"S. pneumoniae" is responsible for 15–50% of all episodes of community acquired pneumonia, 30–50% of all cases of acute otitis media, and a significant proportion of bloodstream infections and bacterial meningitis.

As estimated by WHO in 2005 it killed about 1.6 million children every year worldwide with 0.7–1 million of them being under the age of five. The majority of these deaths were in developing countries.

"S. pneumoniae" is normally found in the nose and throat of 5–10% of healthy adults and 20–40% of healthy children. It can be found in higher amounts in certain environments, especially those where people are spending a great deal of time in close proximity to each other (day-care centers, military barracks). It attaches to nasopharyngeal cells through interaction of bacterial surface adhesins. This normal colonization can become infectious if the organisms are carried into areas such as the Eustachian tube or nasal sinuses where it can cause otitis media and sinusitis, respectively. Pneumonia occurs if the organisms are inhaled into the lungs and not cleared (again, viral infection, or smoking-induced ciliary paralysis might be contributing factors). The organism's polysaccharide capsule makes it resistant to phagocytosis and if there is no pre-existing anticapsular antibody alveolar macrophages cannot adequately kill the pneumococci. The organism spreads to the blood stream (where it can cause bacteremia) and is carried to the meninges, joint spaces, bones, and peritoneal cavity, and may result in meningitis, brain abscess, septic arthritis, or osteomyelitis.

"S. pneumoniae" has several virulence factors, including the polysaccharide capsule mentioned earlier, that help it evade a host's immune system. It has pneumococcal surface proteins that inhibit complement-mediated opsonization, and it secretes IgA1 protease that will destroy secretory IgA produced by the body and mediates its attachment to respiratory mucosa.

The risk of pneumococcal infection is much increased in persons with impaired IgG synthesis, impaired phagocytosis, or defective clearance of pneumococci. In particular, the absence of a functional spleen, through congenital asplenia, surgical removal of the spleen, or sickle-cell disease predisposes one to a more severe course of infection (overwhelming post-splenectomy infection) and prevention measures are indicated (see asplenia).

People with a compromised immune system, such as those living with HIV, are also at higher risk of pneumococcal disease. In HIV patients with access to treatment, the risk of invasive pneumoccal disease is 0.2–1% per year and has a fatality rate of 8%.

There is an association between pneumococcal pneumonia and influenza. Damage to the lining of the airways (respiratory epithelium) and upper respiratory system caused by influenza may facilitate pneumococcal entry and infection.

Other risk factors include smoking, injection drug use, Hepatitis C, and COPD.

Most strains of "H. influenzae" are opportunistic pathogens; that is, they usually live in their host without causing disease, but cause problems only when other factors (such as a viral infection, reduced immune function or chronically inflamed tissues, e.g. from allergies) create an opportunity. They infect the host by sticking to the host cell using trimeric autotransporter adhesins.

Naturally acquired disease caused by "H. influenzae" seems to occur in humans only. In infants and young children, "H. influenzae" type b (Hib) causes bacteremia, pneumonia, epiglottitis and acute bacterial meningitis. On occasion, it causes cellulitis, osteomyelitis, and infectious arthritis. It is one cause of neonatal infection.

Due to routine use of the Hib conjugate vaccine in the U.S. since 1990, the incidence of invasive Hib disease has decreased to 1.3/100,000 in children. However, Hib remains a major cause of lower respiratory tract infections in infants and children in developing countries where the vaccine is not widely used. Unencapsulated "H. influenzae" strains are unaffected by the Hib vaccine and cause ear infections (otitis media), eye infections (conjunctivitis), and sinusitis in children, and are associated with pneumonia.

CAP is common worldwide, and a major cause of death in all age groups. In children, most deaths (over two million a year) occur in newborn period. According to a World Health Organization estimate, one in three newborn deaths are from pneumonia. Mortality decreases with age until late adulthood, with the elderly at risk for CAP and its associated mortality.

