Clinical characteristics and outcomes of macrolide-resistant Mycoplasma pneumoniae infection in hospitalized children: a single-center retrospective cohort study in Chengdu, China
Highlight box
Key findings
• This study identified a high prevalence (54.3%) of macrolide-resistant Mycoplasma pneumoniae (MRMP) in children with pneumonia in Chengdu. MRMP infection was associated with more severe disease and a higher risk of refractory Mycoplasma pneumoniae pneumonia (RMPP). A model using fever duration, D-dimer, and mucus plugs effectively predicted RMPP risk (area under the curve =0.918).
What is known and what is new?
• MRMP is a growing global health concern, particularly prevalent in East Asia. It is a significant cause of community-acquired pneumonia in children and is frequently associated with treatment failure, more severe clinical presentations, and an increased risk of developing extrapulmonary complications.
• This study provides crucial, novel data on the high prevalence and specific molecular characteristics (exclusively the A2063G mutation) of MRMP infections among pediatric pneumonia patients in Chengdu, China. It further proposes a novel, practical prediction model using three readily available parameters—fever duration, D-dimer levels, and mucus plugs—to early identify children with MRMP at highest risk for progressing to RMPP.
What is the implication, and what should change now?
• Clinicians should suspect MRMP in severe or non-responsive cases. The model, after further validation, can help identify high-risk children early, guiding intensified monitoring and timely intervention to improve outcomes and optimize resource use.
Introduction
Mycoplasma pneumoniae (MP) is a leading cause of community-acquired pneumonia in children worldwide (1). Epidemics typically occur cyclically every 3–7 years, each lasting 1–2 years (2,3). Since June 2023, China has experienced a notable surge in MP infections, with emerging evidence suggesting the dominance of macrolide-resistant Mycoplasma pneumoniae (MRMP) strains (4,5). Resistance is primarily mediated by point mutations (e.g., A2063G, A2064G) in domain V of the 23S rRNA gene, hindering macrolide binding (6). First identified in Japan in 1968 (7), MRMP has become increasingly prevalent globally, especially across East Asia (8,9).
Macrolide resistance compromises first-line treatment efficacy, potentially leading to prolonged symptoms, extended hospitalization, disease progression during therapy, and increased complication rates (10,11). Furthermore, MRMP infection is significantly associated with the development of refractory Mycoplasma pneumoniae pneumonia (RMPP), a severe complication characterized by persistent fever and clinical deterioration despite appropriate antibiotic therapy (12). While previous studies have reported on MRMP’s prevalence and impact, findings regarding its effect on disease severity and complications remain inconsistent (13-16). Some studies report no significant differences in clinical severity (13-15), while others, including from China, indicate more severe manifestations and higher complication rates in MRMP infections (11,16). The specific drivers of progression from MRMP to RMPP are not fully elucidated, and predictive tools for early identification are lacking.
This single-center retrospective study aimed to: (I) describe the prevalence and clinical characteristics of MRMP infection among hospitalized children with MPP in Chengdu, China; (II) compare disease severity and outcomes between MRMP and non-MRMP infections; (III) identify risk factors associated with progression to RMPP among MRMP-infected children; and (IV) develop and evaluate a predictive model for early identification of children at high risk for RMPP. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-290/rc).
Methods
Study design and participants
This single-center retrospective study was conducted at Chengdu Women’s and Children’s Central Hospital. We enrolled hospitalized pediatric patients aged from 5 months to 14 years (median: 7 years) who were diagnosed with MPP between February 2023 and May 2024. A total of 298 pediatric patients with MPP were initially deemed eligible for inclusion. After excluding 123 patients based on the criteria, 175 (58.7%) were finally enrolled in the study. Based on the detection of 23S rRNA gene mutations in MP obtained from bronchoalveolar lavage fluid (BALF), the patients were divided into an MRMP group (n=95) and a non-MRMP group (n=80). The MRMP group was further subdivided into RMPP (n=30) and non-RMPP (n=65) subgroups based on clinical criteria. The sample size was determined by the number of eligible cases during the study period; however, we acknowledge that the sample, particularly for subgroup analyses, may limit the statistical power of some findings.
