What are the main causes of bacterial pneumonia. How is bacterial pneumonia classified. What are the key treatment approaches for bacterial pneumonia. How can bacterial pneumonia be prevented. What are the risk factors for developing bacterial pneumonia. How is bacterial pneumonia diagnosed. What are the complications of untreated bacterial pneumonia.

Understanding Bacterial Pneumonia: An Overview

Bacterial pneumonia is a serious respiratory infection that affects millions of people worldwide. This condition occurs when bacteria invade the lungs, causing inflammation and fluid buildup in the air sacs (alveoli). The result is impaired breathing and oxygen exchange, which can lead to severe complications if left untreated.

Pneumonia can be caused by various pathogens, but bacterial infections are among the most common culprits. Understanding the etiology, types, and treatment options for bacterial pneumonia is crucial for effective management and prevention of this potentially life-threatening condition.

Common Bacterial Pathogens Responsible for Pneumonia

Several bacterial species can cause pneumonia, with some being more prevalent than others. The most common bacterial pathogens include:

• Streptococcus pneumoniae (pneumococcus)
• Haemophilus influenzae
• Staphylococcus aureus
• Mycoplasma pneumoniae
• Legionella pneumophila
• Pseudomonas aeruginosa

Each of these bacteria has unique characteristics and virulence factors that contribute to their ability to cause pneumonia. For instance, Streptococcus pneumoniae produces a toxin called pneumolysin, which plays a crucial role in damaging lung tissue and promoting infection.

How do these bacteria cause pneumonia?

Bacterial pneumonia typically develops when pathogens enter the lower respiratory tract and multiply in the alveoli. This process triggers an inflammatory response, leading to the accumulation of fluid and cellular debris in the air sacs. The resulting obstruction impairs gas exchange, causing symptoms such as cough, shortness of breath, and fever.

Classification of Bacterial Pneumonia

Bacterial pneumonia can be classified based on various factors, including the setting in which it is acquired and the causative organism. Understanding these classifications is essential for appropriate diagnosis and treatment.

Community-Acquired Pneumonia (CAP)

CAP refers to pneumonia contracted outside of healthcare settings. It is the most common type of pneumonia and is often caused by Streptococcus pneumoniae, Haemophilus influenzae, or atypical pathogens like Mycoplasma pneumoniae.

Hospital-Acquired Pneumonia (HAP)

HAP develops in patients who have been hospitalized for at least 48 hours. This type of pneumonia is often caused by more resistant bacteria, such as Pseudomonas aeruginosa or methicillin-resistant Staphylococcus aureus (MRSA).

Ventilator-Associated Pneumonia (VAP)

VAP is a subtype of HAP that occurs in patients on mechanical ventilation. It is associated with higher mortality rates and is often caused by multidrug-resistant pathogens.

Healthcare-Associated Pneumonia (HCAP)

HCAP is a category that includes pneumonia in patients who have had recent contact with healthcare systems but are not currently hospitalized. However, recent studies have questioned the utility of this classification, as it may not accurately identify patients at risk for resistant pathogens.

Risk Factors for Developing Bacterial Pneumonia

Several factors can increase an individual’s susceptibility to bacterial pneumonia. Identifying these risk factors is crucial for prevention and early intervention.

• Age: Very young children and older adults are at higher risk
• Chronic medical conditions: Such as COPD, diabetes, or heart disease
• Weakened immune system: Due to HIV/AIDS, cancer treatments, or organ transplantation
• Smoking: Damages the lungs’ natural defense mechanisms
• Alcohol abuse: Impairs the immune system and increases aspiration risk
• Recent viral infections: Particularly influenza, which can predispose to secondary bacterial pneumonia
• Hospitalization: Especially in intensive care units or with mechanical ventilation

Why does influenza increase the risk of bacterial pneumonia?

Influenza virus infection can significantly increase the risk of secondary bacterial pneumonia. This synergistic relationship is due to several factors:

1. Damage to respiratory epithelium, facilitating bacterial adherence
2. Impairment of immune responses, particularly those mediated by neutrophils
3. Upregulation of bacterial adhesion molecules on host cells
4. Enhanced bacterial growth due to the availability of nutrients from damaged tissue

This interaction between influenza and bacteria, particularly Streptococcus pneumoniae, was a significant factor in the high mortality rates observed during the 1918 influenza pandemic.

Diagnosis of Bacterial Pneumonia

Accurate diagnosis of bacterial pneumonia is crucial for appropriate treatment. The diagnostic process typically involves a combination of clinical assessment, imaging studies, and laboratory tests.

Clinical Presentation

Patients with bacterial pneumonia often present with symptoms such as:

• Cough (often productive with purulent sputum)
• Fever and chills
• Shortness of breath
• Chest pain
• Fatigue and weakness

Physical Examination

On examination, healthcare providers may observe:

• Increased respiratory rate
• Decreased breath sounds over affected lung areas
• Crackles or rales on auscultation
• Dullness to percussion over areas of consolidation

Imaging Studies

Chest X-rays are the primary imaging modality for diagnosing pneumonia. They can reveal areas of consolidation, infiltrates, or pleural effusions. In some cases, CT scans may be necessary for more detailed evaluation.

