Pneumonia is an inflammation of the terminal airways, alveoli, and interstitial spaces of the lungs that can be caused by pathogenic microorganisms, physicochemical factors, immune injury, allergies, and medications. Bacterial pneumonia is the most common form of pneumonia.
It is diagnosed on the basis of.
1. Newly developed cough, cough or aggravation of symptoms of pre-existing respiratory disease with purulent sputum, with or without chest pain.
2, fever.
3.Signs of solid lung and/or smell of wet woven grass.
4.WBC>10×109/L or <4×109/L with or without left shift of nucleus.
5, Chest X-ray shows lamellar or patchy infiltrative shadows or interstitial changes with or without pleural effusion. The clinical diagnosis can be established after any 1 of the above items 1-4 plus item 5 and excluding tuberculosis, lung tumor, non-infectious interstitial lung disease, pulmonary edema, pulmonary atelectasis, pulmonary embolism, pulmonary eosinophilic infiltrates and pulmonary vasculitis.
The clinical application of the etiologic classification of pneumonia by etiology is more difficult because of the low rate and uncertainty of positive pathogenic cultures and the lag in culture results. To facilitate guidance of empirical treatment, pneumonia is often clinically classified into community-acquired pneumonia (CAP) and hospital-acquired pneumonia (HAP) according to the setting and site of onset.
1. community-acquired pneumonia (CAP)
1.1 Definition of CAP
Community-acquired pneumonia is an inflammation of the infected lung parenchyma (including the alveolar wall, i.e., the interstitial lung in the broad sense) that develops outside the hospital, including pneumonia with a definite incubation period of pathogenic infection that develops during the incubation period after hospital admission.
1.2 Pathogenesis
1.2.1 Common pathogens
The etiology of patients can be stratified according to their age, underlying disease status and severity of illness: Group I Young patients without underlying disease: Streptococcus pneumoniae, Mycoplasma pneumoniae, Haemophilus bleeding, Chlamydia pneumoniae, etc. Group II Elderly or with underlying disease: Streptococcus pneumoniae, Haemophilus bleeding, aerobic Gram-negative bacilli, Staphylococcus aureus, Catamoras, etc. Group III Patients who need to be hospitalized but do not need to be admitted to ICU: Streptococcus pneumoniae, Haemophilus bleeding, mixed infections (including anaerobes), aerobic Gram-negative bacilli, Staphylococcus aureus, Mycoplasma pneumoniae, Chlamydia pneumoniae, respiratory viruses, etc. Group IV critically ill patients requiring ICU admission Group A, without risk factors for P. aeruginosa infection: Streptococcus pneumoniae, aerobic Gram-negative bacilli, Legionella pneumophila, Mycoplasma pneumoniae, Haemophilus bleeding, Staphylococcus aureus, etc. Group B, with factors for P. aeruginosa infection: common pathogens of Group A + P. aeruginosa
1.2.2 Selection of pathogenic diagnostic methods
(1) Outpatient treatment of mild to moderate patients does not require universal pathogenic examination, but only when initial empirical treatment is ineffective. (2) Routine blood cultures and pathogenic examination of respiratory specimens should be performed simultaneously in hospitalized patients. Any combined pleural effusion and capable of puncture should undergo diagnostic thoracentesis and extract pleural fluid for routine pleural fluid, biochemical and pathogenic examinations. (3) The invasive diagnostic technique is only selectively applied to patients with CAP: (1) when empirical treatment is ineffective or the disease still progresses, especially when antimicrobial drugs have been changed for more than once and are still ineffective; (2) when infection by specific pathogens is suspected and the causative agent cannot be clarified with respiratory specimens obtained by conventional methods; (3) when the immunosuppressed host with CAP is ineffective with antimicrobial drugs; (4) when it needs to be distinguished from non-infectious (4) When the differential diagnosis is needed with non-infectious pulmonary infiltrative lesions.
1.2.3 Diagnostic significance of pathogenic test results
The results with definite significance: ① blood or pleural fluid culture to pathogenic bacteria; ② specimens cultured by fiberoptic bronchoscopy or manual airway suction with pathogenic bacteria concentration ≥ 105 CFU/mL (semi-quantitative culture + +), BALF specimens ≥ 104 CFU/ml (+ to ++), anti-pollution brush or anti-pollution BALF specimens ≥ 103 CFU/ml (+); ③ respiratory specimens cultured to lung Legionella pneumophila; ④ serum Legionella pneumophila antibody titer showed 4-fold or more change (increase or decrease), while Legionella pneumophila antibody titer (indirect fluorescent antibody method) ≥ 1:128; ⑤ positive Legionella pneumophila type I urinary antigen test (enzyme-linked immunoassay) [3]; ⑥ positive Streptococcus pneumoniae urinary antigen test (immunochromatographic method) (except for children).
Meaningful results: (i) moderate or higher growth (≥ +++) of dominant bacteria in culture of eligible sputum specimens; (ii) small amount of bacterial growth in eligible sputum specimens but consistent with smear microscopy results (Streptococcus pneumoniae, Haemophilus influenzae, and Catamobacter); (iii) multiple cultures of the same bacteria within 3 d; (iv) elevated antibody titer of 1:320 in serum Legionella pneumophila test tube agglutination test or ≥1: 1024.
