Acute respiratory tract infection is divided into upper respiratory tract infection and lower respiratory tract infection, of which 70% is upper respiratory tract infection. However, lower respiratory tract infection is the main cause of hospitalization and death of acute respiratory tract infection because it is easy to cause serious diseases and clinical outcomes [3]. Among them, pneumonia is an infectious disease that seriously threatens children's health. According to the survey results of the World Health Organization (WHO), 654.38+55 billion children worldwide suffer from pneumonia every year [4], and the number of children under five years old who die of pneumonia exceeds 2 million, accounting for about 29% of the total number of children in this age group, which is the main cause of child death [5].
Acute respiratory infection is the source of infectious diseases in children [6]
Studies have shown that most acute respiratory infections in children are mycoplasma pneumoniae, chlamydia and viruses, and a few are bacterial infections [1]. According to WHO statistics, about two-thirds of antimicrobial prescriptions are used to treat respiratory tract infections, among which the most commonly used drugs are β-lactams, quinolones, macrolides and so on [7]. The current situation of children's use of antibiotics in China is not optimistic. The abuse of antibacterial drugs and the increase of multi-drug resistant pathogens have made it more and more difficult to treat children's acute respiratory infection [8].
Clear etiological diagnosis and targeted treatment are of great significance to guide the treatment of respiratory tract infection, and also have a positive effect on reducing drug resistance and adverse drug reactions of pathogenic bacteria and reducing medical expenses [7].
Community-acquired pneumonia (CAP) is one of the most common respiratory infections. A total of 4856 children aged 65438 04 years old were tested for multiple pathogens, and 1 13 1 strain was isolated by * * culture (23.29%). Among them, the total detection rate of Mycoplasma pneumoniae, Chlamydia pneumoniae and Streptococcus pneumoniae reached 24% [9].
Macrolide antibiotics are a kind of rapid bacteriostatic drugs, which have strong antibacterial effect on Gram-positive bacteria and good activity on some Gram-negative bacteria, Legionella, Mycoplasma and Chlamydia. Because of the high infection rate of atypical pathogens in children, and quinolones can not be used in children, macrolide antibiotics are favored in clinic and play an important role in the clinical treatment of respiratory tract infections in children [10].
? Extracellular pathogens: Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli.
? Facultative intracellular pathogens: Streptococcus pneumoniae, Group A Streptococcus, Haemophilus influenzae, etc.
? Specific intracellular pathogens: Legionella pneumophila, Mycoplasma pneumoniae, Chlamydia pneumoniae, Chlamydia trachomatis, Mycobacterium tuberculosis, etc.
Figure 1 clarithromycin is effective against both intracellular and extracellular pathogens, while β -lactams are ineffective against specific intracellular pathogens.
It has been reported in China that mycoplasma pneumoniae isolates in children are not sensitive to macrolides, which should attract the attention of pediatricians [2]. Compared with the first generation macrolide erythromycin, the second generation macrolide drugs (clarithromycin, roxithromycin, azithromycin, etc. ) because of its mild gastrointestinal reaction and convenient use, it is widely used in the treatment of bacterial infections [2]. However, studies have shown that some macrolides (such as azithromycin) cause significantly higher selective drug resistance than other macrolides.
A prospective, open and randomized study included 156 children with upper and lower respiratory tract infections from 6 months to 16 years old. Among them, 60 cases in each group were randomly assigned to receive clarithromycin (15mg/kg, taken twice) for 7 days. Or azithromycin (10mg/kg, qd) for 3 days. Swabs were taken every week (***4 weeks) and the 6th week after the start of treatment, and the differences in the proportion of drug-resistant bacteria detected in the oral cavity of children with respiratory tract infection after receiving different macrolide antibiotics were compared. The results showed that the proportion of macrolide antibiotic-resistant bacteria in clarithromycin group was significantly lower than that in azithromycin group. It shows that azithromycin can promote the drug resistance of oral flora in children with respiratory tract infection [1 1].
Similarly, a study on the drug resistance rate of more than 3,300 patients infected with Streptococcus pneumoniae from 65,438+0,995 to 2002 in Canada showed that areas with high azithromycin use rate had higher macrolide resistance rate, while areas with low azithromycin use rate had lower macrolide resistance rate [65,438+0.2].
It is pointed out that azithromycin is widely used in pediatric clinical work to treat virus-induced or nonspecific upper respiratory tract infection and acute bronchitis, which may be one of the reasons for the increase of macrolide resistance rate [2].
Clarithromycin and azithromycin have different high drug resistance, and there are differences in pharmacokinetic characteristics, half-life and bioavailability, as shown in the following table: azithromycin has a long half-life and is prone to drug resistance; Moreover, clarithromycin has good tissue distribution and high bioavailability. The concentration of clarithromycin in lung, bronchus, liver, kidney and spleen is higher than that in blood, and it is absorbed by granulocytes and macrophages with high intracellular concentration. After administration, the concentration in tissue and plasma is much higher than that of azithromycin.
