Evidence‐based guideline for the diagnosis and treatment of Mycoplasma pneumoniae pneumonia in children (2023)

ABSTRACT

Mycoplasma pneumoniae pneumonia (MPP) is the most common atypical pneumonia among children, with non‐specific clinical manifestations. Despite various laboratory diagnostic methods, the diagnostic criteria remain inconsistent, potentially leading to missed or overdiagnosis. The incidence of severe and refractory cases of MPP is increasing, and there are issues with non‐standard treatment in clinical practice. To standardize the diagnosis and treatment of MPP in Chinese children, the Subspecialty Group of Respiratory, the Society of Pediatrics, Chinese Medical Association, China National Clinical Research Center of Respiratory Diseases and the Editorial Board of Chinese Journal of Pediatrics jointly established a guideline expert group to formulate the “Evidence‐Based Guideline for the Diagnosis and Treatment of Mycoplasma Pneumoniae Pneumonia in Children (2023)” based on both domestic and international research findings.

INTRODUCTION

Pneumonia is a common disease in children and the main cause of death under 5 years old. ¹ Mycoplasma pneumoniae pneumonia (MPP) is the most common atypical pneumonia in children and has become the main pneumonia in children aged 6 years and above in China. Studies in Beijing and Shanghai showed that MPP accounts for 37.5%–48.4% of hospitalized children's pneumonia. ² , ³ A study in the United States found that Mycoplasma pneumoniae (MP) is the fifth leading pathogen among hospitalized children with community‐acquired pneumonia (CAP). ⁴ The clinical manifestations of MPP lack specificity, and there are various laboratory diagnostic methods, including antibody and nucleic acid testing. ⁵ , ⁶ , ⁷ However, the diagnostic criteria are not uniform, which may lead to missed or overdiagnosis. The resistance situation of MP to macrolides is severe with a consistently high resistance rate of 81% over the past 20 years in China. ⁸ Clinically, tetracyclines, quinolones, and corticosteroids are occasionally used for treatment, however, the timing and dosage of these medications are not unified, and there is a lack of evidence‐based guidelines for the diagnosis and treatment of MPP in children. To standardize the diagnosis and treatment of pediatric MPP in China, the Subspecialty Group of Respiratory, Society of Pediatrics, Chinese Medical Association, China National Clinical Research Center of Respiratory Diseases, and the Editorial Board of Chinese Journal of Pediatrics jointly established a guideline expert group. Based on domestic and foreign research results, the “Evidence‐based guideline for the diagnosis and treatment of Mycoplasma Pneumoniae pneumonia in children (2023)” (hereinafter referred to as “this guideline”) was formulated over a period of more than 3 years. This guideline is intended for all healthcare workers and management personnel involved in the diagnosis and treatment of MPP in children, especially pediatricians, respiratory physicians, general practitioners, and clinical pharmacists. The target population is MPP children aged 29 days to 18 years old.

GUIDELINE FORMULATION METHOD

This guideline adopts the construction method of evidence‐based clinical practice guidelines, referring to the development process and methodological standards of the “World Health Organization Handbook for Guideline Development” published in 2014, ⁹ and referencing the Appraisal of Guidelines for Research and Evaluation (AGREE) II. ¹⁰ The guideline employs the internationally recognized approach “Grading of Recommendations Assessment, Development, and Evaluation (GRADE)” to assess, develop, and evaluate evidence quality and recommendation. ¹¹ The guideline document was written with reference to the Reporting Items for Practice Guidelines in Healthcare. This guideline is registered on the International Practice Guidelines Registry Platform (IPGRP‐2020CN177).

Guideline working group

It mainly includes four groups of members: the Guideline Steering Committee, the Guideline Development Group (hereinafter referred to as the Development Group), the Guideline Evidence Synthesis and Evaluation Group (hereinafter referred to as the Evaluation Group), and the Guideline External Review Group. The Guideline Steering Committee is composed of pediatric specialists, pharmaceutical experts, clinical epidemiologists, and experts in evidence‐based medicine. The Development Group comprises 39 members, including 31 pediatric experts (from the four economic regions of the east, central, west, and northeast), two pharmacologists, three methodologists, and one expert each from laboratory medicine, medical imaging, and nursing. The Evaluation Group consists of nine members, who are responsible for collecting and selecting clinical questions and outcome indicators, conducting evidence collection, synthesis, and evaluation, as well as coordinating and recording the development process. The Guideline External Review Group comprises 10 members, who review the recommendations of the guideline that have been formulated.

