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*For medical professionals to read for reference or not? Mycoplasma pneumoniae (MP) is a common pathogen causing community-acquired pneumonia (CAP) in children, and preschool or school-age children are susceptible to it
.
Tetracyclines, quinolones, and macrolides can all treat Mycoplasma pneumoniae pneumonia (MPP).
Tetracyclines can affect the development of enamel in children (not recommended for children under 8 years old), and quinolones can cause cartilage lesions (groups under 18 years old).
should not be used); therefore, macrolides are currently the first choice for the treatment of children with MPP.
For children with MPP, if the use of macrolides is standard for anti-infection for ≥7 days, the children still have persistent fever, clinical symptoms and chest imaging.
Exacerbation, extrapulmonary complications and prolonged disease duration are defined as refractory Mycoplasma pneumoniae pneumonia (RMPP) [1]
.
The treatment of RMPP is difficult, and there is a risk of sequelae such as bronchiectasis and bronchiolitis obliterans in children
.
01Clinical features of RMPP 1 Pathogenesis RMPP is mainly related to MP infecting the respiratory tract and stimulating inflammatory response and over-response host immunity, as follows [2]: MP can adhere to and damage respiratory epithelial cells, activate interleukin 2 (IL-2) ), IL-6 and other cytokines are involved in the inflammatory response; highly activated T cells mediate the immune response
.
2 Factors related to the occurrence of RMPP[1] The child has drug-resistant MP infection (that is, resistance to commonly used macrolides); MP infection leads to hypercoagulation in the body and ischemic necrosis of lung tissue; the child has mixed infection (such as Simultaneous infection of MP and bacteria)
.
Glucocorticoids have powerful anti-inflammatory and anti-immune pharmacological effects, which can symptomatically alleviate the pathological process of RMPP; they are recommended for the treatment of RMPP [3]
.
02 Classification of glucocorticoids [4] Table 103 Efficacy of glucocorticoids in children with RMPP The You SY team found that [5], 12 children with RMPP were given methylprednisolone 30 mg/(kg·d), and methylprednisolone was used.
After 2 hours, the fever began to subside (see Figure 1-A, P < 0.
001); after using methylprednisolone for 3±1.
1 days, the value of C-reactive protein (CRP) gradually decreased (Figure 1-B, P < 0.
001)
.
Figure 1 Changes of body temperature and CRP in children before and after methylprednisolone treatment (Note: on HD 4.
3±2.
3 means the child was admitted to hospital for 4.
3±2.
3 days, which was before the use of methylprednisolone; on HD 8.
3±2 means the child was admitted to the hospital at 8.
3±2.
3 days) 2d, after the use of methylprednisolone) Finally, this study believes that methylprednisolone can be used in the treatment of children with RMPP, and the effect is good
.
Another meta-analysis included 1130 children with RMPP [6], in the treatment group (564 cases, azithromycin combined with glucocorticoids) and the control group (566 cases, azithromycin only)
.
The study showed that the treatment group significantly improved the clinical effectiveness of the children, shortened the time for fever reduction, and significantly promoted the absorption of lung lesions
.
In addition, the Children's Hospital Affiliated to Fudan University admitted 6 children with RMPP, with an average age of 7.
1±2.
7 years
.
After communication with the child's guardian and informed consent, the child was given intravenous ciprofloxacin [10mg/(kg·d), course of treatment 7-12d] combined with glucocorticoids [initially 2mg/(kg·d) methylprednisolone Intravenous infusion, when the child's body temperature fell to normal, the treatment plan was changed to oral 1 mg/(kg·d) of prednisone for maintenance, and the dose was gradually reduced in the later period
.
Figure 2 shows the chest imaging changes of one patient in this study (male, 4 years old)
.
