Severe hospital-acquired pneumonia

　　1. Etiology

　　Hospital-acquired pneumonia can be caused by various pathogenic microorganisms, among which bacterial infections account for more than 90%. Understanding the epidemiological data of pathogenic bacteria is of great value for the empirical selection of antibacterial drugs in the early stage of treatment. According to the statistical data of pathogen investigation in 678 hospitals in China (1987-1988), Gram-negative bacilli infections accounted for 57%, Gram-positive cocci accounted for 29%, anaerobic bacteria 4%, fungi 7%, and non-determined 3%. The bronchoalveolar lavage fluid (BALF) pathogen detection rate in the respiratory department of Ruijin Hospital was 84.2%, with Gram-negative bacilli accounting for 66.5% (of which Pseudomonas aeruginosa accounted for 20.9%), Gram-positive cocci accounting for 33.5%, single strain infection accounting for 63.3%, and mixed strain infection accounting for 36.7%. The microbiological data of HAP reported by Barlett are shown in Table 1.

　　1. Gram-negative bacilli:Gram-negative bacilli are the most common pathogenic bacteria (50%～70%), mainly Pseudomonas aeruginosa, often occurring in intensive care units and patients receiving mechanical ventilation treatment, as well as those with immune suppression or chronic obstructive pulmonary disease and other underlying diseases, and those who have been treated with antibiotics and glucocorticoids in advance. Enterobacteriaceae such as Klebsiella pneumoniae, Enterobacter, Proteus, Citrobacter, and Pseudomonas are also common. Other non-fermenting bacteria, such as non-Pseudomonas aeruginosa/Allium pseudomonas, Mucor pseudomonas, Acinetobacter, and Xanthomonas maltophilia are also seen in hospital-acquired pneumonia in immunosuppressed patients.

　　2. Staphylococcus aureus:It is the most common Gram-positive coccus infection (15% to 30%), especially common in patients with coma, trauma, and wound infections, especially those with recent influenza virus infection, diabetes, and renal failure. In recent years, there have been increasing reports of methicillin-resistant Staphylococcus aureus (MRSA) infections.

　　3. Anaerobic bacteria:Due to problems in specimen collection and culture techniques, the incidence of anaerobic bacterial infections is reported differently, and may not accurately reflect the actual incidence. Common bacteria include Peptostreptococcus, Streptococcus anginosus, Fusobacterium, Bacteroides, etc. They are also commonly found in mixed infections with Gram-negative bacilli.

　　4. Legionella:Can be found in the environment of the ward (air, water supply) and contamination of medical devices, also seen in those who have used corticosteroids, and there have been reports of local outbreaks.

　　5. Viruses:Common in children, with respiratory syncytial virus being the most common. Immunosuppressed and transplant recipients are commonly infected with cytomegalovirus, and herpes simplex virus is occasionally seen.

　　6. Fungi:Common in patients with long-term, large-scale use of immunosuppressants, glucocorticoids, and antibiotics, such as burn patients, recipients of bone marrow transplantation or other organ transplantation. Common pathogenic bacteria include Candida, Aspergillus, and Mucor, which often occur in mixed infections with bacterial infections.

　　7. Mycobacterium tuberculosis and non-tuberculous mycobacteria:Common in patients with HIV infection and AIDS, also seen in other immunosuppressed patients, although the incidence rate is

　　8. Other:Certain pathogenic bacteria of community-acquired pneumonia, such as Streptococcus pneumoniae and Haemophilus influenzae, are occasionally found in patients with hospital-acquired pneumonia. Patients who have used antibiotics locally in the gastrointestinal tract for selective digestive decontamination (SDD) may develop enterococcal infection. In addition, infections such as Pneumocystis carinii and Toxoplasma gondii have also attracted attention.

