Causes of pneumonia

The most frequent pathogens of pneumonia are Gram-positive and Gram-negative bacteria, intracellular pathogens, less often fungi and viruses. In young people, pneumonia is more likely to be caused by a single pathogen (monoinfection), whereas in elderly patients and people with concomitant diseases, the cause of pneumonia is often bacterial or viral-bacterial associations (mixed infection), which creates serious difficulties in selecting adequate etiotropic treatment.

For each form of pneumonia (out-of-hospital, hospital, etc.), its own spectrum of the most likely pathogens is characteristic. This is based on both the modern classification of pneumonia and the principles of the initial choice of empirical etiotropic therapy.

[1], [2], [3], [4], [5], [6]

Community-acquired pneumonia

At present, several dozen microorganisms capable of causing community-acquired pneumonia are described. The leading role is assigned to such bacterial pathogens as:

• pneumococci (Streptococcus pneumoniae);
• Haemophilus influenzae;
• Moraxella (Moraxella catatrhalis);
• mycoplasma (Mycoplasma spp.);
• Chlamydia (Chlamydophila or Chlamydia pneumoniae;
• legionella (Legionella spp.).

The share of these pathogens accounts for about 70-80% of cases of community-acquired pneumonia, with pneumococcus still leading the way, which causes infection in 30-50% of patients with community-acquired pneumonia.

Pneumococci are gram-positive bacteria (diplococci), which are surrounded by a polysaccharide capsule, which prevents opsonization and subsequent phagocytosis by their macrophages. In a significant part of the population, pneumococci are one of the components of the normal microflora of the upper respiratory tract. The incidence of asymptomatic pneumococcal carriage in adults reaches 2.5%, and in children attending school and preschool institutions - 56%. Pneumococci can spread by airborne droplets both from patients with pneumonia and from bacterial carriers.

Outbreaks of pneumococcal pneumonia are noted in winter and in crowded places (kindergartens, boarding schools, prisons, army barracks, etc.). The highest risk of pneumococcal pneumonia is in the elderly with concomitant diseases of the internal organs.

About 5-10% of community-acquired pneumonia in adults are caused by Gram-negative haemophilic rods (Haemophilus influenzae), especially in smokers and patients with chronic obstructive bronchitis. In children 6 months to 5 years of age, the frequency of community-acquired pneumonia caused by Haemophilus influenzae reaches 15-20% or more. Haemophilus influenzae spread by airborne droplets As well as pneumococci, haemophilic rods often form part of the normal microflora of the nasopharynx. The incidence of asymptomatic bacterial transport varies widely, reaching 50-70%.

Moraxella catarrhalis - gram-negative coccobacterium - is relatively rarely the cause of community-acquired pneumonia (1-2% of cases), mainly in people with concomitant chronic obstructive bronchitis. Moraxella is also a normal inhabitant of the rotosynopharynx. A distinctive feature of this pathogen is a significant prevalence of strains resistant to beta-lactam antibiotics due to active production of beta-lactamases.

In recent years, the epidemiological significance of the so-called "atypical" pathogens - mycoplasmas, chlamydia, legiopellas, etc. - has increased significantly. As intracellular pathogens, they are able to replicate inside the cell of the macroorganism while maintaining high resistance to antibacterial drugs.

Mycoplasma infection often causes community-acquired pneumonia in children, adolescents, young people (younger than 35 years), who live in isolated or partially isolated groups (kindergartens, schools, military units, etc.). Specific gravity of mycoplasmal pneumonia can reach 20-30% or more of all cases of community-acquired pneumonia, often causing the emergence within these organized groups of epidemics of mycoplasmal infection. In older age groups, mycoplasma is less likely to cause community-acquired pneumonia (1-9%).

Two characteristic biological features of mycoplasmas explaining the stability of this infection to certain antibacterial drugs and the long persistence of mycoplasma in the human body are of practical importance:

1. Mycoplasmas are devoid of a rigid outer cell membrane, on which, primarily, the action of penicillins and other beta-lactam antibiotics is directed.
2. Mycoplasmas are able to firmly bind to the membrane of the infected cell and thus "avoid" phagocytosis and destruction by cells of the natural defense of the macroorganism (macrophages).
3. Being inside the cell of the macroorganism, the mycoplasmas are able to replicate (reproduce).

Chlamydia also belong to the number of "atypical" intracellular pathogens.