Selection and determination of clinical questions and outcome indicators

Based on the themes and scope of the guideline, inclusion and exclusion criteria as well as retrieval strategies for clinical evidence were formulated. The relevant guidelines, systematic reviews, or meta‐analyses pertaining to pediatric MPP were searched, and the initial clinical questions and outcome indicators were selected, encompassing both the diagnosis and treatment aspects of pediatric MPP. An interview outline was designed, and the relevant pediatric experts, primary pediatricians above the attending physician level, and guardians of children with MPP were interviewed based on the principle of information saturation. The selection of clinical questions and outcome indicators underwent two rounds of Delphi surveys and one online consensus meeting, ultimately identifying four diagnostic and nine treatment‐related clinical questions and important and key outcome indicators that are of concern in this guideline. Clinical experts and methodologists jointly constructed clinical questions based on the participants‐interventions‐comparisons‐outcomes principles.

Evidence retrieval, evaluation, and grading

Evidence retrieval

The primary databases searched included PubMed, EMbase, the Cochrane Library, the China Biomedical Literature Service System, and the Wanfang Database, supplemented by searches of core journals in the China National Knowledge Infrastructure and VIP databases. The search covers the period from the databases’ establishment to March 31, 2023, and the publication languages were limited to Chinese and English. Additionally, resources related to the guidelines were searched on websites such as the National Institute for Health and Care Excellence (https://www.nice.org.uk/guidance), the Guidelines International Network (https://www.g‐i‐n.net), the World Health Organization (WHO) (http://www.who.int/publications/guidelines/en/), Uptodate (https://www.uptodate.com/contents/search), and Yi Mai Tong (Medlive); as well as the Prospective Register of Systematic Reviews and the WHO International Clinical Trial Registration Platform (ICTRP). Finally, the references incorporated into the study to supplement our literature acquisition were reviewed.

Evidence evaluation and grading

The methodological quality of published guidelines was evaluated using AGREE II. The methodological quality of included systematic reviews was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR‐2). ¹² If a systematic review or meta‐analysis was of high quality, it was directly adopted. When developing relevant systematic reviews and meta‐analyses, the evaluation group used the Cochrane Risk of Bias Assessment Tool (RoB 2.0) to evaluate the risk of bias in the included randomized controlled trials (RCTs); ¹³ and the Quality Assessment of Diagnostic Accuracy Studies tool to assess the methodological quality of the included diagnostic tests. ¹⁴ GRADE was utilized to grade evidence quality and recommendation strength. ¹¹ The quality of evidence was categorized into four levels: high, moderate, low, and very low; and recommendation strength was classified as strong or weak (Table 1).

TABLE 1.

Grading criteria for evidence quality and recommendation strength

Category	Definition
Quality of evidence
High (A)	We are very confident that the true effect lies close to that of the estimate of the effect.
Moderate (B)	We are moderately confident in the effect estimate: The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
Low (C)	Our confidence in the effect estimate is limited: The true effect may be substantially different from the estimate of the effect.
Very low (D)	We have very little confidence in the effect estimate: The true effect is likely to be substantially different from the estimate of the effect.
Strength of recommendation
Strong (1)	It is clearly demonstrated that the benefits outweigh the drawbacks or vice versa.
Weak (2)	The evidence regarding the pros and cons is inconclusive or indicates that the benefits and drawbacks are comparable regardless of quality.

Formulating recommendations

Based on a systematic review related to various clinical questions, while considering factors such as the preferences and values of Chinese pediatric patients and their guardians, costs, and the balance of benefits and harms, the development group ultimately formulated recommendations and good practice statement (GPS, a statement formed based on indirect evidence, expert opinions, or experience) for 13 clinical questions through four rounds of Delphi surveys and one consensus meeting.

External review and approval

The recommended suggestions in this guideline were reviewed by the Guideline External Review Group. The guideline was refined based on their feedback and suggestions. Finally, the development group submitted it to the Guideline Steering Committee for final approval.

Dissemination, implementation, evaluation, and updating

Following the publication of this guideline, the research team will continue to promote and disseminate the guideline. The team will introduce and disseminate this guideline at relevant academic conferences; systematically organize relevant personnel to study this guideline nationwide; monitor its application and spread, and evaluate its impact on clinical decision‐making. The development group plans to update this guideline in accordance with the international guideline update process 3 to 5 years after its publication.

RELEVANT PROFESSIONAL TERMS AND DEFINITIONS

MPP diagnostic criteria: A diagnosis can be made based on medical history, clinical symptoms, signs, and imaging findings, as well as meeting one of the following positive laboratory diagnostic criteria: (1) MP antibody titer increases by four times or more during the recovery phase compared to the acute phase; (2) MP culture positive or MP‐DNA or RNA positive.