Laboratory Tests

Several laboratory tests can aid in the diagnosis and management of bacterial pneumonia:

• Complete blood count (CBC): Often shows elevated white blood cell count
• Blood cultures: To identify bacteremia
• Sputum Gram stain and culture: To identify the causative organism
• Urinary antigen tests: For detection of Streptococcus pneumoniae or Legionella pneumophila
• Procalcitonin levels: Can help distinguish bacterial from viral infections

Treatment Approaches for Bacterial Pneumonia

The treatment of bacterial pneumonia primarily involves antibiotic therapy, supportive care, and management of complications. The choice of antibiotics depends on several factors, including the suspected pathogen, local antibiotic resistance patterns, and the patient’s risk factors.

Antibiotic Therapy

For community-acquired pneumonia, common empiric antibiotic regimens include:

• Macrolides (e.g., azithromycin)
• Fluoroquinolones (e.g., levofloxacin)
• Beta-lactams (e.g., amoxicillin)
• Combination therapy for more severe cases

For hospital-acquired or ventilator-associated pneumonia, broader-spectrum antibiotics are often necessary, such as:

• Antipseudomonal beta-lactams (e.g., piperacillin-tazobactam)
• Carbapenems (e.g., meropenem)
• Vancomycin or linezolid (for MRSA coverage)

Supportive Care

In addition to antibiotics, supportive measures are crucial for managing bacterial pneumonia:

• Oxygen therapy for hypoxemia
• Fluid management
• Pain control and antipyretics
• Respiratory therapy and chest physiotherapy

Management of Complications

Severe bacterial pneumonia can lead to complications such as:

• Respiratory failure requiring mechanical ventilation
• Sepsis and septic shock
• Pleural effusions or empyema
• Acute respiratory distress syndrome (ARDS)

These complications require prompt recognition and management, often in an intensive care setting.

Prevention Strategies for Bacterial Pneumonia

Preventing bacterial pneumonia involves a multifaceted approach that includes vaccination, lifestyle modifications, and infection control measures.

Vaccination

Vaccines play a crucial role in preventing bacterial pneumonia, particularly against Streptococcus pneumoniae. Two types of pneumococcal vaccines are available:

• Pneumococcal conjugate vaccine (PCV13)
• Pneumococcal polysaccharide vaccine (PPSV23)

Additionally, annual influenza vaccination is recommended to prevent viral infections that can predispose to bacterial pneumonia.

Lifestyle Modifications

Several lifestyle changes can reduce the risk of bacterial pneumonia:

• Smoking cessation
• Limiting alcohol consumption
• Maintaining good overall health and nutrition
• Regular exercise
• Adequate sleep and stress management

Infection Control Measures

In healthcare settings, strict adherence to infection control protocols is essential for preventing hospital-acquired pneumonia:

• Hand hygiene
• Proper use of personal protective equipment
• Environmental cleaning and disinfection
• Isolation precautions for patients with transmissible infections

Oral Decontamination in Ventilated Patients

For patients on mechanical ventilation, oral decontamination techniques have shown promise in reducing the incidence of ventilator-associated pneumonia. These may include:

• Chlorhexidine oral rinse
• Selective digestive decontamination
• Regular oral care and suctioning

Emerging Research and Future Directions

The field of bacterial pneumonia research is continuously evolving, with new insights into pathogenesis, diagnostics, and treatment strategies emerging regularly.

Novel Diagnostic Approaches

Researchers are exploring advanced diagnostic techniques to improve the speed and accuracy of pneumonia diagnosis:

• Molecular diagnostic platforms for rapid pathogen identification
• Biomarker panels for distinguishing bacterial from viral pneumonia
• Artificial intelligence algorithms for interpreting chest imaging

Innovative Treatment Strategies

Several new treatment approaches are under investigation:

• Inhaled antibiotics for ventilator-associated pneumonia
• Immunomodulatory therapies to enhance host defense
• Bacteriophage therapy for multidrug-resistant infections
• Targeted anti-virulence strategies

Antibiotic Stewardship

With the growing concern of antibiotic resistance, there is an increased focus on optimizing antibiotic use in pneumonia treatment:

• Shorter duration of antibiotic therapy when appropriate
• Procalcitonin-guided antibiotic discontinuation
• Implementation of rapid diagnostic tests to guide targeted therapy

As research in these areas continues, our understanding and management of bacterial pneumonia will undoubtedly improve, leading to better outcomes for patients affected by this serious respiratory infection.

Bacterial Pneumonia: Practice Essentials, Background, Pathophysiology

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Bacterial Pneumonia: Symptoms, Causes, and Treatment

What is bacterial pneumonia?

Pneumonia is a common lung infection where the lungs’ air sacks become inflamed. These sacs may also fill with fluid, pus, and cellular debris. It can be caused by viruses, fungi, or bacteria. This article is about pneumonia caused by bacteria.