　　It is noteworthy that there have been changes in the etiology of hospital-acquired pneumonia. Miller et al. pointed out that since the 1980s, the incidence of certain pathogenic bacteria has increased, for example, Pseudomonas aeruginosa from 12% to 17%, Staphylococcus aureus from 13% to 17%, Enterobacteriaceae from 9% to 11%, coagulase-negative Staphylococcus aureus from 1% to 2%, Candida albicans from 3% to 5%, and the incidence of resistance to commonly used antibiotics among various bacteria has also rapidly increased. In addition, the incidence of certain pathogenic bacteria has also decreased, such as Escherichia coli from 9% to 6%, Klebsiella from 11% to 8%, and Proteus from 7% to 3%. The epidemiological investigation of pathogenic bacteria also has important reference value for the research and application strategies of macro-control of antimicrobial drugs and prevention and treatment.

　　Second, Pathogenesis

　　The incidence of hospital-acquired pneumonia is high, which may be related to two factors, namely, the damage to the systemic and local respiratory tract immune defense function, and the existence of various environments and pathways conducive to the invasion of pathogens into the lungs, including aspiration and hematogenous dissemination. Risk factors affecting the incidence of hospital-acquired pneumonia include: old age, chronic lung disease or other underlying diseases, malignant tumors, immune damage, coma, aspiration, recent respiratory tract infection, and long-term hospitalization, especially long-term stay in the ICU, artificial airway and mechanical ventilation treatment, long-term nasal gastric tube placement, thoracoabdominal surgery, long-term antibiotic treatment, the use of glucocorticoids, cytotoxic drugs, and immunosuppressants, H2 receptor antagonists, and acid inhibitors, and these factors interact with each other.

　　The aspiration of oropharyngeal secretions through the respiratory tract is an important cause of hospital-acquired pneumonia. The defense ability of the lower respiratory tract depends on the local and systemic immune defense functions of the respiratory tract, such as the nasopharynx, trachea-bronchus, and others. In healthy people, oropharyngeal secretions are often aspirated in small amounts during sleep, but the number of bacteria in the secretions is small, mainly Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and anaerobic bacteria, and the immune defense function of the whole body and the respiratory tract is intact, so bacteria entering can be effectively cleared, and the lower respiratory tract remains sterile. However, many inpatients have a significant increase in oropharyngeal colonizing bacteria, which is easy to cause aspiration and immune defense dysfunction. As a result, a large number of bacteria are aspirated, exceeding the immune clearance function of the whole body and the local area, leading to pneumonia.

　　Bacterial adhesion may be an important mechanism for the massive proliferation of upper respiratory tract colonizing bacteria. Reasons such as bronchial epithelial damage caused by old age, smoking, malnutrition, tracheal intubation, and others lead to reduced local IgA production, decreased macrophages, and weakened chemotaxis. The action of neutrophil elastase in clearing surface fibronectin promotes cell adhesion and colonization, especially the colonization of Gram-negative bacilli (GNB) in the intestines, which is more common. For example, Pseudomonas aeruginosa directly contacts the binding site of the oropharyngeal epithelial cells and adheres and colonizes. In patients with consciousness disorders and intubation (tracheal intubation, gastric tube), weakened swallowing and cough reflexes are more conducive to the aspiration of secretions in the mouth and pharynx. For example, the incidence of ventilator-associated pneumonia in patients receiving mechanical ventilation treatment is higher than that of general hospital-acquired pneumonia. Because nasal intubation or tracheal intubation and other respiratory channels bypass the nasopharyngeal defense, and because of weakened cough reflex and mucus cilium clearance function, the defense mechanism of the lower respiratory tract is damaged. The pollution and retention of secretions around the tracheal cuff in the lower respiratory tract, especially around the tracheal cuff, is conducive to bacterial proliferation. If the environment of the ward and the disinfection of respiratory treatment equipment is not strictly enough, especially if the tracheotomy care operation is not strictly carried out under sterile conditions, it will cause the implantation of pathogenic bacteria.

　　Gastrointestinal colonization bacteria can become an important source of oropharyngeal colonization through reverse colonization. The gastric juice of healthy individuals is acidic (pH 1.0), maintaining a sterile state in the gastric cavity. In the elderly, malnourished individuals, and alcoholics, especially those using acid-suppressing agents and H2 receptor antagonists as prophylaxis for stress ulcers, the gastrointestinal pH value increases, leading to the large-scale proliferation of gastrointestinal colonization bacteria, which are then refluxed to the pharynx through gastroesophageal reflux. If the patient has a swallowing reflex disorder, consciousness disorder, or the use of gastric tubes and tracheal tubes, it can cause a large amount of esophageal/gastric contents to be aspirated. In addition, it is also believed that bacteria in the gastrointestinal tract can reach the lungs through translocation. Various causes such as inflammation, shock, and chemotherapy can cause ischemic injury to the intestinal wall, damage the integrity of the mucosa, and allow bacteria to bypass the regional lymph nodes, enter the portal venous system, and reach the lungs.