Refractory MPP (RMPP) diagnostic criteria: Patients who meet the aforementioned MPP criteria and continue to exhibit persistent fever and worsening lung imaging findings despite receiving standard treatment with macrolides for 7 days or more. ¹⁵

Severe MPP (SMPP) diagnostic criteria: Patients who meet the aforementioned MPP criteria and the criteria for severe pneumonia outlined in the “Guideline for the management of community‐acquired pneumonia in children”. ¹⁶ , ¹⁷

RECOMMENDATIONS FOR MPP DIAGNOSIS

Question 1: What clinical manifestations in children may suggest MPP?

Recommendation 1

Fever and cough are common symptoms in children with MPP (1B), while high fever, irritating dry cough (GPS), and chest pain (1B) are relatively specific. Physical signs are not specific (1C), and the symptoms and signs are often inconsistent, with most symptoms being severe and signs being mild (GPS). The presence or absence of any clinical signs cannot be used as a basis for confirming or denying MPP. A clear diagnosis requires a combination of clinical signs and laboratory test results to improve diagnostic accuracy.

Evidence summary

A systematic review in 2016 included 11 original studies (14 061 cases), ¹⁸ with sample sizes ranging from 75 to 12 025 cases. It evaluated the value of clinical signs compared to MP serological positivity (single‐serum MP‐IgM significantly elevated, or double‐serum MP‐IgG antibody titer elevated by ≥ 4 times) in identifying MPP. The clinical symptoms and signs included fever, cough, wheezing, increased respiratory rate, chest pain, headache, moist rales, and dry rales. The study results showed that cough and fever had a high pooled sensitivity for identifying MPP [86% (95% confidence interval [CI] 85%–87%), 85% (95% CI 84%–86%)], but a low combined specificity [12% (95% CI 10%–12%), 11% (95% CI 10%–12%)]. However, chest pain had a high pooled specificity [89% (95% CI 88%–90%)], and a low pooled sensitivity [12% (95% CI 10%–13%)]. The pooled sensitivities of moist and dry rales for identifying MPP in children were 66% (95% CI 64%–67%) and 12% (95% CI 11%–14%), respectively, with pooled specificities of 36% (95% CI 35%–37%) and 88% (95% CI 87%–89%), ‌severally‌. However, there is significant heterogeneity among the studies included in this systematic review. A questionnaire survey of pediatric clinical experts in the development group showed that 90% (19/21) of the experts believed that high fever and irritating dry cough were more common in children with MPP, and 95% (20/21) of the experts thought that symptoms and signs were inconsistent, with most symptoms being severe while signs were mild.

Justification

The systematic review results showed that the sensitivity of recognizing MPP through fever and cough is relatively high, but the specificity is low, without specifying the characteristics of fever and cough. A questionnaire survey conducted among pediatric clinical experts within the development group indicated that high fever and irritating dry cough were particularly meaningful for identifying MPP. The systematic review further revealed that the specificity of recognizing MPP through chest pain was relatively high. Thus the recommendation emphasized the diagnostic value of high fever, irritating dry cough, and chest pain in MPP. The signs of MPP in children are non‐specific, and most symptoms are severe, while signs are relatively mild. The diagnosis of MPP necessitates a combination of clinical manifestations and laboratory tests for clarity.

Question 2: What is the diagnostic value of MP nucleic acid testing for pediatric MPP?

Recommendation 2

Nucleic acid testing is recommended for the diagnosis of MPP (1A). The sensitivity and specificity of the fluorescence quantitative PCR detection of MP‐DNA are both high (1B); the sensitivity of real‐time fluorescent nucleic acid simultaneous amplification and testing (SAT) detection of MP‐RNA is high, while the specificity is slightly lower (1C).

Evidence summary

The evaluation group conducted a systematic review by retrieving relevant studies that evaluated the diagnostic value of MP nucleic acid testing for pediatric MPP using a gold standard of a fourfold or greater increase in antibody levels in paired serum samples during the acute and recovery phase or positive MP culture. Seven relevant articles were included for systematic evaluation, involving eight studies (1713 cases) using throat swabs or sputum specimens. ¹⁹ , ²⁰ , ²¹ , ²² , ²³ , ²⁴ , ²⁵ Among them, seven studies evaluated the use of fluorescence quantitative PCR for detecting MP‐DNA (1620 cases), and one study evaluated the use of the SAT method for detecting MP‐RNA (93 cases). The pooled sensitivity, pooled specificity, positive likelihood ratio (PLR) and negative likelihood ratio (NLR) of fluorescence quantitative PCR for the diagnosis of MPP in children were 87% (95% CI 85% to 89%), 89% (95% CI 86%–92%), 5.21 (95% CI 2.85–9.52), and 0.19 (95% CI 0.10–0.37), respectively. The area under the curve (AUC) of the receiver operating characteristic curve for diagnosing MPP in children was 0.9, with a Q index of 0.8. In contrast, the sensitivity and specificity of the SAT method for diagnosing MPP were 85% and 76%, respectively. Studies indicate that the positive rate of SAT is significantly higher in children with MPP with a course of ≤7 days compared to those with a course of >7 days, suggesting that the SAT method is more applicable to the early stage of MPP. ²⁶