More CAP cases occur during the winter than at other times of the year. CAP is more common in males than females, and more common in black people than Caucasians. Patients with underlying illnesses (such as Alzheimer's disease, cystic fibrosis, COPD, tobacco smoking, alcoholism or immune-system problems) have an increased risk of developing pneumonia.

Several studies found that healthcare-associated pneumonia is the second most common type of pneumonia, occurring less commonly than community-acquired pneumonia but more frequently than hospital-acquired pneumonia and ventilator-associated pneumonia. In a recent observational study, the rates for CAP, HCAP and HAP were 60%, 25% and 15% respectively. Patients with HCAP are older and more commonly have simultaneous health problems (such as previous stroke, heart failure and diabetes).

The number of residents in long term care facilities is expected to rise dramatically over the next 30 years. These older adults are known to develop pneumonia 10 times more than their community-dwelling peers, and hospital admittance rates are 30 times higher.

Healthcare-associated pneumonia can be defined as pneumonia in a patient with at least one of the following risk factors:

- hospitalization in an acute care hospital for two or more days in the last 90 days;

- residence in a nursing home or long-term care facility in the last 30 days

- receiving outpatient intravenous therapy (like antibiotics or chemotherapy) within the past 30 days

- receiving home wound care within the past 30 days

- attending a hospital clinic or dialysis center in the last 30 days

- having a family member with known multi-drug resistant pathogens

CAP may be prevented by treating underlying illnesses increasing its risk, by smoking cessation and vaccination of children and adults. Vaccination against "haemophilus influenzae" and "streptococcus pneumoniae" in the first year of life has reduced their role in childhood CAP. A vaccine against "streptococcus pneumoniae", available for adults, is recommended for healthy individuals over 65 and all adults with COPD, heart failure, diabetes mellitus, cirrhosis, alcoholism, cerebrospinal fluid leaks or who have had a splenectomy. Re-vaccination may be required after five or ten years.

Patients who are vaccinated against "streptococcus pneumoniae", health professionals, nursing-home residents and pregnant women should be vaccinated annually against influenza. During an outbreak, drugs such as amantadine, rimantadine, zanamivir and oseltamivir have been demonstrated to prevent influenza.

The serious complications of HiB are brain damage, hearing loss, and even death.

Gram-negative bacteria are seen less frequently: "Haemophilus influenzae" (), "Klebsiella pneumoniae" (), "Escherichia coli" (), "Pseudomonas aeruginosa" (), "Bordetella pertussis", 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 or faeces) are inhaled.

Atypical bacteria causing pneumonia are "Coxiella burnetii", "Chlamydophila pneumoniae" (), "Mycoplasma pneumoniae" (), and "Legionella pneumophila".

The term "atypical" does not relate to how commonly these organisms cause pneumonia, how well it responds to common antibiotics or how typical the symptoms are; it refers instead to the fact that these organisms have atypical or absent cell wall structures and do not take up Gram stain in the same manner as gram-negative and gram-positive organisms.

Pneumonia caused by "Yersinia pestis" is usually called pneumonic plague.

Clinical prediction rules have been developed to more objectively predict outcomes of pneumonia. These rules are often used in deciding whether or not to hospitalize the person.

- Pneumonia severity index (or "PSI Score")

- CURB-65 score, which takes into account the severity of symptoms, any underlying diseases, and age

While the "Haemophilus influenzae" bacteria is unable to survive in any environment outside of the human body, humans can carry the bacteria within their bodies without developing any symptoms of the disease. It spreads through the air when an individual carrying the bacteria coughs or sneezes. The risk of developing "Haemophilus" meningitis is most directly related to an individual's vaccination history, as well as the vaccination history of the general public. Herd immunity, or the protection that unvaccinated individuals experience when the majority of others in their proximity are vaccinated, does help in the reduction of meningitis cases, but it does not guarantee protection from the disease. Contact with other individuals with the disease also vastly increases the risk of infection. A child in the presence of family members sick with "Haemophilus" meningitis or carrying the bacteria is 585 times more likely to catch "Haemophilus" meningitis. Additionally, siblings of individuals with the Haemophilus influenzae meningitis receive reduced benefits from certain types of immunization. Similarly, children under two years of age have a greater risk of contracting the disease when attending day care, especially in their first month of attendance, due to the maintained contact with other children who might be asymptomatic carriers of the Hib bacteria.