Figure 2 (Note: Figure 2-A and Figure 2-B are the chest radiographs of the child before and at the time of admission, respectively, and Figure 2-C, Figure 2-D, and Figure 2-E are the ciprofloxacin combined with sugar, respectively Chest X-ray 3 days after corticosteroid treatment, 7 days after combined treatment, and 12 days after combined treatment) It was finally confirmed that ciprofloxacin combined with glucocorticoids was effective in 6 children with RMPP, and the children were reexamined 1 month after discharge , no bone and joint abnormalities were found [7]
.
04 Discussion: How to grasp the dosage and course of treatment of glucocorticoids? Although glucocorticoids are clearly recommended for the treatment of RMPP, their dosage and duration remain controversial
.
The usual dosage of glucocorticoids: 1-2 mg/(kg·d) prednisolone (which can be equivalently replaced with other types of glucocorticoids, either by oral or intravenous administration) [8]
.
The specific course of treatment should be evaluated according to the clinical symptoms and chest imaging of the child
.
▌High-dose glucocorticoid seems to be more recommended compared with low-dose glucocorticoid group [53 cases, prednisolone <2 mg/(kg·d)], high-dose group [38 cases, prednisolone ≥ 2 mg/day] (kg·d)] treated RMPP children had faster fever reduction [0.
8±1d (high dose) vs.
(1.
5±1.
4 days (low dose)]; hospital stay was significantly shortened [8.
2±2.
4d (high dose) vs.
(10.
7±2.
7 days (low dose)][9]
.
▌The biochemical indexes and chest imaging of children provide a reference for the dosage of glucocorticoids.
If the CRP of children with RMPP is ≥44.
45 mg/L (sensitivity 55%, specificity 85%), lactate dehydrogenase (LDH) ≥ 590 IU/L (sensitivity 76.
3%, specificity 47.
5%), ferritin (FER) ≥ 411 ng/L (sensitivity 86.
4%, specificity 68.
2%) , neutrophil percentage ≥ 73.
75% (sensitivity 75%, specificity 90%), and accompanied by lung consolidation and pleural effusion, high-dose glucocorticoids (such as methylprednisolone: ≥ 200 mg/ d) treatment [2]
.
▌If the clinical response of conventional doses of glucocorticoids is not good, short-term pulse therapy can be considered.
Pulse therapy refers to the use of methylprednisolone 20-30 mg/(kg·d) intravenously for 3 days, and then changed to oral glucocorticoids for maintenance.
treatment [10]
.
References: [1] Liu Hanmin, Ma Rong.
Expert consensus on the diagnosis and treatment of Mycoplasma pneumoniae pneumonia in children with integrated traditional Chinese and Western medicine (formulated in 2017) [J].
Chinese Journal of Practical Pediatrics, 2017.
[2]Zhu Z, Zhang T, Guo W, Ling Y, Tian J, Xu Y.
Clinical characteristics of refractory mycoplasma pneumoniae pneumonia in children treated with glucocorticoid pulse therapy.
BMC Infect Dis.
2021 Jan 28;21(1):126.
[3] Guidelines for the diagnosis and treatment of community-acquired pneumonia in children (2019 2019.
[4] Ministry of Health.
Guidelines for the clinical application of glucocorticoids [J].
Practical blindness prevention technology, 2012, 28(002):2-2.
[5]You SY, Jwa HJ, Yang EA, Kil HR, Lee JH.
Effects of Methylprednisolone Pulse Therapy on Refractory Mycoplasma pneumoniae Pneumonia in Children.
Allergy Asthma Immunol Res.
2014 Jan;6( 1):22-6.
[6]Qiu JL, Huang L, Shao MY, Chai YN, Zhang HJ, Li XF, Sun XX, Zhao QY, Duan F, Zhai WS.
Efficacy and safety of azithromycin combined with glucocorticoid on refractory Mycoplasma pneumoniae pneumonia in children:A PRISMA-compliant systematic review and meta-analysis.
Medicine (Baltimore).
2020 May 29;99(22):e20121.
[7]Lu A, Wang L, Zhang X, Zhang M.
Combined treatment for child refractory Mycoplasma pneumoniae pneumonia with ciprofloxacin and glucocorticoid.
Pediatr Pulmonol.
