Causes of pneumonia

The most common causative agents of pneumonia are gram-positive and gram-negative bacteria, intracellular pathogens, and, less frequently, fungi and viruses. In young people, pneumonia is often caused by a single pathogen (monoinfection), whereas in elderly patients and in people with concomitant diseases, pneumonia is often caused by bacterial or viral-bacterial associations (mixed infection), which creates serious difficulties in selecting adequate etiotropic treatment.

Each form of pneumonia (community-acquired, hospital-acquired, etc.) is characterized by its own spectrum of the most probable pathogens. This is the basis for both the modern classification of pneumonia and the principles of the initial choice of empirical etiotropic therapy.

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Community-acquired pneumonia

Currently, several dozen microorganisms capable of causing community-acquired pneumonia have been described. The leading role is given to such bacterial pathogens as:

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

The listed pathogens account for approximately 70-80% of cases of community-acquired pneumonia, with pneumococcus still taking the leading place, causing infection in 30-50% of patients with community-acquired pneumonia.

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

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

About 5-10% of community-acquired pneumonias in adults are caused by gram-negative Haemophilus influenzae, especially in smokers and patients with chronic obstructive bronchitis. In children aged 6 months to 5 years, the incidence of community-acquired pneumonia caused by Haemophilus influenzae reaches 15-20% and higher. Haemophilus influenzae is spread by airborne droplets. Like pneumococci, Haemophilus influenzae are often part of the normal microflora of the nasopharynx. The incidence of asymptomatic carriage varies widely, reaching 50-70%.

Moraxella (Moraxella catarrhalis) is a gram-negative coccobacillus that is a relatively rare cause of community-acquired pneumonia (in 1-2% of cases), mainly in individuals suffering from concomitant chronic obstructive bronchitis. Moraxella is also a normal inhabitant of the mouth and nasopharynx. A distinctive feature of this pathogen is the significant prevalence of strains resistant to beta-lactamase antibiotics due to the active production of beta-lactamases.

In recent years, the epidemiological significance of so-called "atypical" pathogens - mycoplasmas, chlamydia, legionella, etc. - has increased significantly. Being intracellular pathogens, they are capable of replicating inside the cell of a macroorganism, maintaining high resistance to antibacterial drugs.

Mycoplasma infection most often causes community-acquired pneumonia in children, adolescents, and young people (under 35 years of age) living in isolated or partially isolated communities (kindergartens, schools, military units, etc.). The proportion of mycoplasma pneumonias can reach 20-30% or more of all cases of community-acquired pneumonia, often causing the emergence of mycoplasma infection epidemics within these organized communities. In older age groups, mycoplasmas are less often the cause of community-acquired pneumonia (1-9%).

Two characteristic biological features of mycoplasmas are of practical importance, explaining the resistance of this infection to some antibacterial drugs and the long-term persistence of mycoplasma in the human body:

1. Mycoplasmas lack a rigid outer cell membrane, which is primarily targeted by penicillins and other beta-lactam antibiotics.
2. Mycoplasmas are able to firmly bind to the membrane of an infected cell and thus “avoid” phagocytosis and destruction by the cells of the macroorganism’s natural defense (macrophages).
3. While inside the cell of a macroorganism, mycoplasmas are capable of replicating (reproducing).

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

In adults, chlamydia causes about 10-12% of community-acquired pneumonias, often moderate or severe. Young people are more susceptible to chlamydial pneumonia. Chlamydia is transmitted to humans by airborne droplets, and asymptomatic colonization of the upper respiratory tract by these microorganisms is unlikely. Getting into the body and penetrating into cells, chlamydia form cytoplasmic inclusions there - the so-called elementary and reticular bodies. The cycle of intracellular reproduction of the latter will continue for 40-72 hours, after which the host cell ruptures.

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

A special type of chlamydial pneumonia is ornithosis (psittacosis), caused by Chlamydia psittaci, which is transmitted to humans through contact with infected birds. The incidence of ornithosis pneumonia does not exceed 1-3%.