This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of Chengdu Women’s and Children’s Central Hospital [No. 2024(26)]. Requirement for informed consent was waived due to the retrospective nature of the study.
Diagnostic criteria
The diagnosis of MPP was based on the 2023 edition of the Guidelines for the Diagnosis and Treatment of Mycoplasma Pneumonia in Children (17). The diagnostic criteria for MPP were: (I) patients with symptoms such as fever, cough, wheezing; (II) physical signs presenting dry or wet rales; (III) lungs imaging shows pneumonia; (IV) evidence of MP infection based on MP positivity on multiplex polymerase chain reaction (PCR) performed using nasopharyngeal swab or a highly elevated serological MP-IgM titer ≥1:160. RMPP was defined as still experience persistent fever, symptoms of clinical, radiological deterioration and the occurrence of extrapulmonary complications despite macrolide antibiotic therapy lasting 7 days or more (17).
Inclusion and exclusion criteria
The inclusion criteria were as follows: (I) age between 1 month and 18 years; (II) meeting at least one indication for fiberoptic bronchoscopy (FOB) according to the Guidelines for the Diagnosis and Treatment of MPP in Children and Pediatric Bronchoscopy Standards (17,18), including: (i) severe pneumonia with persistent lobar consolidation or atelectasis; (ii) suspected endobronchial complications (e.g., mucus plugging or bronchial obstruction); (iii) etiological investigation of unresolved lower respiratory tract infection; or (iv) chronic cough lasting >4 weeks; (III) positivity for MP nucleic acid in BALF; and (IV) detection of mutations in domain V of the MP 23S rRNA gene.
The exclusion criteria included: (I) low load of MP nucleic acid in BALF; (II) incomplete medical records; and (III) comorbidities such as malignant hematologic diseases, neuromuscular disorders, or inherited metabolic disorders.
Clinical data collection and detection of mutations in domain V of the MP 23S rRNA gene
The following data were extracted from electronic medical records: demographics; clinical symptoms; physical signs on admission; laboratory parameters; high-resolution computed tomography findings; FOB results; hospital duration; and final diagnosis. Baseline demographic and clinical characteristics assessed at admission included: age, sex, duration of fever and cough prior to admission, presence of dyspnea, and auscultatory findings. Vital signs and basic laboratory tests [white blood cell (WBC), C-reactive protein (CRP), procalcitonin (PCT), D-dimer] were recorded. All laboratory testing was performed within 3 days of admission and before the administration of corticosteroids. Clinical course during hospitalization was monitored, including fever duration (total and post-admission), oxygen requirement, development of complications, treatments received (antibiotics, corticosteroids, bronchoscopy interventions), and length of hospital stay. Clinical outcomes assessed were resolution of symptoms, discharge status, and progression to RMPP. Long-term follow-up data after discharge were not routinely collected in this retrospective study.
FOB and bronchoalveolar lavage were performed on all enrolled children. BALF samples were analyzed in the laboratory using multiplex PCR and next-generation sequencing (NGS) to detect MP nucleic acid and to identify mutations in domain V of the 23S rRNA gene.
Statistical analysis
Statistical analyses were conducted using SPSS version 25.0. Categorical variables were presented as numbers (n) and percentages (%), and were compared using Pearson’s χ2 or Fisher’s exact tests. Continuous variables that were not normally distributed were presented as median [interquartile range (IQR)] and were compared using the Mann-Whitney U test. Receiver operating characteristic (ROC) curves were generated to assess the predictive performance of potential risk factors for progression from MRMP to RMPP. To identify independent risk factors for RMPP progression among MRMP-infected patients, multivariable logistic regression analysis was conducted using a backward stepwise approach. Variables showing a significance level of P<0.05 in univariate analyses were eligible for inclusion in the initial model. The goodness-of-fit of the final model was evaluated using the Hosmer-Lemeshow test. Results of the regression are presented as adjusted odds ratios (aORs) with 95% confidence intervals (CIs). The predictive performance of the significant independent predictors was further evaluated by ROC curve analysis. A two-sided P value <0.05 was considered statistically significant for all tests.