In adults, chlamydia cause about 10-12% of community-acquired pneumonia, often of medium severity or severe. Chlamydial pneumonia is more likely to affect young people. Chlamydia is transmitted to humans by airborne droplets, and the asymptomatic colonization of the upper respiratory tract by these microorganisms is unlikely. Getting into the body and penetrating into the cells, chlamydia form there cytoplasmic inclusions - the so-called elementary and reticular bodies. The cycle of intracellular reproduction of the latter will last 40-72 hours, after which the host cell will burst.

Chlamydial bodies that enter the intercellular space are capable of infecting new cells, causing a progressive damage to the cells of the macroorganism, a corresponding inflammatory reaction of the tissue and organ. It is also possible a long persistence of chlamydia within cells, which for a time is not accompanied by clinical manifestations of the disease.

A particular type of chlamydial pneumonia is ornithosis (psittacosis) caused by Chlamydia psittaci, which are transmitted to a person when in contact with infected birds. The frequency of ornithous pneumonia does not exceed 1-3%.

Legionella cause community-acquired pneumonia in 2-8% of cases and represent an aerobic gram-negative rod and belong to the "atypical" intracellular pathogens. Getting into the human body, they penetrate into the cells and multiply rapidly, mainly in alveolar macrophages, polymorphonuclear neutrophils and blood monocytes. Just like mycoplasma, legionella, persisting inside the cells of the macroorganism, are resistant to the action of beta-lactam antibiotics and are not prone to phagocytosis.

In natural conditions (in nature) legionella are common in freshwater reservoirs, but have the ability to colonize and artificial water systems - air conditioners, water pipes, compressors and shower facilities, a variety of industrial and household aerosol systems, including medical stationary aerosol plants used, for example , for the treatment of patients with bronchoobjective syndrome. Infection is usually spread by airborne droplets, but direct infection from a sick person is almost impossible, since a transmission of infection requires a finely dispersed aerosol.

Legionellosis pneumonia is more likely to affect middle-aged and elderly people, especially if they have co-morbidities and risk factors, usually causing severe pneumonia, which is difficult to treat with beta-lactam antibiotics. Legionellosis pneumonia rank second (after pneumococcal) in the frequency of deaths. In children and young people who do not suffer from concomitant diseases, legionella pneumonia is rare.

The most frequent causative agent of community-acquired pneumonia is pneumococcus. Pneumococci, hemophilic rod and moraxella are part of the normal microflora of the upper respiratory tract, causing a relatively high incidence of asymptomatic bacterial transport.

"Atypical" pathogens (mycoplasmas, chlamydia and legionella), which are intracellular pathogens, are not part of the normal microflora of the mouth and nasopharynx, although they infect the macroorganism and are capable of prolonged persistence inside the cell, while maintaining high resistance to antibacterial therapy. Mycoplasmas and chlamydia often cause pneumonia in young people, and legionella in middle-aged and elderly patients. Most outbreaks of out-of-hospital pneumonia are observed among people in isolated or partially isolated groups.

These pathogens are the most common causes of community-acquired pneumonia. More rarely (in 5-15% of cases) as an etiological factor are some gram-negative bacteria of the Enterobakteriaeae family, Staphylococcus aureus, anaerobic bacteria, Pseudomonas aeruginosa and others. Their role in the etiology of community-acquired pneumonia rises in older age groups and in individuals with concomitant chronic diseases of internal organs.

Staphylococcus aureus (Staphylococcus aureus) is a comparatively rare causative agent of community-acquired pneumonia (about 3-5%), but the pneumonia caused by it differs in severe course and propensity to destruction of lung tissue. Staphylococcus aureus is a gram-positive cocci forming clusters, resembling bunches of grapes. Infection with staphylococcus is more common in the winter season, and in 40-50% of cases it is associated with a viral infection (acute respiratory viral infection, influenza). Staphylococcal pneumonia is more susceptible to elderly patients, drug addicts, patients with cystic fibrosis, patients suffering from concomitant chronic diseases.

Gram-negative enterobacteria of the Enterobakteriaceae family (Klebsiella and Escherichia coli) have a high virulence and are capable of causing a serious disease with lethality reaching 20-30%. It is known that gram-negative enterobacteria are present in the normal microflora of the upper respiratory tract, and this presence increases with age. Community-acquired pneumonia caused by enterobacteria, as a rule, develops in elderly, weakened patients, in persons in nursing homes suffering from severe concomitant diseases of the lungs and heart (COPD, chronic heart failure, etc.).

Cicheciella (Klebsiella pneumoniae) often causes pneumonia in men with chronic alcoholism.

E. Coli (Escherichia coli) more often infects lung tissue, spreading here by hematogenous path from the extrapulmonary focus located in the gastrointestinal tract, the urinary system, and the like. Predisposing factors are also diabetes mellitus, renal failure, chronic heart failure, and others.