2011 Nov;46(11):1093-7.
[8] Liao Xiaoling, Wu Liang.
Correlation analysis of red blood cell distribution width and myocardial damage in children with severe Mycoplasma pneumoniae pneumonia[J].
Chinese General Practice Medicine, 2017, 20 (z1): 11-14.
[9] Okumura T, Kawada JI, Tanaka M, et al.
Comparison of high-dose and low-dose corticosteroid therapy for refractory Mycoplasma pneumoniae pneumonia in children.
J Infect Chemother .
2019 May;25(5):346-350.
[10] Shi Peng.
Study on the effect of different doses of glucocorticoids in the treatment of severe mycoplasma pneumonia [J].
System Medicine, 2018, 3(15):3.
1093-7.
[8] Liao Xiaoling, Wu Liang.
Correlation analysis between red blood cell distribution width and myocardial damage in children with severe Mycoplasma pneumoniae pneumonia [J].
Chinese General Medicine, 2017, 20 (z1): 11-14.
[9] Okumura T, Kawada JI, Tanaka M, et al.
Comparison of high-dose and low-dose corticosteroid therapy for refractory Mycoplasma pneumoniae pneumonia in children.
J Infect Chemother.
2019 May;25(5):346-350.
[10] Shi Peng.
Study on the effect of different doses of glucocorticoids in the treatment of severe mycoplasma pneumonia [J].
System Medicine, 2018, 3(15):3.
1093-7.
[8] Liao Xiaoling, Wu Liang.
Correlation analysis between red blood cell distribution width and myocardial damage in children with severe Mycoplasma pneumoniae pneumonia [J].
Chinese General Medicine, 2017, 20 (z1): 11-14.
[9] Okumura T, Kawada JI, Tanaka M, et al.
Comparison of high-dose and low-dose corticosteroid therapy for refractory Mycoplasma pneumoniae pneumonia in children.
J Infect Chemother.
2019 May;25(5):346-350.
[10] Shi Peng.
Study on the effect of different doses of glucocorticoids in the treatment of severe mycoplasma pneumonia [J].
System Medicine, 2018, 3(15):3.
.
Tetracyclines, quinolones, and macrolides can all treat Mycoplasma pneumoniae pneumonia (MPP).
Tetracyclines can affect the development of enamel in children (not recommended for children under 8 years old), and quinolones can cause cartilage lesions (groups under 18 years old).
should not be used); therefore, macrolides are currently the first choice for the treatment of children with MPP.
For children with MPP, if the use of macrolides is standard for anti-infection for ≥7 days, the children still have persistent fever, clinical symptoms and chest imaging.
Exacerbation, extrapulmonary complications and prolonged disease duration are defined as refractory Mycoplasma pneumoniae pneumonia (RMPP) [1]
.
The treatment of RMPP is difficult, and there is a risk of sequelae such as bronchiectasis and bronchiolitis obliterans in children
.
01Clinical features of RMPP 1 Pathogenesis RMPP is mainly related to MP infecting the respiratory tract and stimulating inflammatory response and over-response host immunity, as follows [2]: MP can adhere to and damage respiratory epithelial cells, activate interleukin 2 (IL-2) ), IL-6 and other cytokines are involved in the inflammatory response; highly activated T cells mediate the immune response
.
2 Factors related to the occurrence of RMPP[1] The child has drug-resistant MP infection (that is, resistance to commonly used macrolides); MP infection leads to hypercoagulation in the body and ischemic necrosis of lung tissue; the child has mixed infection (such as Simultaneous infection of MP and bacteria)
.
Glucocorticoids have powerful anti-inflammatory and anti-immune pharmacological effects, which can symptomatically alleviate the pathological process of RMPP; they are recommended for the treatment of RMPP [3]
.
02 Classification of glucocorticoids [4] Table 103 Efficacy of glucocorticoids in children with RMPP The You SY team found that [5], 12 children with RMPP were given methylprednisolone 30 mg/(kg·d), and methylprednisolone was used.