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

In natural conditions (in nature), legionella are common in freshwater bodies, but they have the ability to colonize artificial water systems - air conditioners, water pipes, compressors and showers, various industrial and household aerosol systems, including medical stationary aerosol installations used, for example, to treat patients with broncho-obstructive syndrome. The infection is usually spread by airborne droplets, but direct infection from a sick person is almost impossible, since a fine aerosol is needed to transmit the infection.

Legionella pneumonia most often affects middle-aged and elderly people, especially if they have concomitant diseases and risk factors, usually causing severe pneumonia that is poorly treatable with beta-lactam antibiotics. Legionella pneumonia is the second most common cause of death (after pneumococcal pneumonia). Legionella pneumonia is quite rare in children and young people who do not have concomitant diseases.

The most common pathogen of community-acquired pneumonia is pneumococcus. Pneumococci, Haemophilus influenzae and Moraxella are part of the normal microflora of the upper respiratory tract, causing a fairly high frequency of asymptomatic carriage of bacteria.

"Atypical" pathogens (mycoplasmas, chlamydia and legionella), which are intracellular pathogens, are not part of the normal microflora of the mouth and nasopharynx, although, infecting a macroorganism, they are capable of long-term persistence inside the cell, maintaining high resistance to antibacterial therapy. Mycoplasmas and chlamydia most often cause pneumonia in young people, and legionella in middle-aged and elderly patients. Outbreaks of community-acquired pneumonia are most often observed among people in isolated or partially isolated groups.

The listed pathogens are the most common causes of community-acquired pneumonia. Less often (in 5-15% of cases), some gram-negative bacteria of the Enterobacillus family, Staphylococcus aureus, anaerobic bacteria, Pseudomonas aeruginosa, and others act as an etiologic factor. Their role in the etiology of community-acquired pneumonia increases in older age groups and in individuals with concomitant chronic diseases of internal organs.

Staphylococcus aureus is a relatively rare pathogen of community-acquired pneumonia (about 3-5%), but the pneumonias it causes are severe and tend to destroy lung tissue. Staphylococcus aureus is a gram-positive cocci that form clusters shaped like bunches of grapes. Staphylococcus infection is more common in winter, and in 40-50% of cases it is associated with a viral infection (ARI, influenza). Elderly patients, drug addicts, patients with cystic fibrosis, and patients with concomitant chronic diseases are more susceptible to staphylococcal pneumonia.

Gram-negative enterobacteria of the Enterobakteriaceae family (Klebsiella and E. coli) are highly virulent and can cause severe illness with a mortality rate of 20-30%. It is known that gram-negative enterobacteria are also present in the normal microflora of the upper respiratory tract, and this presence increases with age. Community-acquired pneumonia caused by enterobacteria usually develops in elderly, weakened patients, in people in nursing homes, suffering from severe concomitant lung and heart diseases (COPD, chronic heart failure, etc.).

Klebsiella pneumoniae often causes pneumonia in men suffering from chronic alcoholism.

Escherichia coli most often infects lung tissue, spreading there hematogenously from an extrapulmonary focus located in the gastrointestinal tract, urinary system, etc. Predisposing factors also include diabetes mellitus, renal failure, chronic heart failure, etc.

Anaerobic bacteria (Fusobacterium spp., Bacteroides spp., Peptostreptococcus spp., etc.) are also part of the normal microflora of the upper respiratory tract. Pneumonia caused by these pathogens develops 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, abusing sleeping pills, tranquilizers. The presence of caries or periodontal disease in these patients significantly increases the risk of aspiration of large quantities of anaerobic bacteria and the development of aspiration pneumonia.

Pseudomonas aeruginosa rarely causes community-acquired pneumonia. The infection can spread through aspiration and hematogenous transmission. As a rule, hospital-acquired pneumonia caused by Pseudomonas aeruginosa develops in patients with bronchiectasis, cystic fibrosis, and in individuals receiving corticosteroid therapy. Pneumonia caused by Pseudomonas aeruginosa is characterized by a severe course and high mortality.

