Bacterial Diseases of the Respiratory System

Pharyngitis

Pharyngitis is an inflammation of the throat that has many causes, some of which are bacterial infections.

Learning Objectives

List the symptoms and bacterial causes associated with pharyngitis

Key Takeaways

Key Points

  • In most cases, pharyngitis is caused by a systemic viral infection and is typified by a painful swelling inflammation of the throat. This can cause difficulty swallowing or breathing.
  • The most common bacterial cause of pharyngitis is streptococcus.
  • Several types of bacteria can cause pharyngitis. The most common and effective treatment for these infections are antibiotics.

Key Terms

  • hemolytic: producing hemolysis; destroying red blood cells
  • peritonsillar abscess: Peritonsillar abscess (PTA), also called a quinsy, or abbreviated as a PTA, is a recognized complication of tonsillitis. It consists of a collection of pus beside the tonsil in what is referred to as Peritonsilar space (Peri – meaning surrounding).

Pharyngitis

Pharyngitis is an inflammation of the throat. In most cases, it is quite painful and is the most common cause of a sore throat. Like many types of inflammation, pharyngitis can be acute or chronic. Acute cases are characterized by a rapid onset and, typically, a relatively short course of inflammation. Pharyngitis can result in very large tonsils. This can make swallowing and breathing difficult. It can be accompanied by a cough or fever, for example, if it is caused by a systemic infection. Most acute cases are caused by viral infections (40–80%). The remainder are caused by bacterial infections, fungal infections, or irritants such as pollutants or chemical substances. The treatment of viral causes is mainly symptomatic. Bacterial or fungal causes are often amenable to antibiotics and anti-fungal treatments, respectively.

Bacterial Causes of Pharyngitis

A number of different bacteria can infect the human throat. The most common is Group A streptococcus, but others include Corynebacterium diphtheriae, Neisseria gonorrhoeae, Chlamydophila pneumoniae, and Mycoplasma pneumoniae.

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Streptococcal pharyngitis: A severe case of strep throat or Streptococcal pharyngitis.

Streptococcal pharyngitis, more commonly known as strep throat, is caused by group A beta-hemolytic streptococcus (GAS). This is the most common bacterial cause of pharyngitis (15–30%). Common symptoms of strep throat include fever, sore throat, and large lymph nodes. It is a contagious infection, spread by close contact with an infected individual. A throat culture is the gold standard for the diagnosis of streptococcal pharyngitis, with a sensitivity of 90–95%. A rapid strep test (also called rapid antigen detection testing, or RADT) is also occasionally used as a diagnostic. While the rapid strep test is quicker, it has a lower sensitivity (70%) and a statistically equal specificity (98%) as a throat culture. For step throat, antibiotics are useful in preventing complications and expediting recovery.

Fusobacterium necrophorum are normal inhabitants of the oropharyngeal flora. Occasionally, however, these bacteria can create a peritonsillar abscess. In 1 out of 400 untreated cases, Lemierre’s syndrome can occur as a result of these abscesses.

Diphtheria is a potentially life threatening upper respiratory infection caused by Corynebacterium diphtheriae. As a result of childhood vaccination programs, diphtheria has has been largely eradicated in developed nations, but it is still reported in the Third World, and, increasingly, in some areas in Eastern Europe. Antibiotics are effective in the early stages, but recovery is generally slow.

Scarlet Fever

Scarlet fever is caused by a bacteriophage that infects Streptococcus pyogenes.

Learning Objectives

Describe the bacterium Streptococcus pyogenes that causes scarlet fever

Key Takeaways

Key Points

  • Scarlet fever usually affects children. Historically, it had devastating effects.
  • While antibiotics are effective against scarlet fever, the illness is actually caused by a bacteriophage infecting Streptococcus that has infected a person.
  • The bacteriophage T12 inserts into the genome of Streptococcus. This leads to the expression of an exotoxin, which causes scarlet fever.

