Polymerase chain reaction (PCR) assays have been proven to be more sensitive than either LAT or culture tests, and highly specific. However, PCR assays have not yet become routine in clinical settings. Countercurrent immunoelectrophoresis has been shown to be an effective research diagnostic method, but has been largely supplanted by PCR.

The latex particle agglutination test (LAT) is a more sensitive method to detect "H. influenzae" than is culture. Because the method relies on antigen rather than viable bacteria, the results are not disrupted by prior antibiotic use. It also has the added benefit of being much quicker than culture methods. However, antibiotic sensitivity testing is not possible with LAT alone, so a parallel culture is necessary.

Due to the importance of disease caused by "S. pneumoniae" several vaccines have been developed to protect against invasive infection. The World Health Organization recommend routine childhood pneumococcal vaccination; it is incorporated into the childhood immunization schedule in a number of countries including the United Kingdom, United States, and South Africa.

Depending on the nature of infection an appropriate sample is collected for laboratory identification. Pneumococci are typically gram-positive cocci seen in pairs or chains. When cultured on blood agar plates with added optochin antibiotic disk they show alpha-hemolytic colonies and a clear zone of inhibition around the disk indicating sensitivity to the antibiotic. Pneumococci are also bile soluble. Just like other streptococci they are catalase-negative. A Quellung test can identify specific capsular polysaccharides.

Pneumococcal antigen (cell wall C polysaccharide) may be detected in various body fluids. Older detection kits, based on latex agglutination, added little value above Gram staining and were occasionally false-positive. Better results are achieved with rapid immunochromatography, which has a sensitivity (identifies the cause) of 70–80% and >90% specificity (when positive identifies the actual cause) in pneumococcal infections. The test was initially validated on urine samples but has been applied successfully to other body fluids. Chest X-rays can also be conducted to confirm inflammation though are not specific to the causative agent.

In hospitalised patients who develop respiratory symptoms and fever, one should consider the diagnosis. The likelihood increases when upon investigation symptoms are found of respiratory insufficiency, purulent secretions, newly developed infiltrate on the chest X-Ray, and increasing leucocyte count. If pneumonia is suspected material from sputum or tracheal aspirates are sent to the microbiology department for cultures. In case of pleural effusion thoracentesis is performed for examination of pleural fluid. In suspected ventilator-associated pneumonia it has been suggested that bronchoscopy(BAL) is necessary because of the known risks surrounding clinical diagnoses.

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

Patients with symptoms of CAP require evaluation. Diagnosis of pneumonia is made clinically, rather than on the basis of a particular test. Evaluation begins with a physical examination by a health provider, which may reveal fever, an increased respiratory rate (tachypnea), low blood pressure (hypotension), a fast heart rate (tachycardia) and changes in the amount of oxygen in the blood. Palpating the chest as it expands and tapping the chest wall (percussion) to identify dull, non-resonant areas can identify stiffness and fluid, signs of CAP. Listening to the lungs with a stethoscope (auscultation) can also reveal signs associated with CAP. A lack of normal breath sounds or the presence of crackles can indicate fluid consolidation. Increased vibration of the chest when speaking, known as tactile fremitus, and increased volume of whispered speech during auscultation can also indicate fluid.

When signs of pneumonia are discovered during evaluation, chest X-rays, are performed to support a diagnosis of CAP, and examination of the blood and sputum for infectious microorganisms and blood tests may be used to support a diagnosis of CAP. Diagnostic tools depend on the severity of illness, local practices and concern about complications of the infection. All patients with CAP should have their blood oxygen monitored with pulse oximetry. In some cases, arterial blood gas analysis may be required to determine the amount of oxygen in the blood. A complete blood count (CBC) may reveal extra white blood cells, indicating infection.

Chest X-rays and X-ray computed tomography (CT) can reveal areas of opacity (seen as white), indicating consolidation. CAP does not always appear on x-rays, because the disease is in its initial stages or involves a part of the lung an x-ray does not see well. In some cases, chest CT can reveal pneumonia not seen on x-rays. However, congestive heart failure or other types of lung damage can mimic CAP on x-rays.

Several tests can identify the cause of CAP. Blood cultures can isolate bacteria or fungi in the bloodstream. Sputum Gram staining and culture can also reveal the causative microorganism. In severe cases, bronchoscopy can collect fluid for culture. Special tests can be performed if an uncommon microorganism is suspected, such as urinalysis for Legionella antigen in Legionnaires' disease.

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.

In pneumonia, a collection of fluid may form in the space that surrounds the lung. Occasionally, microorganisms will infect this fluid, causing an empyema. To distinguish an empyema from the more common simple parapneumonic effusion, the fluid may be collected with a needle (thoracentesis), and examined. If this shows evidence of empyema, complete drainage of the fluid is necessary, often requiring a drainage catheter. In severe cases of empyema, surgery may be needed. If the infected fluid is not drained, the infection may persist, because antibiotics do not penetrate well into the pleural cavity. If the fluid is sterile, it must be drained only if it is causing symptoms or remains unresolved.

In rare circumstances, bacteria in the lung will form a pocket of infected fluid called a lung abscess. Lung abscesses can usually be seen with a chest X-ray but frequently require a chest CT scan to confirm the diagnosis. Abscesses typically occur in aspiration pneumonia, and often contain several types of bacteria. Long-term antibiotics are usually adequate to treat a lung abscess, but sometimes the abscess must be drained by a surgeon or radiologist.

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

Antibiotics are the treatment of choice for bacterial pneumonia, with ventilation (oxygen supplement) as supportive therapy. 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 acquiring 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 always need to be considered when initiating pharmacotherapy. In hospitalized individuals or those with immune deficiencies, local guidelines determine the selection of antibiotics.