Bacterial pneumonia may involve just one small section of your lung, or it may encompass your entire lung. Pneumonia can make it difficult for your body to get enough oxygen to your blood, which can cause cells to not work properly.

Bacterial pneumonia can be mild or serious. The severity of your pneumonia depends on:

• the strength of the bacteria
• how quickly you are diagnosed and treated
• your age
• overall health
• if you have other conditions or diseases

The most common symptoms of bacterial pneumonia are:

• a cough with thick yellow, green, or blood-tinged mucus
• stabbing chest pain that worsens when coughing or breathing
• sudden onset of chills severe enough to make you shake
• fever of 102-105°F or above (fever lower than 102°F in older persons)

Other symptoms that may follow include:

• headache
• muscle pain
• breathlessness or rapid breathing
• lethargy or severe fatigue
• moist, pale skin
• confusion, especially among older persons
• loss of appetite
• sweating

Older adults will share all the symptoms with younger adults, but are much more likely to experience confusion and dizziness. Older adults may also be less likely to have a fever.

Symptoms in children

Pneumonia can be particularly dangerous for infants, children, and toddlers. They may display similar symptoms to the ones above. In infants, difficulty breathing may show up as flaring nostrils or chest sinking when breathing. They may also exhibit blueish lips or nails, which indicates that they aren’t getting enough oxygen.

Emergency symptoms

Seek immediate medical attention if you are experiencing:

• blood in mucus
• trouble breathing
• high fever of 102.5°F of higher
• confusion
• rapid heartbeat
• skin with a bluish tone

Bacteria pneumonia is caused by bacteria that works its way into the lungs and then multiplies. It can occur on its own or develop after another illness, like a cold or the flu. People who have a higher risk for pneumonia may:

• have weakened immune systems (due to age, diseases, or malnutrition)
• have respiratory diseases
• be recovering from surgery

Doctors classify bacterial pneumonia based on whether it developed inside or outside a hospital.

Community-acquired pneumonia (CAP): This is the most common type of bacterial pneumonia. CAP occurs when you get an infection after exposure to bacterial agents outside of a healthcare setting. You can get CAP by breathing in respiratory droplets from coughs or sneezes, or by skin-to-skin contact.

Hospital-acquired pneumonia (HAP): HAP occurs within two to three days of exposure to germs in a medical setting, such as a hospital or doctor’s office. This is also called a “nosocomial infection.” This type of pneumonia is often more resistant to antibiotics and more is difficult to treat than CAP.

Types of bacteria

Streptococcus pneumonia is the leading cause of bacterial pneumonia. It can enter your lungs through inhalation or through your bloodstream. There is a vaccination for this type.

Haemophilus influenzae is the second most common cause of bacterial pneumonia. This bacterium may live in your upper respiratory tract. It doesn’t usually cause harm or illness unless you have a weakened immune system.

Other bacteria that can cause pneumonia include:

• Staphylococcusaureus
• Moraxellacatarrhalis
• Streptococcuspyogenes
• Neisseriameningitidis
• Klebsiellapneumoniae

Environmental and lifestyle factors

These include:

• smoking
• working in an environment with a lot of pollution
• living or working in a hospital setting or nursing facility

Medical risk factors

People who have these conditions may be at an increased risk for pneumonia:

• recent viral respiratory infection, such as the flu
• difficulty swallowing due to neurological conditions such as dementia or stroke
• chronic lung diseases
• weakened immune system due to illness or medications

Age groups

People over the age of 65 and children 2 and younger are also at a higher risk for developing pneumonia. Make an appointment with your doctor if you or someone you know has symptoms of pneumonia. Pneumonia for this group can be life-threatening.

The two most common causes of pneumonia are bacteria and viruses. The flu is one of the most common causes of viral pneumonia in adults, though post-flu complications can also cause bacterial pneumonia.

In bacterial pneumonia, there will likely be a much more visible presence of fluid in the lungs than viral pneumonia. Bacterial pneumonia is also more likely to enter the blood stream and infect other parts of the body.

To diagnose bacterial pneumonia, your doctor will:

• Listen for abnormal chest sounds that indicate a heavy secretion of mucus.
• Take a blood sample to determine if your white blood cell count is high, which usually indicates infection.
• Take a blood culture, which can help determine if the bacteria have spread to your bloodstream and also help identify the bacterium causing the infection.
• Take a sample of mucus, or a sputum culture, to identify the bacterium causing the infection.
• Order chest X-rays to confirm the presence and extent of the infection.

Most cases can be treated at home, with medications, to prevent complications from a hospital setting. A healthy person may recover within one to three weeks. Someone with a weakened immune system may take longer before they feel normal again.

Hospital care

Some cases of bacterial pneumonia will require hospitalization for treatment. Young children and the elderly are more likely to need to go to the hospital to receive intravenous antibiotics, medical care and respiratory therapy.

In the hospital, you’ll be given antibiotics to treat the specific type of bacteria causing your pneumonia. This will likely be given intravenously, along with fluids to prevent dehydration.

