Research Progress in the Treatment of Refractory Mycoplasma Pneumoniae Pneumonia

Currently, the main clinical treatment methods for refractory Mycoplasma pneumoniae pneumonia (RMPP) after diagnosis include bronchoscope lavage, antibiotic therapy, glucocorticoid therapy, immune modulation treatment, antithrombotic therapy, and integrated traditional Chinese and Western medicine therapy.

According to the consensus proposed by the Respiratory Group of the Chinese Medical Association's Respiratory Branch, refractory Mycoplasma pneumoniae pneumonia (RMPP) refers to cases where children present with pulmonary disease manifestations and show no improvement or a worsening trend despite regular and continuous treatment with macrolide antibiotics for more than 7 days. Imaging diagnostic analysis reveals that these children have multiple extra-pulmonary tissue and organ injuries, with persistent and unresolved illness lasting up to 3 to 4 weeks. RMPP often exhibits severe intra-pulmonary complications such as pleural effusion and atelectasis, while also affecting extra-pulmonary tissues, resulting in clinical symptoms like abnormal liver function, rash, myocarditis, and encephalitis. In severe cases, it can lead to neonatal respiratory distress syndrome (RDS), necrotizing pneumonia, bronchiolitis obliterans (BO), or even death. Currently, the main clinical treatment methods for RMPP after diagnosis are as follows.

1.Bronchoalveolar lavage

Bronchoalveolar lavage enables the collection of inflammatory fluid from the alveolar surface, timely removing inflammatory substances and sputum plugs located within the alveoli. It also examines the collected inflammatory substances and immune cells to achieve the purpose of definitive diagnosis and treatment. Due to the pathological impact of refractory bronchial pneumonia in children, a decrease in the immune response of the body can lead to an increase in tumor necrosis factor and interleukin levels. Therefore, in clinical treatment, a combination of antibacterial drugs and fiberoptic bronchoscopy is often used for intervention. This is because fiberoptic bronchoscopy treatment offers several significant advantages. Firstly, bronchoalveolar lavage can efficiently and quickly clear respiratory secretions, dislodge sputum plugs, and effectively promote lung expansion. Secondly, it can rapidly eliminate pathogenic bacterial toxins and immune complexes, significantly enhancing therapeutic efficacy. Thirdly, fiberoptic bronchoscopy allows for targeted local drug administration, directly applying clinical medications to the site of the lesion to alleviate inflammatory manifestations. Fourthly, the use of fiberoptic bronchoscopy can visually detect intrapulmonary lesions that are not easily detected by imaging examinations.

2.Antibiotic Treatment

Mycoplasma pneumoniae, due to its lack of a cell wall, is resistant to many antibiotics such as penicillin, cephalosporins, vancomycin, sulfonamides, trimethoprim, and rifampin. It is crucial to distinguish other bacterial infections from Mycoplasma pneumoniae pneumonia (MPP) to determine the appropriate treatment plan, which directly impacts the recommendation for empirical antibiotic therapy. Antibiotics that inhibit bacterial DNA synthesis tend to be more effective, with common drugs including tetracyclines, quinolones, and macrolides. Macrolides are the commonly used drugs, including erythromycin, azithromycin, and roxithromycin. They have high drug concentrations and long half-lives, requiring only once-daily administration, making them the clinical first-choice for treating MPP in children.

There is also a single-drug azithromycin regimen, which requires a longer treatment cycle and can cause significant gastrointestinal reactions after administration, making it difficult for children and their families to accept. More effective clinical treatment plans are needed to achieve the desired results. As macrolide antibiotics become more widely used, drug resistance to this class of antibiotics has also gradually increased, which is a recognized mechanism for the progression to RMPP.

When Mycoplasma pneumoniae infection is complicated by bacterial co-infection in children, fever is an important clinical indicator for assessing RMPP patients. If the child's fever subsides within 72 hours of treatment, it suggests a favorable response. However, if the fever persists after 72 hours of continuous treatment, it indicates that the child's condition may be progressing to RMPP. The clinically recommended first-line drugs are azithromycin, erythromycin, and clarithromycin, while moxifloxacin and levofloxacin are considered second-line alternatives.

3.Glucocorticoids

Generally, glucocorticoids are not required for ordinary MPP, but their efficacy in MPP cases with particularly rapid progression and acute onset has been confirmed. When glucocorticoids bind to receptors within human cells, they form hormone-receptor complexes that produce biological effects. These effects include: ① promoting the production and activation of human cell membrane activating protein I, inhibiting phospholipase A2 to a certain extent, and further suppressing the release of leukotrienes, prostaglandins, and arachidonic acid. ② Inhibiting the production of phospholipase A2 and inflammatory proteins by inducing the product MAPK-phosphatase-1 (MKP1). ③ Blocking the function of nuclear factor (NF-κB), further suppressing the expression of cell adhesion factors, chemokines, and cytokines. Additionally, glucocorticoids can reduce the number of mast cells, promote the apoptosis of eosinophils, inhibit inflammatory cells, reduce capillary leakage, and improve clinical symptoms such as cough and thick sputum. A randomized controlled study showed that adding glucocorticoids to conventional treatment for RMPP can improve clinical efficacy to a certain extent with good safety. A meta-analysis comparing the efficacy and safety of high-dose and low-dose methylprednisolone in the treatment of severe MPP in children indicated that high-dose methylprednisolone significantly shortened hospital stay and treatment time, as well as the time for lung rales and cough to disappear, without significant side effects of high-dose glucocorticoids.

