There is a lack of unified understanding of the diagnostic criteria for acute exacerbation of chronic obstructive pulmonary disease (COPD), which is usually considered to be a short-term increase in cough, sputum, shortness of breath and/or wheezing, increased sputum volume, purulent or mucopurulent, fever and other inflammatory manifestations. The manifestations may be accompanied by a significant increase in inflammation such as fever. In addition, symptoms such as general malaise, insomnia, drowsiness, fatigue, depression and mental disturbances may occur. Decreased exercise tolerance, fever, and/or abnormal chest imaging may be signs of COPD exacerbation. Infection is the most important cause of acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and antimicrobial drugs can reduce the bacterial load in the respiratory tract to avoid the development of pneumonia; prevent viral infection secondary to bacterial infection; eradicate pathogenic bacteria or reduce the pathogenic bacterial load, break the vicious cycle of infection, save the respiratory tract from further damage, and reduce the number of recurrences; and reduce the overall cost of treatment during acute exacerbations of COPD. Although there are controversies about whether to apply antimicrobial drugs in acute exacerbation of COPD, the results of most trials at home and abroad have shown that the application of antimicrobial drugs in acute exacerbation can significantly improve patients’ symptoms, prolong remission time, reduce the number of hospitalizations and improve prognosis. Therefore, understanding and mastering the rational application of antimicrobial drugs in AECOPD is the key to controlling COPD, saving medical resources and avoiding the abuse of antimicrobial drugs. The main pathogenic bacteria in the lower respiratory tract of patients with acute exacerbation of COPD are Haemophilus influenzae, Streptococcus pneumoniae, and Catamorax. conditions (inability to distinguish between asymptomatic acute acquisition and chronic carriage, etc.), the role of these pathogens in AECOPD is not well understood. However, a recent randomized double-blind trial conducted by Diederen et al. by real-time PCR method to study the etiological relationship between atypical pathogenic bacteria and COPD showed that Legionella, Chlamydia pneumoniae, and Mycoplasma pneumoniae were not found in the stable phase of moderate-to-severe COPD and its acute exacerbation, although this conclusion needs to be confirmed by more studies. Gram-negative Enterobacteriaceae and Pseudomonas aeruginosa infections may be present in patients with severe AECOPD requiring mechanical ventilation. Other studies have shown that the severity of AECOPD affects the type and distribution of pathogenic bacteria. In patients with acute exacerbations of mild COPD, the main causative organism is mostly Streptococcus pneumoniae, and the frequency of Haemophilus influenzae and Catamorax increases with decreasing FEV1 and frequent episodes of acute exacerbations and/or comorbidities. In acute exacerbations of severe and very severe COPD, in addition to the above common bacteria, penicillin-resistant Streptococcus pneumoniae, Enterobacteriaceae (Klebsiella pneumoniae, Escherichia coli, Aspergillus, etc.), and Pseudomonas aeruginosa may also be present. The poorer the lung function, the increased isolation rate of G-bacteria such as Enterobacter and Pseudomonas aeruginosa. Risk factors for the occurrence of P. aeruginosa infection are: recent hospitalization, frequent application of antimicrobial drugs (4 courses in the last 1 year), previous history of P. aeruginosa isolation or colonization. Long-term application of broad-spectrum antibacterial drugs and glucocorticoids also predispose to deep fungal infections, and clinical signs of fungal infections should be closely observed. 2. Indications for antimicrobial therapy in AECOPD A randomized controlled trial by Saint et al. showed a small benefit of antimicrobial therapy on lung function during acute exacerbations of COPD, while a classic randomized controlled trial by Anthonisen et al. showed a significant benefit of antimicrobial therapy in patients with three typical symptoms: increased dyspnea, increased sputum and purulent sputum, and a significant benefit in patients with two typical symptoms. Antimicrobial therapy is also relevant in patients with two typical symptoms. A study of patients with ambulatory AECOPD showed a relationship between purulent sputum and bacterial infection, and antimicrobial agents were recommended in the presence of purulent sputum and one of the other two classic symptoms (dyspnea or increased sputum), but this indication for antimicrobial agents has not been confirmed in other studies. There are also trials demonstrating that the absence of antimicrobials in patients with acute exacerbations of COPD receiving mechanical ventilation (invasive or noninvasive) increases mortality and the incidence of hospital-acquired pneumonia. Therefore, based on the available evidence, GOLD 2006 recommends the use of antimicrobials in patients with acute exacerbations of COPD who present with three main symptoms: dyspnea, increased sputum, and pus; 2. two of the three main symptoms, one of which is pus; and 3. patients with acute exacerbations of COPD who require mechanical ventilation (invasive or noninvasive). Recently Puhan et al. conducted a randomized controlled trial through a systematic review of 1557 patients in 13 trials, and showed that for patients with severe AECOPD, antimicrobial therapy can reduce the rate of treatment failure and mortality, while patients with mild and moderate AECOPD are not indications for the application of antimicrobial drugs, and the timing of antimicrobial drug application needs to be further clarified for this group of patients. Meta-analysis of nine prospective randomized controlled trials by Saint et al [8] showed that antimicrobial therapy could shorten the duration of disease and prolong the interval between acute exacerbations of COPD, and several other studies also showed that antimicrobial therapy was effective in patients with frequent acute exacerbations of C0PD. The bacterial threshold hypothesis proposed by Miravitlles et al. can explain the difference in the efficacy of steroid hormones and the effect of antimicrobial therapy in AECOPD, and to a certain extent, antimicrobial therapy not only rapidly relieves the symptoms of acute exacerbations, but also reduces the bacterial load in the airway, thereby reducing the number of acute COPD exacerbations. In addition, it is suggested that antimicrobial therapy not only rapidly relieves acute exacerbations, but also reduces the bacterial load in the airways, thereby reducing the number of acute COPD exacerbations and improving patient prognosis. Therefore, the author believes that further research is needed on the indications for the application of antimicrobial drugs in patients with frequent AECOPD exacerbations. Although the indications for antimicrobial drug application in AECOPD are still controversial, it is noteworthy that currently there is more clinical overuse of antimicrobial drugs and waste of medical resources in China, and most of them are only one of the three main symptoms, which may be accompanied by any of the increased number of coughs, croup, respiratory rate or increased heart rate. As early as 1987, the results of a well-recognized randomized, double-blind trial by Anthonisen et al. confirmed that there was no difference between treatment with antimicrobial drugs and placebo at this time. 3. antimicrobial therapy for AECOPD Before the pathogenic results are available, sensitive antimicrobial drugs can be selected as early as possible based on the stratification of bacteria in combination with the type of common causative organisms in the region and the prevalence of drug resistance and drug sensitivity. Antimicrobial therapy should reduce the bacterial load to the lowest level possible to prolong the interval between acute exacerbations of COPD. For patients with mild or moderate COPD acute exacerbations: penicillin, β-lactam/β-lactamase inhibitors (ampicillin, amoxicillin/clavulanic acid), macrolides (azithromycin, clarithromycin, roxithromycin), first- or second-generation cephalosporins, doxycycline, levofloxacin, etc. are available. For patients with acute exacerbation of moderate or very severe COPD without risk factors for P. aeruginosa infection: β-lactam/β-lactamase inhibitors, second- or third-generation cephalosporins, fluoroquinolones (levofloxacin, moxifloxacin, gatifloxacin). For patients with acute exacerbation of moderate or very severe COPD and risk factors for Pseudomonas aeruginosa infection: β-lactam antibacterial drugs with anti-Pseudomonas aeruginosa activity, such as ceftazidime, cefoperazone/sulbactam, piperacillin/tazobactam, imipenem, meropenem, etc., also combined with aminoglycosides, fluoroquinolones (ciprofloxacin, etc.) Recommended antibacterial application for acute exacerbation of COPD The duration of medication is 3-7 days (2 weeks for Pseudomonas aeruginosa infection course). Evaluate the efficacy 3-5 days after treatment. If the efficacy is poor, promptly identify the causative organism and change the antimicrobial drug and look for other possible causes of AECOPD. If intravenous administration is necessary, it is recommended to convert to oral administration when the clinical situation is stable. In addition, a study by Lode et al. showed that levofloxacin was superior to clarithromycin in eradicating bacteria, but there was no significant difference between the two in changing the frequency of acute exacerbation episodes. Two prospective antimicrobial controlled clinical studies showed that newer antimicrobials with high in vitro antimicrobial activity, such as gemifioxacin and moxifloxacin, not only improved the short-term efficacy of AECOPD but also prolonged the time until the next acute exacerbation and reduced the hospitalization rate compared with other antimicrobials. In terms of antiviral, macrolide antibacterial drugs have immunomodulatory and interfering antiviral properties, which make them useful as prophylactic treatment for acute exacerbations of COPD. Erythromycin also reduces intercellular adhesion molecules I-1, IL-1β, IL-6, IL-8 and TNF-α, reducing the likelihood of rhinovirus infection. However, a recent study by Canut et al. showed that fluoroquinolones, cephalosporins, and high-dose amoxicillin/clavulanic acid were most effective in the treatment of patients with mild to moderate and severe AECOPD, while cefaclor, azithromycin, erythromycin, and clarithromycin did not compare favorably with placebo in the treatment of patients with mild to moderate and severe AECOPD. However, some studies have also shown similar therapeutic effects and side effects of high-dose amoxicillin (500 mg/8h) and azithromycin (500 mg/d) in the treatment of AECOPD caused by infection. 