　　In addition, various respiratory treatment equipment such as nebulizers, humidifiers, tracheal tubes, and suction tubes, as well as breathing machine respiratory circuit pipelines and fiberoptic bronchoscopes, may become contaminated, leading to a large number of bacteria entering the lungs directly. Long-term placement of intravenous catheters, urinary catheters, and other catheters can reach the lungs through hematogenous dissemination.

　　Clinical complications often include pleural effusion.

　　There is a potential space between the visceral and parietal layers of the pleura, known as the pleural cavity. Normally, the width between the two pleural layers in the pleural cavity is about 10-20μm, containing serous fluid, approximately 0.1-0.2ml per kilogram of body weight, usually colorless and transparent, and serving as a lubricant for the pleura. Its exudation and reabsorption are in a balanced state. Any factor that causes an increase in exudation and/or a decrease in reabsorption will result in the accumulation of fluid in the pleural cavity, forming pleural effusion.

　　General symptoms are similar to community-acquired pneumonia, including fever, cough, sputum, shortness of breath, and chest pain, etc. On physical examination of the chest, signs of consolidation and rales can be found in the affected area, but these usually appear after hospitalization, or are a worsening of symptoms on the basis of pre-existing respiratory tract infection, accompanied by purulent sputum. However, they may sometimes be masked by the manifestations of pre-existing underlying diseases and are not easily discovered early. Therefore, it is necessary to be vigilant among high-risk populations and to conduct further examinations promptly upon the discovery of suspicious clinical manifestations.

　　The prognosis of hospital-acquired pneumonia is poor, with a high mortality rate. In addition to early detection and aggressive treatment, preventive measures should be taken actively to reduce the incidence, which has received widespread attention and many studies. The pathways of hospital-acquired pneumonia include two major categories: exogenous and endogenous. The former is related to environmental factors in hospitals and wards, various invasive and non-invasive treatment procedures, etc., while the latter is related to the body's own factors, such as respiratory and gastrointestinal colonization, underlying diseases, and immune status, etc. Therefore, prevention should be targeted at these links.

　　1. Prevent exogenous infection:Strict disinfection and isolation procedures and the implementation of aseptic techniques are crucial, and attention should be paid to education and management. Medical personnel should wash their hands before contacting patients and before various invasive procedures, wear sterile gloves, masks, and isolation gowns. For patients with multidrug-resistant bacterial infections, appropriate isolation should be practiced to avoid cross-infection as much as possible. Pay attention to the disinfection of ward air (laminar air) and medical equipment, especially the strict disinfection of various respiratory treatment devices, such as nebulizer inhalation devices, suction devices, oxygen therapy devices, etc.

　　The incidence of ventilator-associated pneumonia is extremely high. Aggressive treatment of the primary disease, striving to discontinue ventilation as soon as possible, can significantly reduce the incidence by shortening the time of artificial airway placement and mechanical ventilation. During the period of ventilator treatment, particular attention should be paid to aseptic procedures for the respiratory tract to maintain airway patency. Ventilator devices (bacterial filters) may reduce the number of bacteria in inhaled air and prevent the contamination of the ward environment by exhaled air.