People who have difficulty breathing due to pneumonia may require extra oxygen. An extremely sick individual may require artificial ventilation and intensive care as life-saving measures while his or her immune system fights off the infectious cause with the help of antibiotics and other drugs.

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

Antibiotics do not help the many lower respiratory infections which are caused by parasites or viruses. While acute bronchitis often does not require antibiotic therapy, antibiotics can be given to patients with acute exacerbations of chronic bronchitis. The indications for treatment are increased dyspnoea, and an increase in the volume or purulence of the sputum. The treatment of bacterial pneumonia is selected by considering the age of the patient, the severity of the illness and the presence of underlying disease. Amoxicillin and doxycycline are suitable for many of the lower respiratory tract infections seen in general practice.

Chest radiographs (X-ray photographs) often show a pulmonary infection before physical signs of atypical pneumonia are observable at all.

This is occult pneumonia. In general, occult pneumonia is rather often present in patients with pneumonia and can also be caused by "Streptococcus pneumoniae", as the decrease of occult pneumonia after vaccination of children with a pneumococcal vaccine suggests.

Infiltration commonly begins in the perihilar region (where the bronchus begins) and spreads in a wedge- or fan-shaped fashion toward the periphery of the lung field. The process most often involves the lower lobe, but may affect any lobe or combination of lobes.

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.

The diagnosis of group A beta-hemolytic streptococcus (GABHS) tonsillitis can be confirmed by culture of samples obtained by swabbing both tonsillar surfaces and the posterior pharyngeal wall and plating them on sheep blood agar medium. The isolation rate can be increased by incubating the cultures under anaerobic conditions and using selective growth media. A single throat culture has a sensitivity of 90–95% for the detection of GABHS (which means that GABHS is actually present 5–10% of the time culture suggests that it is absent). This small percentage of false-negative results are part of the characteristics of the tests used but are also possible if the patient has received antibiotics prior to testing. Identification requires 24 to 48 hours by culture but rapid screening tests (10–60 minutes), which have a sensitivity of 85–90%, are available. Older antigen tests detect the surface Lancefield group A carbohydrate. Newer tests identify GABHS serotypes using nucleic acid (DNA) probes or polymerase chain reaction. Bacterial culture may need to be performed in cases of a negative rapid streptococcal test.

True infection with GABHS, rather than colonization, is defined arbitrarily as the presence of >10 colonies of GABHS per blood agar plate. However, this method is difficult to implement because of the overlap between carriers and infected patients. An increase in antistreptolysin O (ASO) streptococcal antibody titer 3–6 weeks following the acute infection can provide retrospective evidence of GABHS infection and is considered definitive proof of GABHS infection.

Increased values of secreted phospholipase A2 and altered fatty acid metabolism in patients with tonsillitis may have diagnostic utility.

Mycoplasma is found more often in younger than in older people.

Older people are more often infected by Legionella.

Diagnosis is confirmed by direct inspection using laryngoscopy, although this may provoke airway spasm. If epiglottitis is suspected, attempts to visualise the epiglottis using a tongue depressor are strongly discouraged for this reason; therefore, diagnosis is made on basis of direct fibreoptic laryngoscopy carried out in controlled environment like an operating room. Imaging is rarely useful, and treatment should not be delayed for this test to be carried out.

The epiglottis and arytenoids are cherry-red and swollen. The most likely differential diagnostic candidates are croup, peritonsillar abscess, and retropharyngeal abscess.

On lateral C-spine X-ray, the thumbprint sign describes a swollen, enlarged epiglottis; usually with dilated hypopharynx and normal subglottic structures.

On CT imaging, the "halloween sign" describe a normal thickness epiglottis. It can safely exclude the acute epiglottitis. Furthermore, CT imaging can help to diagnose other conditions such as peritonsillar abscess or retropharyngeal abscess which had similar clinical features.

Meningitis can be diagnosed after death has occurred. The findings from a post mortem are usually a widespread inflammation of the pia mater and arachnoid layers of the meninges. Neutrophil granulocytes tend to have migrated to the cerebrospinal fluid and the base of the brain, along with cranial nerves and the spinal cord, may be surrounded with pus – as may the meningeal vessels.

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.

Bacterial and viral meningitis are contagious, but neither is as contagious as the common cold or flu. Both can be transmitted through droplets of respiratory secretions during close contact such as kissing, sneezing or coughing on someone, but cannot be spread by only breathing the air where a person with meningitis has been. Viral meningitis is typically caused by enteroviruses, and is most commonly spread through fecal contamination. The risk of infection can be decreased by changing the behavior that led to transmission.

The basic method for control of the conjunctivitis includes proper hygiene and care for the affected eye. If the conjunctivitis is found to be caused by "H. aegyptius" Biogroup III then prompt antibiotic treatment preferably with rifampin has been shown to prevent progression to BPF. If the infected person resides in Brazil, it is mandatory that the infection is reported to the health authority so that a proper investigation of the contacts can be completed. This investigation will help to determine the probable source of the infection.

The diagnosis of mastoiditis is clinical—based on the medical history and physical examination. Imaging studies provide additional information; The standard method of diagnosis is via MRI scan although a CT scan is a common alternative as it gives a clearer and more useful image to see how close the damage may have gotten to the brain and facial nerves. Planar (2-D) X-rays are not as useful. If there is drainage, it is often sent for culture, although this will often be negative if the patient has begun taking antibiotics. Exploratory surgery is often used as a last resort method of diagnosis to see the mastoid and surrounding areas.

The Hib vaccine is very effective at preventing the disease.

In household contacts of any unvaccinated child infected with H. influenzae, rifampicin is used as prophylaxis.