After 2 hours, the fever began to subside (see Figure 1-A, P < 0.
001); after using methylprednisolone for 3±1.
1 days, the value of C-reactive protein (CRP) gradually decreased (Figure 1-B, P < 0.
001)
.
Figure 1 Changes of body temperature and CRP in children before and after methylprednisolone treatment (Note: on HD 4.
3±2.
3 means the child was admitted to hospital for 4.
3±2.
3 days, which was before the use of methylprednisolone; on HD 8.
3±2 means the child was admitted to the hospital at 8.
3±2.
3 days) 2d, after the use of methylprednisolone) Finally, this study believes that methylprednisolone can be used in the treatment of children with RMPP, and the effect is good
.
Another meta-analysis included 1130 children with RMPP [6], in the treatment group (564 cases, azithromycin combined with glucocorticoids) and the control group (566 cases, azithromycin only)
.
The study showed that the treatment group significantly improved the clinical effectiveness of the children, shortened the time for fever reduction, and significantly promoted the absorption of lung lesions
.
In addition, the Children's Hospital Affiliated to Fudan University admitted 6 children with RMPP, with an average age of 7.
1±2.
7 years
.
After communication with the child's guardian and informed consent, the child was given intravenous ciprofloxacin [10mg/(kg·d), course of treatment 7-12d] combined with glucocorticoids [initially 2mg/(kg·d) methylprednisolone Intravenous infusion, when the child's body temperature fell to normal, the treatment plan was changed to oral 1 mg/(kg·d) of prednisone for maintenance, and the dose was gradually reduced in the later period
.
Figure 2 shows the chest imaging changes of one patient in this study (male, 4 years old)
.
Figure 2 (Note: Figure 2-A and Figure 2-B are the chest radiographs of the child before and at the time of admission, respectively, and Figure 2-C, Figure 2-D, and Figure 2-E are the ciprofloxacin combined with sugar, respectively Chest X-ray 3 days after corticosteroid treatment, 7 days after combined treatment, and 12 days after combined treatment) It was finally confirmed that ciprofloxacin combined with glucocorticoids was effective in 6 children with RMPP, and the children were reexamined 1 month after discharge , no bone and joint abnormalities were found [7]
.
04 Discussion: How to grasp the dosage and course of treatment of glucocorticoids? Although glucocorticoids are clearly recommended for the treatment of RMPP, their dosage and duration remain controversial
.
The usual dosage of glucocorticoids: 1-2 mg/(kg·d) prednisolone (which can be equivalently replaced with other types of glucocorticoids, either by oral or intravenous administration) [8]
.
The specific course of treatment should be evaluated according to the clinical symptoms and chest imaging of the child
.
▌High-dose glucocorticoid seems to be more recommended compared with low-dose glucocorticoid group [53 cases, prednisolone <2 mg/(kg·d)], high-dose group [38 cases, prednisolone ≥ 2 mg/day] (kg·d)] treated RMPP children had faster fever reduction [0.
8±1d (high dose) vs.
(1.
5±1.
4 days (low dose)]; hospital stay was significantly shortened [8.
2±2.
4d (high dose) vs.
(10.
7±2.
7 days (low dose)][9]
.
▌The biochemical indexes and chest imaging of children provide a reference for the dosage of glucocorticoids.
If the CRP of children with RMPP is ≥44.
45 mg/L (sensitivity 55%, specificity 85%), lactate dehydrogenase (LDH) ≥ 590 IU/L (sensitivity 76.
3%, specificity 47.
5%), ferritin (FER) ≥ 411 ng/L (sensitivity 86.
4%, specificity 68.
2%) , neutrophil percentage ≥ 73.
75% (sensitivity 75%, specificity 90%), and accompanied by lung consolidation and pleural effusion, high-dose glucocorticoids (such as methylprednisolone: ≥ 200 mg/ d) treatment [2]
.
▌If the clinical response of conventional doses of glucocorticoids is not good, short-term pulse therapy can be considered.
