Bacterial pneumonia overview

# Overview
Bacterial pneumonia is an infection of the lungs by bacteria.
Streptococcus pneumoniae is the most common bacterial cause of pneumonia in all age groups except newborn infants. Streptococcus pneumoniae is a gram-positive bacteria which often lives in the throat of people who do not have pneumonia. Another important gram-positive cause of pneumonia is Staphylococcus aureus.
Gram-negative bacteria are seen less frequently; Haemophilus influenzae, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa and Moraxella catarrhalis are the most common. These bacteria often live in the gut and enter the lungs when contents of the gut (such as vomit) are inhaled.
The "atypical" bacteria are Coxiella burnetti, Chlamydophila pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila. They are "atypical" because they commonly affect teenagers and young adults, are less severe, and require different antibiotics than typical bacteria such as Streptococcus pneumoniae.

# Historical Perspective
Since the 20th century, bacterial pneumonia has been identified as a formidable infectious disease and was largely held responsible for deaths during the Influenza Pandemic of 1918. It was often referred to as captain of the men of death during this timeframe. The most common causative bacterial strain, Streptococcus pneumoniae, was first isolated in 1880 by Louis Pasteur and George Sternberg. In general, the disease has varying outcomes. The discovery of modern-day antibiotics have entirely changed how treatment is approached but, before them, blood letting was a common method of treatment as was described by William Osler in his textbook, The Principles and Practice of Medicine, written in 1892.

# Pathophysiology
Causative bacteria can be inhaled from the surrounding environment but organisms are also commonly found within the upper respiratory tract of many individuals from where they can be directed towards the alveoli. Once in the bloodstream of the lungs, the immune system triggers a response by mobilizing white blood cells into the affected area. Neutrophils and cytokine help in ridding the body of infectious organisms but also result in systemic symptoms such as fever, chills, and fatigue. If bacteria enters the systemic blood stream, sepsis may ensue and can involve other organs including the brain, kidney, and heart.

# Causes
Bacterial pneumonia may be due to a variety of underlying causes. The microorganisms responsible are divided into typical and atypical. Typical bacteria often result in a classic pneumonia whereas atypical bacteria lead to a much milder presentation often referred to as "walking pneumonia". These patients appear near normal but have extensive findings on chest x-ray. Apart from typical and atypical classifications, bacterial pneumonia can be categorized based on demographics by differentiating into neonates (65 years). Underlying characteristics may also help determine the specific cause. These include alcoholics, those at risk of aspiration, cystic fibrosis, intravenous drug users, and those that are immunocompromised or at risk of nosocomial pneumonia.

# Differential Diagnosis
Symptoms related to pulmonary diseases may overlap and so, it is important to differentiate bacterial causes from other diseases. This can be done with the assistance of laboratory examinations such as chest x-ray findings and throat culture and sensitivity bacterial cultures. Some pulmonary diseases that must be differentiated include bronchitis, bronchiolitis obliterans, empyema, lung abscess and pulmonary carcinomas. Other diseases to be ruled out include bacterial endocarditis, especially in patients with an underlying history of intravenous drug abuse, GERD, and sinusitis.

# Epidemiology and Demographics
Pneumonia is a condition seen in the vast majority of regions, but pneumonia related deaths have been disproportionally higher in low and middle income nations, including the sub-Saharan African and South Asian regions. Pneumonia case rates are primarily affected by factors relating to seasonal variations. Studies show that a majority of Streptococcus pneumoniae cases were most prevalent during the winter, whereas far fewer cases presented in the summertime in comparison. Specifications regarding geography are of considerable importance in regards to fungal pneumonia.

# Risk Factors
Bacterial pneumonia can affect individuals of any age, gender, or race and has minimal significance in relation to family history. Individuals with underlying immunoglobulin defects have a significantly higher likelihood of infection. Bacterial pneumonia tends to affect men more often than women, and is more common in African Americans compared to Caucasians. Socioeconomic status is an important contributing factors and may explain the increased prevalence rate in low to middle-income nations. Pneumonia may also be affected by the use of medications such as proton pump inhibitors and ACE inhibitors. Immunocompromised patients requiring in-hospital treatment may develop nosocomial pneumonia but this can also present in seemingly healthy patients with prolonged durations of stay. A majority of nosocomial pneumonia will developed within 48 hours but some may present later on. The most common pathogens causing nosocomial pneumonia include Gram-positive cocci (e.g, Staphylococcus aureus, which includes methicillin-resistant S. aureus, and Streptococcus species) and Aerobic gram-negative bacilli (e.g. Pseudomonas Aeruginosa, Escherichia Coli, Klebsiella Pneumoniae, Enterobacter species, Acinetobacter species).