Thus, the specific clinical and epidemiological situation in which community-acquired pneumonia developed - the age of the patients, the presence of concomitant diseases and some risk factors (alcoholism, smoking, drug addiction) largely determine which of the pathogens is the community-acquired cause of pneumonia in a given specific case.

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

Clinical and epidemiological situation and risk factors	Most likely pathogens
Children aged 6 months to 6 years	Pneumococcus. Staphylococcus. Haemophilus influenzae. Moraxella. Respiratory viruses. Mycoplasmas
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 time of year, being in an isolated group	Pneumococcus
Outbreak of pneumonia during flu epidemic	Pneumococcus. Staphylococcus aureus. Haemophilus influenzae. Viral-bacterial associations
Pneumonia outbreak in military unit	Pneumococcus. Chlamydia. Adenoviruses. Mycoplasmas. Viral-bacterial associations
Outbreak of pneumonia in shelters, prisons	Pneumococcus. Mycobacterium tuberculosis
Pneumonia outbreak in nursing homes	Chlamydia. Pneumococcus. Influenza A virus. Viral-bacterial associations
Nursing home patients (sporadic cases of pneumonia)	Pneumococcus. Klebsiella. Escherichia coli. Haemophilus influenzae. Staphylococcus aureus. Anaerobes. Chlamydia.
Recent stay in hotels using air conditioning and closed water supply systems	Legionella
Smoking, presence of COPD	Pneumococcus. Haemophilus influenzae. Mycoplasma. Legionella.
Presence of airway obstruction	Anaerobes. Pneumococcus. Hemophilus influenzae. 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 diseases, 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, despite all their uncertainty, may be useful for selecting the initial empirical etiotropic therapy, as well as the optimal choice of diagnostic tests necessary for verifying the causative agents of pneumonia.

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

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

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

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Hospital-acquired (nosocomial) pneumonia

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

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

Frequency of detection of individual pathogens of nosocomial pneumonia.

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

The table shows that among the pathogens of hospital-acquired pneumonia, the proportion 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 in pneumonia caused by Klebsiella, Escherichia coli or Staphylococcus aureus reaches 32-36%, and mortality in case of infection with Pseudomonas aeruginosa is 51-70%.

As in the case of community-acquired pneumonia, the specific type of pathogen causing nosocomial pneumonia largely depends on the clinical situation in which the disease develops. For example, the most common causes of aspiration pneumonia that occurs in hospitals in patients with impaired consciousness, gastrointestinal or neuromuscular diseases due to pathogenic microorganisms entering the lower respiratory tract are:

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

It should be remembered that the spectrum of pathogens causing aspiration nosocomial pneumonia is somewhat different from the spectrum of pathogens causing hospital-acquired pneumonia that developed as a result of aspiration. The latter are more often caused, in addition to anaerobic pathogens, by Staphylococcus aureus and Pneumococcus.

Currently, a special form of nosocomial pneumonia is also distinguished, developing in patients on artificial ventilation of the lungs (AVL), which is called ventilator-associated pneumonia (VAP). In this case, a distinction is made between early VAP, developing less than 7 days from the start of ALV, and late VAP, occurring when ALV lasts more than 7 days. The main difference between these two forms of ventilator-aspiration pneumonia is the etiological heterogeneity of these forms of nosocomial pneumonia (RG Wunderik).

The most common causes of early ventilator-aspiration pneumonia are pneumococci, Haemophilus influenzae, Staphylococcus aureus and anaerobic bacteria. In late VAP, drug-resistant strains of Enterobacteriaceae, Pseudomonas aeruginosa, Acinetobacner spp. and methicillin-resistant Staphylococcus aureus (MRSA) are of greater importance.