　　2. Reduce endogenous infection:The inhalation of endogenous pathogens from the oropharynx and gastrointestinal tract is an important route of endogenous infection. Good nursing measures can reduce the occurrence of aspiration of oropharyngeal secretions and gastric contents, such as frequently changing body positions, feeding at a high oral position, chest physiotherapy, oral care, proper tracheal intubation care, and gastrointestinal drainage techniques. For long-term bedridden patients, bed rotation can be used to promote the excretion of respiratory secretions. For critically ill patients who may develop stress ulcers, the use of acid-suppressing agents to prevent gastrointestinal bleeding may increase the chance of aspiration-induced hospital-acquired pneumonia due to the increase in gastric pH. Therefore, it is recommended to use gastric mucosal protective agents such as sucralfate. Three meta-analyses compared the use of sucralfate, H2 receptor blockers (cimetidine), and acid-suppressing agents. The hospital-acquired pneumonia incidence was lowest in the sucralfate group, highest in the acid-suppressing agent group, and although higher than the sucralfate group, the use of cimetidine did not increase the incidence of hospital-acquired pneumonia compared to the placebo group. This may be because although cimetidine increases gastric pH, it does not increase gastric volume, resulting in fewer opportunities for reflux and aspiration. In addition, if intestinal nutrition therapy is performed through a jejunostomy instead of placing a nasogastric tube, the opportunity for reflux is even less.

　　There is still controversy about the method of using prophylactic antibiotics to reduce the potential pathogenic bacteria in the oropharynx and gastrointestinal tract. Many studies believe that whether the application of local antibiotics in the respiratory tract, selective digestive tract decontamination, or systemic application of antibiotics can reduce the incidence of pneumonia is not certain, and it may lead to the emergence of drug-resistant strains, increase the difficulty of treatment, and should be cautious. Treated with gentamicin or polymyxin B by气管内滴入或吸入, although the colonization of Gram-negative bacilli in the oropharynx was reduced, the incidence and treatment rate of hospital-acquired pneumonia did not improve, which may be related to the emergence of drug-resistant bacteria. In recent years, there have been many reports on selective digestive tract decontamination (SDD), which believe that compared with the control group, the incidence of SDD is lower, but most of them are not double-blind randomized controlled trials. There have been many reports on the use of oral polymyxin, tobramycin, and gentamicin, etc., which are not absorbed in the gastrointestinal tract and maintain a high drug concentration, effective against变形杆菌, Morganella, Pseudomonas, and other Gram-negative bacilli. Other alternative drugs include fluoroquinolones and vancomycin, but they have not been widely accepted, and may be selectively applied to surgical cases, which is still a worth exploring method.

　　3. Immune prevention:Adopt comprehensive measures, such as nutritional support and correction of internal environment imbalance, in order to reduce the occurrence of hospital-acquired pneumonia. Malnutrition increases the risk of pneumonia, and nutritional support treatment plays an important role. Enteral nutrition has the effect of stimulating the small intestinal mucosa and preventing bacterial translocation, but attention should be paid to the method. For example, if the amount of nasogastric infusion is too large, it may cause reflux of gastric contents and aspiration, especially when the nasogastric tube is long-term retained in the supine position, it may also cause rhinitis. Enteral nutrition support by jejunostomy may avoid the phenomenon of reflux.

　　Pneumococcal vaccine and influenza virus vaccine can be selectively applied to some high-risk patients. The preventive effects of Pseudomonas aeruginosa immunoglobulin, antitoxin serum and immunoglobulin are limited. Some biological preparations with immunomodulatory effects are being studied, such as IL-1 receptor antagonists, tumor necrosis factor (TNF) antibodies, broad-spectrum anti-lipopolysaccharide antibodies, cyclooxygenase inhibitors, etc.

　　Section 1: Blood routine:Commonly, the blood leukocyte count is elevated (>10×10^9/L), the number of neutrophils is increased, or accompanied by nuclear left shift, if the white blood cell count is >20×10^9/L or

　　Section 2: Blood gas analysis:Help to judge the severity of the disease, the arterial blood oxygen partial pressure (PaO2) of the patient under breathing air conditions is 50mmHg, or PaO2/FiO2

　　3. Blood electrolyte and liver, kidney function tests, etc.It is of great significance to comprehensively evaluate the condition, promptly detect the occurrence of internal environment disorder and multi-organ dysfunction in the body, and take appropriate rescue measures in time.