Results
Clinical characteristics of patients
One hundred and seventy-five (58.7%) patients were finally enrolled in the study finally. PCR and NGS was performed on 175 BALF samples from these patients to identify MP nucleic acid sequences and mutations in domain V of 23S rRNA gene. In total, 80 (45.7%) patients with no mutations were defined as non-MRMP group, while 95 (54.3%) patients with mutations were defined as MRMP group. All mutations were A-to-G transition mutations at position 2,063 in domain V of 23S rRNA gene (A2063G). Subsequently, the 95 patients with MRMP infection were further subdivided into RMPP (n=30) and non-RMPP (n=65) subgroups based on diagnostic criteria. Figure 1 presents a flowchart of the study. The median age of the 175 patients was 7 years. Eighty patients were male, and all achieved clinical cure before discharge. The general and clinical characteristics of the 175 analyzed patients are shown in Table 1.
Table 1
| Characteristics | Total (n=175) | MRMP group (n=95) | Non-MRMP group (n=80) | P value |
|---|---|---|---|---|
| Male | 80 (45.7) | 41 (43.2) | 39 (48.8) | 0.46 |
| Age (years) | 7.00 (5.00, 8.00) | 7.00 (5.00, 8.00) | 7.00 (5.00, 8.00) | 0.51 |
| Cough | 173 (98.9) | 94 (99.0) | 79 (98.8) | >0.99 |
| Dyspnea | 20 (11.4) | 13 (13.7) | 7 (8.8) | 0.31 |
| Peak temperature ≥40 ℃ | 54 (30.9) | 24 (25.3) | 30 (37.5) | 0.08 |
| Fever duration (days) | 6.00 (4.00, 8.00) | 6.00 (3.00, 8.00) | 7.00 (5.00, 9.00) | 0.06 |
| Moist rales | 87 (49.7) | 41 (43.2) | 46 (57.5) | 0.059 |
| Diminished breath sound | 62 (35.4) | 45 (47.4) | 17 (21.3) | <0.001* |
| Extrapulmonary complications | 71 (40.6) | 45 (47.4) | 26 (32.5) | 0.046* |
| RMPP | 39 (22.3) | 30 (31.6) | 9 (11.3) | 0.001* |
| WBC count (×109/L) | 7.27 (5.90, 9.96) | 7.79 (6.44, 10.22) | 6.74 (5.48, 9.33) | 0.02* |
| Neutrophils percentage (%) | 64.8 (55.1, 72.8) | 63.8 (54.4, 74.4) | 65.0 (57.3, 70.7) | 0.89 |
| CRP (mg/L) | 19.40 (5.70, 39.80) | 18.29 (5.40, 42.00) | 22.50 (5.85, 38.78) | 0.78 |
| PCT (ng/mL) | 0.12 (0.05, 0.21) | 0.12 (0.06, 0.25) | 0.11 (0.05, 0.17) | 0.23 |
| D-dimer (µg/mL) | 0.49 (0.31, 1.28) | 0.49 (0.30, 1.78) | 0.52 (0.32, 1.07) | 0.63 |
| Lung consolidation | 105 (60.0) | 71 (74.7) | 34 (42.5) | <0.001* |
| Atelectasis | 35 (20.0) | 25 (26.3) | 10 (12.5) | 0.02* |
| Pleural effusion | 47 (26.9) | 30 (31.6) | 17 (21.3) | 0.13 |
| Airway occlusion | 28 (16.0) | 22 (23.2) | 6 (7.5) | 0.005* |
| Mucus plug | 47 (26.9) | 24 (25.3) | 23 (28.8) | 0.60 |
| Mucosal necrosis | 13 (7.4) | 12 (12.6) | 1 (1.3) | 0.01* |
| Corticosteroid application | 97 (55.4) | 66 (69.5) | 31 (38.8) | <0.001* |
| Hospital duration (days) | 11.00 (9.00, 14.00) | 11.00 (9.00, 13.00) | 11.00 (8.25, 14.00) | 0.82 |
All continuous variables were abnormally distributed and are described as the median (P25, P75). Categorical variables are presented as numbers (percentages). *, P<0.05. CRP, C-reactive protein; MRMP, macrolide-resistant Mycoplasma pneumoniae; PCT, procalcitonin; RMPP, refractory Mycoplasma pneumoniae pneumonia; WBC, white blood cell.