The spectrum of pathogens of hospital-acquired pneumonia largely depends on the profile of the hospital where the patient is staying, as well as on the nature of the pathology for which hospital treatment is carried out. Thus, pathogens of hospital pneumonia in patients with a urological profile are most often Escherichia coli, Proteus, enterococci, in hematological patients - Escherichia coli, Klebsiella, Pseudomonas aeruginosa and Staphylococcus aureus. In patients who have undergone surgery, nosocomial pneumonia is most 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 most often enterococci, Pseudomonas aeruginosa, Klebsiella.

"Atypical" pneumonias that develop in hospital conditions are most often caused by Legionella infection. The risk of developing the disease increases in patients who have been receiving glucocorticoid therapy or cytostatics for a long time, as well as when using autonomous water supply sources in the hospital. It should be remembered that mycoplasmas and chlamydia are very rarely the cause of hospital pneumonia.

In patients receiving long-term antibiotics or glucocorticoids, nosocomial pneumonia may be caused by fungi, such as Aspergillus spp.

The viral etiology of hospital-acquired pneumonia is associated with infection by influenza viruses A and B, as well as respiratory syncytial virus (RSV), although the probability of a "purely" viral lesion of the pulmonary parenchyma is questionable. As in the case of community-acquired pneumonia, viral infections in hospital patients are apparently a factor contributing to the suppression of elements of their own defense, and contribute to the development of a bacterial infection characteristic of nosocomial pneumonia.

It should be emphasized that the recommendations given for the approximate causative agent of nosocomial pneumonia are only of the most general and probabilistic nature. The spectrum of these pathogens and their sensitivity to antibacterial therapy may 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 pathogens of hospital-acquired (nosocomial) pneumonias depend on the clinical situation in which the pneumonia developed

Clinical situations	Most likely pathogens
Reparative pneumonia in patients with impaired consciousness, gastrointestinal diseases, 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 VAP	Pneumococcus. Haemophilus influenzae. Staphylococcus aureus. Anaerobic bacteria
Late VAP	Enterobacteriaceae. Pseudomonas aeruginosa. Acinetobacter spp. Staphylococcus aureus
Stay in a urological hospital	Escherichia coli. Proteus. Enterococci.
Hematological patients	Escherichia coli. Kpebsiella. Pseudomonas aeruginosa. Staphylococcus aureus
Postoperative period	Staphylococcus aureus. Escherichia coli. Proteus. Pseudomonas aeruginosa.
Associated chronic bronchopulmonary diseases	Enterococci. Pseudomonas aeruginosa. Kpebsiella
"Atypical" pneumonia in patients who have received glucocorticoids, cytostatics, etc. for a long time.	Legionella
Use of autonomous water supply sources and air conditioners in the hospital	Legionella
Patients who have received antibiotics or glucocorticoids for a long time	Fungi (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 states are:

1. Malignant neoplasms.
2. Organ or bone marrow transplantation.
3. Congenital or acquired humoral or cell-mediated immunodeficiency (multiple myelomas, acquired hypogammaglobulipemia, thymoma with hypogammaglobulipemia, 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 mellitus;
   • renal failure;
   • liver failure;
   • amyloidosis;
   • corticosteroid therapy;
   • berylliosis;
   • old age.

In various immunodeficiency states, including those associated with taking medications, all links of the human defense system that prevents the occurrence of lung disease are disrupted. This involves a change in the normal composition of the oral cavity microflora, disruption of the mucociliary transport of tracheobronchial secretion, damage to local non-specific defense mechanisms (reduced levels of complement and secretory IgA, alveolar macrophages), as well as specific (humoral and cell-mediated) defense mechanisms. This creates conditions for colonization of the lower respiratory tract by pathogenic and opportunistic microorganisms and the occurrence of inflammation of the lung parenchyma.

The most common pathogens that cause pneumonia in people with immunodeficiency conditions are:

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

Pneumonia caused by Pneumocystis carini is particularly lethal. In relatively young and middle-aged patients, up to 20-30% of pneumonias that develop against the background of immunodeficiency conditions are due to "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 remain pneumococci, Haemophilus influenzae and viruses.

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