsp;\u0026plusmn;\u0026thinsp;3.15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocytes (\u0026times;10\u003csup\u003e9\u003c/sup\u003e /L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.75\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.96\u0026thinsp;\u0026plusmn;\u0026thinsp;1.63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.214\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.89\u0026thinsp;\u0026plusmn;\u0026thinsp;1.23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.83\u0026thinsp;\u0026plusmn;\u0026thinsp;1.67\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.823\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count (\u0026times;10\u003csup\u003e9\u003c/sup\u003e /L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e78.76\u0026thinsp;\u0026plusmn;\u0026thinsp;104.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e158.40\u0026thinsp;\u0026plusmn;\u0026thinsp;123.82\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e113.80\u0026thinsp;\u0026plusmn;\u0026thinsp;124.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e155.43\u0026thinsp;\u0026plusmn;\u0026thinsp;131.69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.078\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCRP (mg/L), median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.26 (19.45, 4.69)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.21 (13.19, 4.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.173\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.60 (16.20, 5.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.80 (13.62, 4.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c8\"\u003e \u003cp\u003e0.330\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Outcome Measures Before and After Matching Between the DXC Group and the AZM\u0026thinsp;+\u0026thinsp;Methylprednisolone Group\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eBefore matching\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c9\" namest=\"c6\"\u003e \u003cp\u003eAfter Match\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDXC (n\u0026thinsp;=\u0026thinsp;269)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eAZM\u0026thinsp;+\u0026thinsp;methylprednisolone\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;113)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDXC (n\u0026thinsp;=\u0026thinsp;70)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eAZM\u0026thinsp;+\u0026thinsp;methylprednisolone\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;70)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eMD(95%CI)/\u003c/p\u003e \u003cp\u003eOR(95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAntipyretic time day,median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1, 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1, 3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.240\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2 (1, 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 (1, 3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (1, 0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.703\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCough relief time day,median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (2, 5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (3, 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.048\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (2, 5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4 (2, 6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1 (0, 1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.111\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDays in hospital,median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (5, 7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (7, 9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6 (5, 7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8 (7, 9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e2 (1, 2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of adverse reactions.(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (3.72%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (5.31%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.668\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (5.80%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2 (2.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.18 (0.46, 38.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.681\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of cases of refractory MPP (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (2.97%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (10.62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (4.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e10 (14.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e3.72 (0.98, 14.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of cases with significantly effective discharge imaging (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e155 (57.62%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (23.01%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e33 (47.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e19 (27.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.42 (0.21, 0.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of cases with ineffective discharge imaging (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (4.46%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (26.55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4 (5.71%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e16 (22.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.89 (1.54, 15.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of effective cases shown by discharge imaging no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e257 (95.54%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83 (73.45%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e66 (94.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e54 (77.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e4.89 (1.54, 15.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of rehospitalizations due to MPP within 3 months (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (0.74%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.77%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.585\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1 (1.43%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e9.54 (2.90, 31.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of new infections or diseases within 3 months (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (8.55%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42 (37.17%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3 (4.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e23 (32.86%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e10.93 (3.10, 38.