Comparison of clinical characteristics between the MRMP and non-MRMP groups
The MRMP (n=95) and non-MRMP (n=80) groups showed no significant differences in age or sex distribution (P>0.05). Compared to the non-MRMP group, the MRMP group had a significantly higher incidence of diminished breath sounds (P<0.05). Furthermore, patients in the MRMP group were more likely to have extrapulmonary complications, progress to RMPP, and require corticosteroid treatment than those in the non-MRMP group (P<0.05). Conversely, no intergroup differences were observed in cough, dyspnea, peak temperature ≥40 ℃, fever duration, moist rales, or hospital duration (P>0.05) (Table 1).
The MRMP group had higher WBC count than the non-MRMP group (P<0.05). Additionally, the MRMP group had a higher incidence of lung consolidation, atelectasis, airway occlusion, and mucosal necrosis compared to non-MRMP group. Conversely, no significant intergroup differences were observed in the level of CRP, neutrophil percentage, PCT, and D-dimer (P>0.05). The incidence of pleural effusion and mucus plug showed no statistically significant differences between the two groups (P>0.05) (Table 1).
Comparison of clinical characteristics between the RMPP and non-RMPP subgroups in patients with MRMP infection
In the MRMP cohort, 30 of 95 patients (31.6%) were diagnosed with RMPP, constituting the RMPP subgroup, while the remaining 65 patients comprised the non-RMPP subgroup. Sex distribution showed no significant difference between RMPP and non-RMPP subgroups (P>0.05). The RMPP subgroup exhibited a higher median age than the non-RMPP subgroup [7.00 (IQR, 6.00–9.00) vs. 6.00 (IQR, 4.38–7.46) years; P<0.05], as well as a significantly higher incidence of dyspnea, peak temperature ≥40 ℃, and diminished breath sounds (all P<0.05). RMPP patients demonstrated significantly higher rates of extrapulmonary complications (P<0.05), increased corticosteroid application, prolonged fever duration, and extended hospital duration (all P<0.05). No significant differences were observed in cough incidence or moist rales (P>0.05) (Table 2).
Table 2
| Characteristics | Total (n=95) | RMPP group (n=30) | Non-RMPP group (n=65) | P value |
|---|---|---|---|---|
| Male | 41 (43.2) | 17 (56.7) | 24 (36.9) | 0.07 |
| Age (years) | 7.00 (5.00, 8.00) | 7.00 (6.00, 9.00) | 6.00 (4.38, 7.46) | 0.009* |
| Cough | 94 (99.0) | 30 (100.0) | 64 (98.5) | >0.99 |
| Dyspnea | 13 (13.7) | 10 (33.3) | 3 (4.6) | <0.001* |
| Peak temperature ≥40 ℃ | 24 (25.3) | 12 (40.0) | 12 (18.5) | 0.03 |
| Fever duration (days) | 6.00 (3.00, 8.00) | 9.00 (7.00, 10.00) | 5.00 (3.00, 6.00) | <0.001* |
| Moist rales | 41 (43.2) | 14 (46.7) | 27 (41.5) | 0.64 |
| Diminished breath sound | 45 (47.4) | 21 (70.0) | 24 (36.9) | 0.003* |
| Extrapulmonary complications | 45 (47.4) | 25 (83.3) | 20 (30.8) | <0.001* |
| WBC count (×109/L) | 7.79 (6.44, 10.22) | 8.64 (6.65, 10.84) | 7.66 (6.30, 10.22) | 0.46 |
| Neutrophil percentage (%) | 63.80 (54.40, 74.40) | 71.50 (58.20, 82.30) | 61.70 (50.55, 71.20) | 0.003* |
| CRP (mg/L) | 18.29 (5.40, 42.00) | 24.75 (9.50, 57.67) | 17.30 (3.80, 38.75) | 0.09 |
| PCT (ng/mL) | 0.12 (0.06, 0.25) | 0.12 (0.05, 0.36) | 0.12 (0.06, 0.20) | 0.52 |