Complications

Without treatment, pneumonia may develop into:

• organ failure, due to bacterial infection
• difficulty breathing
• pleural effusion, buildup of fluid in the lungs
• lung abscess, cavity in the lung

Bacterial pneumonia itself is not contagious, but the infection that caused bacterial pneumonia is contagious. It can spread through coughs, sneezes, and contamination on objects. Practicing good hygiene can help prevent the spread of pneumonia or the risk of catching it.

The Centers for Disease Control and Prevention (CDC) also recommends a pneumonia vaccine for infants, young children, and adults age 65 and older.

Bacterial lung infections. Animal models

Keywords:

bacterial pneumonia

laboratory animals

rats

mice

rabbits

primates

Streptococcus pneumoniae

Klebsiella pneumoniae

Pseudomonas aeruginosa

Pneumonia is a leading cause of morbidity and mortality worldwide, especially among children and the elderly. Nosocomial pneumonia in a hospital setting is one of the most serious infectious complications often caused by opportunistic pathogens. There is an urgent need for better methods of treating and preventing pneumonia. Therefore, animal models have been developed to better understand the pathogenesis of the disease and to test new drugs and vaccines. This review summarizes data from scientific studies of animal modeled bacterial pneumonia, as well as the main causative agents of the disease, the route of administration of infectious agents, and the assessed indicators. The causative agents of bacterial pneumonia are various microorganisms, this review considers Streptococcus pneumoniae, Legionella pneumophila, Haemophilus influenzae, Neisseria meningitidis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Acinetobacter baumannii, Klebsiella pneumoniae.

The most popular microorganism used to model pneumonia is Streptococcus pneumoniae . According to the data given in scientific articles, mice, rats, rabbits, pigs and primates are used as a test system for modeling bacterial pneumonia. The most suitable animals for the study of bacterial pneumonia are mice. This type of animal is easy to handle, and a sufficient number of individuals can be used to evaluate the results. The main evaluated parameters of the pneumonia study are the results of clinical manifestations, survival rates, bacteremia, the number of bacteria in the lungs, pathological and histological characteristics, quantitative assessment of antibody titers, inflammation markers, etc. Depending on the purpose of the study, different methods of introducing the inoculum are used. To determine virulence, intravenous and intraperitoneal routes of administration are used, to study the effectiveness of new antibiotics – intratracheal, in the development of new vaccines against bacterial pneumonia, animals are injected with inoculum intramuscularly. The choice of animals depends on the purpose of the study, the tasks and the type of microorganism, the method of infection and the estimated parameters.

Introduction

Pneumonia is not a separate disease, but a group of specific infections, each of which has a different epidemiology, pathogenesis and clinical course [1].

Children and the elderly are at risk. Most people who have had pulmonary pneumonia are prone to complications associated with cognitive decline, depression, cardiovascular disease, and reduced life expectancy [2]. Despite the use of effective antibiotics and intensive care, pneumonia-related mortality has not significantly decreased from 1960s [3].

Worldwide, pneumonia is the leading cause of child mortality, especially among children under 5 years of age [4]. In children, bacterial pneumonia is most often caused by microorganisms such as Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). In the first place among the causative agents of pneumonia is Streptococcus pneumoniae, , while the second most important pathogen is Haemophilus influenzae type b (Hib) [5].

The increased risk in the elderly is likely due to impaired body defenses and existing comorbidities (heart failure, liver disease, and underlying lung disease) that increase the risk of aspiration pneumonia, which can occur due to dysphagia and gastroesophageal reflux disease [6] .

Among nosocomial diseases, pneumonia ranks first in terms of the number of deaths. Patients in the intensive care unit are at greater risk [7]. The main causative agents of nosocomial pneumonia during mechanical ventilation (ALV) were most often Pseudomonas aeruginosa, Staphylococcus aureus and Acinetobacter baumannii . However, recent data show that bacteria of the Enterobacteriaceae family, in particular Escherichia coli , are currently common causative agents of nosocomial pneumonia during mechanical ventilation [8].

At the moment, there is an urgent need in the world for more advanced methods of treatment and prevention of the disease, new knowledge about the pathogenesis of pneumonia is required. Pharmacological models using laboratory animals are needed to better understand the mechanisms underlying the emergence of resistant strains and to decipher host-pathogen interactions, especially when it comes to polymicrobial invasion, while exploring new treatments and the complications that pneumonia causes.

This review describes the most commonly used animal models in the study of bacterial pneumonia, summarizing the data from scientific studies of bacterial pneumonia modeled on rodents, rabbits, pigs and primates.

Bacterial strains

Streptococcus pneumoniae is a gram-positive bacterium, an extracellular, opportunistic microorganism that colonizes the surface of the human mucosa. About 27-65% of children and 10% of adults are carriers of S. pneumoniae [9]. The bacterium leads to the development of such diseases as pneumonia, local infections of the middle ear, purulent meningitis, and is able to actively penetrate into the bloodstream, causing bacteremia and sepsis [10].

