As a new generation of 15-membered cyclic macrolides, azithromycin is a time-dependent antibacterial drug with a long after-antibiotic effect (PAE).
By binding to the subunit of the 50 s ribosome of sensitive microorganisms, the bacterial transpeptide process is hindered, and the bacterial protein synthesis is inhibited to achieve antibacterial effect.
In addition, it also has anti-inflammatory effects, regulates airway secretion, immunomodulatory related antimicrobial effects and antiviral effects. It is widely used in clinical practice for its advantages of acid stability, good tissue permeability, long plasma half-life, wide clinical indications, significant efficacy, few adverse reactions, and good patient compliance.
<h1 class="pgc-h-arrow-right" > antimicrobial spectrum of azithromycin</h1>
Gram-positive aerobic bacteria
Staphylococcus aureus, Corynebacter diphtheriae, Streptococcus pyogenes, Streptococcus pneumoniae, α Hemolytic Streptococcus and other streptococcus.
Gram-negative aerobic bacteria
Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Yersinia, Legionella pneumophila, Bacillus pertussis, Bacillus paraphotericus, Shigella, Pasteurella, Vibrio cholerae, Vibrio parahaemolyticus, Proxima centauriae.
Anaerobic bacteria
Bacillus fragile, Bacillus, Pseudocellus, Gastrococcus, Streptococcus gastrointestinalis, Clostridium necrosis, Propionibacterium acnes.
Sexually transmitted disease microorganisms
Chlamydia trachomatis, Treponema syphilis, gonococcus, Haemophilus Duke.
Conditional pathogenic bacteria associated with HIV infection
Avian-intracellular mycobacterium complex (MAC), Pneumocystis carinii, and Toxoplasma gondii.
Other microorganisms
Pertusus spirochetes, Chlamydia pneumoniae, Mycoplasma pneumoniae, Mycoplasma humanoida, Ureaplasma urealysis, Campylobacter species, Lystystella mononucleus.
<h1 class = "pgc-h-arrow-right" > pharmacokinetics</h1>
The figure shows the chemical structural formula of azithromycin. The addition of the N atom at position 9 on the inner lipid ring gives it a very strong positive end that easily passes through the bacterial cell wall.
This structure improves azithromycin resistance to acids, increases tissue penetration and resistance to gram-negative bacteria, while also prolonging the half-life. Its tissue concentration is 10-100 times higher than the blood drug concentration. With a single dose of 0.5 g, the concentration in target tissues such as lung, tonsils and prostate is higher than the minimum inhibitory concentration (MIC) of most common pathogens, but it basically cannot enter the central nervous system.
Peak time: within 2-3 h
Oral: excreted mainly in the biliary tract with prototype drugs; intravenous: 12% in prototype drugs excreted with urine.
Food can reduce the absorption of azithromycin. Foreign sources suggest that the tablet or dry suspension can be taken with or without food, while the sustained-release dry suspension can be taken on an empty stomach. In China, it is recommended to take 1 h before a meal or 2 h after a meal.
<h1 class="pgc-h-arrow-right" > clinical application</h1>
At present, it is mainly approved for treatment in China
1. Upper respiratory tract infection caused by sensitive bacteria (sinusitis, pharyngitis, tonsillitis, etc.)
2. Lower respiratory tract infection (bronchitis, pneumonia, etc.)
3. Skin and soft tissue infection, otitis media
4. Chlamydia trachomatis and non-multi-drug resistant Neisseria caused by urethritis, cervicitis and pelvic inflammatory disease
5. Simple genital infection caused by Chlamydia trachomatis, simple genital infection caused by non-multidrug-resistant gonococcus or chancroid caused by Haemophilus Duque;
6. It is used alone or in combination with rifabutin to prevent avian-intracellular mycobacterial complex (MAC) infection.
Because of the wide application of azithromycin, when using azithromycin, it is more necessary to standardize the course of treatment and rationalize the use of drugs to achieve the best efficacy and less adverse reactions.
In clinical practice, azithromycin circulates the use of "eat three stops four" or "eat five stop two", in the end this statement is unreliable, is there any theoretical basis?
< h1 class="pgc-h-arrow-right" > the theoretical basis for "eating three stops four" and "eating five stops two"</h1>
1. Azithromycin has a long half-life
The plasma half-life after a single dose of azithromycin is 35 to 48 hours, and it is discontinued after taking azithromycin for 3 to 5 days, and by 12 days, there is still a certain concentration in white blood cells and phagocytes.