Key Terms

  • scarlet fever: a streptococcal infection, mainly occurring among children, and characterized by a red skin rash, sore throat and fever
  • Shine-Dalgarno sequence: A ribosomal binding site in the mRNA of prokaryotes.
  • exotoxin: Any toxin secreted by a microorganism into the surrounding environment.
  • enterotoxin: Any of several toxins produced by intestinal bacteria

A Bacteriophage Hitchhiker

Scarlet fever is an infectious disease which most commonly affects 4-8 year-old children. Symptoms include sore throat, fever, and a characteristic red rash. It is usually spread by inhalation. There is no vaccine, but the disease is effectively treated with antibiotics. Scarlet fever is caused by an erythrogenic toxin, a substance produced by the bacterium Streptococcus pyogenes (group A strep. ) when it is infected by a certain bacteriophage.

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Scarlet Fever: The rosy cheeks and white area around the mouth are typical symptoms of scarlet fever.

Scarlet fever is caused by secretion of pyrogenic (fever inducing) exotoxins by the infected Streptococcus. Exotoxin A (speA) is probably the best studied of these toxins. It is carried by the bacteriophage T12, which integrates into the Streptococcal genome, from where the toxin is transcribed.

The phage itself integrates into a serine tRNA gene on the chromosome. The T12 virus itself has not been placed into a taxon by the International Committee on Taxonomy of Viruses. It has a double stranded DNA genome; on morphological grounds it appears to be a member of the Siphoviridae. The speA gene was cloned and sequenced in 1986. It is 753 base pairs in length and encodes a 29.244 kiloDalton (kDa) protein. The protein contains a putative 30 amino acid signal peptide. Removal of the signal sequence gives a predicted molecular weight of 25.787 (kDa) for the secreted protein. Both a promoter and a ribosome-binding site (Shine-Dalgarno sequence) are present upstream of the gene. A transcriptional terminator is located 69 bases downstream from the translational termination codon. The carboxy terminal portion of the protein exhibits extensive homology with the carboxy terminus of Staphylococcus aureus enterotoxins B and C1. Streptococcal phages other than T12 may also carry the speA gene.

Diphtheria

Diphtheria is an upper respiratory infection that is largely benign unless left untreated, at which point very harmful toxins are produced.

Learning Objectives

Discuss the role of diphtheria toxin in diphtheria

Key Takeaways

Key Points

  • Diptheria is caused bu the bacteria Corynebacterium diphtheriae, and is easily treated with antibiotics. It is now a fairly rare disease in developed countries.
  • If left untreated and if infected by a bacteriophage, then Corynebacterium diphtheriae produces toxins that can lead to mortality.
  • Diphtheria toxinis comprised of two fragments, fragment A and fragment B;. Fragment B binds to the target cell surface and allows entry into cells through endosomes; fragment A inhibits protein translation.
  • Fragment A inhibits protein synthesis by catalyzing EF-2 a protein essential for tRNA movement during protein translation.

Key Terms

  • ribosylation: The attachment of a ribose or ribosyl group to a molecule, especially to a polypeptide or protein
  • translation: A process occurring in the ribosome, in which a strand of messenger RNA (mRNA) guides assembly of a sequence of amino acids to make a protein.

Overview of Diphtheria

Diphtheria is an upper respiratory tract illness caused by Corynebacterium diphtheriae, a facultative, anaerobic, Gram-positive bacterium. It is characterized by sore throat, low fever, and an adherent membrane (a pseudomembrane) on the tonsils, pharynx, and/or nasal cavity. A milder form of diphtheria can be restricted to the skin. Less common consequences include myocarditis (about 20% of cases) and peripheral neuropathy (about 10% of cases).

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Graph of y=x2

Diphtheria is a contagious disease spread by direct physical contact or breathing the aerosolized secretions of infected individuals. Historically quite common, diphtheria has largely been eradicated in industrialized nations through widespread vaccination. In the United States, for example, there were 52 reported cases of diphtheria between 1980 and 2000; between 2000 and 2007, there were only three cases as the diphtheria–pertussis–tetanus (DPT) vaccine is recommended for all school-age children. Boosters of the vaccine are recommended for adults, since the benefits of the vaccine decrease with age without constant re-exposure; they are particularly recommended for those traveling to areas where the disease has not been eradicated.

Advanced Cases of Diphtheria

In cases that progress beyond a throat infection, diphtheria toxin spreads through the blood and can lead to potentially life-threatening complications that affect other organs, such as the heart and kidneys. The toxin can cause damage to the heart that affects its ability to pump blood or the kidneys’ ability to clear wastes. It can also cause nerve damage, eventually leading to paralysis. About 40% to 50% of those left untreated can die.