| D-dimer (µg/mL) | 0.49 (0.31, 1.78) | 1.56 (0.94, 3.02) | 0.35 (0.21, 0.70) | <0.001* |
| Lung consolidation | 71 (74.7) | 27 (90.0) | 44 (67.7) | 0.04* |
| Atelectasis | 25 (26.3) | 14 (46.7) | 11 (16.9) | 0.002* |
| Pleural effusion | 30 (31.6) | 19 (63.3) | 11 (16.9) | <0.001* |
| Airway occlusion | 22 (23.2) | 12 (40.0) | 10 (15.4) | 0.008* |
| Mucus plug | 24 (25.3) | 16 (53.3) | 8 (12.3) | <0.001* |
| Mucosal necrosis | 12 (12.6) | 9 (30.0) | 3 (4.6) | 0.002* |
| Corticosteroid application | 66 (69.5) | 28 (93.3) | 38 (58.5) | 0.001* |
| Hospital duration (days) | 11.00 (9.00, 13.00) | 13.00 (10.75, 16.00) | 10.00 (8.00, 12.00) | <0.001* |
All continuous variables were abnormally distributed, and are described as median (P25, P75). Categorical variables are presented as numbers (percentages). *, P<0.05. CRP, C-reactive protein; MRMP, macrolide-resistant Mycoplasma pneumoniae; PCT, procalcitonin; RMPP, refractory Mycoplasma pneumoniae pneumonia; WBC, white blood cell.
The RMPP subgroup had elevated neutrophil percentages and D-dimer levels (P<0.05), and a higher incidence of lung consolidation, atelectasis, pleural effusion, airway occlusion, mucus plugs, and mucosal necrosis. WBC count, CRP, and PCT levels showed no significant differences (P>0.05) (Table 2).
Risk factors for progression from MRMP infection to RMPP
ROC curves were constructed to investigate the optimum predictive values of risk factors for progression from MRMP infection to RMPP, and the optimal cutoff values with maximum sensitivities and specificities were determined (Table 3). ROC curve analyses revealed that the cut-off points for age, fever duration, and neutrophils percent, and D-dimer were 5.84 years, 6.5 days, 74.80%, and 0.54 µg/mL, respectively.
Table 3
| Risk factors | Cutoff value | Sensitivity | Specificity | AUC (95% CI) | P value |
|---|---|---|---|---|---|
| Age (years) | 5.84 | 0.800 | 0.462 | 0.665 (0.552–0.779) | 0.01* |
| Fever duration (days) | 6.5 | 0.867 | 0.815 | 0.907 (0.841–0.973) | <0.001* |
| Neutrophils percentage (%) | 74.80 | 0.467 | 0.877 | 0.691 (0.572–0.809) | 0.003* |
| D-dimer (µg/mL) | 0.54 | 0.900 | 0.723 | 0.847 (0.768–0.925) | <0.001* |
*, P<0.05. AUC, area under the curve; CI, confidence interval; MRMP, macrolide-resistant Mycoplasma pneumoniae; RMPP, refractory Mycoplasma pneumoniae pneumonia.
The results of univariate logistic analysis indicated that age >5.84 years, dyspnea, peak temperature ≥40 ℃, fever duration >6.5 days, diminished breath sound, extrapulmonary complications, neutrophils percent >74.80%, D-dimer >0.54 µg/mL, lung consolidation, atelectasis, pleural effusion, airway occlusion, mucus plug, and mucosal necrosis all showed significant associations. Based on the above results, we assessed the associations between these variables and RMPP by multivariate logistic regression. This identified fever duration >6.5 days (OR =12.342, 95% CI: 3.002–50.744, P<0.001), D-dimer >0.54 µg/mL (OR =5.537, 95% CI: 1.215–25.245, P=0.03), and mucus plug (OR =4.586, 95% CI: 1.094–19.231, P=0.04) as independent risk factors for progression from MRMP infection to RMPP (Table 4).