With treatment, most types of bacterial pneumonia will stabilize in 3–6 days. It often takes a few weeks before most symptoms resolve. X-ray finding typically clear within four weeks and mortality is low (less than 1%). In the elderly or people with other lung problems, recovery may take more than 12 weeks. In persons requiring hospitalization, mortality may be as high as 10%, and in those requiring intensive care it may reach 30–50%. Pneumonia is the most common hospital-acquired infection that causes death. Before the advent of antibiotics, mortality was typically 30% in those that were hospitalized.

Complications may occur in particular in the elderly and those with underlying health problems. This may include, among others: empyema, lung abscess, bronchiolitis obliterans, acute respiratory distress syndrome, sepsis, and worsening of underlying health problems.

Before the widespread use of the Hib vaccine, "Haemophilus" meningitis accounted for 40%-60% of all meningitis cases in children under the age of fifteen, and 90% of all meningitis cases in children under the age of five. Vaccination can reduce incidence. Vaccination has reduced the occurrences of "Haemophilus" meningitis by 87-90% in countries with widespread access to the Hib vaccine. Rates are still high in areas with limited levels of vaccination. Less-developed countries as well as countries with medical infrastructure that has been damaged in any way, such as from warfare, do not have such widespread access to the vaccine and thus experience higher rates of meningitis cases. Multiple conjugate Hib vaccines are available for use, though, and are extremely effective when given to infants. Additionally, the vaccine has only the side effects of reddened skin and swelling at the location of the injection.

Vaccination helps prevent bronchopneumonia, mostly against influenza viruses, adenoviruses, measles, rubella, streptococcus pneumoniae, haemophilus influenzae, diphtheria, bacillus anthracis, chickenpox, and bordetella pertussis.

When comparing the bacterial-caused atypical pneumonias with these caused by real viruses (excluding bacteria that were wrongly considered as viruses), the term "atypical pneumonia" almost always implies a bacterial cause and is contrasted with viral pneumonia.

Known viral causes of atypical pneumonia include respiratory syncytial virus (RSV), influenza A and B, parainfluenza, adenovirus, severe acute respiratory syndrome (SARS)

and measles.

The most common causative organisms are (often intracellular living) bacteria:

- "Chlamydophila pneumoniae": Mild form of pneumonia with relatively mild symptoms.

- "Chlamydophila psittaci": Causes psittacosis.

- "Coxiella burnetii": Causes Q fever.

- "Francisella tularensis": Causes tularemia.

- "Legionella pneumophila": Causes a severe form of pneumonia with a relatively high mortality rate, known as legionellosis or Legionnaires' disease.

- "Mycoplasma pneumoniae": Usually occurs in younger age groups and may be associated with neurological and systemic (e.g. rashes) symptoms.

Atypical pneumonia can also have a fungal, protozoan or viral cause.In the past, most organisms were difficult to culture. However, newer techniques aid in the definitive identification of the pathogen, which may lead to more individualized treatment plans.

Lower respiratory infectious disease is the fifth-leading cause of death and the combined leading infectious cause of death, being responsible for 2·74 million deaths worldwide. This is generally similar to estimates in the 2010 Global Burden of Disease study.

This total only accounts for "Streptococcus pneumoniae" and "Haemophilus Influenzae" infections and does not account for atypical or nosocomial causes of lower respiratory disease, therefore underestimating total disease burden.

The risk factors associated with BPF are not well known. However, it has been suggested that children under 5 years of age are more susceptible to BPF since they lack serum bactericidal activity against the infection. Older children and adults have much higher titers of bactericidal antibodies, which serve as a protective measure. Also children residing in warmer geographic areas have been associated with a higher risk of BPF infection.

An overwhelming post-splenectomy infection (OPSI) or Overwhelming post-splenectomy sepsis (OPSS) is a rare but rapidly fatal infection occurring in individuals following removal of the spleen. The infections are typically characterized by either meningitis or sepsis, and are caused by encapsulated organisms including "Streptococcus pneumoniae".