Diphtheria toxin is produced by C. diphtheriae only when it is infected with a bacteriophage that integrates the toxin-encoding genetic elements into the bacteria. Diphtheria toxin is a single, 60,000 dalton molecular weight protein composed of two peptide chains, fragment A and fragment B, held together by a disulfide bond. Fragment B is a recognition subunit that gains the toxin entry into the host cell by binding to the EGF-like domain of heparin-binding EGF-like growth factor (HB-EGF) on the cell surface. This signals the cell to internalize the toxin within an endosome via receptor-mediated endocytosis. Inside the endosome, the toxin is split by a trypsin-like protease into its individual A and B fragments. The acidity of the endosome causes fragment B to create pores in the endosome membrane, thereby catalyzing the release of fragment A into the cell’s cytoplasm.

Fragment A inhibits the synthesis of new proteins in the affected cell. It does this by catalyzing ADP-ribosylation of elongation factor EF-2—a protein that is essential to the translation step of protein synthesis. This ADP-ribosylation involves the transfer of an ADP-ribose from NAD+ to a diphthamide (a modified histidine) residue within the EF-2 protein. Since EF-2 is needed for the moving of tRNA from the A-site to the P-site of the ribosome during protein translation, ADP-ribosylation of EF-2 prevents protein synthesis. ADP-ribosylation of EF-2 is reversed by giving high doses of nicotinamide (a form of vitamin B3), since this is one of the reaction ‘s end-products, thus high amounts will drive the reaction in the opposite direction counteracting the toxin.

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Diphtheria toxin induced lesion: Corynebacterium diphtheriae produces toxins that can affect the skin by causing skin lesions, as shown here.

Otitis Media

Otitis media, or earache, is the inflammation of the middle ear and is often due to bacterial infections.

Learning Objectives

Discuss the causes and symptoms associated with otitis media

Key Takeaways

Key Points

  • Bacterial-caused earaches are often due to Streptococcus pneumoniae, a common bacterial infection.
  • Trimeric Autotransporter Adhesins on the surface of bacteria are the proteins responsible for earaches.
  • TAA proteins bind to host cells, allowing the invading bacteria to transfer virulence factors which then cause inflammation of the middle ear.

Key Terms

  • Eustachian tube: In humans and other land vertebrates, a tube that links the pharynx to the cavity of the middle ear to allow the equalization of the pressure on both sides of the eardrum.
  • tympanic: relating to the eardrum or middle ear; tympanal

Otitis media is inflammation of the middle ear. It occurs in the area between the tympanic membrane and the inner ear, also effecting a duct known as the eustachian tube. It is one of the two most common causes of earache – the other being otitis externa. Diseases other than ear infections can also cause ear pain, including various cancers of any structure that share nerve supply with the ear. Though painful, otitis media is not threatening and usually heals on its own within 2–6 weeks. Typically, acute otitis media follows a cold. After a few days of a stuffy nose, the ear becomes involved and can cause severe pain. The pain will usually settle within a day or two, but can last over a week. Sometimes the ear drum ruptures, discharging pus from the ear, but the ruptured drum will usually heal rapidly.

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Acute Otitis Media: This is a view of the tympanic membrane showing inflammation and redness, typical of acute otitis media.

Otitis media is most commonly caused by infection with viral, bacterial, or fungal pathogens. The most common bacterial pathogen is Streptococcus pneumoniae. Others include Pseudomonas aeruginosa, nontypeable Haemophilus influenzae and Moraxella catarrhalis. Among older adolescents and young adults, the most common cause of ear infections is Haemophilus influenzae. Viruses like respiratory syncytial virus (RSV) and those that cause the common cold may also result in otitis media by damaging the normal defenses of the epithelial cells in the upper respiratory tract. A major risk factor for developing otitis media is Eustachian tube dysfunction, which leads to the ineffective clearing of bacteria from the middle ear.

Otitis media caused by bacterial infections are due to Trimeric Autotransporter Adhesins (TAA; proteins found on the outer membrane of Gram-negative bacteria. Bacteria use TAAs in order to infect their host cells via a process called cell adhesion. TAAs are virulence factors; an infective agent that infects the host cell by attaching to them and secreting the virulence factor by a secretion pathway. The UspA1 protein domain is a TAA found in the bacteria Moraxella catarrhalis, which causes middle ear infections in humans.