　　4. Etiological examination:Etiological examination provides an important basis for the diagnosis of hospital-acquired pneumonia and plays a key guiding role in the rational selection of antimicrobial agents for treatment. Sputum specimens are usually used for examination, but due to contamination by upper respiratory tract secretions, the sensitivity and specificity of the diagnosis are not high. In recent years, many methods have been developed to reduce the chance of contamination in specimens, such as tracheal puncture aspiration, bronchoalveolar lavage, protective bronchoalveolar lavage, protective specimen brushing, percutaneous pleural aspiration, bronchoscope biopsy, thoracoscope biopsy, and open chest lung biopsy, etc.

　　1. Sputum:Collecting sputum specimens for etiological examination is simple, non-invasive, and cost-effective, thus widely used. However, sputum specimens are prone to contamination by upper respiratory tract secretions, leading to low reliability. Many studies have found that sputum culture results are inconsistent with those from protective brush examinations and open chest lung biopsies. To obtain more satisfactory test results, patients should be advised to rinse their mouth first, then cough up deep sputum, and the sputum specimens should be subjected to smears for Gram staining and microscopic screening. If the microscopic examination shows 25 squamous epithelial cells per low-power field, or a ratio of both, then...

　　2. Techniques for collecting lower respiratory tract secretions for anti-contamination:Currently, the commonly used measures for preventing contamination, such as bronchoalveolar lavage (BAL) and protective specimen brush (PSB) sampling, have achieved relatively satisfactory sensitivity and specificity. The respiratory department of Ruijin Hospital collects specimens for bacterial culture using PSB in patients with hospital-acquired pneumonia, and compares the results with those obtained from BAL and sputum specimens. Only 25% of the positive sputum culture results are pathogenic bacteria, 71% of the positive BAL culture results are pathogenic bacteria, and 81.2% of the positive PSB culture results are pathogenic bacteria. Both BAL and PSB methods reduce the chance of contamination by upper respiratory tract pathogens. The diagnostic specificity of PSB sampling is high, but due to the smaller amount of specimens collected, the diagnostic sensitivity is low. BAL sampling involves a wider range and a larger amount of specimens, resulting in a higher positive rate. By using quantitative culture methods, with a colony count of 103 CFU/ml as the positive diagnostic criterion, relatively satisfactory diagnostic sensitivity and specificity can be achieved. According to a meta-analysis of 524 cases of ventilator-associated pneumonia, quantitative culture using PSB specimens, with a bacterial count greater than 103 CFU/ml as positive, achieved a diagnostic sensitivity of 90% and a specificity of 94.5%. Other reports have shown that the use of protective (anti-contamination) bronchoalveolar lavage for specimen collection achieved a diagnostic sensitivity of 97% and a specificity of 92%. For patients receiving mechanical ventilation, it is possible to directly perform protective bronchoalveolar lavage through artificial airways (tracheal intubation) or to aspirate specimens for bacteriological examination using flexible catheters with top-located stoppers or other anti-contamination measures.

　　Bronchoscope lavage or brushing for specimen collection is an invasive examination that may have adverse effects on the body, such as arrhythmia, bronchospasm, hypoxemia, hemorrhage, and fever, etc. Therefore, it should be strictly controlled for indications, standardized examination procedures, strict monitoring and observation. The relative contraindications for the examination are:

　　(1) Severe hypoxemia, when inhaling pure oxygen (FIO2 1.0), the arterial oxygen partial pressure (PaO2) is below 75mmHg.

　　(2) Severe bronchospasm.

　　(3) Acute myocardial ischemia (acute myocardial infarction, unstable angina).

　　(4) Severe hypotension, the mean arterial pressure when using pressor drugs

　　(5) Increased intracranial pressure.

　　(6) Severe hemorrhagic constitution.

　　Tracheal puncture aspiration (TTA) was once used in the 1970s and 1980s, but it had a high rate of false positives, low specificity, and could cause discomfort to patients, easily leading to complications such as hemorrhage and pneumothorax. It is now rarely used. Thoracic puncture biopsy is more commonly used for patients with pleural effusion. Thoracoscope lung biopsy and open chest lung biopsy have high diagnostic rates and specificity, but they are more traumatic and are suitable for patients with severe immunosuppression and high-risk opportunistic infections. Lung tissue samples are taken for further examination, including Pneumocystis carinii infection, cytomegalovirus infection, and aspergillosis infection, and are used to differentiate non-infectious lung diseases.