Legionella pneumophila is a gram-negative intracellular bacterium that is a common pathogen that causes hospital-acquired and community-acquired pneumonia. It is one of the most common causative agents of severe pneumonia, with a mortality rate of 10% in Europe and North America [11]. Only one case of 9 transmission has been reported so far0005 L. pneumophila from person to person [12], the vast majority of cases are associated with infection by airborne droplets due to contaminated water. Contaminated water is distributed as a water-air aerosol by air conditioning systems [13].

Haemophilus influenza is a gram-negative coccobacillus, encapsulated and non-encapsulated strains occur (untypable H. influenzae , NTHi). NTHi is a dangerous pathogen that causes otitis media, sinusitis, conjunctivitis, and pneumonia in children and respiratory infections in adults, mainly in patients with chronic obstructive pulmonary disease [14]. Encapsulated strains are divided into 6 serotypes (Hia-f). The Hib serotype is the main causative agent of bacterial meningitis in children worldwide [15].

Neisseria meningitidis is a Gram-negative bacterium that asymptomatically colonizes the nasopharynx in 4–20% of people [16]. The main route of transmission of the pathogen is airborne from person to person. Meningococci can cause diseases dangerous to humans, such as meningococcal septicemia, meningitis, or pneumonia [17].

Escherichia coli — Gram-negative, non-sporing, facultative anaerobic bacterium of the family Enterobacteriaceae [18]. Despite the fact that a huge amount of data has been accumulated on the pathogenicity of E. Coli , which causes intestinal, urological, central nervous system and blood flow diseases, there is little evidence of infections in the lungs [19].

Pseudomonas aeruginosa – Gram-negative obligate aerobe. It is an opportunistic pathogen that causes disease in immunocompromised people. Most often becomes the causative agent of nosocomial infections. P. aeruginosa provokes diseases of various etiologies, often affecting the respiratory system and urinary tract [20].

Staphylococcus aureus is a Gram-positive opportunistic pathogen that causes a wide range of diseases. Approximately 30% of people worldwide carry S. aureus. It is a frequent causative agent of nosocomial infections [21].

Acinetobacter baumannii – Gram-negative coccobacillus. Causes mostly nosocomial infections. A. baumannii is the main causative agent of ventilator-associated nosocomial pneumonia [22].

Klebsiella pneumonia is a gram-negative, encapsulated, immobile bacterium that lives in the environment, including soil and surface water [23]. K. pneumoniae can cause serious infections in immunocompromised people such as pneumonia, bacteremia, or meningitis [24].

Animal models of pneumonia

The pneumonia model can be replicated in a variety of animal species. The choice of animal species depends on the objectives of the study. Non-mammals (insects and fish) are the least expensive and ethically most attractive. The use of such models gives limited results, but can be useful for obtaining information about the innate immune responses of the body and the virulent properties of pathogenic microorganisms that cause bacterial infections of the lungs [25].

You can also find studies on pigs and dogs. The most preferred model in translational studies of the lungs are small animals (eg, rodents). Such models ideally comply with the 3R principles; their small size and high reproduction rate make them the most practical and accessible for laboratory research [26].

Mouse models

Mouse models are often used in the study of pneumococcal pneumonia. Since the main research is carried out on mice, there is a huge amount of scientific work related to the study of the mouse body and immunity in general. Mice are most commonly used to evaluate antibiotic efficacy, pharmacokinetics, disease pathogenesis, virulence factors, and vaccine testing [27].

Mouse models of pneumonia allow the analysis of various parameters, including animal survival after infection, the presence of bacteria in the lungs and blood, levels of inflammation, and lung tissue histology. In addition, they are used in the quantitative assessment of antibody and antimicrobial titers, in pharmacokinetic studies of vaccines and drugs [28]. In the study of pneumonia, mice are kept in an individually ventilated system to protect personnel and the environment from infectious agents [29].

In both humans and mice, pneumococcal infection is the result of a complex interaction between bacterial and host factors that strongly influences the severity and location of the disease. Different strains of mice respond differently to pneumococcal stress in terms of timing, severity, and disease outcome, and this may not always translate to humans.

Rat models

Rat models are rarely used compared to mice for modeling bacterial infections of the lungs. Larger organ sizes compared to mice allow more biological material to be collected, but experimental groups are usually smaller, which can lead to significant statistical error. Induction of pulmonary pneumonia is carried out with the introduction of an infectious agent by intravenous, intrabronchial or intrapulmonary route. Research design is usually based on the study of survival of animals, observation of the overall clinical picture, histological examination of the lungs, determination of the number of bacteria in the lungs and blood. Rats are mainly used in studies to study the features of the course of pneumonia that occurs in patients with concomitant diseases [30]. You can also find scientific works where models of experimental pneumonia in rats are used to study the virulence of various pneumococcal serotypes [31] and evaluate the efficacy and safety of anti-pneumococcal vaccination [32].