Pulse therapy refers to the use of methylprednisolone 20-30 mg/(kg·d) intravenously for 3 days, and then changed to oral glucocorticoids for maintenance.
treatment [10]
.
References: [1] Liu Hanmin, Ma Rong.
Expert consensus on the diagnosis and treatment of Mycoplasma pneumoniae pneumonia in children with integrated traditional Chinese and Western medicine (formulated in 2017) [J].
Chinese Journal of Practical Pediatrics, 2017.
[2]Zhu Z, Zhang T, Guo W, Ling Y, Tian J, Xu Y.
Clinical characteristics of refractory mycoplasma pneumoniae pneumonia in children treated with glucocorticoid pulse therapy.
BMC Infect Dis.
2021 Jan 28;21(1):126.
[3] Guidelines for the diagnosis and treatment of community-acquired pneumonia in children (2019 2019.
[4] Ministry of Health.
Guidelines for the clinical application of glucocorticoids [J].
Practical blindness prevention technology, 2012, 28(002):2-2.
[5]You SY, Jwa HJ, Yang EA, Kil HR, Lee JH.
Effects of Methylprednisolone Pulse Therapy on Refractory Mycoplasma pneumoniae Pneumonia in Children.
Allergy Asthma Immunol Res.
2014 Jan;6( 1):22-6.
[6]Qiu JL, Huang L, Shao MY, Chai YN, Zhang HJ, Li XF, Sun XX, Zhao QY, Duan F, Zhai WS.
Efficacy and safety of azithromycin combined with glucocorticoid on refractory Mycoplasma pneumoniae pneumonia in children:A PRISMA-compliant systematic review and meta-analysis.
Medicine (Baltimore).
2020 May 29;99(22):e20121.
[7]Lu A, Wang L, Zhang X, Zhang M.
Combined treatment for child refractory Mycoplasma pneumoniae pneumonia with ciprofloxacin and glucocorticoid.
Pediatr Pulmonol.
2011 Nov;46(11):1093-7.
[8] Liao Xiaoling, Wu Liang.
Correlation analysis of red blood cell distribution width and myocardial damage in children with severe Mycoplasma pneumoniae pneumonia[J].
Chinese General Practice Medicine, 2017, 20 (z1): 11-14.
[9] Okumura T, Kawada JI, Tanaka M, et al.
Comparison of high-dose and low-dose corticosteroid therapy for refractory Mycoplasma pneumoniae pneumonia in children.
J Infect Chemother .
2019 May;25(5):346-350.
[10] Shi Peng.
Study on the effect of different doses of glucocorticoids in the treatment of severe mycoplasma pneumonia [J].
System Medicine, 2018, 3(15):3.
1093-7.
[8] Liao Xiaoling, Wu Liang.
Correlation analysis between red blood cell distribution width and myocardial damage in children with severe Mycoplasma pneumoniae pneumonia [J].
Chinese General Medicine, 2017, 20 (z1): 11-14.
[9] Okumura T, Kawada JI, Tanaka M, et al.
Comparison of high-dose and low-dose corticosteroid therapy for refractory Mycoplasma pneumoniae pneumonia in children.
J Infect Chemother.
2019 May;25(5):346-350.
[10] Shi Peng.
Study on the effect of different doses of glucocorticoids in the treatment of severe mycoplasma pneumonia [J].
System Medicine, 2018, 3(15):3.
1093-7.
[8] Liao Xiaoling, Wu Liang.
Correlation analysis between red blood cell distribution width and myocardial damage in children with severe Mycoplasma pneumoniae pneumonia [J].
Chinese General Medicine, 2017, 20 (z1): 11-14.
[9] Okumura T, Kawada JI, Tanaka M, et al.
Comparison of high-dose and low-dose corticosteroid therapy for refractory Mycoplasma pneumoniae pneumonia in children.
J Infect Chemother.
2019 May;25(5):346-350.
[10] Shi Peng.
Study on the effect of different doses of glucocorticoids in the treatment of severe mycoplasma pneumonia [J].
System Medicine, 2018, 3(15):3.