　　Chest X-ray examination and chest CT scan are of great value in diagnosis, which can help to detect lung lesions, determine the location, judge the nature and severity, usually manifested as pulmonary patchy infiltration shadow or interstitial changes, and may have空洞 or combined with pleural effusion and other manifestations. Chest X-ray findings may be affected by chest underlying diseases or affected by photography technology, conditions, and limitations, which may affect the correct judgment, especially in the early stage. Chest CT scan may more clearly show the nature of lung lesions and the condition of pleural effusion. Chest X-ray findings may also be caused by other non-infectious lung diseases, such as atelectasis, pulmonary hemorrhage, acute respiratory distress syndrome, pulmonary edema, pulmonary embolism, tumors, etc. Therefore, abnormal chest X-ray findings are not specific for etiological diagnosis and should be comprehensively analyzed with various clinical and examination data.

　　The dietary adjustment for pneumonia patients should be based on the principle of recovery, supplementing nutrients, and enhancing the body's resistance to diseases. The general principle is to consume easily digestible or semi-liquid foods that are high in calories, vitamins, and proteins. For pneumonia patients with fever, it is especially important to drink plenty of water, which not only helps to replenish the body's water loss but also facilitates the excretion of bacterial toxins and reduces body temperature. Pneumonia can be treated with traditional Chinese medicine 'He's Xuanfu Formula', which is effective in clearing lung toxins through decocting and internal administration, and improves symptoms such as chest pain and dyspnea caused by pneumonia.

　　1. Treatment

　　The condition of hospital-acquired pneumonia is complex, evolves rapidly, and the mortality rate is 25% to 60%, while the mortality rate of Pseudomonas aeruginosa pneumonia can reach 70% to 80%. Early effective antibacterial treatment is the key. A group of patients in Ruijin Hospital had a mortality rate of 40%, including 8 cases of respiratory failure, 3 cases of circulatory failure, 5 cases of multiple organ failure, 4 cases of lung cancer, and 3 cases of uncontrolled infection. Therefore, while treating pneumonia, it is necessary to comprehensively treat complications such as heart and lung failure, electrolyte imbalance, acid-base imbalance, and multiple organ failure, as well as various underlying diseases that may exist at the same time.

　　The fundamental treatment for hospital-acquired pneumonia is to select effective antibacterial drugs in a timely and correct manner. The importance of etiological diagnosis should be emphasized in order to select antibacterial treatment drugs targetedly. Due to the reasons of monitoring technology, it is often difficult to immediately determine the pathogen, so early treatment is mostly empirical. However, empirical treatment also relies to some extent on the epidemiological data of the local area or the hospital, and is evaluated in combination with the condition, in order to avoid blindness and arbitrariness. Therefore, clinical doctors and laboratory staff must closely cooperate to strive for specific etiological diagnosis. For example, it is advisable to obtain good sputum specimens, even through bronchoscopy for bronchoalveolar lavage (BAL) and protected specimen brush (PSB) to obtain uncontaminated respiratory secretions for examination, and to carry out various new monitoring technologies with higher specificity, providing a basis for clinical diagnosis and treatment. After the empirical application of antibacterial drugs, once the etiological diagnosis data is obtained, the treatment plan should be adjusted accordingly. Throughout the entire course of treatment, it is also necessary to carry out bacterial monitoring at any time to understand the changes in the flora during the evolution of the disease and the possibility of the emergence of drug-resistant bacteria. If the etiological diagnosis results are still not obtained, it is still necessary to re-examine the clinical data at any time and adjust the treatment plan accordingly.

　　The selection of antibacterial drugs and the design of treatment plans also need to consider the severity of the disease, the immune status of the body, the basic pulmonary or systemic diseases, pharmacodynamics, pharmacology, pharmacokinetics, and other pharmacological knowledge.

