"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.

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

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.

Although children older than one month tend to be at risk for the same microorganisms as adults, children under five are much less likely to have pneumonia caused by "Mycoplasma pneumoniae", "Chlamydophila pneumoniae" or "Legionella pneumophila". In contrast, older children and teenagers are more likely to acquire "Mycoplasma pneumoniae" and "Chlamydophila pneumoniae" than adults.

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.

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.

In some studies, the bacteria found in patients with HCAP were more similar to HAP than to CAP; compared to CAP, they could have higher rates of "Staphylococcus aureus" ("S. aureus") and "Pseudomonas aeruginosa", and less "Streptococcus pneumoniae" and "Haemophilus influenzae". In European and Asian studies, the etiology of HCAP was similar to that of CAP, and rates of multi drug resistant pathogens such as "Staphylococcus aureus" and "Pseudomonas aeruginosa" were not as high as seen in North American studies. It is well known that nursing home residents have high rates of colonization with MRSA. However, not all studies have found high rates of S. aureus and gram-negative bacteria. One factor responsible for these differences is the reliance on sputum samples and the strictness of the criteria to discriminate

between colonising or disease-causing bacteria. Moreover, sputum samples might be less frequently obtained in the elderly.Aspiration (both of microscopic drops and macroscopic amounts of nose and throat secretions) is thought to be the most important cause of HCAP. Dental plaque might also be a reservoir for bacteria in HCAP.

Bacteria have been the most commonly isolated pathogens, although viral and fungal pathogens are potentially found in immunocompromised hosts (patients on chronic immunosuppressed medications, solid organ and bone marrow transplant recipients). In general, the distribution of microbial pathogens varies among institutions, partly because of differences in patient population and local patterns of anti microbial resistance in hospitals and critical care units' Common bacterial pathogens include aerobic GNB, such as "Pseudomonas aeruginosa", "Acinetobacter baumanii", "Klebsiella pneumoniae", "Escherichia coli" as well as gram-positive organisms such as "Staphylococcus aureus". In patients with an early onset pneumonia (within 5 days of hospitalization), they are usually due to anti microbial-sensitive bacteria such as "Enterobacter" spp, "E. coli", "Klebsiella" spp, "Proteus" spp, "Serratia mare scans", community pathogens such as "Streptococcus pneumoniae, Haemophilus influenzae", and methicillin-sensitive "S. aureus" should also be considered.

Pneumonia that starts in the hospital tends to be more serious than other lung infections because: people in the hospital are often very sick and cannot fight off germs. The types of germs present Ina hospital are often more dangerous and more resistant to treatment than those outside in the community. Pneumonia occurs more often in people who are using a respirator. This machine helps them breathe. Hospital-acquired pneumonia can also be spread by health care workers, who can pass germs from their hands or clothes from one person to another. This is why hand-washing, wearing grows, and using other safety measures is so important in the hospital.

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.

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.

"Streptococcus pneumoniae" () is the most common bacterial cause of pneumonia in all age groups except newborn infants. "Streptococcus pneumoniae" is a Gram-positive bacterium that often lives in the throat of people who do not have pneumonia.

Other important Gram-positive causes of pneumonia are "Staphylococcus aureus" () and "Bacillus anthracis".

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

Smoking cessation and reducing indoor air pollution, such as that from cooking indoors with wood or dung, are both recommended. Smoking appears to be the single biggest risk factor for pneumococcal pneumonia in otherwise-healthy adults. Hand hygiene and coughing into one's sleeve may also be effective preventative measures. Wearing surgical masks by the sick may also prevent illness.

Appropriately treating underlying illnesses (such as HIV/AIDS, diabetes mellitus, and malnutrition) can decrease the risk of pneumonia. In children less than 6 months of age, exclusive breast feeding reduces both the risk and severity of disease. In those with HIV/AIDS and a CD4 count of less than 200 cells/uL the antibiotic trimethoprim/sulfamethoxazole decreases the risk of "Pneumocystis pneumonia" and is also useful for prevention in those that are immunocomprised but do not have HIV.

Testing pregnant women for Group B Streptococcus and "Chlamydia trachomatis", and administering antibiotic treatment, if needed, reduces rates of pneumonia in infants; preventive measures for HIV transmission from mother to child may also be efficient. Suctioning the mouth and throat of infants with meconium-stained amniotic fluid has not been found to reduce the rate of aspiration pneumonia and may cause potential harm, thus this practice is not recommended in the majority of situations. In the frail elderly good oral health care may lower the risk of aspiration pneumonia. Zinc supplementation in children 2 months to five years old appears to reduce rates of pneumonia.

When influenza outbreaks occur, medications such as amantadine or rimantadine may help prevent the condition; however are associated with side effects. Zanamivir or oseltamivir decrease the chance that those exposed will develop symptoms; however, it is recommended that potential side effects are taken into account.

Congential rubella is still a risk with higher risk among immigrant women from countries without adequate vaccination programs.

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.

Sixty percent of mothers of preterm infants are infected with cytomegalovirus (CMV). Infection is asymptomatic in most instances but 9% to 12% of postnatally infected low birth weight, preterm infants have severe, sepsis-like infection. CMV infection duration can be long and result in pneumonitis in association with fibrosis. CMV infection in infants has an unexpected effect on the white blood cells of the immune system causing them to prematurely age. This leads to a reduced immune response similar to that found in the elderly.

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 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.

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.

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.

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

A study conducted on 452 patients revealed that the genotype responsible for higher IL-10 expression makes HIV infected people more susceptible to tuberculosis infection. Another study on HIV-TB co-infected patients also concluded that higher level of IL-10 and IL-22 makes TB patient more susceptible to Immune reconstitution inflammatory syndrome (IRIS). It is also seen that HIV co-infection with tuberculosis also reduces concentration of immunopathogenic matrix metalloproteinase (MMPs) leading to reduced inflammatory immunopathology.