Anaerobic bacteria (Fusobacterium spp., Bacteroides spp., Peptostreptococcus spp., Etc.) also form part of the normal microflora of the upper respiratory tract. Pneumonia caused by these pathogens develop as a result of massive aspiration of the contents of the upper respiratory tract in patients with neurological diseases accompanied by impaired consciousness, swallowing, in persons suffering from alcoholism, drug addiction, abusers of sleeping pills, tranquilizers. The presence of caries or paradontic diseases in these patients significantly - it affects the risk of aspiration of large amounts of anaerobic bacteria and the occurrence of aspiration pneumonia.

Pseudomonas aeruginosa rarely causes community-acquired pneumonia. Infection can spread due to aspiration and hematogenous way. As a rule, vnebolnichnye pneumonia, caused by Pseudomonas aeruginosa, develop in patients with bronchiectasis, cystic fibrosis, as well as in persons receiving corticosteroid therapy. Pneumonia, caused by Pseudomonas aeruginosa, is characterized by severe course and high lethality.

Thus, the specific clinical and epidemiological situation in which out-of-hospital pneumonia developed - the age of patients, the presence of concomitant diseases and certain risk factors (alcoholism, smoking, drug addiction) largely determine which of the causative agents is a community cause of pneumonia in this particular case.

The most likely causative agents of community-acquired pneumonia, depending on the clinical and epidemiological situation and the presence of risk factors

Clinical-epidemiological situation and risk factors	The most likely pathogens
Children aged 6 months. Up to 6 years	Pneumococcus. Staphylococcus aureus. Haemophilus influenzae. Moraxella. Respiratory viruses. Mycoplasma
Children from 7 to 15 years old	Pneumococcus. Haemophilus influenzae. Moraxella. Respiratory viruses. Mycoplasma. Chlamydia
Age from 16 to 25 years	Mycoplasma. Chlamydia. Pneumococcus
Age over 60 years	Pneumococcus. Haemophilus influenzae. Gram-negative enterobacteria
Winter season, stay in an isolated team	Pneumococcus
Outbreak of pneumonia during the flu epidemic	Pneumococcus. Staphylococcus aureus. Haemophilus influenzae. Virus-bacterial associations
Outbreak of pneumonia in the military unit	Pneumococcus. Chlamydia. Adenovirus. Mycoplasma. Virus-bacterial associations
Outbreak of pneumonia in shelters, prisons	Pneumococcus. Mycobacterium tuberculosis
Outbreak of pneumonia in nursing homes	Chlamydia. Pneumococcus. Influenza virus A. Virus-bacterial associations
Patients from nursing homes (sporadic cases of pneumonia)	Pneumococcus. Klebsiella. Intestinal bacillus. Haemophilus influenzae. Staphylococcus aureus. Anaerobes. Chlamydia.
Recent accommodation in hotels using air conditioning and closed water systems	Legionella
Smoking, the presence of COPD	Pneumococcus. Haemophilus influenzae. Mycoplasma. Legionella
The presence of airway obstruction	Anaerobes. Pneumococcus. Hemophilous daddy. Staphylococcus aureus
Bronchiectasis and cystic fibrosis	Pseudomonas aeruginosa. Staphylococcus aureus
Alcoholism	Pneumococcus. Klebsiella. Staphylococcus aureus. Anaerobes
Intravenous drug use	Staphylococcus aureus. Anaerobes. Mycobacterium tuberculosis. Pneumococcus
Antibacterial therapy in the previous 3 months	Penicillin-resistant strains of pneumococci. Pseudomonas aeruginosa
Recent contact with birds	Chlamydia psittaci
Recent contact with cats, cattle, sheep, goats	Chlamydia burnetii
Diabetes mellitus, diabetic ketoacidosis	Pneumococcus. Staphylococcus aureus
Periodontal disease, caries	Anaerobic bacteria
Increased risk of aspiration (strokes, neurological diseases, impaired consciousness, etc.)	Anaerobic bacteria

Note: * - respiratory viruses: PC, influenza, parainfluenza, adenoviruses, enteroviruses.

The data presented in the table, for all its uncertainty, may be useful for selecting the initial empirical etiotropic therapy, as well as the optimal choice of diagnostic studies needed to verify the pathogens of pneumonia.

It should be added that there is also a certain interdependence of the etiologic factor of community-acquired pneumonia and the severity of the course of the disease.

In patients with severe community-acquired pneumonia, the most common pathogens are:

• pneumococci,
• Staphylococcus aureus,
• legionella,
• Klebsiella.

