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How to combine them for better results?
Written by | Chang Yiyong
Montelukast is a leukotriene receptor antagonist, which is often used in the treatment of childhood asthma in clinical practice, which can specifically block the binding of leukotrienes to their receptors, inhibit bronchospasm caused by leukotrienes, and reduce airway hyperresponsiveness.
The study found that[1] the prevalence of Mycoplasma pneumoniae (MP) infection in patients with acute asthma was higher than that in asthma control stage, and the percentage of forced expiratory volume in 1 second to predicted value (FEV1%pred), asthma control test (ACT) value, total number of eosinophils, and serum IgE levels in patients with MP infection were significantly higher than those in patients without MP infection.
Therefore, for patients with Mycoplasma pneumoniae pneumonia (MPP), montelukast should be treated as soon as possible [2] to reduce chronic inflammation of the airways, reduce cough symptoms, further improve lung function, and reduce the incidence of asthma. This article only summarizes the application of five combinations of montelukast in the treatment of MPP patients for clinical reference.
01
Montelukast + azithromycin
MPP is atypical pneumonia caused by MP infection and has a high incidence in children. Azithromycin is the preferred basic treatment for pediatric MPP [3], and as a macrolide antibiotic, it can play an antibacterial and baccidal effect on Mycoplasma pneumoniae, but it does not control lung inflammation adequately. Montelukast sodium can control cysteinyl leukotriene secretion, thereby alleviating leukotriene-mediated airway responses, inflammatory responses, and tissue damage.
The results of clinical treatment [4-5] showed that montelukast sodium tablets combined with azithromycin in the treatment of pediatric MPP had good clinical efficacy, which could reduce the lung ultrasound score (LUS), improve ultrasound characteristics, reduce inflammatory response related factors in children, thereby improving lung function and immune function, and reducing airway inflammation.
Medication:
On the basis of conventional treatment (including antipyretic, oxygen inhalation and correction of water and electrolyte imbalances, etc.), azithromycin 10mg/kg, plus 200mL of glucose injection intravenously, once a day (10mg/kg plus 200mL of 5% glucose injection can also be used as a daily infusion, continuous intravenous infusion for 3 days and then discontinued for 4 days, as a course of treatment). Montelukast sodium tablets are taken orally, 4mg orally for 5 years old and younger, and 5mg orally for people over 5 years old, once a day before bedtime. Treatment for 2 weeks.
Another clinical study [6] showed that montelukast sodium and azithromycin (oral, 7 days for 1 course of treatment, the first 3 days dose of 5 mg/kg, once a day, and then 4 days after discontinuation. Combined treatment of children with refractory mycoplasma pneumonia (RMPP) can effectively inhibit inflammatory response, improve clinical symptoms, and improve immune function, lung function and clinical efficacy.
The results of azithromycin combined with montelukast sodium in the treatment of MPP in the elderly [7] showed that it could improve the effective rate of treatment, help accelerate the improvement time of various symptoms, reduce the body's inflammatory response, and promote the recovery of patients.
Medication:
On the basis of conventional symptomatic treatment, the patient was sequentially administered azithromycin with 50mg of azithromycin plus 250mL of 0.9% sodium chloride solution intravenously, the infusion time was ≥ 1h, once / d, continuous treatment for 2~5d, and adjusted to oral administration after the patient's body temperature dropped: 50mg on the 1st day, 25mg on the 2nd ~ 5th day, and then stopped taking the drug for 5 days and repeated for 1 cycle, the course of treatment was 2~3 weeks. Oral administration of montelukast sodium tablets 10mg, once a day, continuous medication for 3 days, then stop the drug for 4 days, and repeat for 4 cycles.
02
Montelukast + erythromycin
Erythromycin is also an anti-MP macrolide antibiotic recommended by the guideline [3], which has a broad antibacterial spectrum and can play a good role in most gram-positive bacteria, some gram-negative bacteria and atypical pathogenic bacteria. However, with the large and irrational use in clinical practice, the drug resistance of pathogenic bacteria has been enhanced, so it is difficult to obtain good results with erythromycin alone.
The clinical treatment results [8] showed that compared with erythromycin alone, montelukast sodium combined with erythromycin had a better therapeutic effect on MP infection in children, significantly shortened the disappearance time of fever, cough and other symptoms, and significantly improved the level of lung function and serum stress indicators.