　　1. Empirical treatment:In the absence of definite etiological and clinical information, it is advisable to use broad-spectrum antibacterial drugs for empirical treatment. Currently, hospital-acquired pneumonia is most commonly caused by aerobic Gram-negative bacilli, therefore, it is recommended to first select antibacterial drugs with bactericidal activity against Gram-negative bacilli, and to make a comprehensive judgment based on the condition and relevant risk factors, considering either single or combined treatment plans. For example, in patients with NP who are comatose, have head trauma, recent influenza virus infection, diabetes, renal failure, etc., there is a higher chance of Staphylococcus aureus infection. For those who have been in the ICU for a long time, have long-term use of corticosteroids, early antibiotic use, bronchiectasis, granulocytopenia, and late-stage AIDS, Pseudomonas aeruginosa is more common. For those who have abdominal surgery or are suspected of aspiration, consideration should be given to anaerobic bacterial infection.

　　(1) Mild to moderate hospital-acquired pneumonia: Common pathogens include Enterobacteriaceae bacteria, Haemophilus influenzae, Streptococcus pneumoniae, methicillin-sensitive Staphylococcus aureus (MSSA), and so on. Second and third-generation cephalosporins can be chosen (excluding those with anti-Pseudomonas activity), such as cefuroxime, cefotaxime, ceftriaxone, and cefodizime, or beta-lactamase class/beta-lactamase inhibitors, such as ampicillin/sulbactam or coamoxilline. For those allergic to penicillin, fluoroquinolones such as ofloxacin, ciprofloxacin, and levofloxacin can be chosen, as well as other new quinolones and monoamine antibiotics, such as aztreonam, etc.

　　Since patients often have been treated with antibacterial drugs, the incidence of drug-resistant bacteria is high, and some pathogenic bacteria show multiple drug resistance. Therefore, combination therapy is often considered, such as Aminopenicillin combined with Flucloxacillin or Nafcillin, or second and third-generation cephalosporins combined with aminoglycosides or fluoroquinolones. Aminoglycosides have a broad antibacterial spectrum, rapid bactericidal activity, and good synergistic effects, but have poor permeability in respiratory secretions and lung tissue, and a low efficacy/toxicity ratio, so their clinical application value is controversial. Quinolone antibiotics have seen many developments in recent years and are effective against Gram-negative bacillary infections, but levofloxacin, as well as third and fourth-generation quinolones such as sparfloxacin (sparfloxacin), have more potent bactericidal activity against Gram-negative bacilli, atypical pathogens, and some anaerobic bacteria.

　　(2) Severe hospital-acquired pneumonia: The patient's condition is severe, characterized by widespread lung inflammation, accompanied by persistent hypoxemia and multi-organ failure, long-term hospitalization or mechanical ventilation treatment, and those who have been treated with various broad-spectrum antibiotics. In addition to the pathogenic bacteria seen in (mild to moderate pneumonia), Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), Acinetobacter, Enterobacteriaceae bacteria, and anaerobic bacteria are more common. Fluoroquinolones or aminoglycosides can be combined with one of the following drugs:

　　① Anti-pseudomonal beta-lactamases, such as ceftriaxone (Ceftazidime), cefoperazone (Cefoperazone), piperacillin (Piperacillin), ticarcillin (Ticarcillin) and others.

　　② Broad-spectrum beta-lactamases/beta-lactamase inhibitors, such as sulbactam (ampicillin/sulbactam sodium), ticarcillin/clavulanate potassium, cefoperazone/sulbactam (Cefoperazone/Sulbactam), piperacillin/triazolone (piperacillin/tezabantam) and others.

　　③ Carbapenems, such as imipenem/cilastatin sodium and meropenem (moxifloxacin). In case of suspected Staphylococcus aureus infection, vancomycin (Vancomycin) should be used in combination. In case of suspected fungal infection, antifungal drugs should be used in combination.

　　2. Antimicrobial therapy

　　(1) Staphylococcus aureus (MSSA): First choice is oxacillin and cloxacillin alone or combined with rifampicin, gentamicin; secondly, cefazolin and cefuroxime, clindamycin, sulfamethoxazole-trimethoprim, fluoroquinolones. MRSA first choice is (desmethoxy) vancomycin alone or combined with rifampicin or netilmicin; secondly, fluoroquinolones, carbapenems or tecafloxacin can be selected (must undergo in vitro drug sensitivity test).