Table 4
| Risk factors | Univariate logistic analysis | Multivariate logistic analysis | |||
|---|---|---|---|---|---|
| OR (95% CI) | P value | OR (95% CI) | P value | ||
| Age >5.84 (years) | 3.429 (1.238–9.497) | 0.02* | – | – | |
| Dyspnea | 10.333 (2.586–41.286) | 0.001* | – | – | |
| Peak temperature ≥40 ℃ | 2.944 (1.125–7.708) | 0.03* | – | – | |
| Fever duration >6.5 (days) | 28.708 (8.433–97.732) | <0.001* | 12.342 (3.002–50.744) | <0.001* | |
| Diminished breath sound | 3.986 (1.574–10.095) | 0.004* | – | – | |
| Extrapulmonary complications | 11.250 (3.763–33.634) | <0.001* | – | – | |
| Neutrophils percentage >74.80 (%) | 6.234 (2.224–17.473) | 0.001* | – | – | |
| D-dimer >0.54 (µg/mL) | 23.500 (6.336–87.155) | <0.001* | 5.537 (1.215–25.245) | 0.03* | |
| Lung consolidation | 4.295 (1.169–15.779) | 0.03* | – | – | |
| Atelectasis | 4.295 (1.633–11.296) | 0.003* | – | – | |
| Pleural effusion | 8.479 (3.164–22.724) | <0.001* | – | – | |
| Airway occlusion | 3.667 (1.357–9.905) | 0.01* | – | – | |
| Mucus plug | 8.143 (2.905–22.821) | <0.001* | 4.586 (1.094–19.231) | 0.04* | |
| Mucosal necrosis | 8.857 (2.190–35.817) | 0.002* | – | – | |
*, P<0.05. CI, confidence interval; MRMP, macrolide-resistant Mycoplasma pneumoniae; OR, odds ratio; RMPP, refractory Mycoplasma pneumoniae pneumonia.
Predictors for progression from MRMP infection to RMPP
The ROC curve analysis revealed that the areas under the curve (AUC) for fever duration >6.5 days, D-dimer >0.54 µg/mL, and mucus plug were 0.841 (95% CI: 0.751–0.931, P<0.001), 0.812 (95% CI: 0.720–0.903, P<0.001), and 0.705 (95% CI: 0.584–0.826, P=0.001), respectively. Thus, all had moderate diagnostic accuracy. A prediction model including the three indicators was subsequently established. The predictive values of this model were assessed by ROC curve analysis, yielding an AUC of 0.918 (95% CI: 0.863–0.973, P<0.001), which showed that the model had a high level of diagnostic accuracy, as shown in Figure 2.
Discussion
This single-center retrospective study investigated the clinical characteristics and outcomes of MRMP infection in children and developed a prediction model for progression to RMPP. We found a high prevalence (54.3%) of MRMP among hospitalized children with MPP in Chengdu, consistent with recent reports from other regions in China highlighting a significant public health concern (4,5,19). All detected resistant strains harbored the A2063G mutation, the most common resistance mechanism in Asia (6,8).
Our findings indicate that children with MRMP infection present with more severe respiratory manifestations, as evidenced by higher rates of lung consolidation, atelectasis, airway occlusion, and mucosal necrosis observed during bronchoscopy, compared to those with non-MRMP infection. They also experienced a greater burden of extrapulmonary complications and were more likely to progress to RMPP, aligning with some previous reports (11,16) but contrasting with others (13,14). This discrepancy might be attributed to regional differences in bacterial virulence, host factors, or treatment protocols. The more severe mucosal inflammation and lung damage observed in MRMP patients could stem from delayed effective treatment due to macrolide failure, allowing unchecked bacterial load and potentiating a exaggerated host immune response (20).