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThe number of cases with complete imaging absorption within 3 months no. (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e264 (98.14%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e107 (94.69%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e69 (98.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e66 (94.29%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.24 (0.03, 2.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e \u003cp\u003e0.366\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eComparison of Therapeutic Efficacy and Imaging Findings at Discharge Between the Two Groups\u003c/h2\u003e \u003cp\u003eFollowing PSM, the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group had a longer length of hospital stay [8 (7, 9) vs. 6 (5, 7) days, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, statistical power\u0026thinsp;=\u0026thinsp;0.999] and a higher refractory rate (14.29% vs. 4.29%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, statistical power\u0026thinsp;=\u0026thinsp;0.543) compared with the DXC group. The DXC group exhibited higher rates of marked efficacy (47.14% vs. 27.14%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, statistical power\u0026thinsp;=\u0026thinsp;0.849) and efficacy (94.29% vs. 77.14%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, statistical power\u0026thinsp;=\u0026thinsp;0.706) in imaging findings at discharge than the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group.\u003c/p\u003e \u003cp\u003eThere were no significant differences between the two groups in the days to defervescence after medication, days to cough resolution after medication, or adverse reaction rate (all P\u0026thinsp;\u0026gt;\u0026thinsp;0.05, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eComparison of 3-Month Follow-Up Outcomes and Prognosis Between the Two Groups\u003c/h2\u003e \u003cp\u003eDuring the 3-month follow-up, new infections or diseases occurred in 23 cases of the DXC group, including 2 cases of acute urticaria, 1 case of pertussis, 17 cases of upper respiratory tract infection, and 3 cases of lower respiratory tract infection. In the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group, 42 cases developed new infections or diseases, including 25 cases of upper respiratory tract infection, 7 cases of lower respiratory tract infection, 5 cases of acute urticaria, 3 cases of bronchial asthma, 1 case of acute enteritis, and 1 case of viral encephalitis. The incidence of new infections or diseases was significantly higher in the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group than in the DXC group (32.86% vs. 4.29%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05, statistical power\u0026thinsp;=\u0026thinsp;0.997).\u003c/p\u003e \u003cp\u003eTwo cases in the DXC group and two cases in the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group were readmitted due to MPP during the follow-up period, with no significant difference in the 3-month readmission rate between the two groups (0.00% vs. 1.43%, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). There was also no significant difference in the rate of complete pulmonary imaging resolution between the two groups (98.57% vs. 94.29%, P\u0026thinsp;\u0026gt;\u0026thinsp;0.05, Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). No adverse reactions such as tooth discoloration were observed in the 269 children of the doxycycline group during the 3-month follow-up.\u003c/p\u003e "},{"header":"Discussion","content":"\u003cp\u003eMycoplasma pneumoniae (M. pneumoniae) is one of the most important pathogens of community-acquired pneumonia (CAP) in children. MPP is typically mild and even exhibits self-limiting characteristics [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. During 2023\u0026ndash;2024, China experienced a large-scale Mycoplasma pneumoniae (MP) outbreak, with notably increased reports of RMPP and SMPP compared to previous years [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Since 2000, the prevalence of Pneumonia Mycoplasma resistant to macrolide (MRMP) has been rising annually, particularly in East Asian countries such as Japan, China, and South Korea, with macrolide resistance rates reaching up to 90% in some regions [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. MRMP infections inevitably lead to a series of clinical challenges, including prolonged fever, extended hospital stays, increased severe cases, and difficulties in antibiotic selection [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Early identification of MRMP is particularly critical. Tong et al. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] recommended that if MPP children show no response to macrolide therapy within the initial 3 days, MRMPP should be suspected, and further treatment initiated.In this study, the prevalence of MUMPP was 44.33%, higher than the 16.3% reported by Ha et al. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] during January 2015 to April 2017 in South Korea. Due to the lack of facilities for MP resistance testing in our hospital, we could not determine the proportion of MRMP. RMPP cases numbered 20 (5.19%, 20/385), lower than the 21.17% (47/173) reported by Ma et al. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] in 173 MUMPP children from Baoji, China, during 2023. This discrepancy might relate to over two-thirds of children in our study being switched to doxycycline treatment.\u003c/p\u003e \u003cp\u003eIt is currently recognized that abnormal host immune responses, mixed infections, or macrolide resistance may be associated with MUMPP [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In this study, 36 cases of mixed infections were excluded, accounting for 7.30% (36/493), which was slightly lower than the 8%-60% incidence of viral/bacterial co-infections with MP reported in previous pediatric studies [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Macrolide antibiotics have long been the first-line treatment for MPP, though the clinical relevance of macrolide-resistant strains in refractory MPP remains controversial [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Tong et al. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] recommended suspecting MRMP in MPP children unresponsive to macrolides within 3 days, with doxycycline suggested as the preferred alternative antibiotic for macrolide-resistant MPP. However, Ha et al. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] reported that second-line therapy showed no better efficacy than prolonged macrolide treatment in MUMPP. Additionally, concerns exist regarding the use of tetracyclines or fluoroquinolones in children due to potential toxicities, such as tooth discoloration and enamel hypoplasia in children under 8 years with tetracyclines, and irreversible arthropathy with fluoroquinolones [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].This study found that compared with the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group, the DXC group had shorter hospital stays [8 (7,9) vs. 6 (5,7) days, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05], fewer refractory MPP cases (14.29% vs. 4.29%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and higher imaging improvement rates at discharge (77.14% vs. 94.29%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), consistent with Ahn et al. [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] who reported that tetracyclines shorten fever duration and hospital stays in MRMP-infected patients. No tooth discoloration was observed in DXC group children during the 3-month follow-up, suggesting that switching to doxycycline is more effective and relatively safe for short-term use in MUMPP compared with azithromycin plus methylprednisolone. Todd et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] reported that short-course doxycycline (\u0026le;\u0026thinsp;10 days) in children\u0026thinsp;\u0026lt;\u0026thinsp;8 years for MPP treatment does not cause tooth darkening, visible staining, or increased enamel hypoplasia risk. Furthermore, Lee et al.suggest in countries where macrolide-resistance rates are high, a second-line antibiotic such as doxycycline should be used for severe MPP early, even in children younger than 2 years old. However, 8 cases in the DXC group developed refractory MPP, 6 of which required combined methylprednisolone treatment, indicating that abnormal host immune responses may contribute to some RMPP cases.\u003c/p\u003e \u003cp\u003eThe direct correlation between host immune responses and RMPP remains undefined. Evidence shows that children with MPP receiving immunosuppressive therapy exhibit significantly lower incidences of severe MPP and complications than those not receiving immunotherapy [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Some studies report that pulmonary neutrophil infiltration is widely recognized as a hallmark of MPP, with disease exacerbation linked to enhanced T-cell activation and neutrophil-mediated immune responses [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Researchers suggest that early glucocorticoid therapy in children with RMPP or SMPP can effectively suppress abnormal immune responses, mitigate excessive release of inflammatory cytokines, and prevent disease progression and organ damage [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. A 2020 meta-analysis of 12 randomized controlled trials (RCTs) found that systemic glucocorticoids combined with azithromycin significantly improved total effective rate in children with RMPP compared to conventional therapy (OR\u0026thinsp;=\u0026thinsp;6.37, 95% CI\u0026thinsp;=\u0026thinsp;4.03\u0026ndash;10.07, P\u0026thinsp;\u0026lt;\u0026thinsp;0.001) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. However, the efficacy of glucocorticoids in MPP treatment remains controversial, prompting increasing calls for prudent use of these agents. Zhang et al. [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] suggested that low-dose corticosteroids may not benefit hospitalized children with MPP, while Bleecker et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] reported no benefits of low-dose glucocorticoids even in severe or refractory pneumonia. Additionally, Wang et al. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] recommended against routine use of systemic glucocorticoids in MRMP pneumonia.This study found that compared with the DXC group, the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group had longer hospital stays, a higher rate of refractory MPP, and lower imaging improvement rates at discharge. Twelve cases in the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group developed refractory MPP, of which 10 were switched to doxycycline and 2 to levofloxacin.\u003c/p\u003e \u003cp\u003eCurrently, there is limited literature on the follow-up of azithromycin combined with methylprednisolone therapy. Studies have shown that systemic intravenous glucocorticoids can induce multiple side effects, including immunosuppression, growth suppression, and neuropsychological impacts [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. During the 3-month follow-up period of this study, new infections or diseases occurred in 23 cases of the doxycycline group and 42 cases of the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group. The AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group exhibited a significantly higher incidence of post-discharge new infections or diseases than the DXC group (36.52% vs. 7.43%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). No significant intergroup difference was observed in the rate of drug-related adverse reactions. Additionally, Tashiro et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] reported that adjunctive therapy with low-dose or high-dose corticosteroids was associated with prolonged hospital stays and higher medication costs during hospitalization.\u003c/p\u003e \u003cp\u003eThis study has several limitations that require acknowledgment. First, it was a retrospective, single-center study with a relatively small sample size, and findings should be validated by prospective, multicenter studies. Second, the follow-up period for adverse reactions of doxycycline (e.g., tooth discoloration) was short, precluding a comprehensive safety assessment of doxycycline in this population. Third, chest radiographs were the primary imaging modality used during follow-up, which may have underestimated pulmonary sequelae such as bronchiolitis obliterans in some children. Fourth, macrolide resistance testing was not performed, preventing us from determining the prevalence of macrolide-resistant strains in this cohort.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn summary, this study demonstrates that oral doxycycline more effectively improves pulmonary imaging findings at discharge and reduces the risk of refractory pneumonia in children with MUMPP compared with azithromycin plus methylprednisolone. Combination therapy with methylprednisolone may be necessary for severe or refractory cases but should be used judiciously. Patients treated with azithromycin plus methylprednisolone had prolonged hospital stays and a higher risk of developing new infections or diseases post-discharge.