The risk of OPSI is 0.23–0.42 percent per year, with a lifetime risk of 5 percent. Most infections occur in the first few years following splenectomy, but the risk of OPSI is lifelong. OPSI is almost always fatal without treatment, and modern treatment has decreased the mortality to approximately 40–70 percent. Individuals with OPSI are most commonly treated with antibiotics and supportive care. Measures to prevent OPSI include vaccination and prophylactic antibiotics.

Some patients may develop pneumonia, lymphadenopathy, or septic arthritis.

Epiglottitis is typically due to a bacterial infection of the epiglottis. While it historically was most often caused by Haemophilus influenzae type B with immunization this is no longer the case. Bacteria that are now typically involved are "Streptococcus pneumoniae", "Streptococcus pyogenes", or "Staphylococcus aureus".

Other possible causes include burns and trauma to the area. Epiglottitis has been linked to crack cocaine usage. Graft versus host disease and lymphoproliferative disorder can also be a cause.

The spleen contains many macrophages (part of the reticuloendothelial system), which are immune cells that phagocytose (eat) and destroy bacteria. In particular, these macrophages are activated when bacteria are bound by IgG antibodies (IgG1 or IgG3) or the complement component C3b. These types of antibodies and complement are immune substances called opsonizers, molecules that bind to the surface of bacteria to facilitate phagocytosis.

When the spleen is no longer present (asplenia), IgG and C3b are still bound to bacteria, but they cannot be removed from the blood circulation due to the loss of the splenic macrophages. Hence the bacteria are free to cause infection.

Patients without spleens often need immunizations against pathogens that normally require opsonization and phagocytosis by macrophages in the spleen. These include common human pathogens with bacterial capsules ("Streptococcus pneumoniae, Salmonella typhi, Neisseria meningitidis, E. coli, Hemophilus influenzae, Streptococcus agalactiae, Klebsiella pneumoniae"). Capsules made of polysaccharides (sugars) permit bacteria to evade phagocytosis by macrophages alone, since only proteins are directly recognized by macrophages in phagocytosis. So humoral immunity in forms of IgG and complement proteins is the human immune system's response against bacterial capsules.

The most common cause is viral infection and includes adenovirus, rhinovirus, influenza, coronavirus, and respiratory syncytial virus. It can also be caused by Epstein-Barr virus, herpes simplex virus, cytomegalovirus, or HIV. The second most common cause is bacterial infection of which the predominant is Group A β-hemolytic streptococcus (GABHS), which causes strep throat. Less common bacterial causes include: "Staphylococcus aureus" (including methicillin resistant Staphylococcus aureus or MRSA ),"Streptococcus pneumoniae", "Mycoplasma pneumoniae", "Chlamydia pneumoniae", "Bordetella pertussis", "Fusobacterium" sp., "Corynebacterium diphtheriae", "Treponema pallidum", and "Neisseria gonorrhoeae".

Anaerobic bacteria have been implicated in tonsillitis and a possible role in the acute inflammatory process is supported by several clinical and scientific observations.

Under normal circumstances, as viruses and bacteria enter the body through the nose and mouth, they are filtered in the tonsils. Within the tonsils, white blood cells of the immune system destroy the viruses or bacteria by producing inflammatory cytokines like phospholipase A2, which also lead to fever. The infection may also be present in the throat and surrounding areas, causing inflammation of the pharynx.

Sometimes, tonsillitis is caused by an infection of spirochaeta and treponema, in this case called Vincent's angina or Plaut-Vincent angina.

The eye gnat ("Liohippelates") was thought to be the cause of the conjunctivitis epidemic which occurred in Mato Grosso do Sul in 1991. These gnats were extracted from the conjunctival secretions of the children who were infected with conjunctivitis. 19 of those children developed BPF following the conjunctivitis. Other modes of transmission include contact with the conjunctival discharges of infected people, ophthalmic instruments which have not been properly sterilized, sharing eye makeup applicators or multiple-dose eye medications.