Progress in the diagnosis and treatment of community-acquired pneumonia

1. Definitions and epidemiology

1. Definitions

• Infectious parenchymal inflammation of the lungs that occurs outside the hospital
• Includes pneumonia that develops during the incubation period after admission to the hospital for pathogens infected with pathogens with a definite incubation period
• Clinical manifestations are mixed
• Mild symptoms – characterized by fever and productive production
• Severe disease – can progress to respiratory distress and sepsis

2. Epidemiology

• The incidence and mortality rate of CAP in adults is high, and medical resources are expensive

2. Risk factors

1.高龄

• In people aged ≥ 65 years, the annual hospitalization rate for CAP is about 2,000 per 100,000
• 3 times the general population, indicating that 2% of older people are hospitalized with CAP each year

2. Chronic comorbidities

• COPD、支气管扩张、哮喘
• Chronic heart disease (heart failure)
• Stroke
• diabetes
• malnutrition
• Immunodeficiency

3. Viral respiratory tract infection

• flu
• Covid

4. Impaired airway protection

• Increased risk of massive aspiration of gastric contents and/or microaspiration of upper respiratory secretions
• Altered consciousness (e.g., stroke, epilepsy, anesthesia, drug or alcohol use)
• Dysphagia (due to esophageal lesions or motility disorders)

5. Miscellaneous

• smoking
• Sake
• Opioid use
• Living conditions (prisons, shelters, paint, petrol)
• poor

3. Microorganisms

(1) Types of microorganisms

1. Bacteria

• Streptococcus pneumoniae (most common)
• Haemophilus influenzae
• Moraxella catarrhalis
• Staphylococcus aureus
• Group A streptococcus
• Gram-negative aerobic bacteria
• Klebsiella spp. of the Enterobacteriaceae family
• Escherichia coli
• Microaerophiles and anaerobes (associated with aspiration)

2. Atypical pathogens

• Legionella
• Mycoplasma pneumoniae
• Pneumonia garment
• Chlamydia psittaci

3. Viruses

• Flow A and B
• COVID-19
• Other coronaviruses
• Middle East respiratory syndrome coronavirus (MERS-CoV).
• Severe acute respiratory syndrome coronavirus, etc
• rhinovirus
• Parainfluenza virus
• adenovirus
• Respiratory syncytial virus
• Human metapneumovirus
• Human bocavirus

(2) Influencing factors of microorganisms

1. Underlying medical conditions

2. Viral infection

(3) Trends in pathogens

1. Decreased incidence of Streptococcus pneumoniae

• The widespread use of pneumococcal vaccine has led to a decrease in the individual incidence of pneumococcal pneumonia and the formation of herd immunity
• There are regional differences in pneumococcal vaccination rates – as do the rates of pneumococcal infection
• About 30% of CAP cases in Europe are due to Streptococcus pneumoniae, compared with 10% to 15% in the United States, where pneumococcal vaccination rates are higher

2.COVID-19全球流行

3. Use of mNGS – methodological advances

• Respiratory viruses are detected in one third of adult CAP cases
• The role of respiratory viruses is uncertain: as a single pathogen, as a cofactor in the development of bacterial CAP, or as triggering a dysregulated host immune response.

4. The detection rate of total pathogens is low

• Despite extensive evaluation using molecular diagnostics and other microbiological assays, only half of cases of CAP can identify the causative organism
• The pathogenesis of CAP is not well understood

5. Discovery of the lung microbiota

• Previously thought to be sterile—non-culture techniques (i.e., high-throughput 16S rRNA gene sequencing) have identified complex and diverse microbial communities within the alveoli
• This finding suggests that alveolar resident microorganisms play a role in the development of pneumonia, either by modulating the host's immune response to infecting pathogens, or by direct overgrowth of specific pathogens within the alveolar microbiota