Medication:
On the basis of conventional treatment, erythromycin was used for anti-infection treatment, erythromycin lactobionate for injection at a dose of 15 mg/kg, plus 250mL of 5% glucose injection intravenously for 2 times/d, and after continuous treatment for 5 days, erythromycin enteric-coated tablets were changed to oral at the same dose. Oral montelukast sodium chewable tablets 4mg (2~5 years old)-5mg (6~14 years old), once a day, taken before bedtime. Continuous treatment for 14 days.
Another clinical study [9-10] has shown that erythromycin combined with montelukast sodium in the treatment of allergic cough caused by MP infection in children can help improve the efficiency of clinical treatment, shorten the recovery time of cough, rapidly improve the clinical symptoms and lung function of children, reduce inflammation, and have fewer adverse reactions.
03
Montelukast + moxifloxacin
Quinolone antimicrobials (including moxifloxacin, etc.) are recommended by guidelines [3] as alternatives to MPP and have definite efficacy against macrolide-resistant MPP, and are used for the treatment of suspected or confirmed mycoplasma resistance, macrolide non-responsive Mycoplasma pneumoniae pneumonia (MUMPP), RMPP, and Mycoplasma pneumoniae pneumonia (SMPP). Due to the risk of cartilage damage in juvenile animals and tendon rupture in humans, the use of off-label drugs in children under 18 years of age requires a full evaluation of the benefits and harms and the informed consent of parents.
Clinical treatment results have shown [11-13] that moxifloxacin combined with montelukast sodium in the treatment of MPP can not only quickly alleviate clinical symptoms, shorten the length of hospital stay, but also improve lung function, alleviate C-reactive protein and white blood cell count, effectively reduce the level of inflammatory indicators, and improve clinical efficacy, and the treatment safety is controllable.
Medication:
On the basis of conventional treatment (symptomatic supportive treatment such as cooling, cough suppressant, phlegm, and asthma), the child was treated with moxifloxacin intravenous infusion of 10 mg/(kg·d) qd; Montelukast sodium is 5 mg orally once a day. Treatment continued for 2 weeks.
Emphasis: Fluoroquinolones such as moxifloxacin can only be used as recommended by the guidelines, and are not used as routine drugs for MPP.
0404
Montelukast + gamma globulin
Guidelines [3] do not recommend gamma globulin for the conventional treatment of ordinary MPP, but consider it recommended when MPP is complicated with severe extrapulmonary complications such as central nervous system manifestations, severe mucocutaneous and mucosal lesions, hematologic manifestations, SMPP mixed with adenovirus infection, or hyperimmune inflammatory response, and severe intrapulmonary injury. It is recommended to inject 1g/(kg·times) intravenously every day, and the course of treatment is 1-2 days. Experts have also made it clear [2] that gamma globulin is not routinely recommended for the treatment of ordinary MPP, and that intravenous gamma globulin combined with glucocorticoids will be more effective in children with RMPP with severe extrapulmonary complications.
At present, the clinical application of gamma globulin is not rigorous enough and is suspected of abuse. According to the latest reports [14], montelukast sodium combined with gamma globulin in the treatment of MPP (SMPP or RMPP is not clearly indicated) has achieved significant results, and it is believed that it can improve the pulmonary function and immune function of children, and the use of gamma globulin is 400 mg/kg intravenous infusion once a day for 14 days.
Although the above reports have achieved "obvious results", the author believes that the application of gamma globulin has problems in the selection of indications, dosage, duration of treatment and pharmacoeconomics, which is inconsistent with the guidelines and expert opinions, and needs to be discussed and verified.
05
Montelukast + budesonide
Guidelines [3] do not explicitly recommend budesonide for the treatment of MPP, but consider that the glucocorticoid methylprednisolone can be routinely used in severely and critically ill children. Patients with acute exacerbations of bronchial asthma should also be routinely treated with glucocorticoids; The use of hormones in remission can be referred to the guidelines for the diagnosis and treatment of bronchial asthma.
Clinical treatment results have shown [15-16] that budesonide nebulized inhalation combined with montelukast sodium oral treatment of children with MPP and chronic cough has a definite therapeutic effect, which can quickly alleviate clinical symptoms, promote the recovery of respiratory function, significantly reduce the levels of cytokines macrophage-derived chemokine (MDC) and monocyte chemoattractant protein-4 (MCP-4) in children with mycoplasma pneumonia, and reduce inflammation, with high safety.
Medication:
Montelukast chewable tablets are chewed at bedtime, 5 mg < 12 years old, 10 mg ≥ 12 years old, once a day; Continuous treatment for 4 weeks. Budesonide suspension 2mL + 0.9% sodium chloride solution 10mL mixture is inhaled by oral and nasal nebulization, once in the morning and once in the evening. Treatment continued for 4 weeks.