Justification

Although MP‐DNA testing exhibits high sensitivity and specificity, it fails to differentiate between live and dead MP. Furthermore, the duration of positivity after infection can be prolonged, potentially extending up to 7 months. Therefore, a positive MP‐DNA result needs to be interpreted in conjunction with clinical manifestations for a final diagnosis. Since RNA only exists in live bacteria and degrades swiftly after MP death, a positive MP‐RNA test may indicate a recent MP infection. Specimen types for MP nucleic acid testing include throat swabs, nasopharyngeal swabs, sputum, and bronchoalveolar lavage fluid.

Question 3: What is the diagnostic value of acute phase MP‐specific antibody detection in children with MPP?

Recommendation 3

Acute phase testing for MP‐specific antibodies can be used for the diagnosis of MPP in children (2C). Positive IgM results from the enzyme‐linked immunosorbent assay (ELISA) indicate a possible MP infection, which should be clinically evaluated in conjunction with the disease course to avoid misdiagnosis (2C). The sensitivity of the latex agglutination test for diagnosing acute MPP in children is low, leading to potential missed diagnoses. Therefore, attention should be paid to monitoring its dynamic changes (2C). Both methods mentioned above should be combined with clinical manifestations when diagnosing children with MPP, and if necessary, dynamic monitoring of titer changes should be performed.

Evidence summary

The evaluation group conducted a systematic review of studies that assessed the diagnostic value of acute‐phase specific MP antibodies (such as ELISA, latex agglutination, and colloidal gold) for diagnosing MPP in children, using the gold standard of a fourfold or greater increase in paired serum antibody titers during the convalescent phase or a positive MP culture. This review included four relevant articles, involving a total of six original studies (1058 cases), including two ELISA‐related studies (305 cases) ¹⁹ , ²⁷ and four latex agglutination method‐related studies (753 cases). ¹⁹ , ²⁰ , ²¹ , ²⁷

There is inconsistency and publication bias between the two studies (305 cases) that using ELISA to detect MP‐IgM antibodies. ¹⁹ , ²⁷ The pooled sensitivity and specificity of single serum IgM antibody for diagnosing MPP in children were 86% (95% CI 79% –91%) and 66% (95% CI 57%–73%), respectively. The PLR and NLR were 2.48 (95% CI 1.97–3.13) and 0.22 (95% CI 0.14–0.33), separately, with an AUC of 0.5 and a Q index of 0.5. The positive criteria in the aforementioned studies were referenced from the kit manuals. Upon reviewing the instructions for commercial kits, it was found that the positive standards varied among different manufacturers. In four studies (753 cases) using latex agglutination assay, the positive standard for serum MP antibody was a titer of ≥ 1:80. ¹⁹ , ²⁰ , ²¹ , ²⁷ There were inconsistencies and publication bias among studies. The systematic review indicated that the pooled sensitivity and specificity for diagnosing MPP in children were 49% (95% CI 44%–55%) and 79% (95% CI 75%–83%), ‌severally‌. The PLR and NLR were 3.05 (95% CI 1.34–6.93) and 0.54 (95% CI 0.37–0.79), ‌respectively‌, with an AUC of 0.7 and a Q index of 0.7.

Justification

MP‐IgM antibody usually appears 5–7 days after MP infection, reaches its peak titer at 3–4 weeks, and gradually declines over 2–3 months. However, due to the window period in MP infection, MP‐IgM may be negative when the course of illness is shorter than 7 days. Therefore, when using acute‐phase MP‐specific antibodies to diagnose MPP in children, it is necessary to fully combine the disease course and medical history. Dynamic monitoring may be required when necessary to establish a clear diagnosis. A ≥4‐fold increase in specific antibody titers in convalescent serum compared to the acute phase is one of the gold standards for diagnosing MP infection. The ELISA method is relatively more sensitive than the latex agglutination assay, but its specificity is slightly lower, which may lead to misdiagnosis. In the included literature on detecting MP‐IgM using the ELISA method, the positive criteria were all indicated with reference to the instructions of the reagent kit. When detecting MP mixed antibodies using latex agglutination, a positive standard of 1:80 showed low sensitivity and acceptable specificity, and there is a need to be vigilant against potential missed diagnoses. When there is a strong suspicion of MPP in clinical practice, the antibody titer changes should be dynamically monitored, or combined with other microbiological testing methods for a clear diagnosis.