　　(2) Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, Proteus, Enterobacter, etc.): First choice is second and third generation cephalosporins combined with aminoglycosides (can be used alone according to the drug sensitivity test); secondly, fluoroquinolones, aztreonam, imipenem, beta-lactamases/beta-lactamase inhibitors can be selected.

　　(3) Haemophilus influenzae: First choice is second and third generation cephalosporins, new macrolides, sulfamethoxazole-trimethoprim, fluoroquinolones. Second choice is beta-lactamases/beta-lactamase inhibitors (ampicillin/sulbactam sodium, amoxicillin/clavulanate potassium).

　　(4) Pseudomonas aeruginosa: First choice is aminoglycosides, anti-pseudomonas beta-lactams (such as piperacillin/triazolone sodium, ticarcillin/clavulanate potassium, aztreonam, ceftriaxone, cefoperazone/sulbactam sodium, etc.) and fluoroquinolones; secondly, aminoglycosides combined with aztreonam, imipenem can be selected.

　　(5) Acinetobacter: First choice is imipenem or combined with fluoroquinolones, amikacin or ceftriaxone, cefoperazone/sulbactam sodium.

　　(6) Legionella: First choice is erythromycin or combined with rifampicin, ciprofloxacin, levofloxacin; secondly, new macrolides combined with rifampicin, doxycycline combined with rifampicin, ofloxacin can be selected.

　　(7) Anaerobic bacteria: First choice is penicillin combined with metronidazole, clindamycin, beta-lactamases/beta-lactamase inhibitors; secondly, tinidazole, ampicillin, amoxicillin, cefadroxil can be selected.

　　(8) Fungi: Fluconazole is the first choice, yeast (Cryptococcus neoformans), yeast-like fungi (Candida species) and histoplasma are mostly sensitive to fluconazole. Amphotericin B has the widest spectrum of activity, but has serious adverse reactions, and can be chosen when the infection is severe or the above drugs are ineffective. Alternatives: 5-fluorocytosine (candida, cryptococcus); miconazole (blastomyces).

　　During the process of antibacterial treatment, the changes in the condition should be closely observed, and the efficacy should be assessed by integrating clinical, X-ray, and bacteriological data. Usually, clinical conditions begin to improve after 72 hours of effective antibacterial treatment; while the improvement of chest X-ray absorption often lags behind clinical symptoms, especially in patients with chronic obstructive pulmonary disease and other underlying lung diseases. At the same time, attention should be paid to whether the pathogen is eliminated or new pathogenic bacteria appear. If the treatment is ineffective for more than 3 days, the following factors should be considered: ①Unreliable diagnosis: non-infectious causes such as acute respiratory distress syndrome, pulmonary embolism, pulmonary edema, etc.; incorrect etiological assessment; ②Difficult to clear pathogens: the appearance of drug-resistant strains, especially multidrug-resistant strains, insufficient respiratory drug concentrations (due to drugs or anatomical factors); extrapulmonary spread of infection, such as empyema; persistent contamination sources related to ventilators; damage to the host's immune defense mechanism, such as in the elderly, malnutrition, chronic underlying diseases, the use of immunosuppressants, etc.; ③Secondary infection, especially fungal infection; ④Adverse drug reactions, limited medication.

　　When treatment is ineffective or the condition changes rapidly, active re-examination of etiology should be performed, including invasive methods (fiberoptic bronchoscopy) for specimen collection for testing, and a comprehensive assessment of clinical data should be made while waiting for further examination results, adjusting the treatment plan accordingly.

　　3. Treatment duration:The duration of treatment should be determined according to the condition. Usually, the duration is 7 to 10 days, but for patients with multi-lobar pneumonia or lung tissue necrosis, cavitation, those with malnutrition and chronic obstructive pulmonary disease and other underlying diseases, immunological diseases and immunodeficiency, and those infected with Pseudomonas aeruginosa, the duration may need to be 14 to 21 days to reduce the possibility of recurrence.

　　II. Prognosis

　　The incidence of the disease is reported to be 0.9% to 3.8% abroad, 0.5% to 5.0% in China, accounting for 26% to 42% of the total number of inpatients with infections, and it is the leading cause of various hospital-acquired infections. The mortality rate is as high as 20% to 50%.