What Is a Lower Respiratory Tract Infection?

Lower respiratory tract infections are the most common infectious diseases. The pathogens that cause infections must be identified during treatment to select effective antibiotics. The number of clinically available antibiotics is increasing, and the number of resistant strains is also increasing. The application of high-dose cephalosporins has led to an increase in nosocomial infections, especially Pseudomonas aeruginosa and Enterococcus infections. Advances in serology and molecular biology research have greatly improved people's understanding of Mycoplasma, Chlamydia infection or Legionella infection. Fluoroquinolones and macrolides have attracted much attention.

Lower respiratory tract infection

Respiratory infections are divided into upper respiratory infections and lower respiratory infections. Upper respiratory tract infections are classified as viral (70-80%) and bacterial (20-25%). The common cold (commonly known as cold) is usually caused by rhinovirus, adenovirus, respiratory syncytial virus, and so on. It manifests as sneezing, runny nose, sore throat, and a few have symptoms such as fatigue and low fever. The flu is caused by the flu virus, with pandemic or outbreak, high fever, muscle aches and conjunctivitis.

Basic overview of lower respiratory infections

Lower respiratory tract infections are the most common infectious diseases. The pathogens that cause infections must be identified during treatment to select effective antibiotics. The number of clinically available antibiotics is increasing, and the number of resistant strains is also increasing. The application of high-dose cephalosporins has led to an increase in nosocomial infections, especially Pseudomonas aeruginosa and Enterococcus infection. Advances in serology and molecular biology research have greatly improved people's understanding of Mycoplasma, Chlamydia infection or Legionella infection. Fluoroquinolones and macrolides have attracted much attention.

Types of lower respiratory tract infections

Lower respiratory tract infections include acute trachea-bronchitis, chronic bronchitis, pneumonia, and bronchiectasis. Is caused by viruses, bacteria, mycoplasma, chlamydia, legionella and other microorganisms.

Lower respiratory tract infection prevention

The prevention and treatment of respiratory infections should follow the principles of prevention first, accurate diagnosis and timely treatment. The main points of prevention include: 1. Vaccination of susceptible people; including pneumonia vaccine, influenza vaccine, etc. 2 The application of antibiotics in susceptible people, elderly patients with chronic bronchitis, bronchiectasis, diabetes, heart disease (heart failure) and children under the immune system, antibiotics can be appropriately applied to prevent bacterial infections when suffering from a cold. 3 In the case of a common cold or bacterial lower respiratory tract infection that is not correct, you should receive medical guidance from a respiratory specialist. Accurate diagnosis mainly refers to distinguishing common cold from bacterial lower respiratory tract infection. Timely treatment mainly refers to the treatment of bacterial infections. It should be noted that: sputum is taken for bacterial culture before the application of antibiotics; empirical antibiotic treatment of community-acquired pneumonia recommended by the Chinese Medical Association is used; general antibiotics are not effective within 3 days before considering replacement It is not advisable to change antibiotics frequently; the elderly can appropriately relax the application conditions of antibiotics; pay attention to the severe drug-resistant bacteria pneumonia in adolescents; use antipyretics as little as possible, especially do not use hormones frequently.

Lower respiratory tract infections quinolone antibiotics

Fluoroquinolones are important drugs for the treatment of lower respiratory tract infections in recent years. The generation of a new generation of fluoroquinolones derivatives has significantly broadened their pharmacological activity and has a strong antibacterial activity against Gram-negative bacilli, especially Pseudomonas aeruginosa. These antibiotics have the characteristics of high tissue concentration and low minimum bacteriostatic concentration (mIC), and have been clinically used to treat nosocomial respiratory infections and infections in intensive care units. Although it is currently recognized that quinolones such as ciprofloxacin are effective against community-acquired lower respiratory tract infections, they are not the first choice and are only used for patients with respiratory infections who are resistant to commonly used antibiotics and allergic to multiple drugs. The main cause is quinolone The mIC was higher for Streptococcus pneumoniae. It is mainly used in Europe and North America to treat mild community-based lower respiratory tract infections.