Question 4: What are the chest imaging manifestations of pediatric MPP?

Recommendation 4

The chest imaging manifestations of children with MPP are diverse. Common findings on chest X‐rays during the acute phase include lobar or segmental consolidation and pleural effusion. When children aged 6 years and above present with the aforementioned imaging manifestations, MPP should be considered (2C). However, MPP cannot be ruled out even in the absence of these findings. When diagnosing MPP, it is necessary to closely integrate clinical manifestations with laboratory tests and to exclude bacterial pneumonia (GPS).

Evidence summary

A systematic review in 2016 included 11 original studies (14 061 cases) to evaluate the value of chest X‐ray findings compared with MP seropositivity (defined as a significant increase in single serum MP‐IgM or a ≥ 4‐fold increase in MP‐IgG antibody titers in paired serum) in identifying MPP in children. ¹⁸ The results showed that the pooled sensitivity of chest X‐ray findings of pleural effusion, lung consolidation, and emphysema was low in identifying MPP in children, at 4% (95% CI 2%–8%), 32% (95% CI 26%–39%), and 22% (95% CI 17%–29%), respectively, with pooled specificity of 98% (95% CI 96%–99%), 87% (95% CI 84%–90%), and 73% (95% CI 69%–77%), separately. Notably, lung consolidation and pleural effusion demonstrated higher specificity. A questionnaire survey conducted among pediatric clinical experts within the development group found that 43% (9/21) of the experts believed chest imaging changes could assist in the diagnosis of MPP, but it needed to be combined with age, clinical features, and laboratory test results while excluding bacterial pneumonia.

Justification

The imaging manifestations of MPP in children are diverse and commonly present as lobar or segmental consolidation and pleural effusion but also include lobular lesions, interstitial infiltration, emphysema, atelectasis, etc. Therefore, the presence of any single imaging change cannot serve as a definitive basis to confirm or rule out MPP. A clear diagnosis requires a combination of clinical manifestations and laboratory tests. Since MPP is more prevalent in children aged 6 years and above, it should be considered when consolidation of lung lobes or segments and pleural effusion are observed in this age group, while bacterial pneumonia should be ruled out.

RECOMMENDATIONS FOR MPP TREATMENT

Question 5: What are the first‐line antibiotic treatments for mild MPP in children?

Recommendation 5

Macrolides are recommended as the first‐line treatment for mild MPP in children, with azithromycin being the preferred choice, followed by erythromycin or clarithromycin (GPS). Oral administration is prioritized (1C), and the drug dosage is referred to the medication instructions.

Evidence summary

The evaluation group initially identified two systematic reviews on the efficacy of azithromycin for treating pediatric MPP. The AMSTAR2 scale scores indicated that their credibility was extremely low, thus they were not included. A total of 760 RCT studies were initially reviewed, but none of them were included due to the lack of randomization methods or single‐author studies. A questionnaire survey was conducted among pediatric clinical experts in the development group, and the results showed that all experts preferred to use azithromycin, citing its advantages of a long half‐life, convenient administration, good compliance, and minimal adverse reactions; erythromycin or clarithromycin were chosen secondarily.

Justification

For the usage and dosage of azithromycin, a quick recommendation guide and instructions for intravenous administration of azithromycin in children are referred. The recommended dosage is 10 mg/(kg·dose), administered once daily, with a maximum dose of 500 mg per administration. Oral administration is preferred, and a sequential treatment course should not exceed 10 days. ²⁸ For the usage and dosage of erythromycin or clarithromycin, the instructions are referred to.

Question 6: What are the antibiotic treatments for SMPP in children?

Recommendation 6

Tetracyclines are recommended for children aged 8 years and above, while macrolides are recommended for children under 8 years old (GPS). When administering quinolones in children and tetracyclines in those under 8 years, it is crucial to weigh the benefits and risks and to fully inform parents and caregivers about potential adverse drug reactions and off‐label use. Such medications should only be used with the consent of the patient's guardian (and children over 8 years old) as appropriate (GPS). During the medication, attention should be paid to monitoring any drug‐related adverse reactions.