Fourth, pathogenesis

1. Mainly caused by bacterial or viral respiratory pathogens

• Droplet/aerosol inhalation transmission
• Inhalation—colonization of the pathogen in the nasopharynx—microaspiration to reach the alveoli
• Infection occurs when the inoculum is adequate and/or the host immune defenses are impaired
• Pathogen replication, causative agent production, and host immune response lead to inflammation and damage to the lung parenchyma, ultimately causing pneumonia

2. Alveolar microbiota changes (alveolar dysbiosis)

• Compete with resident microorganisms to replicate
• Resident microorganisms influence or modulate the host's immune response to infecting pathogens

3. Uncontrolled replication of resident microorganisms within the alveoli

• The alveolar microbiota is similar to the oral microbiota
• 主要为厌氧菌[如普氏菌（Prevotella）和韦荣球菌(Veillonella)]以及微需氧性链球菌
• Exogenous injuries such as viral infections or smoke exposure can alter the composition of the alveolar microbiota and trigger the overgrowth of certain microorganisms
• Because the microorganisms that make up the alveolar microbiota are often not cultured using standard culture methods—this may explain the low rate of pathogen detection in patients with CAP

5. Diagnostic criteria

6. Assessment of the severity of the disease

1.CURB-65

2. PSI score

7. Pathogen inference and empirical treatment

1. Overview

• The 2016 edition of the Guidelines for the Diagnosis and Treatment of Community-Acquired Pneumonia in Chinese Adults proposes a "six-step approach" in the diagnosis and treatment of CAP: the core and difficulty is still to speculate on the possible pathogens and their drug resistance and initiate empirical anti-infective therapy in time, because it is related to the success of initial treatment and affects the prognosis of the disease

• The most difficult part of the diagnosis process is to determine the pathogen, and the following questions are often considered

• The 2019 ATS/IDSA guidelines recommend sputum cultures or blood cultures only in patients with severe CAP
• Therefore, it is relatively more difficult to diagnose the etiology of patients with mild to moderate CAP, and the most likely pathogens are analyzed and the risk of drug resistance is assessed only according to the patient's age, underlying disease, clinical characteristics, disease severity, liver and kidney function, and previous medications

2. Epidemiological characteristics of CAP pathogens in mainland China

• Mycoplasma pneumoniae and Streptococcus pneumoniae are important pathogens of CAP in adults in mainland China
• Other common pathogens include Haemophilus influenzae, Chlamydia pneumoniae, Klebsiella pneumoniae and Staphylococcus aureus
• Pseudomonas aeruginosa and Acinetobacter baumannii are rare

3. Recommendations of the 2016 Chinese CAP guidelines for etiological examination

4. The problem of drug resistance of pathogens in patients with CAP is severe

5. Pneumonia drug resistance score

6. Individualized assessment

(1) Streptococcus pneumoniae

• 2009-2010—CARTIPS
• Insensitive Streptococcus pneumoniae (PNSP) accounted for 10.8% and penicillin-resistant Streptococcus pneumoniae (PRSP) accounted for only 2%
• Azithromycin – resistance up to 88.8%
• Risk factors for PRSP
• These include antibiotic exposure in the past 3 months, recent hospitalization, bipolar age, exposure to child care providers, etc
• Once Streptococcus pneumoniae is insensitive to penicillin, it predicts significant cross-resistance to lactam antimicrobials

(2) Staphylococcus aureus

• : One of the causes of severe pneumonia in neonates and infants, manifested as shortness of breath and fever, imaging can show multiple coarse thin-walled cavities, prone to pneumothorax and empyema
• : The resulting CAP mostly occurs on the basis of pre-influenza, and patients may have fever, bloody sputum production, and necrotizing pneumonia
• For Staphylococcus aureus, caution is required to assess whether it is resistant to methicillin
• CA-MRSA
• As early as the 80s of the 20th century, it led to skin and soft tissue infections (SSTIs) in dense groups of people who had physical contact
• CA-MRSA has been reported to lead to CAP around 2000
• United States – MRSA-CAP accounts for 2.4% of all CAPs and 5% of ICU-CAPs
• China – Results from a prospective cohort study of SSTI showed that only 5 strains of CA-MRSA were isolated from 501 patients with SSTI in the included patients, with an isolation rate of 3% (5/164)
• CAP requires empiric coverage of MRSA
• Critically ill disease requires intensive care unit (ICU) admission, imaging shows necrosis or cavity infiltrate, and empyema
• If there is no MRSA growth in qualified respiratory secretions, empiric therapy is discontinued.
• MRSA is not a common cause in mainland CAP, but a high degree of vigilance is still required
• He has been treated with antibiotics in the past 30 days
• MRSA infection or colonization within the past 1 year
• Pneumonia Severity Index (PSI) score ≥ 120

