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Macrolide antibiotics are currently the first choice for the treatment of children with Mycoplasma pneumoniae pneumonia (MPP). Among them, azithromycin has become the drug of choice for the treatment of MPP because it only needs to be administered once a day, with fewer days of use, high bioavailability, high intracellular concentration, and high compliance and tolerance.
“Expert Consensus on Diagnosis and Treatment of Mycoplasma Pneumonia in Children (2015)” pointed out that the usage of azithromycin is 10mg/(kg·d), once a day, and 3 days for mild cases. 1 course of treatment, severe cases can be used for 5-7 days, and the second course of treatment can be repeated after 4 days. ThenWhy should I stop azithromycin for 4 days and repeat the second course of treatment? See text for details.
1. Azithromycin has a unique pharmacokinetic profile
half-life Long and high tissue concentration: Azithromycin is widely distributed in tissues and metabolized slowly. The blood elimination half-life (t1/2β) after a single dose is 35-48 hours; the half-life in tissues is longer, up to 68-76 hours.
Because of its slow elimination, the plasma concentration and tissue free concentration of azithromycin after oral administration for 3-5 days were higher. Therefore, after taking the drug for 3 days, even if the drug is stopped, it can still continue to act in the body for 3-4 days.
2. Post-antibiotic effects of azithromycin
< strong>Post-antibiotic effect (PAE) refers to the effect that bacterial growth and replication are still inhibited when the drug concentration drops below the minimum inhibitory concentration (MIC) after contact with antibiotics, or is eliminated.
Azithromycin is a typical drug with post-antibiotic effect, it can still promote phagocytosis below the MIC Phagocytosis of bacteria by cells. It is generally believed that its mechanism of action is the post-antibiotic leukocyte-promoting effect (PLAE), that is, after a short contact between bacteria and antibiotics, non-lethal damage occurs. The synergistic effect of antibacterial drugs and phagocytic cells was produced, significantly prolonged the time of bacterial recovery and regrowth.
For pediatric patients, azithromycin 10 mg/kg daily for 3 days, then stopped for 4 days, is based on pharmacokinetics, efficacy According to the relationship between the tissue concentration of azithromycin on the 4th day and the MIC90 of pathogenic bacteria (the minimum concentration that inhibits the reproduction of 90% of pathogenic microorganisms or kills 90% of the survival of pathogenic microorganisms). Azithromycin has bacteriostatic and bactericidal effects on Mycoplasma pneumoniae when the content of azithromycin is above 0.40ug/L.
3. Gastrointestinal reactions of azithromycin
Due to the long course of MPP, it usually lasts for 3 weeks, or even longer. And the gastrointestinal reaction of azithromycin was positively correlated with the time of administration. In addition, the children’s treatment compliance is relatively poor, and the long-term continuous intravenous drip treatment is prone to serious gastrointestinal adverse reactions, accompanied by symptoms such as pain at the puncture site, rash, and phlebitis. Therefore, using 3 days and stopping for 4 days can reduce the adverse reactions of azithromycin.
4. Continuous medication, easy to develop drug resistance
Previous studies have investigated the efficacy and drug resistance of continuous and intermittent administration of azithromycin in the treatment of MPP, and found that the MIC value increased after 3 days of administration, but there was no statistical significance. After 12 days of administration, the MIC value of the continuous administration group increased significantly, and the blood drug concentration was lower than the MIC value at this time, thereby increasing the risk of developing drug-resistant MPP.
In summary, whether it is from the pharmacokinetics and pharmacodynamics of azithromycin, or the prevention of its adverse reactions and resistance In terms of medicinal properties, azithromycin treatment of children with MPP needs to be used for 3 days and stopped for 4 days.
References:
[1] Chen Zhimin, Shang Yunxiao , Zhao Shunying, et al. Expert consensus on the diagnosis and treatment of Mycoplasma pneumoniae pneumonia in children (2015 edition)[J]. Chinese Journal of Practical Pediatrics, 2015,30(17):1304-1308.
[2] Lei Meisheng.A brief discussion on the clinical application of azithromycin and its post-antibiotic effect[J].Northern Pharmacy,2012,9(08):80.
[ 3] Bai Pingsheng, Xiong Fengmei. Adverse reactions and pharmaceutical care of azithromycin in pediatric clinical application [J]. Northwest Pharmaceutical Journal, 2011, 26(04): 312-314.
< span>[4]Wei Wei.Efficacy and drug resistance of azithromycin continuous and intermittent administration in the treatment of mycoplasma pneumonia[J].Journal of Southern Medical University,2010,30(08):1918-1919+1922.
[5] Yuan Zhuang, Dong Zongqi, Lu Jirong, et al. Several problems in the diagnosis and treatment of Mycoplasma pneumoniae pneumonia in children [J]. Chinese Journal of Practical Pediatrics, 2002(08):449 -457.