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eMP Mycoplasma pneumoniae\u003c/p\u003e \u003cp\u003eMPP Mycoplasma pneumoniae pneumonia\u003c/p\u003e \u003cp\u003eMUMPP Macrolide-unresponsive mycoplasma pneumoniae pneumonia\u003c/p\u003e \u003cp\u003eMRMP Macrolide-resistant Mycoplasma pneumoniae\u003c/p\u003e \u003cp\u003eRMPP Refractory Mycoplasma pneumoniae pneumonia\u003c/p\u003e \u003cp\u003eSMPP Severe Mycoplasma pneumoniae pneumonia\u003c/p\u003e \u003cp\u003eWBC White blood cell count\u003c/p\u003e \u003cp\u003eCRP C-reactive protein\u003c/p\u003e \u003cp\u003eAST Aspartate transaminase\u003c/p\u003e \u003cp\u003eALT Aalanine transaminase\u003c/p\u003e \u003cp\u003eLDH Lactate dehydrogenase\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study strictly adhered to the ethical principles outlined in the Declaration of Helsinki for human medical research and was approved by the Ethics Committee of the Bishan Hospital of Chongqing Medical University (approval number: Cqbykyll-29240918-79).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs a retrospective study, consent and informed consent were obtained from \u0026nbsp; all patients or the patient\u0026rsquo;s legal guardian(s) and/or their parents prior to study commencement.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contribution\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eKZ.wrote the main text of the manuscript. S.h.Z.Sprepared all the fgures of the manuscript. Z.b.H. contributed to drafting and revising the article. All authors read and approved \u0026nbsp;the fnal version of the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll cases source was the electronic medical records of Bishan Hospital of Chongqing Medical University from November 2023 to June 2024. We assure the accuracy and reliability of the data used, and the datasets used and/or analysed during the current study available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conficts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by Chongqing Bishan District Science and Technology Bureau(No. BSJ2024013,BSJ2024012).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study would not have been possible without the excellent support from \u0026nbsp; clinical staf from the Department of paediatrics,Bishan Hospital of Chongqing Medical University.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eDepartment of paediatrics,Bishan Hospital of Chongqing Medical University, Chongqing 402760, China (Chongqing Bishan District People\u0026apos;s Hospital). \u003csup\u003e2\u003c/sup\u003eDepartment of Nursing, Chongqing Medical University, Chongqing 402760, China.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDing G, Zhang X, Vinturache A, et al. 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BMC Pulm Med. 2017;17(1):219. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12890-017-0566-4\u003c/span\u003e\u003cspan address=\"10.1186/s12890-017-0566-4\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Azithromycin, doxycycline, macrolide-unresponsive Mycoplasma pneumoniae pneumonia, children","lastPublishedDoi":"10.21203/rs.3.rs-6821333/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6821333/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe escalating prevalence of macrolide-resistant Mycoplasma pneumoniae (MRMP) in China has posed substantial challenges for pediatricians managing mycoplasma pneumoniae pneumonia (MPP). This study aimed to compare the clinical efficacy and prognostic outcomes between two treatment strategies for pediatric patients with macrolide-unresponsive mycoplasma pneumoniae pneumonia (MUMPP) following initial 72-hour intravenous azithromycin therapy: 1) continuation of intravenous azithromycin combined with methylprednisolone, versus 2) switch to oral doxycycline monotherapy.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe performed a retrospective analysis of children hospitalized for MPP at our institution between November 2023 and October 2024. Children with MPP who showed no clinical response to an initial 72-hour course of intravenous azithromycin were assigned to two groups: 1) intravenous azithromycin combined with methylprednisolone (AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group), and 2) doxycycline monotherapy (DXC group). Clinical efficacy and prognosis were compared between groups using 1:1 propensity score matching (PSM) to adjust for baseline confounding, followed by calculation of statistical power for the primary outcomes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA total of 1,112 children with MPP were screened, of whom 493 (44.33%) met the criteria for MUMPP, and 382 were included in the final analysis. The DXC group showed a significantly higher rate of pulmonary imaging improvement at discharge compared to the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group (94.29%vs.77.14%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). No significant intergroup differences were observed in the time to fever resolution or cough relief (P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group had a significantly longer hospital stay than the DXC group [8 (7, 9) days vs. 6 (5, 7) days, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05]. Additionally, the refractory rate was higher in the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group (14.29% vs. 4.29%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05). At 3-month follow-up, the incidence of new infections or diseases was significantly higher in the AZM\u0026thinsp;+\u0026thinsp;methylprednisolone group (32.86% vs. 4.29%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), whereas no significant difference was found in the complete imaging absorption rate between groups within 3 months (98.57% vs. 94.29%,P\u0026thinsp;\u0026gt;\u0026thinsp;0.05). Notably, no cases of tooth discoloration-related adverse reactions were observed in the DXC group.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eDXC demonstrated significantly greater efficacy than AZM\u0026thinsp;+\u0026thinsp;methylprednisolone in resolving radiographic abnormalities at discharge among MUMPP patients. AZM\u0026thinsp;+\u0026thinsp;methylprednisolone combination therapy correlated with longer hospital stays, higher rates of refractory MPP, and increased post-discharge risks of new infections or diseases.\u003c/p\u003e","manuscriptTitle":"Clinical Efficacy Comparison of Doxycycline versus Azithromycin Combined with Methylprednisolone in the Treatment of macrolide-unresponsive Mycoplasma pneumoniae pneumonia in children","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-06-17 15:49:11","doi":"10.21203/rs.3.rs-6821333/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"94979533-a0dd-42a8-a100-5b68884b19a9","owner":[],"postedDate":"June 17th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-11-01T01:53:11+00:00","versionOfRecord":[],"versionCreatedAt":"2025-06-17 15:49:11","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6821333","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6821333","identity":"rs-6821333","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}