Evidence summary

The evaluation group did not find any systematic reviews or RCT studies on the treatment of SMPP with tetracyclines or quinolones. Through a questionnaire survey conducted among pediatric clinical experts in the development group, 57% (12/21) of the experts preferred tetracycline drugs for the treatment of SMPP in children 8 years and above. For children under 8 years of age with SMPP, 100% (21/21) of the experts preferred macrolides. Regarding the use of tetracyclines, 81% (17/21) chose minocycline and 48% (10/21) selected doxycycline. In terms of efficacy, 16/17 experts believed that minocycline was effective and 11/17 believed that doxycycline was effective. Regarding adverse reactions, 11/17 and 7/17 experts believed that the incidence of adverse reactions for minocycline and doxycycline was 1% to 10% respectively. Regarding the use of quinolones, 57% (12/21) of the experts chose levofloxacin, 33% (7/21) selected moxifloxacin, and 10/11 believed that levofloxacin was effective and safe.

Justification

Dosage and administration of tetracyclines (for ages 8 years and above) ²⁹ , ³⁰ : The recommended dosage for doxycycline is 2.2 mg/(kg·dose), administered every 12 h, with a maximum dose of 100 mg per dose. It can be administered orally or intravenously, for a course of 10 days. Minocycline is initiated with a dosage of 4 mg/kg for the first dose, with a maximum dose of 200 mg, followed by 2 mg/(kg·dose) for subsequent doses, with a maximum dose of 100 mg, also administered every 12 h, either orally or via intravenous infusion. Tetracycline is used according to the instructions: 6.25–12.5 mg/(kg·dose), with a maximum dose of 500 mg, once every 6 h, for a course of 10–14 days. According to the “Guideline for Clinical Use of Antimicrobial Agents” in China, quinolones should be avoided for minors under 18 years old. ³¹ The usage and dosage of quinolones are based on foreign literature. Levofloxacin is administered orally or intravenously, with 8–10 mg/(kg·dose) twice daily for children aged 6 months–<5 years; for children ≥ 5 years, the recommended dosage is 8–10 mg/(kg·dose), once daily, with a maximum of 750 mg/d. ³⁰ , ³² Moxifloxacin has limited available data and can be administered orally or intravenously: for children aged 3 months–<2 years, 6 mg/(kg·dose), for children aged 2–<6 years, 5 mg/(kg·dose), for children aged 6–<12 years, 4 mg/(kg·dose), administered once every 12 h, with a maximum of 200 mg per dose; for children aged 12–< 18 years, weighing less than 45 kg, 4 mg/(kg·dose), administered once every 12 h, with a maximum dose of 200 mg per administration; and for children weighing ≥ 45 kg, 400mg/dose, administered once a day. ³² , ³³ , ³⁴

Question 7: Can corticosteroids be used for the treatment of pediatric SMPP? How to choose the medication? What are the recommended dosages and course of treatment?

Recommendation 7

Using corticosteroids in combination with antimicrobial drugs for the treatment of pediatric SMPP is recommended (GPS). Due to the good efficacy and low adverse reactions of methylprednisolone, it is preferred, but dexamethasone can also be chosen (GPS). The recommended dosage of methylprednisolone is 2 mg/(kg·d), with a maximum dosage of generally 60 mg/d, and the general treatment course should not exceed 2 weeks (1B).

Evidence summary

The evaluation group did not retrieve any systematic reviews that met the criteria. A preliminary review of 313 RCT studies was conducted, but they were excluded due to the absence of randomization methods or single‐author studies. A questionnaire survey was conducted among pediatric clinical experts in the development group, and 100% (21/21) of the experts opted for the use of methylprednisolone combined with antibiotics for treatment, 29% (6/21) chose dexamethasone, and 10% (2/21) opted for prednisone. The efficacy rate of methylprednisolone ranges from 60% to 100% with a low incidence of adverse reactions (approximately 5%). Regarding the dosage of corticosteroids, an unpublished multicenter registered RCT study ³⁵ compared the efficacy and safety of azithromycin combined with high‐dose methylprednisolone [10 mg/(kg·d)] versus conventional‐dose methylprednisolone [2 mg/(kg·d)] in children with SMPP. The maximum dose was 60 mg/d and the treatment duration did not exceed 2 weeks.

Justification

The dosage and treatment duration of methylprednisolone were derived from an unpublished multicenter registered RCT study. ³⁵ The dosage of dexamethasone and other corticosteroids refers to the “Guideline for the Management of Community‐Acquired Pneumonia in Children”. ¹⁶ , ¹⁷ According to these guidelines, ¹⁶ , ¹⁷ prednisone, prednisolone, or hydrocortisone may also be used.