1.3 Empirical antibacterial therapy
In young adults or patients without underlying disease: penicillins (penicillin, amoxicillin, etc.), doxycycline (doxycycline); macrolides; first- or second-generation cephalosporins; respiratory quinolones (e.g., levofloxacin, moxifloxacin, etc.).
Elderly or patients with underlying disease: second-generation cephalosporins (cefuroxime, cefprozil, cefaclor, etc.) alone or in combination with macrolides; β-lactams/β-lactamase inhibitors (e.g., amoxicillin/clavulanic acid, ampicillin/sulbactam) alone or in combination with macrolides; respiratory quinolones.
Patients who need to be admitted to hospital but do not need to be admitted to ICU: intravenous second-generation cephalosporins alone or in combination with macrolides; intravenous respiratory quinolones; intravenous β-lactams/β-lactamase inhibitors (e.g., amoxicillin/clavulanic acid, ampicillin/sulbactam) alone or in combination with macrolides; cefotaxime, ceftriaxone alone or in combination with macrolides
Critically ill patients requiring ICU admission without risk factors for P. aeruginosa infection: Ceftriaxone or cefotaxime in combination with intravenous macrolides; intravenous β-lactams/β-lactamase inhibitors (e.g., amoxicillin/clavulanic acid, ampicillin/sulbactam) in combination with macrolides; ertapenem in combination with intravenous macrolides.
Critically ill patients with risk factors for P. aeruginosa infection who require ICU admission: β-lactams with anti-P. aeruginosa activity (e.g., ceftazidime, cefoperazone/sulbactam, piperacillin/tazobactam, imipenem, meropenem, etc.) in combination with injectable macrolides or, if necessary, aminoglycosides; β-lactams with anti-P. aeruginosa activity in combination with intravenous fluoroquinolones (ciprofloxacin, etc.); intravenous ciprofloxacin or levofloxacin combined with aminoglycosides.
The epidemiological distribution of CAP pathogens and antimicrobial drug resistance rates are not consistent across the vast territory of China, and there are great differences in the natural environment and socio-economic development of different regions, so further research and data accumulation are needed.
1.4 A few notes and precautions
(1) Treatment with oral anti-infective drugs with good bioavailability should be recommended as much as possible for previously healthy patients with mild disease and normal gastrointestinal function. (2) The resistance rate of Streptococcus pneumoniae to penicillin in China is about 22.7% [5]. For moderately penicillin-susceptible Streptococcus pneumoniae (PISP), increased doses of penicillins are still the drugs of choice. The available treatment options are high-dose amoxicillin, amoxicillin/clavulanic acid, cefotaxime, ceftriaxone, or neoquinolone antibacterial drugs; for penicillin-resistant Streptococcus pneumoniae (PRSP), cefotaxime, ceftriaxone, neoquinolones, or vancomycin should be chosen, and the combination can be used if necessary. (3) China’s Streptococcus pneumoniae resistance rate to macrolides is generally above 60%, and most of them are at a high level of resistance, therefore, macrolides alone should not be applied when CAP is suspected to be caused by Streptococcus pneumoniae. (4) Bronchiectasis complicated by pneumonia, Pseudomonas aeruginosa is a common pathogen, empirical treatment drug selection should take into account this. In addition to the above recommended drugs, some advocate the combination of quinolones or macrolides, which are thought to penetrate or destroy the bacterial biofilm. (5) When aspiration factors are suspected, ampicillin/sulbactam sodium, amoxicillin/potassium clavulanate and other drugs with anti-anaerobic effect should be preferred, or combined with metronidazole, clindamycin, etc. Moxifloxacin and other respiratory quinolones that are effective against anaerobic bacteria can also be used. (6) China’s 2006 CAP guidelines recommend that the first dose of antimicrobial therapy should be administered within 4 h after the diagnosis of CAP to improve the efficacy, reduce the morbidity and mortality rate, and shorten the hospital stay. (7) Anti-infective treatment can generally be stopped 3-5 d after the fever subsides and the main respiratory symptoms improve significantly, but the course of treatment varies depending on the pathogen and severity of the disease. For common bacterial infections, such as Streptococcus pneumoniae, medication can be administered until 72 h after the patient’s fever subsides; for infections caused by pathogenic bacteria such as Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella spp. or anaerobic bacteria that can easily lead to lung tissue necrosis, a course of antibacterial drugs for ≥2 weeks is recommended. The recommended duration of therapy for Legionella spp. infections is 10-21 d. (8) The condition and diagnosis should be evaluated 48-72 h after initial treatment. Where there is significant improvement in symptoms, the original treatment can still be maintained without necessarily considering what the sputum pathogenic test results are. After stabilization of the disease is converted to sequential treatment with oral antibacterial drugs. The conventional wisdom is that intravenous antimicrobial drugs should be continued in patients with severe CAP until the patient is clinically cured, but foreign multicenter randomized trials have shown that early conversion from intravenous to oral antimicrobial drugs results in better outcomes compared with conventional intravenous antimicrobial drug use for 7 days for severe non-ICU CAP, i.e., 81% of patients converted to oral antimicrobial drugs on day 3 had a mean reduction in hospital stay of at least 1.9 days, although of course evidence-based medical evidence is needed to support whether this theory is appropriate for our national situation.