# Natural History, Complications and Prognosis
Bacterial pneumonia is often transmitted via oral secretions and undergoes a variety of stages including congestion, hepatization and resolution. Symptoms may vary amongst individuals but commonly include abrupt fever, chills, rigors, and cough. Infectious organisms are commonly transmitted via oral secretions containing droplets and the incubation period is generally short and ranges from 1-3 days. Germs can also be transferred by touching unclean surfaces with hands that may later come in contact with the eyes, nostrils, or mouth allowing bacteria to enter the body. There are a multitude of pulmonary and extra-pulmonary complications that contribute to determining the outcome of recovery. Common complications include acute respiratory distress, pleural effusion, sepsis and shock. Prognosis varies according to age and underlying conditions such as bronchiectasis, abscesses, and neoplasms. The CURB-65 scale takes into account confusion, BUN, respiratory rate, blood pressure, and age. A score of 3 or more requires a prolonged hospital duration and has a higher risk of mortality. This criteria has proven to be a useful tool in predicting the outcome of disease.

# History and Symptoms
Detailed information pertaining to a patient's history may greatly assist in determining the underlying cause of pneumonia. Some common symptoms seen in a majority of patients include cough, fever, and a pleuritic chest pain. Specific signs and symptoms, such as diarrhea, hyponatremia, and anemia may increase the suspiciousness of specific causative organisms. Details pertaining to cough may assist in identifying the underlying cause. It is also important to inquire about risk factors and comorbidities as they can provide important information regarding the bacterial infection.

# Physical Examination
Although physical examination may differ amongst patients, many presents with similar findings. Variations may be due to the severity and extent of disease, the causative bacteria, as well as the presence or absence of any complications. Much of the systemic examination may appearently be normal with the exception of some in cases of specific infections. All patients present with significant pulmonary findings and changes in vital signs. With the development of complications such as sepsis, neurological findings such as confusion can also develop.

# Laboratory Findings
Patients infected with bacterial pneumonia present with a high leukocyte count as well as elevated inflammatory biomarkers. including ESR and C-RP. Red blood cell and platelet count can also be affected presenting as anemia and thrombocytopenia. Arterial blood gasses will often show changes in pH leading to a respiratory acidosis. Other tests routinely done include electrolyte assessment, renal function tests, pulse oximetry, gram staining and sputum samples. Blood cultures and PCR tests are sensitive tests that can provide a definitive diagnosis and aid in the selection of antibiotics.

# Chest X-Ray
Imaging with chest x-rays remains the gold standard of diagnosis when supported with other laboratory findings. Although x-ray findings provide reliable findings, it is recommended that the entire clinical picture along with supporting laboratory findings be taken into consideration before treatment is started. Patterns commonly found on imaging include lobar or focal nonsegmental pneumonia, lobular or multifocal bronchopneumonia, and diffuse or interstitial (atypical) pneumonia. Radiological findings may take 6-12 weeks to clear.

# CT Scan
Although CT scans are not a primary modality of testing for bacterial pneumonia, they may be utilized in complex cases where the underlying cause is unknown and or when empiric antibiotic use yields no symptomatic relief in the patient. CT scans may be very informative and assist in differentiating infectious and noninfectious pneumonia. Similar to chest x-rays, CT findings can also be described according to the type of pneumonia including lobar or focal nonsegmental pneumonia, lobular or multifocal bronchopneumonia, and diffuse or interstitial (atypical) pneumonia.

# Other Imaging Findings
Bacterial pneumonia is primarily diagnosed with chest x-ray and, in complex cases, CT scans. Other diagnostic tests are available but are frequently not utilized compared to the aforementioned two modalities. These include ultrasonography, chest MRI, and biopsy of the affected lung. Ultrasonography can help identify the pleural fluid including its amount, viscosity and loculations as well as pulmonary septations. Lung biopsy is a reliable but invasive method of diagnosing pneumonia so they are often reserved for cases in which the underlying cause can not be identified. Bronchopsy may also be utilized in diagnosing pneumonia, especially in non-immunocompromised and mechanically ventilated patients.