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Trimeric Autotransporter Adhesin structure: The structure on the top (outside) of the outer membrane is a TAA protein. Various parts of the TAA are labelled, including the N-terminal head, stalk domain and C-terminal membrane anchor.

Whooping Cough

Pertussis, more commonly known as whooping cough, is a bacterial infection of the upper respiratory system.

Learning Objectives

Describe the mechanism of action and causes of pertussis causing bacteria

Key Takeaways

Key Points

  • Whooping cough is caused by the bacteria Bordetella pertussis, which infects the respiratory system.
  • There is no zoonotic reservoir of Bordetella pertussis, meaning that humans appear to be the only host of this bacteria.
  • Bordetella pertussis produces a number of virulence factors, notably Ptx, which inhibits the ability of phagocytes to respond to infections. This helps Bordetella pertussis spread throughout a host.

Key Terms

  • zoonotic: of or relating to zoonosis, the transmission of an infectious disease between species.
  • glottis: an organ of speech, located in the larynx, and consisting of the true vocal cords and the opening between them
  • lymphocytes: type of white blood cells in the vertebrate immune system

Pertussis

Pertussis, also known as whooping cough, is an infection of the respiratory system characterized by a “whooping” sound that an afflicted person makes when breathing inwards. Only 50% of patients actually display the classic sound as they attempt to draw breath over a partially closed glottis. In the U.S., the infection was responsible for 5,000 to 10,000 deaths per year before a vaccine was developed and made available. Vaccination has transformed this. Between 1985 and 1988, fewer than 100 children died from pertussis. In 2000, according to the WHO, around 39 million people worldwide were being infected annually. Of these, about 297,000 died.

Causes of Pertussis

Pertussis is caused by the bacteria, Bordetella pertussis, a gram-negative, aerobic coccobacillus capsulate of the genus Bordetella. Bordetella pertussis infects its host by colonizing lung epithelial cells. The bacterium contains a surface protein, filamentous haemagglutinin adhesin, which binds to the sulfatides found on the cilia of epithelial cells. Once anchored, the bacterium produces tracheal cytotoxin, which stops the cilia from beating. This prevents the cilia from clearing debris from an organism ‘s lungs, and the body responds by sending the host into a coughing fit. These coughs expel some bacteria into the air, which are free to infect other hosts. There does not appear to be a zoonotic reservoir for B. pertussis. Humans are its only host. The bacterium is spread by airborne droplets, and its incubation period is one to two weeks.

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Graph of y=x3

B. pertussis has the ability to inhibit the function of a host’s immune system, through virulence factors. Its virulence factors include pertussis toxin, filamentous hæmagglutinin, pertactin, fimbria, and tracheal cytotoxin. The pertussis toxin, or PTx, inhibits G protein coupling that regulates an adenylate cyclase-mediated conversion of ATP to cyclic AMP. The end result is that phagocytes convert too much ATP to cyclic AMP, which can cause disturbances in cellular signaling mechanisms. This prevents phagocytes from correctly responding to an infection. PTx, formerly known as lymphocytosis -promoting factor, causes a decrease in the entry of lymphocytes into lymph nodes. This can lead to a condition known as lymphocytosis, which is a large increase in the number of lymphocytes in an organism’s blood.

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Bordetella pertussis: Bordetella pertussis, the bacteria that causes whooping cough

Tuberculosis

Tuberculosis is a common, and in many cases lethal, infectious bacterial disease that mainly affects the lungs.

Learning Objectives

Summarize the risk factors associated with tuberculosis (TB)

Key Takeaways

Key Points

  • Tuberculosis is spread through the air when people who have an active TB infection cough, sneeze, or otherwise transmit their saliva through the air.
  • The classic symptoms of active TB infection are a chronic cough with blood -tinged sputum, fever, night sweats, and weight loss.
  • Diagnosis of active TB relies on radiology (commonly chest x-rays) as well as microscopic examination and microbiological culture of body fluids. Diagnosis of latent TB relies on the Mantoux tuberculin skin test.
  • Antibiotic resistance is a growing problem in the treatment of tuberculosis.