Table 1 Comparison of Clarithromycin and Azithromycin
Domestic and foreign guidelines recommend macrolide antibiotics such as clarithromycin, which can be used as the initial choice for the treatment of lower respiratory diseases. Among them, clarithromycin dry suspension has a wide antibacterial spectrum and can cover common pathogens of respiratory tract infection; Clarithromycin dry suspension is more suitable for children because of its rich and colorful fruit flavor.
Macrolide antibiotics recommended by domestic and foreign guidelines for the treatment of lower respiratory diseases.
Table 3 Clarithromycin dry suspension has a wide antibacterial spectrum and can cover common pathogens of respiratory tract infection [18]
In the antibiotic treatment of pediatric respiratory tract infection, the problem of bacterial resistance has brought great challenges to clinic [19]. Macrolide antibiotics are often used in the empirical treatment of respiratory tract infections, and the overuse of some macrolide antibiotics is closely related to the prevalence of bacterial resistance. Therefore, it is imperative to advocate the rational use of macrolide antibiotics while improving the health knowledge level of the whole people and strengthening scientific guidance, publicity, supervision, management and education at different levels such as government, academic groups, hospitals and infection management [2].
References:
1. He, et al. Overview of antibiotic use in children with respiratory infection. Electronic journal of clinical medical literature, 2019.6 (29): p.195-196.
2. The severity of macrolide antibiotic resistance in children in China and its countermeasures. China Journal of Practical Pediatrics, 2010.25 (1): p.7-10.
3. Scotia. Study on pneumonia to reduce child mortality in developing countries. J Clin Invest, 2008, 1 18: Page 129 1 1300.
4.Bradley, J.S. et al., Management of Community-acquired Pneumonia in Infants and Children Over 3 Months: Clinical Practice Guidelines of Pediatric Infectious Diseases Society and American Infectious Diseases Society. Clinical infectious diseases, 20 1 1. Page 53(7): Page e25-76.
5. Pneumonia: the main killer of children. The Lancet, 2006. 368(954 1):p . 1048- 1050。
6. Guidelines for Rational Use of Antibiotics in Children with Acute Respiratory Infection (Trial) by the Department of Respiratory Medicine of Pediatrics Branch of Chinese Medical Association and the Editorial Committee of Pediatrics Journal of Chinese Medical Association. China community physician, 2004.20 (17): p.21-25.
7. Liu Xueru, Xiong Xiaoli, Chen Peng, Distribution and drug resistance of pathogenic bacteria in children with lower respiratory tract infection. Chinese journal of nosocomiology, 2017.27 (4): p.911-914.
8. Lower respiratory tract infection caused by respiratory syncytial virus: current management and new treatment. The Lancet Respiratory Medicine, 20 15. 3( 1 1): Page 888-900.
9. Lin Zengrong. Study on the epidemic distribution, characteristics and changes of common bacteria in children's community-acquired pneumonia. Hainan medical college, 2014 (8): p.1146-1149.
10. Pharmacokinetics and pharmacodynamics of macrolides in the treatment of lower respiratory tract infection. People's Military Doctor, 2015.58 (1): p.102-104.
1 1.Kastner, U. and J.P. Guggenbichler, The Effect of Maloprolide Antibiotics on Promoting the Drug Resistance of Children's Oral Flora. Infection, 200 1. 29(5): Page 2565438 +0-6.
12. Different effects of macrolides on the insensitive Streptococcuspneumoniae.pdf selection of macrolides. Treatment, 2005. 2(6): Page 8 13-8 18.
13. Department of Respiratory Medicine, Pediatrics Branch of Chinese Medical Association and Editorial Board of Chinese Journal of Pediatrics "Guidelines for the Management of Community-acquired Pneumonia in Children (Revised 20 13)" (1). Chinese journal of pediatrics, 2013.51(10): p.745.
14. Management Guidelines for Children's Community-acquired Pneumonia (Revised 20 13) by the Department of Respiratory Medicine, Pediatrics Branch of Chinese Medical Association and Editorial Board of Chinese Pediatrics Journal (below). Chinese journal of pediatrics, 2013.51(11);
15. Editorial Committee of Pediatrics Branch of Chinese Medical Association, Chinese Journal of Applied Clinical Pediatrics, and expert in diagnosis and treatment of mycoplasma pneumoniae pneumonia in children (version 20 15) 30,2015.17 (1304-650)
16.Tapiainen, T. et al. Guidelines for the treatment of community-acquired pneumonia and whooping cough in Finnish children. Journal of Pediatrics, 20 16. 105( 1): Page 39-43.
17.NICEguideline: pneumonia (community-acquired): antibacterial prescription www.nice.org UK/guidance/ ng 138.
18. David n. Fever, 46th edition. Peking Union Medical College Press.
19. Fu Pan. Surveillance of bacterial infection and drug resistance in 20 18 children in China children's bacterial resistance monitoring group. China journal of evidence-based pediatrics, 2019.14 (5): p.321-326.