(3) Gram-negative bacteria

1) Haemophilus influenzae and Moraxella catarrhalis

• ESP: For smokers and people with chronic obstructive pulmonary disease (COPD).
• Penicillinase is produced
• Haemophilus influenzae produces 15%-20% of enzymes, while Moraxella catarrhalis produces up to 90%
• Commonly used cephalosporins, macrolides, and fluoroquinolones are effective

2) Klebsiella pneumoniae

• In 2006, 12 countries in Asia, CAP pathogens and susceptibility studies showed that Klebsiella pneumoniae accounted for 9.7% of patients and ESBL (lower than the conclusion based on intra-abdominal infection)
• History of recent antibiotic exposure, advanced age, aspiration, healthcare admission, and underlying cardiopulmonary disease (excluding structural lung disease)

3) Pseudomonas aeruginosa

• Risks of infection include severe structural lung disease, severe COPD, recent history of antibiotic exposure, and recent hospitalization, particularly ICU admission, and mechanical ventilation

(4) Atypical pathogens

1) Mycoplasma

• The proportion of in vitro resistance to macrolides is high
• There are few studies on the relationship between in vitro resistance and clinical treatment failure
• Studies have shown that in vitro resistance to macrolides can lead to a prolonged duration of fever, but does not affect the prognosis
• Switching to respiratory quinolones is recommended in patients with a high suspicion of treatment failure due to macrolide resistance

2) Legionella

• Epidemiological data are lacking
• Suspicion of Legionella pneumonia is high
• Patients with CAP present with fever with relative bradypulse, episodic headache, nonpharmacologic psychoneurological symptoms, extrapulmonary manifestations such as nonpharmacologic diarrhea and acute liver and kidney damage, hyponatremia, particularly hypophosphatemia on laboratory tests, and β failure to respond to antimicrobial therapy
• Radiographic findings of Legionella pneumonia are often nonspecific, with multiple lobes, multiple lung segments, cavitation, and significant pleural effusion in some patients, which can progress rapidly.

8. Treatment plan

1. Comparison of the two classic schemes

2. Novel tetracyclines

• The antimicrobial spectrum is extensive, but it is inactive against Pseudomonas aeruginosa

• It has good security advantages

• Metabolically stable with few drug-drug interactions

• It can be used in the elderly, patients with impaired liver and kidney function, etc., without dose adjustment

• It can be given sequentially intravenously and orally

9. Evaluation of treatment effect

1.72 hours of evaluation

• Most patients with CAP experience clinical improvement 72 hours after initial treatment, but radiographic improvement lags behind clinical symptoms
• The condition should be evaluated 72 hours after initial treatment, and observation can continue as long as there is no clinical deterioration without rushing to change anti-infective drugs (IA)

2. Risk factors for initial treatment failure

10. Summary

• CAP is the leading cause of morbidity and mortality worldwide
• Risk factors: advanced age, comorbidities, viral infection, decreased airway protection
• Microorganisms: the most common are Streptococcus pneumoniae, G-bacteria, atypical pathogens, anaerobic bacteria, etc
• Three elements of diagnosis
• Assessment of the condition – site of treatment and prognosis
• Pathogen inference, resistance prediction, and empirical antibiotic selection—the most difficult—an organism assessment
• Novel therapeutics
• Omadacycline - broad antibacterial spectrum, safe, small drug interaction, no effect on liver and kidney function, can be continued orally

来源:Dobutamine