On the surface, it only took 3 days of medicine, but in fact, a certain amount of azithromycin was still working in the body in the next few days.
2. Azithromycin has a strong effect after antibiotics
After-antibiotic effect (PAE): refers to the effect of continuous inhibition of bacterial growth after brief contact with antibiotics, when the antibiotic concentration decreases, falls below the MIC (minimum inhibitory concentration) or disappears completely. Azithromycin has a significant after-antibiotic effect.
It is precisely because of the long half-life of azithromycin and the obvious after-antibiotic effect that it provides theoretical support for the unique administration method of azithromycin "eating for three days and stopping for four days".
<h1 class="pgc-h-arrow-right" > clinically, where did "eat three stops four" and "eat five stop two" come from? </h1>
1. Azithromycin needs to "eat for three days, stop for four days" The earliest came from the "Expert Consensus on the Diagnosis and Treatment of Mycoplasma pneumoniae in Children (2015 Edition)", which mentioned the use of azithromycin: 10mg/(kg·d), once a day, mild disease 3d for 1 course, severe disease can be used for 5 to 7d, and the second course of treatment can be repeated after 4 days; but for infants, the use of azithromycin, especially intravenous preparations, should be cautious.
2. Later "Specifications for the Diagnosis and Treatment of Community-Acquired Pneumonia in Children (2019 Edition)", the text also mentioned: For Mycoplasma pneumonia, the first choice of azithromycin: 10mg /(kg·d), once a day, mild disease 3d for 1 course, severe disease can be used for 5 to 7d, 2 to 3d can repeat the second course of treatment; but infants should be cautious when using azithromycin, especially intravenous preparations.
It can be seen that the 2015 "Expert Consensus on Mycoplasma Pneumoniae in Children" mentions that mild azithromycin should be "eaten for three days and stopped for four days";
The 2019 Code for the Diagnosis and Treatment of Community-Acquired Pneumonia in Children reduced the interval between azithromycin and changed it to 2 to 3 days instead of 4 days, and severe Mycoplasma pneumoniae infection can be "eaten for 5 days and stopped for 2 days".
<h1 class="pgc-h-arrow-right" > mentioned in the instructions for azithromycin tablets</h1>
Adult dosage: Sexually transmitted diseases caused by Chlamydia trachomatis or susceptible Neisseria gonorrhoeae, only a single oral dose of this product 1.0g; for other infections, take 0.5g on the 1st day, 0.25g a day on the 2nd to 5th day, or 0.5g a day for 3 days. Regardless of the way of taking it, it can be found that the total dose of azithromycin is 1.5 g.
Dosage for children: treatment of otitis media, pneumonia, pediatric pharyngitis, tonsillitis Although the dosage is different, the course of administration is 5 days.
The instructions did not mention discontinuation, but informed that the course of treatment with azithromycin was "3 days" or "5 days".
Generally in the clinic, the doctor's empiric treatment to prescribe azithromycin will make the patient "eat for 3 days, stop the drug for 4 days" or "eat for 5 days, stop the drug for 2 days or 3 days" after the review, and confirm whether to add a course of treatment according to the patient's review, and then eat for 3 days or 5 days.
<h1 class="pgc-h-arrow-right" > summary</h1>
1. There is a certain basis for the doctor to prescribe azithromycin "eat three stop four" and "eat five stop two".
2, but not everyone is suitable for azithromycin. Patients with abnormal liver function, heart disease, azithromycin allergy, and patients with myasthenia gravis are contraindicated. Breastfeeding is contraindicated in lactating women for 10 days of use of azithromycin.
3. Because of the high concentration of azithromycin in the inflammatory tissue of the lungs, it has a good bactericidal effect on the pathogenic bacteria infected by the lungs, and once a day, the advantages of convenient administration and few adverse reactions have been widely used in the clinic.
4, but because of this, we should pay more attention to the drug problem of azithromycin, so as not to produce serious drug resistance and the situation that no drug is available.
bibliography:
[Norms for the diagnosis and treatment of community-acquired pneumonia in children (2019 edition)[J]. Journal of Clinical Medical Research and Practice,2019,4(06):201.]
Expert consensus on the diagnosis and treatment of community-acquired pneumonia in children (2015 edition)[J]. Chinese Clinical Journal of Practical Pediatrics,2015,30(17).