2. Hospital-acquired pneumonia
2.1. Definition and diagnostic process
Hospital-acquired pneumonia (HAP) is defined as pneumonia that occurs ≥48 h after admission without an incubation period at the time of admission. Ventilator-associated pneumonia (VAP) is pneumonia that occurs 48 to 72 h after a patient is extubated or incised. 2005 HAP guidelines developed by the American Thoracic Society (ATS) proposed healthcare-associated pneumonia (HCAP), a new concept that includes patients with the following pneumonia: those who have been hospitalized for more than 2 d in the last 90 d for acute patients; those who live in nursing homes or long-term care facilities; those who have received intravenous antimicrobial therapy, chemotherapy, or wound management in the last 30 d; and those who receive hemodialysis treatment in hospitals or outpatient clinics.
2.2 Pathogens of HAP, VAP, and HCAP
The common pathogens of HAP, VAP and HCAP are Gram-negative bacteria: Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumoniae and Proteus spp; Gram-positive bacteria: Staphylococcus aureus (especially MRSA is rapidly increasing). Anaerobic bacteria are rare in VAP. The time of onset of HAP patients is closely related to the pathogenic spectrum and drug resistance of pneumonia: early-onset HAP (defined as less than 5 days of admission), mostly infections with sensitive organisms, with the causative agents being mainly community-acquired pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, MSSA and non-drug-resistant gram-negative enterobacteria (Escherichia coli, Enterobacter spp. Most HAP, especially VAP, is often caused by multiple drug-causing bacteria, including Pseudomonas aeruginosa, Acinetobacter baumannii, drug-resistant Enterobacter spp. and Streptococcus maltophilia, as well as gram-staining positive cocci, some of which are MRSA. Most HAP, especially VAP, is caused by multiple pathogens, and the pathogenic distribution of early-onset or late-onset VAP should be the same as that of late-onset HAP if combined with risk-promoting factors, taking into account Legionella infections [12].
2.3 Antibacterial drug therapy
The principles of antibacterial therapy for HAP, VAP and HCAP are early, appropriate, adequate dose and short course.
2.3.1 Types and doses of initial antimicrobial drug applications
Early appropriate and effective antimicrobial therapy is the main method to cure HAP and reduce HAP mortality. Initially, a sufficient amount of broad-spectrum empirical antimicrobial drug therapy should be given rapidly to cover all possible pathogenic bacteria (including MDR bacteria) to improve the success rate of the first dose. Step-down therapy can then be administered based on culture results and the patient’s clinical response. For early-onset, no risk factors for MDR infection or/and no serious underlying disease HAP initial empiric therapy is recommended: ceftriaxone or levofloxacin, moxifloxacin, ciprofloxacin or ampicillin/sulbactam or ertapenem. For initial empiric treatment of HAP with delayed onset or with risk factors for MDR infection or/and severe underlying disease, the recommended antimicrobial combination is: anti-Pseudomonas aeruginosa cephalosporins (cefepime, ceftazidime) or anti-Pseudomonas aeruginosa carbapenems (imipenem, meropenem) or b-lactam/b-lactam inhibitors (piperacillin/tazobactam) in combination with anti-Pseudomonas aeruginosa of fluoroquinolones (levofloxacin, ciprofloxacin) or aminoglycosides (amikacin, gentamicin, tobramycin), in combination with linezolid or vancomycin if there are risk factors for MRSA infection, and neo-cocyclic lactones or neoquinolones in case of Legionella pneumophila infection. For the treatment of inactive bacillus infections sensitive drugs are carbapenems, sulbactam, colistin and polymyxin E. For the treatment of Enterobacteriaceae producing ESBLs and Ampc enzymes: carbapenems are the most sensitive and quadruple cephalosporins are still controversial.
Patients with HAP or VAP who have severe and/or MDR infections must be treated with adequate doses of antimicrobial agents to ensure optimal efficacy. the ATS recommends an adequate therapeutic dose of 2g, q8h for cefepime and ceftazidime in adult patients with normal renal function; while the therapeutic dose of meropenem (1g, q8h) is usually slightly greater than imipenem (0.5g, q6h or 1g, q8h) Among the aminoglycosides, the daily dose of amikacin is 20 mg/kg, gentamicin, tobramycin 7 mg/kg, vancomycin 15 mg/kg q12h, linezolid 600 mg q12h, and among the quinolones, ciprofloxacin 400 mg, In our clinical practice, there may be inadequate therapeutic doses, which should be taken seriously by clinicians, but of course, evidence-based medical evidence is needed to support whether the doses recommended by ATS are suitable for our specific situation.