Key Terms

  • latent: Existing or present but concealed or inactive.
  • tuberculosis: An infectious disease of humans and animals caused by a species of mycobacterium mainly infecting the lungs where it causes tubercles characterized by the expectoration of mucus and sputum, fever, weight loss, and chest pain. It is transmitted through inhalation or ingestion of bacteria.
  • pleurisy: inflammation of lung pleura
  • sputum: Matter coughed up and expectorated from the mouth, composed of saliva and discharges from the respiratory passages such as mucus, phlegm, or pus.
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Electron micrograph of Mycobacterium tuberculosis.: This bacteria is primarily responsible for TB.

Tuberculosis (TB; short for tubercle bacillus) is a common, and in many cases lethal, infectious disease caused by various strains of mycobacteria, usually Mycobacterium tuberculosis . Tuberculosis typically attacks the lungs, but can also affect other parts of the body. It is spread through the air when people who have an active TB infection cough, sneeze, or otherwise transmit their saliva through the air. Most infections are asymptomatic and latent, but about one in 10 latent infections eventually progresses to active disease which, if left untreated, kills more than 50% of those infected. One third of the world’s population is thought to have been infected with M. tuberculosis with new infections occurring at a rate of about one per second.

Symptoms

The classic symptoms of active TB infection are a chronic cough with blood-tinged sputum, fever, chills night sweats, and weight loss. Tuberculosis may infect any part of the body, but most commonly occurs in the lungs, known as pulmonary tuberculosis. Extrapulmonary TB occurs when tuberculosis develops outside of the lungs, but may co-exist with pulmonary TB as well. Extrapulmonary TB occurs more commonly in immunosuppressed persons and young children. In those with HIV this occurs in more than 50% of cases. Notable extrapulmonary infection sites include the pleura (in tuberculous pleurisy), the central nervous system (in tuberculous meningitis), the lymphatic system (in scrofula of the neck), the genitourinary system (in urogenital tuberculosis), and the bones and joints (osseous tuberculosis). Tuberculosis may become a chronic illness and cause extensive scarring in the upper lobes of the lungs.

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Tuberculosis Symptoms.: Diagram depicting various TB symptoms.

Diagnostics

Diagnosing active tuberculosis based merely on signs and symptoms is difficult, as is diagnosing the disease in those who are immunosuppressed. A diagnosis of TB should, however, be considered in those with signs of lung disease or constitutional symptoms lasting longer than two weeks. A chest x-ray and multiple sputum cultures for acid-fast bacilli are typically part of the initial evaluation. A definitive diagnosis of TB is made by identifying M. tuberculosis in a clinical sample such as sputum, pus, or a tissue biopsy. However, the difficult culture process for this slow-growing organism can take two to six weeks for blood or sputum culture.

The Mantoux tuberculin skin test is often used to screen people at high risk for TB. It involves injecting an protein extraction of the tuberculosis bacteria under the skin, and then examining the site 36-48 hours later. A person who has been exposed to the bacteria and has previously formed antibodies is expected to mount an immune response, displaying a raised, red area of skin at the site of injection. The test does have limited accuracy, especially in immunosuppressed people, and is typically used in combination with clinical findings and x-rays to reach a diagnosis.

Risk Factors

A number of factors make people more susceptible to TB infections. The most important risk factor globally is HIV; 13% of all TB cases are infected by the virus. This is a particular problem in sub-Saharan Africa, where rates of HIV are high. Tuberculosis is closely linked to both overcrowding and malnutrition, making it one of the principal diseases of poverty. Those at high risk thus include: people who inject illicit drugs, inhabitants and employees of locales where vulnerable people gather, such as prisons and homeless shelters; medically underprivileged and resource-poor communities; high-risk ethnic minorities, children in close contact with high-risk category patients, and health care providers serving these clients. Chronic lung disease is another significant risk factor. Those who smoke cigarettes have nearly twice the risk of TB than non-smokers. Other disease states can also increase the risk of developing tuberculosis, including alcoholism and diabetes mellitus. Certain medications that cause immunosuppression such as corticosteroids and infliximab, are becoming increasingly important risk factors, especially in the developed world.