# Other Diagnostic Studies
Diagnostic studies apart from routine laboratory test helpful in diagnosing bacterial pneumonia include bronchoalveolar lavage and urine antigen, which is helpful in the diagnosis of legionella. Bronchoalveolar lavage provides accurate results but obtaining a sample may present some difficulties therefore it is done in patients who are intubated and can provide a sample therefore, it is usually reserved for patients that are on mechanical ventilation.

# Medical Treatment
Antibiotics are the treatment of choice for bacterial pneumonia. The antibiotic choice depends on the nature of the pneumonia, the microorganisms most commonly causing pneumonia in the geographical region, and the immune status and underlying health of the individual. In the United Kingdom, amoxicillin is used as first-line therapy in the vast majority of patients who acquire pneumonia in the community, sometimes with added clarithromycin. In North America, where the "atypical" forms of community-acquired pneumonia are becoming more common, clarithromycin, azithromycin, or fluoroquinolones as single therapy, have displaced the amoxicillin as first-line therapy. Local patterns of antibiotic-resistance should always be considered when initiating pharmacotherapy. In hospitalized individuals or those with immune deficiencies, local guidelines determine the selection of antibiotics. These antibiotics are typically given through an intravenous line.

# Primary Prevention
The goal of Primary prevention is to prevent the occurrence of an illness or a disease before it ever occurs. In the case of bacterial pneumonia, primary prevention can be achieved by the administration of vaccination as well as attempting to control underlying comorbidities that may predispose an individual to pneumonia. Pneumococcus Vaccines include the PCV13 (Conjugate vaccine) and the PPSV23 (Polysaccharide vaccine). The PCV13 vaccine is indicated in infants and childhood routine vaccines (children younger than 2 years) as well as all adults aged 65 years or older whereas the PPSV23 vaccine is recommended for all adults over the age of 65 as well as adults aged 19-64 with certain medical conditions including chronic heart, lung, or liver diseases, diabetes, smokers and alcoholics. The killed intramuscular influenza vaccine should be given annually. Strict blood glucose and blood pressure control can help in preventing disease prevalence. When certain conditions are present, such as in children that have asplenia, it may also be helpful to treat with prophylactic antibiotics. Educating the public as well as identifying those most susceptible to infection can help reduce the risk of pneumonia.

# Secondary Prevention
Secondary prevention occurs once the disease has occurred and aims to prevent progression and complication development. Protective measurements include controlling the tidal volume, plateau pressure, PEEP, and FiO2. Measures taken to reduce the risk of aspiration such as elevation of the head end of bed and maintaining oral hygiene also help preventing aspiration pneumonia. Common complications that can develop due to bacterial pneumonia include acute respiratory distress, pleural effusion, heart failure due to pneumonia, sepsis and septic shock.

# Cost-effectiveness of Therapy
The use of antibiotics and corticosteroids had proven to be a cost-effective strategy in treating community-acquired pneumonia. Together, they resulted in savings of $142,795 per death averted. In severe cases of community-acquired pneumonia, the combination of antibiotics and corticosteroids yielded savings of $70,587 and had an 82.6% chance of being cost-effective. The cost effectiveness of ceftolozane/tazobactam versus meropenem was also analyzed and resulted in significant savings in early treatment.

# Future or Investigational Therapies
Due to increasing antibiotic resistance and emerging organisms, it is important that the approaches to diagnosing pneumonia continue to advance. Currently, the host factors predisposing one to pneumonia are being studied in detail. Host directed therapeutic approaches against pneumonia infection may prove to be very advantageous. These include host susceptibility, host response to pneumonia and host consequences. Host susceptibility takes into consideration the age, genetic factors, exposures, acute and chronic diseases. The genetic factors being focused on right now include variants in the NGR1, PAK6, MATN1 and FER genes. The host response take into account Immune resistance and repair mechanisms. Host consequences refer to the development of complications and exacerbation of existing chronic conditions.