Rabbit models

Rabbit models of pneumococcal pneumonia are suitable for studying the pathogenesis, survival, disease progression, and pharmacokinetic and pharmacodynamic characteristics of novel therapeutics and immunizations [33]. Rabbits are also generally useful in assessing different pneumococcal serotypes and resistance phenotypes in strains [34]. Rabbit models are also suitable for studying sepsis. Injected intraperitoneally pneumococci allow researchers to assess clinical parameters during disease progression [35].

Pig models

Pigs are similar to humans in terms of anatomy, genetics and physiology. Animals are omnivorous and have an adaptive and innate immune system that is 80% similar to the human one [36]. Compared to rodents and smaller animals, porcine models, due to their size and similar anatomy to humans, are used for a variety of surgical and non-surgical procedures [37]. Experiments on pigs have greater prognostic and therapeutic value than studies conducted on rodents [38]. Pig models are most suitable for assessing ventilator-associated pneumonia, as animals must be in the supine position (to prevent atelectasis) [39].

Primate models

The most attractive models are primates, whose immunity and physiology are similar to those of humans and are generally susceptible to human pathogens. However, the use of primates in research raises serious ethical issues [40]. Primates are not natural carriers of pneumococci, and there are no studies on the isolation of pneumococci from the nasopharynx in primates. However, there is evidence of experimental infection of primates with the human strain S. pneumoniae , as a result, about 100% of the animals had signs of colonization after 2 weeks and about 60% of the animals after 7 weeks after infection, these data indicate that primates are an excellent human-like model for studying carriage [41]. Primates infected with S. pneumoniae, develop similar symptoms to those seen in humans with a lower respiratory tract infection characterized by fever, bacteremia, cough, and labored breathing [42]. Primates are suitable for research related to the study of pathogenesis. Studies of lung infections in baboons have confirmed that increasing doses of pneumococcal inoculation (serotype 19A-7) elicit a host response ranging from mild illness (106 cfu) to severe pneumonia (109 cfu). Cytokine levels in bronchoalveolar lavage confirmed severe pneumonia [43]. Another group of researchers showed that a baboon infected with S. pneumoniae (serotype 4) 109 CFU developed symptoms of bacterial pneumonia 4 days after infection. Clinical findings were similar to those that developed in humans and included cough, tachypnea, dyspnea, tachycardia, and fever. All animals developed leukocytosis and bacteremia 24 hours after infection. The severe inflammatory response after infection was reflected in an increase in serum cytokines, including interleukins (IL) 1Ra, IL-6 and IL-8. Ultrasound of the lungs revealed lobes of the lungs affected by pneumonia, which was confirmed by pathomorphological examination. The severity of lung pathology had a high degree of correlation with the severity of the disease [44].

Pneumonia Model Types

One Punch Acute Pneumonia Model

This pneumonia model is considered simple because of the method of introducing bacterial inoculum into the lungs. Intratracheal instillation is the most commonly used method for investigating pneumonia and involves injecting a bacterial suspension directly into the trachea or lungs [45]. This method provides the most precise control over the set dose. However, in this method, one has to resort to surgical opening of the trachea, which entails subsequent suturing of the incision, which provokes an inflammatory reaction in the organ, which can have a significant impact on the final result. On the other hand, endotracheal administration of bacteria requires intubation of the animal to facilitate instillation of the bacterial solution into the lungs and is as accurate as the intratracheal instillation method [46]. Less invasive methods are intranasal administration, in which a fixed bacterial dose is injected into the nostrils of animals [47], or aerosol administration, which is used for aggressive animals [48]. However, the exact dose reaching the lower respiratory tract in both methods cannot be calculated, and animals often develop upper respiratory tract infections [47] or infections other than pneumonia [48]. In the aerosol method, to control the established dose, it is required immediately after aerosolization to subject several animals to euthanasia for quantitative counting of bacteria [48].

Mechanical ventilation as a model of pneumonia

Mechanical ventilation is an important component in the pathogenesis of pneumonia. Ventilation has been shown to develop a sterile inflammatory response in the lung that causes various tissue damage such as lung overstretching, barotrauma and overvolume trauma, air leakage due to airspace wall breach, pulmonary edema, and atelectasis (reopening and closure of the alveoli) [49].

Two main methods have been used to create animal models of ventilation. In the first method, the bacterial suspension is injected into the lungs before mechanical ventilation [50], in the second, the bacterial suspension is injected after ventilation, which mimics a more natural evolution of the disease [51]. However, when using the second method, the results show an increased bacterial load on the lungs, a more severe course of the disease and a high mortality compared with the first method [51].

Experimentally induced tracheal stenosis along with prolonged mechanical ventilation (up to 4 days) has been shown to cause spontaneous development of pneumonia with endogenous microbiota in piglets, and opportunistic pathogens of human pneumonia, species such as Pseudomonas and Klebsiella [39].

Agar (chronic) pneumonia model

This model was originally developed in rats and is used in the field of cystic fibrosis [52]. To form a biofilm, agar or algae alginate granules are used as extracellular polymeric substances, into which bacteria are loaded, mixed with mineral oil and sorbitan monooleate emulsifier to increase the uniformity of the granules. For control groups of animals, sterile pellets are prepared using phosphate-buffered saline or saline, however, sterile pellets can themselves induce an inflammatory response leading to increased cellular infiltrates in the lungs and increased release of cytokines, which can significantly affect the results of the study [53] .