Treatment

Treatment of TB uses antibiotics to kill the bacteria. Effective TB treatment is difficult, due to the unusual structure and chemical composition of the mycobacterial cell wall, which hinders the entry of drugs and makes many antibiotics ineffective. The two antibiotics commonly used are isoniazid and rifampicin. Treatments can be prolonged, from months to even years. A barrier to effective treatment is patient noncompliance. Due to the long duration of treatment, patients will often forget to take their antibiotics periodically or stop taking them altogether. This contributes to the development of drug-resistant tuberculosis. Many strains of tuberculosis have already become resistant to previous treatments, including a strain that is resistant to all antibiotics.

Latent TB treatment usually employs a single antibiotic, while active TB disease is best treated with combinations of several antibiotics to reduce the risk of the bacteria developing antibiotic resistance. People with latent infections are also treated to prevent them from progressing to active TB disease later in life.

Bacterial Pneumonias

Pneumonia is an inflammatory lung disease that can lead to problems with breathing, often caused by bacterial infections.

Learning Objectives

List the various causes of bacterial pneumonia

Key Takeaways

Key Points

  • Most cases of pneumonia are caused by bacterial infections, and most of the bacterial infections are caused by the bacteria Streptococcus pneumoniae.
  • The bacteria that cause pneumonia are split into three groups, gram-negative, gram-positive and atypical.
  • Alcoholism is asociated with Streptococcus pneumoniae induced pneumonia and smoking exacerbates the situation.

Key Terms

  • pneumonia: Pneumonia is an inflammatory condition of the lung, affecting primarily the microscopic air sacs known as alveoli.
  • infection: An uncontrolled growth of harmful microorganisms in a host.
  • Alveoli: alveolus (plural alveoli) a small air sac in the lungs, where oxygen and carbon dioxide are exchanged with the blood.

Pneumonia is an inflammatory condition of the lung, affecting primarily the microscopic air sacs known as alveoli. It is usually caused by infection with viruses or bacteria and less commonly other microorganisms, certain drugs and other conditions such as autoimmune diseases. Typical symptoms include a cough, chest pain, fever, and difficulty breathing. Diagnostic tools include x-rays and culture of the sputum. Vaccines to prevent certain types of pneumonia are available. Treatment depends on the underlying cause. Presumed bacterial pneumonia is treated with antibiotics. If the pneumonia is severe, the affected person is generally admitted to hospital.

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Bacterial pneumonia: A chest X-ray showing a very prominent wedge-shaped bacterial pneumonia in the right lung.

Bacteria are the most common cause of community-acquired pneumonia (CAP), with Streptococcus pneumoniae isolated in nearly 50% of cases. Other commonly isolated bacteria include: Haemophilus influenzae in 20%, Chlamydophila pneumoniae in 13%, and Mycoplasma pneumoniae in 3% of cases; Staphylococcus aureus; Moraxella catarrhalis; Legionella pneumophila and Gram-negative bacilli. A number of drug-resistant versions of the above infections are becoming more common, including drug-resistant Streptococcus pneumoniae (DRSP) and methicillin-resistant Staphylococcus aureus (MRSA). The spreading of organisms is facilitated when risk factors are present. Alcoholism is associated with Streptococcus pneumoniae, anaerobic organisms and Mycobacterium tuberculosis; smoking facilitates the effects of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Legionella pneumophila. Exposure to birds is associated with Chlamydia psittaci; farm animals with Coxiella burnetti; aspiration of stomach contents with anaerobic organisms; and cystic fibrosis with Pseudomonas aeruginosa and Staphylococcus aureus. Streptococcus pneumoniae is more common in the winter, and should be suspected in persons who aspirate a large amount anaerobic organisms.

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Streptococcus pneumoniae: The bacterium Streptococcus pneumoniae, a common cause of pneumonia, imaged by an electron microscope

Bacteria caused pneumonia fall into 3 groups:

  1. Gram Positive. 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.
  2. Gram Negative. 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 or faeces) are inhaled.
  3. Atypical bacteria. “Atypical” bacteria are Coxiella burnetii, Chlamydophila pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila. Many people falsely believe they are called “atypical” because they are uncommon and/or do not respond to common antibiotics and/or cause atypical symptoms. In reality, they are “atypical” because they do not gram stain as well as gram-negative and gram-positive organisms. Pneumonia caused by Yersinia pestis is usually called pneumonic plague.