Our study demonstrates a significantly higher incidence of RMPP in pediatric patients with MRMP infection compared to those with non-MRMP infection (31.6% vs. 11.3%, P<0.05). Although the pathogenesis of RMPP typically involves multifactorial mechanisms, studies suggest that macrolide resistance is clinically associated with RMPP development (12). While resistance acquisition does not enhance virulence, it may act as an aggravating factor. Indeed, prior research has shown that patients with MRMP infection will exhibit prolonged fever and worsened chest X-ray findings without early and effective anti-MP therapy, collectively contributing to the development of RMPP (21). Ineffective treatment due to drug-resistant strains prolongs infection duration and provokes excessive host immune responses (20). Studies confirm that pediatric patients with MRMP exhibit significantly elevated levels of serum inflammatory markers—including CRP, lactate dehydrogenase—compared to those harboring macrolide-sensitive strains, with these increases positively correlating with pulmonary tissue damage (22,23). The persistence of drug-resistant strains may activate CARDS toxin (community-acquired respiratory distress syndrome toxin), aggravating lung injury (24,25).
To identify risk factors for progression of MRMP infection to RMPP, we performed ROC curve and logistic regression analyses. We identified three independent risk factors for this progression: fever duration >6.50 days, elevated D-dimer >0.54 µg/mL, and the presence of mucus plugs on bronchoscopy. Persistent fever is a common clinical indicator of an excessive inflammatory reaction. Prior studies (26,27) have shown fever duration to be an independent risk factor for RMPP. D-dimer is a degradation product of fibrin, reflects hypercoagulability when elevated (28). The degree of D-dimer elevation correlates positively with MPP severity and is more pronounced in RMPP. This likely relates to the severity of post-MP infection pulmonary inflammation, indicating that vascular endothelial injury and coagulation abnormalities contribute to RMPP pathogenesis (29). Mucus plug formation, often a consequence of ciliary dysfunction and impaired mucociliary clearance due to MP infection, can lead to airway obstruction and complicate disease course (30-33). The prediction model combining these readily available clinical parameters demonstrated excellent discriminatory power (AUC =0.918) for stratifying risk of RMPP progression early in the hospitalization course. While promising, this model requires further validation in larger, multi-center prospective studies before widespread clinical application.
Our study has several limitations. First, this was a single-center retrospective study, which may introduce selection bias and limit the generalizability of our findings to other regions or healthcare settings. Second, the small sample size may affect the statistical results, particularly the power of the subgroup analyses involving patients with RMPP (n=30). Third, this prediction model is applicable only to patients who have undergone FOB, restricting its utility in other settings. Furthermore, our model was developed without an external validation cohort, which is necessary to confirm its general applicability. Fourth, we lacked data on long-term outcomes (e.g., pulmonary function) and did not perform a detailed analysis of the impact of different antibiotic treatment strategies on the progression to RMPP, which could be important confounding factors. Finally, despite multivariate adjustment, residual confounding from unmeasured factors, such as prior antibiotic exposure before admission or underlying comorbidities, may persist and influence the observed associations.
Conclusions
In conclusion, this study confirms the high prevalence of MRMP among children with MPP in Chengdu and its association with more severe disease and a higher risk of RMPP. We identified prolonged fever, elevated D-dimer, and mucus plugs as key independent risk factors for RMPP progression in MRMP-infected children. The integrative prediction model based on these factors showed high accuracy for early risk stratification. As the model’s application is currently limited to settings where bronchoscopy is performed, and it requires external validation, these findings should be considered preliminary until confirmed in larger, prospective studies. Nevertheless, the use of these readily available clinical parameters provides a practical framework for early risk stratification that could potentially improve management strategies for children with MRMP infection.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-290/rc
Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-290/dss
Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2025-290/prf
Funding: This study was supported by grants from
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2025-290/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of Chengdu Women’s and Children’s Central Hospital [No. 2024(26)]. Requirement for informed consent was waived due to the retrospective nature of the study.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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