Interestingly, although bacteria can migrate from agarose beads in vivo, bacterial growth is slow and limited to beads, similar to the process observed in bacteria living in biofilms [54]. In addition, bacterial clearance is impaired and animals are less likely to develop acute sepsis. The agar model is able to better model the chronic lung infection seen in humans in terms of histopathological features, elevated lung neutrophil levels, and fluid accumulation of cytokines [55].

Conclusions and conclusions

Most often, researchers model pneumonia in mice. The main parameters of the studies to be assessed are: collection of data on pathogenesis, survival, determination of the number of bacteria in the lungs and blood, pathological and histological characteristics, quantitative assessment of antibody titers. Also on mice, the virulence of bacterial strains is being studied, the effectiveness of new antibiotics and the mechanisms of body defense are being studied. Methods of introducing the inoculum depend on the objectives of the study, for example, to assess virulence, an intravenous route of administration is used. When studying the effectiveness of new antibiotics, the bacterial inoculum is administered intratracheally. Rats are mainly used in research to study the course of pneumonia, the virulence of various pneumococcal serotypes, and to evaluate the efficacy and safety of pneumococcal vaccination. The bacterial pneumonia model in rabbits is suitable for determining clinical parameters during disease progression and drug efficacy using the intrabronchial and intraperitoneal routes of inoculum administration. Experiments in pigs are of great prognostic and therapeutic value, so pig models are used in the development of therapies aimed at the treatment of pneumococcal pneumonia and vaccines. Primate models are suitable for studies related to the assessment of the severity of the disease. We tried to systematize all of the above in a table, which can allow the researcher to navigate through a variety of models and choose the design of the study that meets the objectives.

Pneumococcal disease in humans is diverse and multifaceted, and no animal model can fully mimic human disease. Nevertheless, despite the limitations, animal experiments remain undoubtedly a valuable tool for elucidating the pathogenetic mechanisms of the disease. This review provides insight into the development and application of various animal models used to mimic and study pneumonia. All animal models are useful tools for elucidating aspects of disease pathogenesis and testing the efficacy of antibiotics and other treatments. The main methods of infection are described in this review. The use of mice as models is convenient from an economic point of view, they are easy to handle, which allows screening drugs and vaccines with high statistical power. Larger animals have the advantage of increased ease of performing surgical procedures, but they are more expensive and the results may not be statistically significant due to the use of smaller groups.

The development of pneumococcal disease depends on both bacterial factors (eg, capsular serotype and other determinants of virulence) and host factors (eg, genetic background, immune response, age, sex). Before embarking on the study of pneumococcal infection in vivo, one should carefully consider the choice of not only animals, but also bacterial strains.

Acknowledgments

The work was done without sponsorship.

Author contributions

L.R. Khaibunasova – collection of data from literary sources, collection and analysis of data, writing and editing the text of the article

M.N. Makarova – concept and design of the study, editing the text of the article, scientific advice and approval of the final version of the article for publication

К.Е. Borovkova – editing the text of the article, scientific consulting

Yu.V. Salmova – drafting the text of the article

Bacterial pneumonia of dogs and cats

Description and causes

Pneumonia – inflammation of the lung tissue. Bacterial pneumonia in dogs and cats is characterized by inflammation of the lower respiratory tract secondary to bacterial infection. Bacteria can colonize the airways, alveoli, or interstitium. A bacterial infection limited to the airways and peribronchial tissues is called bacterial bronchitis. With the involvement of both the respiratory tract and the interstitium of the lungs, the disease is referred to as bacterial pneumonia or bronchopneumonia. Interstitial pneumonia – inflammation of the interstitium of the lungs (rarely noted), lobar pneumonia – inflammation limited to any lobe of the lungs.

Bacterial pneumonia in dogs and cats develops when the number of opportunistic pathogenic bacteria exceeds the protective capacity of the animal’s body, or when highly pathogenic bacteria enter the lungs. Bacterial pneumonia also develops in case of insufficiency of the body’s defense systems, impaired immune response or inhalation (inhalation) of foreign bodies and caustic substances. Bacterial pneumonia in animals releases a large variety of bacterial pathogens, including Bordetella bronchiseptica, Streptococcus spp., Staphylococcus spp., Escherichia coli, Pasteurella spp., Klebsiella spp., Proteus spp., and Pseudomonas spp. Anaerobic organisms may be part of a mixed infection, especially in animals with aspiration pneumonia or lung lobe consolidation. In dogs and cats, Mycoplasma spp. is also isolated, but its exact role in the pathogenesis of pneumonia has not been determined.

Primary pneumonia is caused by exposure to a pathogen, is extremely rare in dogs and cats, has been described in puppies, and is most commonly caused by B. bronchiseptica (about half of cases). Exposure to primary respiratory pathogens ( Bordetella or Mycoplasma ) can cause lung infections and life-threatening pneumonia in puppies and kittens. In adult animals, bacterial pneumonia almost always develops against the background of some predisposing factors.