[7], [8], [9], [10], [11], [12], [13], [14], [15]

Hospital (hospital, nosocomial) pneumonia

Hospital-acquired (nosocomial) pneumonia in most cases is caused by highly virulent autogenous microflora of patients, including those exposed to the neck by antibiotics, or by pathogenic strains of microorganisms circulating in the hospital:

• pneumococcus (Streptococcus pneumoniae);
• Staphylococcus aureus (Staphylococcus aureus);
• klebsiella (Klebsiella pneumoniae);
• E. Coli (Escherichiae coli);
• Proteus (Proteus vulgaris);
• Pseudomonas aeruginosa;
• Legionella (Legionella pneumophila);
• anaerobic bacteria (Fusobacterium spp., Bacteroides spp., Peptostreptococcus spp.)

The frequency of detection of individual pathogens of nosocomial pneumonia.

Causative agent	Detection rate,%
Streptococcus pneumoniae	10-16.3
Staphylococcus aureus	2.7-30
Escherichiae coli	17.3-32.3
Legionella pneumophila	Up to 23
Proteus vulgaris	8.2-24
Klebsiella pneumoniae	8,2-12
Pseudomonas aeruginosa	17th
Anaerobic flora	5-10

It can be seen from the table that among the pathogens of nosocomial pneumonia the specific gravity of gram-negative microflora and anaerobic bacteria is very high, as a rule, causing the development of severe nosocomial pneumonia, characterized by high mortality. For example, hospital mortality due to pneumonia caused by Klebsiella, Escherichia coli or Staphylococcus aureus reaches 32-36%, and the lethality when infected with Pseudomonas aeruginosa is 51-70%.

Just as in the case of community-acquired pneumonia, the specific type of pathogen of nosocomial pneumonia depends largely on the clinical situation in which the disease develops. For example, the cause of aspiration pneumonia arising in a hospital in patients with impaired consciousness, gastrointestinal or neuromuscular diseases due to the entry of pathogenic microorganisms into the lower respiratory tract, are most often:

• anaerobic microorganisms (Bacteroides spp., Peptostreptoxoccus spp., Fusobakterium nucleatum, Prevotella spp.);
• Staphylococcus aureus (often antibiotic-resistant strains);
• Gram-negative esterobacteria (Klebsiella pneumoniae, Escherichiae coli);
• Pseudomonas aeruginosa;
• Proteus vulgaris.

It should be remembered that the spectrum of pathogens of aspirated nosocomial pneumonia differs somewhat from the spectrum of pathogens of obstructive pneumonia that have developed as a result of aspiration. The latter are more often caused, in addition to anaerobic pathogens, by Staphylococcus aureus and pneumococcus.

Currently, there is also a special form of nosocomial pneumonia that develops in patients who are on artificial ventilation (IVL), which is known as ventilator-associated pneumonia (VAP). In this case, the early VAP, which develops within a period of less than 7 days from the onset of mechanical ventilation, and the late VAP that occurs with a duration of mechanical ventilation for more than 7 days are distinguished. The main difference between these two forms of ventilating aspiration pneumonia is the etiological heterogeneity of these forms of nosocomial pneumonia (RG Wunderik).

The most common cause of early ventilator-aspiration pneumonia are pneumococci, hemophilic rod, Staphylococcus aureus and anaerobic bacteria. With late VAP, drug resistant strains of enterobacteria, Pseudomonas aeruginosa, Acinetobacner spp. And methicillin-resistant strains of Staphylococcus aureus (MRSA).

The spectrum of pathogens of nosocomial pneumonia depends largely on the profile of the hospital in which the patient resides, as well as the nature of the pathology in respect of which inpatient treatment is performed. So, the causative agents of hospital pneumonia in patients with a urological profile are more often Escherichia coli, Proteus, Enterococcus, in hematological patients - Escherichia coli, Klebsiella, Pseudomonas aeruginosa and Staphylococcus aureus. In operated patients, nosocomial pneumonia is more often caused by Staphylococcus aureus, Escherichia coli, Proteus, Pseudomonas aeruginosa. The cause of hospital pneumonia in patients with chronic diseases of the bronchopulmonary system is more often enterococci, Pseudomonas aeruginosa, Klebsiella.

"Atypical" pneumonia, developed in hospital conditions, is more often due to legionella infection. The risk of disease occurrence increases in patients receiving long-term glucocorticoid therapy or cytotoxic drugs, as well as when using autonomous water sources in the hospital. It should be remembered that mycoplasmas and chlamydia very rarely cause hospital pneumonia.

In patients receiving long-term antibiotics or glucocorticoids, nosocomial pneumonia can be caused by fungi, for example, Aspergillus spp.