Question 8: Can intravenous immunoglobulin be used to treat children with SMPP?

Recommendation 8

The routine use of intravenous immunoglobulin (IVIG) is not recommended for the treatment of children with SMPP (GPS).

Evidence summary

The evaluation group did not retrieve any relevant systematic reviews or RCT studies. Through a questionnaire survey conducted among pediatric clinical experts in the development group, 76% (16/21) of the experts believed that IVIG could be used in combination therapy, but14 out of 16 experts thought that its efficacy was inferior to the combination with corticosteroids and it is expensive.

Justification

There is currently no direct clinical evidence supporting the use of IVIG for the treatment of SMPP in children, and it is not recommended for routine use based on expert opinions. However, if neurological, hematological, or other systemic complications occur that require its use, it should be applied according to the corresponding disease treatment protocols.

Question 9: What are the antibiotic treatments for RMPP in children ?

Recommendation 9

Tetracyclines are recommended for children aged 8 years and above, while macrolides are recommended for children under 8 years old (GPS). When using quinolones in children and tetracyclines in children under 8 years, the benefits and risks should be carefully weighed, and the potential adverse drug reactions and off‐label use should be fully disclosed. The drugs should be used, as appropriate, with the consent of the patients’ guardians (and children over 8 years old) (GPS). During the treatment, close monitoring for drug‐related adverse reactions is necessary.

Evidence summary

The evaluation group initially identified one systematic review on minocycline treatment for pediatric RMPP, but the AMSTAR2 scale scoring results indicated that its credibility was extremely low, thus it was not included. Ten RCT studies were initially identified, but none were included due to the lack of randomization methods, single authorship, and absence of diagnostic criteria. Through a questionnaire survey conducted among pediatric clinical experts in the development group, 76% (16/21) of the experts preferred tetracyclines for the treatment of RMPP in children aged 8 years and above, while 52% (11/21) preferred macrolides for children under 8 years of age. For the treatment of RMPP in children with tetracyclines, 76% (16/21) of the experts chose minocycline, and 38% (8/21) selected doxycycline. In terms of efficacy, 16/16 of the experts believed that minocycline was effective, and 13/16 thought that doxycycline was effective. Regarding adverse effects, 11/16 and 8/16 of the experts believed that the incidence of adverse reactions to minocycline and doxycycline was 1% to 10%, respectively. For the use of quinolones, 38% (8/21) of the experts chose levofloxacin and 29% (6/21) selected moxifloxacin. Ten out of 12 experts considered levofloxacin to be effective and safe.

Question 10: Can corticosteroids be used to treat RMPP in children? How to choose the medication? What are the dosage and duration of the treatment?

Recommendation 10

Antibacterial drugs combined with corticosteroids are recommended for the treatment of RMPP in children. Due to the good efficacy and low adverse reactions of methylprednisolone, it is preferred, and dexamethasone may also be used (GPS). The recommended dose of methylprednisolone is 2 mg/(kg·d), with a maximum dose of generally 60 mg/d (GPS). No treatment duration recommendation can be made yet.

Evidence summary

The evaluation group initially identified eight systematic reviews, but the AMSTAR2 scale scoring results indicated that their credibility was extremely low, and thus they were not included. Initially, 319 RCT studies were identified, but none were included due to the lack of randomization methods and single authorship. Through a questionnaire survey conducted among pediatric experts in the development group, all experts preferred the combination of methylprednisolone, believing its efficacy rate to be between 50% and 100%. Additionally, 29% (6/21) of the experts believed that dexamethasone could be an option. Furthermore, 52% (11/21) of them thought conventional doses of corticosteroids to be more effective and 81% (17/21) considered conventional doses of corticosteroids to be safer.

Justification

There is currently no direct clinical evidence to support the use of antimicrobial drugs in combination with corticosteroids for treating RMPP in children. The recommendation is based on expert opinion.

Question 11: Can IVIG be used to treat RMPP in children?

Recommendation 11

Routinely use of IVIG is not recommended for the treatment of RMPP in children (GPS).

Evidence summary

The evaluation group did not retrieve any relevant systematic reviews or RCT studies. Through a questionnaire survey conducted among pediatric clinical experts in the development group, 62% (13/21) believed that IVIG could be used in combination with antibiotics, but 11/13 thought its efficacy was inferior to corticosteroids and it is expensive.

Justification

There is currently no direct evidence supporting the use of IVIG for the treatment of RMPP in children. Based on expert opinion, routine use is not recommended. However, if neurological, hematological, or other systemic complications occur that necessitate its use, it should be applied according to the corresponding disease treatment protocols.