4.Immunomodulatory Therapy

Intravenous administration of gamma globulin results in an antigen-IgG reaction, forming antigen-antibody complexes that can effectively prevent pathogen-induced damage to the body and inhibit the production of inflammatory factors and cytokines, thus controlling the damage caused by inflammatory reactions. Gamma globulin, as a blood product, is relatively expensive and is mostly used for severe clinical supportive treatment. Gamma globulin can be a hormone substitute for children who are insensitive to hormones or have contraindications to hormone therapy. It can also be used to treat children with extrapulmonary complications. Studies have shown that when gamma globulin is used in cases of Mycoplasma pneumoniae pneumonia complicated with encephalitis, the symptoms of encephalitis can be immediately relieved. While gamma globulin treatment for Mycoplasma pneumoniae pneumonia patients can actively improve the patient's sequelae, it does not shorten the fever duration when used in combination with azithromycin, and its control effect on reducing inflammatory markers is also not ideal. Therefore, gamma globulin is rarely used in domestic clinical treatment of RMPP.

5.Antithrombotic Therapy

Due to the hypercoagulable state of their blood, children with RMPP are prone to thromboembolism, especially deep vein thrombosis in the lungs, brain, and lower extremities. Clinical antithrombotic therapy, including anticoagulation, thrombolysis, and surgical procedures, can achieve good results. Thrombolytic therapy should be administered for organ failure caused by thromboembolism. Implementing thrombolytic therapy after anticoagulation can ensure the safety of clinical treatment. It is used for patients with severe embolism who are contraindicated for thrombolysis, to avoid misdiagnosis of the condition as embolism caused by other diseases. Determining the timing and dosage of thrombolytic therapy requires further data support from clinical studies to establish thrombolytic indications. However, the high risk associated with surgery limits its clinical application.

6.Integrated Chinese and Western Medicine Treatment

Chinese medicine theories have a long history and tradition in China, and medical interventions based on these theories can also achieve good clinical treatment results in the treatment of RMPP. According to Chinese medicine, the main pathogenesis of refractory bronchopneumonia in children is due to heat stagnation and phlegm congestion. Therefore, the clinical treatment focuses on ventilating the lungs, restoring normal function, and clearing heat and detoxifying. On the basis of conventional macrolide antibiotic treatment, an integrated Chinese and Western medicine approach is adopted, combining it with prescriptions that clear heat and detoxify. Through the effective ingredients of herbs such as Coptis chinensis, Gardenia jasminoides, Phellodendron chinense, Huanglin (a traditional Chinese medicinal herb, the exact species may vary), almond, and licorice, the prescriptions can assist in clearing heat, detoxifying, ventilating the lungs, relieving cough, and calming asthma. This further reduces the number of Mycoplasma pneumoniae bacteria and enhances the effect of macrolide antibiotics in eliminating pathogens. The integrated Chinese and Western medicine treatment method has good clinical application value in many disease areas. By combining traditional Chinese medicine prescriptions with antibiotic drugs, it not only optimizes clinical symptoms but also significantly improves treatment efficacy, making effective contributions to improving the physiological state of children.

References

[1] Wu Xue, Chen Xiao. Advances in Pathogenesis, Diagnosis and Treatment of Refractory Mycoplasma Pneumoniae Pneumonia in Children [J]. World Latest Medicine Information Digest (Continuous Electronic Journal), 2022, (Issue 0).

[2] Zheng Xiaoxiao, Chen Jing. Research Progress on Pathogenesis, Diagnosis and Treatment of Mycoplasma Pneumoniae Pneumonia [J]. World Latest Medicine Information Digest, 2021, (Issue 67).

[3] Deng Yanbin. Research Progress on Pathogenesis and Treatment of Refractory Mycoplasma Pneumoniae Pneumonia in Children [J]. Chinese Science and Technology Periodicals Database: Medicine, 2023, (Issue 2).

[4] Wang Zelun, Long Xuhao. Research Progress on Pathogenesis and Hormone Treatment of Mycoplasma Pneumoniae Pneumonia [J]. Chinese Prescription Drug, 2024, 22(01): 191-194.

About the Author

Xiaomichong, a pharmaceutical quality researcher, has long been dedicated to the research of drug quality and validation of drug analysis methods. Currently, she is employed by a large domestic pharmaceutical research and development company, engaged in drug inspection, analysis, and verification of analytical methods.