The following predisposing factors can be distinguished in the development of bacterial pneumonia in adult animals:

• Aspiration of food (eg cleft palate, megaesophagus and other conditions predisposing to the development of aspiration pneumonia).
• Reduced lung clearance from normal debris (eg chronic bronchitis, bronchiectasis, primary ciliary dyskinesia).
• Immunosuppression (drugs, systemic diseases).
• Other infectious diseases (canine influenza, canine distemper, feline immunodeficiency virus infection, feline leukemia virus infection).
• Foreign body inhalation.
• Prolonged lying down (atelectasis, hypostatic stasis).
• Neoplasia of the lungs and parasitic and fungal infections of the lungs (rarely reported).

The main routes of bacterial penetration into lung tissues are: inhalation (most often), hematogenous drift (various septic conditions) and direct penetration (wounds, foreign body, iatrogenic trauma, etc.). With the penetration of bacteria through the respiratory tract, the cranial lobes of the lungs are more often affected, with hematogenous drift, a diffuse lesion of the parenchyma often develops.

After the penetration of bacteria, the exudative phase first develops – vasodilation and serous exudation of a fluid with a high content of protein into the interstitium of the lungs and the perialveolar space occurs. This is followed by the second phase – the migration of leukocytes, infiltration of tissues, their restructuring, impaired blood supply up to ischemia and necrosis, as well as obstruction of the alveoli. As a result of the above processes, there is a significant violation of blood oxygenation with oxygen, in severe cases, hypoxemia develops, death occurs from a lack of oxygen and sepsis.

Clinical signs

Pneumonia can develop at any age of the animal, puppies and kittens are more likely to suffer from primary pneumonia (see above), young hunting or sporting dogs are more likely to develop pneumonia when inhaling foreign bodies, middle-aged and older animals – pneumonia is more often observed against the background of immunosuppression and aspiration. Due to the fact that bacterial pneumonia in adult animals is often secondary, the age of seeking help in a veterinary clinic largely depends on the primary disease.

Reasons for seeking help may be signs of respiratory dysfunction, signs of systemic illness, or both. Respiratory signs in dogs may include cough (often mild and productive), bilateral purulent nasal discharge, exercise intolerance, and respiratory distress. In cats with pneumonia, coughing is extremely rare. Dogs and cats may show systemic signs such as lethargy, depression, fever, and weight loss. When contacting the owner to the veterinary clinic, it is important to carefully ascertain the signs of possible predisposing diseases (cough, regurgitation, vomiting, etc.).

On physical examination, fever is noted in only half of the cases. When asculting dogs and cats with bacterial pneumonia, various respiratory sounds can be identified.

Diagnosis

The diagnosis of feline and canine bacterial pneumonia is based on the sum of the findings: changes in the complete blood count, radiographic changes and the results of the analysis of the tracheal lavage specimen (cytology, bacterial culture).

Changes in the complete blood count are not always detected, about 60% of patients with bacterial pneumonia show neutrophilic leukocytosis with a shift to the left, neutropenia with a left shift is sometimes noted.

Abnormal radiographic pattern varies with underlying disease. Usually, with bacterial pneumonia, an alveolar pattern is noted, signs of consolidation in the affected lobes of the lungs are likely. Often there is a pronounced discharge of the bronchi and interstitium, in the presence of a foreign body, its detection is likely. Only the bronchial pattern can be presented in animals with a primary bronchial infection. On radiographic examination, attention is also paid to possible primary diseases (ex. megaesophagus).

Wash specimens are evaluated cytologically and microbiologically (culture ± PCR), tracheal wash results are usually sufficient to make a diagnosis.

In adult animals, in addition to the diagnosis of bacterial pneumonia as such, a thorough search for underlying diseases is carried out.

Treatment

Treatment of bacterial bronchopneumonia consists of antibiotic therapy and supportive care. The sensitivity of microorganisms in bacterial pneumonia of cats and dogs is difficult to predict, so the administration of drugs is best done on the basis of a culture study. The initial selection of antibiotics is based on the severity of the condition and the results of a cytological study (bacterial morphology, gram stain).

In animals with mild signs, amoxiclav, cephalexin, and sulfonamides may be given until culture results are available. Fluoroquinolones are reserved for animals with resistant gram-negative microflora. Kittens with suspected Bordetella infection should receive amoxiclav, doxycycline, or fluoroquinolones. In animals with severe systemic signs of bacterial pneumonia, treatment begins with intravenous antibiotic therapy, possibly broad-spectrum drugs (ex. meropenem) or a combination of ampicillin with sulbactam and fluoroquinolones. Cancellation of antibacterial drugs for bacterial pneumonia is carried out no earlier than a week after the resolution of clinical signs.

Hydration of the respiratory tract in bacterial pneumonia is carried out in order to reduce the viscosity of the secret and improve its removal. If general dehydration is suspected, it is corrected with appropriate infusion therapy, air humidification is also carried out.