Question 12: What is the threshold for D‐dimer to initiate prophylactic anticoagulation therapy? How should the drug be selected? What are the dosage and treatment duration?

Recommendation 12

For MPP children with D‐dimer levels elevated to 5 times or more above the normal upper limit, low molecular weight heparin prophylactic anticoagulant therapy may be administered with a recommended dose of 50–100 U/(kg·dose), once every 12 h, for a course of 7–14 days, or until the D‐dimer level essentially returns to normal (GPS).

Evidence summary

The evaluation group did not retrieve any systematic reviews on prophylactic anticoagulant therapy for pediatric MPP. Initially, seven studies related to D‐dimer levels and preventive anticoagulation therapy in MPP patients were identified, but none of them were included due to non‐randomization, lack of randomized methods, absence of diagnostic criteria, or being single‐author studies. Through a questionnaire survey conducted among pediatric experts in the development group, 33% (7/21) of the experts believed that prophylactic anticoagulant therapy could be initiated when D‐dimer levels in children with MPP elevated to five times or more above the upper limit of normal, while 29% (6/21) considered that it could be administered when D‐dimer levels elevated to 10 times or more of the normal upper limit. Among the experts, 81% (17/21) preferred low molecular weight heparin for prophylactic anticoagulant therapy. Furthermore, 62% (13/21) of the experts believed that the dosage of low molecular weight heparin should be 50–100 U/(kg·dose), administered subcutaneously once every 12 h, with a treatment duration of 7–14 days, or until D‐dimer levels essentially returned to normal.

Justification

The recommendations regarding the timing, drug dosage, and duration of prophylactic anticoagulant therapy when D‐dimer levels elevated are based on expert opinions and still require further clarification through high‐quality research. During the process of prophylactic anticoagulant therapy, attention should be paid to monitoring platelet and coagulation functions. It should be noted that D‐dimer levels may not return to normal levels in some MPP children who have underlying diseases such as thrombophilia.

Question 13: What are the indications for bronchoscopic lavage therapy in children with MPP? When is the optimal time for this treatment?

Recommendation 13

When MPP children are suspected of having airway mucus plug formation, and chest imaging indicates atelectasis, airway obstruction, or unilateral or bilateral lung lobe consolidation, bronchoscopic lavage therapy is recommended (GPS). It is generally performed between 7 and 14 days of illness (GPS).

Evidence summary

The evaluation group did not retrieve any systematic reviews on the timing of bronchoscopic lavage therapy for children with MPP. Initially, eight relevant studies on the timing of bronchoscopic lavage therapy for children with MPP were identified, but they were excluded due to being retrospective studies. Through a questionnaire survey conducted among pediatric experts in the development group, it was found that patients with unilateral or bilateral lung lobe consolidation [57% (12/21)], atelectasis [86% (18/21)], suspected airway mucus plug formation [90% (19/21)], and signs of airway obstruction [81% (17/21)] require bronchoscopic lavage therapy. Additionally, 76% (16/21) of experts believed that the appropriate timing for bronchoscopic lavage therapy was between 7 and 14 days after the onset of illness.

Justification

The indications for bronchoscopic lavage therapy are recommended based on expert opinions, but it is important to consider whether the patient's condition is stable and whether there are contraindications to bronchoscopy therapy. Adequate antimicrobial and necessary anti‐inflammatory treatment should also be administered. Although bronchoscopic lavage therapy is generally recommended to be performed between 7 and 14 days after the onset of the disease, the specific timing of lavage for different patients should be determined in close conjunction with their individual condition.

LIMITATIONS

Due to the influence of evidence quality, most of the recommendations in this guideline have a relatively low level. This guideline covers only 13 major clinical issues related to the diagnosis and treatment of pediatric MPP and does not address the management issues related to complications and sequelae which will be gradually improved in subsequent updates of this guideline.

LISTING OF EXPERTS

See Supporting Information file S1.

CONFLICT OF INTEREST

A conflict of interest management plan was developed. All members involved in the formulation of the guidelines have filled out a conflict of interest declaration form, and none of them have any relevant conflicts of interest.

Supporting information

Supporting information

The Subspecialty Group of Respiratory, the Society of Pediatrics, Chinese Medical Association , China National Clinical Research Center of Respiratory Diseases , Editorial Board, Chinese Journal of Pediatrics . Evidence‐based guideline for the diagnosis and treatment of Mycoplasma pneumoniae pneumonia in children (2023). Pediatr Investig. 2025;9:1–11. 10.1002/ped4.12469