In addition, clinical studies have shown that the combination of azithromycin, montelukast sodium, and budesonide in the treatment of pediatric MPP can improve lung function and reduce serum inflammatory factor levels, with high safety [17]; The combination of the above three drugs has a satisfactory effect in the treatment of mycoplasma pneumonia and secondary asthma in children, which can shorten the duration of symptoms such as cough, improve lung function and immune function, and inhibit the body's inflammatory response, and has a high drug safety [18].
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参考资料：[1] GAO S，WANG L，ZHU W，et al．Mycoplasma pneumonia infection and Pak J Med SciQ，2015，31（3）：548-551．
[2] Han Xiaohua. Medicine and Philosophy,2018,39(2):12-15.
[3] National Health Commission of the People's Republic of China. Guidelines for the diagnosis and treatment of Mycoplasma pneumoniae pneumonia in children (2023 edition)[J].Exploration of rational drug use in China,2023,20(3):16-24.)
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[5] Li Yan, Qi Ji. Effect of azithromycin combined with montelukast sodium on immune function and airway inflammation in children with Mycoplasma pneumoniae pneumoniae[J].Modern Diagnosis and Treatment,2023,34(2):223-226.)
[6] Ma Limin. Efficacy analysis of montelukast sodium combined with azithromycin in the treatment of refractory mycoplasma pneumonia in children[J].Huaihai Medicine,2023,41(5):502-505.
[7] Zhang Yongfen, Li Zefen. Clinical Research,2022,30(9):56-59.
[8] Liu Jia, Jia Yujing. Effect of montelukast sodium combined with erythromycin in the treatment of Mycoplasma pneumoniae infection in children[J].Journal of Practical Clinical Medicine,2023,27(7):129-132,148.
[9] Xu Huan. Discussion on the effect of erythromycin combined with montelukast sodium in the treatment of allergic cough caused by Mycoplasma pneumoniae infection in children[J].Chinese and Foreign Medical,2022,41(18):101-104,121.
[10] Lin Shuqiao, Xu Hongtao. Effect of erythromycin combined with montelukast sodium on recovery time of allergic cough symptoms induced by Mycoplasma pneumoniae infection in children[J].Chinese Journal of Pharmacoeconomics,2020,15(1):58-60,64.
[11] Ma Xiao. Clinical efficacy and adverse reactions of moxifloxacin combined with montelukast sodium in the treatment of pediatric mycoplasma pneumonia[J].Journal of Clinical Rational Medication, 2022,15(11):36-38.
[12] Zhang Dongjiao. Clinical efficacy and safety evaluation of moxifloxacin combined with montelukast sodium in the treatment of pediatric mycoplasma pneumonia[J].China Modern Drug Appl,2021,15(3):144-146.
[13] Xue Lili. Clinical efficacy and safety evaluation of the combination of moxifloxacin and montelukast sodium in the treatment of mycoplasma pneumonia in children[J].Chinese and Foreign Women's Health Research,2021,(18):59-60.
[14] Yang Liguo, Chen Wei. Effect of montelukast sodium combined with gamma globulin in the treatment of children with Mycoplasma pneumoniae pneumonia and its effect on immune function[J].Clinical Medical Engineering,2024,31(1):71-72.)
[15] Cai Qingyong, Hu Zhijun. Efficacy and safety of budesonide nebulized inhalation combined with montelukast sodium in the oral treatment of pediatric mycoplasma pneumonia with chronic cough[J].Clinical Rational Medication,2023,16(24):126-129.
[16] Chen Licheng, Zhou Fengqia. Effect of budesonide combined with montelukast sodium on pulmonary function and MDC MCP-4 in children with mycoplasma pneumonia[J].Primary Medicine Forum,2022,26(22):29-31,58.
[17] Wang Zhifang, He Luwei. Effect of montelukast and budesonide combined with azithromycin on the efficacy of pediatric patients with Mycoplasma pneumoniae pneumonia[J].Chinese Journal of Clinical Pharmacology,2022,38(16):1851-1854.
[18] Huang Jiamin, Lin Dongfu. Clinical effect of montelukast sodium combined with azithromycin and budesonide in the treatment of pediatric mycoplasma pneumonia and secondary asthma[J].Clinical Rational Medication,2023,16(32):129-132.Source of this article: Respiratory Channel of the medical community
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