A new generation of quinolone drugs for lower respiratory tract infections

Other new-generation quinolones such as fleroxacin, romifloxacin, and sabafloxacin have higher activity against pneumococci, and have higher activity against pneumococci than ciprofloxacin, which is more effective than ciprofloxacin 4 to 8 times higher. Most quinolone drugs are distributed through an active transport mechanism. The concentration is 2 times higher in the bronchial mucosa than in blood, 2 to 3 times higher in the alveolar epithelium than blood, and 9 to 15 times higher in the alveolar macrophages. The drug concentration of sparfloxacin in different parts of lung tissue was significantly higher than that in blood. Therefore, it has been used clinically to treat atypical pneumonia caused by drug-resistant Mycobacterium tuberculosis and non-tuberculous mycobacteria, as well as mycoplasma and chlamydia. Levofloxacin is more than 2 times more active than its precursors, and its efficacy against pneumococci is as high as 4-8 times. The drug resistance is mainly due to the change in drug permeability of bacterial cell membranes. In addition, such drugs act on bacterial dNA helicases, preventing double-stranded dNA chains from turning into helical dNA and playing an antibacterial role. Mutations in bacterial dNA helicase subunits are also important resistance mechanisms. cFC-222 is a new fluoroquinolone antibiotic with strong activity against Gram-negative bacilli and Staphylococcus aureus. Its in vitro activity is not affected by the amount of inoculated bacteria, the composition of the culture medium and the serum. If it can reduce its drug resistance and reduce its side effects clinically, the new generation of quinolone drugs will be more widely used in respiratory infections.

respiratory lactam antibiotics for lower respiratory tract infections

-lactam antibiotics are the most widely used in the treatment of respiratory infections. It mainly includes penicillins, cephalosporins, and other atypical -lactam antibiotics such as cephalomycins, monoamides, and carbapenems. Compared with some antibiotics in the past, the new-generation cephalosporin antibiotics have better pharmacokinetics, are relatively stable to bacterial hydrolases such as -lactamase, and are effective in treating respiratory infections caused by various Gram-negative and positive aerobic bacteria. . Lactamase inhibitors such as clavulanate and sulbactam are rarely used alone. Combining them with -lactam antibiotics with good pharmacokinetics can significantly increase their antibacterial activity and reduce the production of resistant strains. Amoxicillin Ogmentin and Temetine, a combination formulation of clavulanic acid with ticarcillin, have begun to be used clinically. Taineng is a new type of broad-spectrum -lactam antibiotics, which has a strong inhibitory effect on the bacterial cell wall synthesis, and has a strong bactericidal activity against most important clinical Gram-positive and negative aerobic bacteria and anaerobic bacteria. It has a significant clinical effect on septicemia of nosocomial infection caused by Gram-negative bacilli and severe bacterial infections due to immunodeficiency. Mylopecin and imipenem are similar in structure and are both carbapenems, but unlike their precursors, they are highly stable to lactamase and do not need to be combined with enzyme inhibitors, so enzyme inhibitors can be used to treat some Severe infection in the hospital. Oral cephalosporin antibiotics are increasing. Although they are more expensive than earlier compounds, they have strong antibacterial activity, good oral absorption, and strong stability to -lactamase. Cefaclor, the number one nemesis of Haemophilus influenzae, has been proven to be effective in pneumococcal pneumonia by clinical practice and animal tests, and its susceptibility to Moraxaka has also been reported in the literature. The third-generation oral cephalosporin antibiotics such as cefixime, cefotaxime, and ceftazidime have been used in many countries and are effective against some early out-of-hospital infection pathogens. Penicillin and ampicillin, which are sensitive to common pathogens of lower respiratory tract infections, are gradually resistant, mainly due to the production of lactamase. Genetic analysis revealed that this resistance originated from a single clone, most of which were serotype 6B. In the treatment of patients with severe pneumonia, once the resistance develops, the third-generation cephalosporins or macrolide antibiotics should be replaced. Therefore, it is particularly clinically important to detect the development of this resistance for early control.

Macrolide antibiotics for lower respiratory tract infections

Macrolides represented by erythromycin are most commonly used to treat out-of-hospital bacterial lung infections, and have strong antibacterial activity against various Gram-positive cocci such as pneumococcus, Staphylococcus aureus, and Streptococcus; it is hemophilic to influenza Bacillus, pertussis, brucella and various anaerobic bacteria other than fragile bacilli and clostridial bacteria also have considerable antibacterial activity; because they can enter cells, they are atypical pneumonia such as chlamydia, mycoplasma, legionnaires Bacterial pneumonia has a positive clinical effect. In recent years, through research on community-acquired respiratory tract infections, it has been found that these atypical pathogens have obvious invasiveness in lung tissues and the upper respiratory tract, making them more and more widely used.