4. the drug resistance situation of AECOPD-causing bacteria and their countermeasures The results of the recent Asian network for surveillance of resistant pathogens (ANSORP) study showed that the total resistance rate of Streptococcus pneumoniae to penicillin in Asia was as high as 51.7%, of which, China The total resistance rate of Streptococcus pneumoniae to penicillin in Asian region was as high as 51.7%, among which, the neighboring areas including Japan, Korea and Vietnam exceeded 60%, and even up to 90% in individual countries. Wang Hui et al. studied patients with respiratory tract infections from 2000 to 2003 in five regions, including Beijing and Shanghai, and found that the resistance rate of Streptococcus pneumoniae to penicillin was 22.7%. For moderately penicillin-susceptible Streptococcus pneumoniae (PISP), increased doses of penicillins are still the drug of choice. The treatment options available are high-dose amoxicillin, amoxicillin/clavulanic acid, cefotaxime, ceftriaxone, or neoquinolones; for penicillin-resistant Streptococcus pneumoniae (PRSP), cefotaxime, ceftriaxone, and neoquinolones should be chosen. The mechanisms of resistance of Streptococcus pneumoniae to macrolide antimicrobial drugs [18] are mainly ermB gene-mediated altered ribosomal targeting and active exocytosis system encoded by mef gene and ribosomal protein variants. Erythromycin-resistant Streptococcus pneumoniae are less sensitive to penicillin, benzocillin, cefaclor, cefuroxime, and clindamycin, and levofloxacin, amoxicillin/clavulanic acid, or third-generation cephalosporins such as ceftriaxone and cefotaxime can be used. Clindamycin and azithromycin should be effective in the treatment of erythromycin-resistant Streptococcus pneumoniae infections carrying the mefA gene because of their special pharmacokinetics and high concentrations in tissues and infection sites. Haemophilus influenzae is mostly resistant to ampicillin or amoxicillin caused by the production of β-lactamase, but has good susceptibility to cephalosporins, β-lactam antibacterial drugs/enzyme inhibitors, azithromycin, and quinolones. The rate of β-lactamase production of C. catarrhalis increased sharply, leading to its general resistance to penicillin antibacterial drugs, for β-lactamase-positive strains, regardless of the drug sensitivity results should be regarded as resistant to penicillin, amoxicillin and ampicillin. Catamoras are still sensitive to β-lactam antimicrobial drugs/enzyme inhibitors, second and third generation cephalosporins, macrolides, and fluoroquinolones. Enterobacteriaceae such as Klebsiella pneumoniae and Escherichia coli as well as Pseudomonas aeruginosa have more serious drug resistance and more difficult treatment, and can have ESBLs and AmpC enzyme producing strains. ESBLs can hydrolyze penicillins, first, second and third generation cephalosporins and monocyclic β-lactamase antibacterial drugs, and carbapenems (imipenem, meropenem, panipenem, etc.), cephalosporins ( β-lactam antibacterial drugs/enzyme inhibitors, such as cefoperazone/sulbactam, piperacillin/tazobactam, etc., can also be chosen. Whether fourth-generation cephalosporins can be used for the treatment of ESBLs strain infections is still controversial. In China, ESBLs-producing bacteria have some cross-resistance to aminoglycosides and quinolones, and the results of in vitro drug sensitivity tests should be referred to when selecting non-β-lactam antibacterial drugs for the treatment of ESBLs-producing bacterial infections. In China, Escherichia coli and Klebsiella pneumoniae have high resistance rates to quinolones (up to 50% or higher in the former and up to 30% in the latter), and the selection of this class of drugs is generally not advocated as empirical treatment [19]. AmpC enzyme-producing bacteria are resistant to penicillins, first-, second-, and third-generation cephalosporins, cephalexin, and enzyme inhibitors. For the biofilm of P. aeruginosa, early (within 72 h) killing of the bacteria with sufficient amounts of effective bactericides before the formation of a stable biofilm is the most effective method. In conclusion, early empirical use of antibacterial drugs for anti-infective treatment in combination with local microbiological data and timely evaluation of their efficacy, as well as adjustment of treatment according to microbiological results; the use of antibacterial drugs in reasonable, appropriate, adequate doses and short courses is essential to reduce or avoid the development of bacterial drug resistance.