The viral etiology of hospital pneumonia is associated with infection with influenza A and B viruses, as well as the respiratory syncytial virus (PC), although the probability of a "purely" viral lesion of the pulmonary parenchyma is doubtful. Just as in the case of community-acquired pneumonia, viral infections in hospital patients appear to be a factor contributing to the inhibition of self-defense elements and contribute to the development of bacterial infection characteristic of nosocomial pneumonia.

It should be emphasized that the above recommendations on the orienting agent of nosocomial pneumonia are only the most general and probabilistic nature. The spectrum of these pathogens and the sensitivity to antibiotic therapy can differ significantly in different institutions and even in different departments of the same hospital, which should be taken into account when prescribing empirical etiotropic therapy.

The most likely causative agents of nosocomial pneumonia depend on the clinical situation in which pneumonia developed

Clinical situations	The most likely pathogens
Reparation pneumonia in patients; a violation of consciousness, diseases of the gastrointestinal tract, neuromuscular diseases, etc.	Anaerobes: Bacteroides spp. Peptostreptococcus spp, Fusobacterium nucleatum Prevotella spp. Gram-negative enterobacilli: Klebsiella pneumoniae, Escherichiae coli Staphylococcus aureus Pseudomonas aeruginosa Proteus vulgaris
Early WAP	Pneumococcus. Haemophilus influenzae. Staphylococcus aureus. Anaerobic bacteria
Late WAA	Enterobacteria. The pseudoagropsy. Acinetobacter spp. Staphylococcus aureus
Stay in the urological hospital	Intestinal bacillus. Proteus. Enterococcus
Hematologic patients	Intestinal bacillus. Kpebsiella. Pseudomonas aeruginosa. Staphylococcus aureus
Postoperative period	Staphylococcus aureus. Intestinal bacillus. Proteus. Pseudomonas aeruginosa
Concomitant chronic bronchopulmonary diseases	Enterococcus. Pseudomonas aeruginosa. Kpebsiella
"Atypical" pneumonia in patients who received long-term glucocorticoids, cytostatics, etc.	Legionella
Inpatient use of autonomous water sources, as well as air conditioners	Legionella
Patients with long-term antibiotics or glucocorticoids	Mushrooms (Aspergillus spp.)

Pneumonia, developed against the background of immunodeficiency states

Immune status disorders are extremely common in clinical practice. In addition to AIDS, the most common causes of immunodeficiency are:

1. Malignant neoplasms.
2. Transplantation of organs or bone marrow.
3. Congenital or acquired humoral or cell-mediated immunodeficiency (multiple myeloma, acquired hypogammaglobulinemia, thymoma with hypogammaglobulinemia, selective: IgA or IgG deficiency, chronic lymphocytic leukemia, lymphogranulomatosis, acquired human immunodeficiency (HIV).
4. Chronic diseases or clinical conditions:
   • diffuse connective tissue diseases;
   • COPD;
   • diabetes;
   • kidney failure;
   • liver failure;
   • amyloidosis;
   • therapy with corticosteroids;
   • berylliosis;
   • elderly age.

With various immunodeficiency conditions, including those associated with taking medications, there is a violation of all links in the human protection system that prevents the onset of lung disease. In this case, the normal composition of the oral microflora changes, the mucociliary transport of the tracheobronchial secretion is disrupted, local non-specific defense mechanisms are damaged (decreased level of complement and secretory IgA, alveolar macrophages), and specific (humoral and cell-mediated) defense mechanisms. This creates conditions for colonization of the lower respiratory tract by pathogenic and conditionally pathogenic microorganisms and the occurrence of inflammation of the lung parenchyma.

The most common causative agent of pneumonia in persons with immunodeficiency states are:

• Hemophilus influenzae;
• Legionella species;
• Staphylococcus aureus;
• Pneumocystis carini;
• protozoa;
• mushrooms;
• viruses (herpes virus, cytomegalovirus);
• Mycobacterium tuberculosis.

Particularly high mortality is caused by pneumonia caused by Pneumocystis carini. In relatively young and middle-aged patients, up to 20-30% of pneumonias that develop against the background of immunodeficient conditions occur in "atypical" intracellular pathogens:

• Mycoplasma;
• Legionella species;
• Chlamydia species.

However, in elderly patients mycoplasma almost never causes the development of pneumonia (EL Aronseu), and the most relevant pathogens are pymmococci, hemophilic rod and viruses.

It should be remembered that prolonged use of chemotherapeutic drugs or high doses of corticosteroids increases the risk of pneumonia caused by Pneumocystis carina or Nocardia asteroids.