In recent years, the resistance of erythromycin has increased significantly. At the same time, due to its gastrointestinal side effects, people have begun to look for some new drugs. The new generation of macrolide antibiotics such as roxithromycin, azithromycin, clarithromycin, etc. It overcomes a series of side effects of erythromycin in the low pH state due to the disturbance of its own molecular structure that stimulates gastrointestinal peristalsis. Its main advantages are stable gastric acid and high bioavailability; high blood concentration, tissue cell concentration and long-lasting maintenance; long half-life, few side effects, complete oral absorption, short course of treatment, and significantly increased patient tolerance, making it a promising future Wider.

Macrolide animal test for lower respiratory tract infection

Animal tests have confirmed that clarithromycin has a high concentration in serum and tissues and has strong intracellular permeability, so it has a good effect on pneumococcal pneumonia, refractory Legionella infection, and mycoplasma infection. Azithromycin alone After 96 hours of dosage, the concentration in the tissues increased significantly, and the concentration in the serum was relatively low. Therefore, it was used in patients with severe episodes of chronic bronchitis and some patients with pneumonia. . Other studies have confirmed that the new generation of macrolide antibiotics has a positive clinical effect on non-tuberculous mycobacteria by changing the local or overall immune function of the body, and provides valuable clues for the treatment of multidrug-resistant tuberculosis.

Aminoglycoside antibiotics for lower respiratory tract infections

Aminoglycosides have strong antibacterial activity against Gram-negative bacteria such as Klebsiella pneumoniae and Enterobacteriaceae, have poor activity against streptococci, and are resistant to anaerobic bacteria. Combined with penicillins or cephalosporins, it has good antibacterial activity against some Gram-positive cocci such as staphylococci. The main side effects are nephrotoxicity and ototoxicity. Through renal function tests, histology and electrophysiological studies, it has been found that its toxicity is closely related to blood drug concentration [9]. Compared with short courses and large doses of continuous or multiple doses, the accumulation of renal cortical drugs increased significantly, and the concentration of lymphatic fluid in the inner ear also increased significantly, while increasing the dose and shortening the course did not increase or even reduce ototoxicity. Pharmacokinetics and renal toxicity of aminoglycoside antibiotics have been observed in rats and mice to exhibit circadian rhythms, and circadian rhythm fluctuations are attributed to rhythmic changes in glomerular filtration rate (gFR), both Animals have the lowest gFR during the resting period, so the chance of nephrotoxicity during resting period administration will be significantly increased. Based on the results of the above studies, short courses and high-dose treatment options are currently recommended at home and abroad. The maximum peak concentration of aminoglycoside antibiotics is positively correlated with mIC. The higher the correlation, the better the curative effect. Choose a reasonable dose that can reach the highest peak concentration to obtain a satisfactory curative effect.

Aminoglycosides have a long antibiotic follow-up effect (pAE) on Gram-negative bacilli and staphylococci. This phenomenon is concentration- and time-dependent, which determines that cells will not continue to grow for several hours after high-dose administration, and repeated administration will weaken the pAE of aminoglycoside antibiotics. Through in vitro simulation of human pharmacokinetic studies, it was found that Pseudomonas aeruginosa was resistant to gentamicin after several hours of administration, and its bactericidal activity had not recovered after 24 hours of administration, and a large daily dose Administration can eliminate this phenomenon.

Aminoglycosides enter the cells mainly through cellular uptake, and the speed is very slow. Nebulization inhalation and cyclomembrane puncture and injection of gentamicin and high concentration of tobramycin can maintain good sputum and tissue concentrations. It has a good clinical effect on patients with bronchopneumonia infected by Gram-negative bacilli. However, the topic of topical administration of the respiratory tract is still controversial. Dissidents believe that topical administration can easily lead to drug resistance, and contamination of inhaled therapeutic devices actually increases the chance of infection.

Changes in focus of lower respiratory tract infection treatment

The management of acute respiratory infections must take into account both the antibacterial activity of the antibiotics and the variation of the pathogen itself. Cassiere et al suggested a combined treatment plan for severe community-acquired lower respiratory tract infections. The currently recommended medication is penicillin (or amoxicillin) combined with macrolides and high-dose aminoglycoside antibiotics. In recent years, researchers' focus has shifted from specific pathogens to host-pathogen interaction studies and pathogenic factors produced by bacteria. Therefore, changing the clinician's medication habits for inpatients can not only reduce the hospitalization costs of patients, but also significantly reduce the side effects and adverse reactions of drugs.