Mycoplasma pneumonia

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Yazan Daaboul, M.D. Serge Korjian M.D.

Mycoplasma pneumonia is a common atypical pneumonia caused by the bacterium M. pneumoniae. In the USA, the incidence of Mycoplasma pneumonia is approximately 600 per 100,000 individuals.^[1] Mycoplasma pneumoniae is transmitted through airborne droplets from person to person. M. pneumoniae is primarily an extracellular pathogen that has evolved a specialized attachment organelle for close association with host cells. The organism’s tropism for respiratory epithelial cells and its synthesis of hydrogen peroxide aid in the pathogenesis of Mycoplasma. Mycoplasma pneumonia must be differentiated from other causes of pneumonia, chest pain, and cough, such as other infectious causes, aspiration pneumonia, pneumonitis, lung abscess, empyema, COPD exacerbation, asthma, interstitial lung disease, cardiac diseases, and malignancies. Patients younger than 40 years of age (especially between 5 and 20 years of age) are more commonly affected with Mycoplasma pneumonia.^[1] In contrast, Mycoplasma pneumonia is less common (but still incident) among children < 5 years of age or adults > 40-60 years of age. There is no gender predilection to the development of Mycoplasma pneumonia. The incidence of Mycoplasma pneumonia is higher in regions with temperate climate during the Summer and Fall.^[2] Additional risk factors include living in closed communities (healthcare settings, prisoners, military, college students), active lung disease, immunocompromised status, history of sickle cell disease, and active smoking. Following transmission, Mycoplasma incubation period is approximately 1 to 4 weeks. During this time, the patient remains asymptomatic. Onset of symptoms can be gradual and subacute. If left untreated, Mycoplasma pneumonia slowly progresses, and patients typically report high-grade fever, sore throat, headache, and a persistent dry cough. While the disease can persist for weeks or months, it is frequently mild and self-resolving. In children < 5 years of age, the infection may run subclinical, mild, and non-pneumonia courses. Complications of Mycoplasma pneumonia include otitis, hemolytic anemia, asthma exacerbation, bronchiectasis, Swyer-James syndrome (post-infectious obliterative bronchiolitis), acute kidney injury, Guillain-Barré syndrome, Stevens-Johnson syndrome, pericarditis, myocarditis, transverse myelitis, or meningoencephalitis. Prognosis is usually good, and the majority of patients recover completely even without antimicrobial therapy. Elderly individuals and patients with sickle cell disease and other immunocompromised patients are at increased risk of developing complications of Mycoplasma pneumonia. Mycoplasma pneumonia is diagnosed by either culture, serology, or molecular methods. Antimicrobial therapy using either a macrolide, doxycycline, or a fluoroquinolone is the mainstay of therapy for atypical pneumonia caused by Mycoplasma. There is no vaccine against Mycoplasma, but avoiding infected individuals helps reduce risk of infection.

Mycoplasma pneumoniae was first described by Hobart A. Reimann in 1938 in a patient with a self-limited “atypical” pneumonia.

Mycoplasma pneumoniae is transmitted through airborne droplets from person to person. M. pneumoniae is primarily an extracellular pathogen that has evolved a specialized attachment organelle for close association with host cells. The organism’s tropism for respiratory epithelial cells and its synthesis of hydrogen peroxide aid in the pathogenesis of Mycoplasma. Additionally, Mycoplasma produces community acquired respiratory distress syndrome (CARDS) toxin, a unique virulence factor which activates the host’s inflammatory pathways and airway dysfunction.

Mycoplasma pneumonia is caused by Mycoplasma pneumoniae, a very small bacterium that lacks cell wall and periplasmic space. On Gram-stain, Mycoplasma stains pink, i.e. it is Gram-negative by staining. However, it is structurally different from other Gram-negative organisms because it lacks a cell wall.

Mycoplasma pneumonia must be differentiated from other causes of pneumonia, chest pain, and cough, such as other infectious causes, aspiration pneumonia, pneumonitis, lung abscess, empyema, COPD exacerbation, asthma, interstitial lung disease, cardiac diseases, and malignancies.

In the USA, the incidence of Mycoplasma pneumonia is approximately 600 per 100,000 individuals.^[1] Patients younger than 40 years of age (especially between 5 and 20 years of age) are more commonly affected with Mycoplasma pneumonia.^[1] In contrast, Mycoplasma pneumonia is less common (but still incident) among children < 5 years of age or adults > 40-60 years of age. There is no gender predilection to the development of Mycoplasma pneumonia. The incidence of Mycoplasma pneumonia is higher in regions with temperate climate during the Summer and Fall.^[2]

Risk factors in the development of Mycoplasma pneumonia include age between 5-40 years, living in closed communities (healthcare settings, prisoners, military, college students), active lung disease, immunocompromised status, history of sickle cell disease, active smoking, and living in regions with temperate climates.

Following transmission, Mycoplasma incubation period is approximately 1 to 4 weeks. During this time, the patient remains asymptomatic. Onset of symptoms can be gradual and subacute. If left untreated, Mycoplasma pneumonia slowly progresses, and patients typically report high-grade fever and a persistent cough. While the disease can persist for weeks or months, it is frequently mild and self-resolving. In children < 5 years of age, the infection may run subclinical, mild, and non-pneumonia courses. Complications of Mycoplasma pneumonia include otitis, hemolytic anemia, asthma exacerbation, bronchiectasis, Swyer-James syndrome (post-infectious obliterative bronchiolitis), acute kidney injury, Guillain-Barré syndrome, Stevens-Johnson syndrome, pericarditis, myocarditis, transverse myelitis, or meningoencephalitis. Prognosis is usually good, and the majority of patients recover completely even without antimicrobial therapy. Elderly individuals and patients with sickle cell disease and other immunocompromised patients are at increased risk of developing complications of Mycoplasma pneumonia.

Common symptoms of Mycoplasma pneumonia include malaise, fever, dry cough, chest pain, night sweats, sore throat, and headache. Less common symptoms include eye pain, arthralgia, myalgia, dyspnea, rash, vomiting, and diarrhea.

Patients with Mycoplasma pneumonia generally appear well. Common physical examination findings include fever, decreased oxygen saturation on room air, tachycardia, tachypnea, non-exudative pharyngitis, and decreased breath sounds with crackles and increased tactile fremitus on lung auscultation. Other physical examination findings include rash, pallor, sinus tenderness, cervical lymphadenopathy, and possibly bullous myringitis.

Mycoplasma pneumonia is diagnosed by either culture, serology, or molecular methods. Other laboratory findings include elevated CRP and/or ESR, leucocytosis, or hemolytic anemia.

Findings of Mycoplasma pneumonia on chest x ray include either interstitial pneumonia or bronchopneumonia with evidence of patchy consolidation that may be unilateral (more common) or bilateral. Involvement of the lower lobes is common.^[3]

On chest CT scan, findings of Mycoplasma pneumonia include areas of ground-glass attenuation, air-space consolidation, and formation of intra-pulmonary nodules.^[3]

Antimicrobial therapy is the mainstay of therapy for atypical pneumonia caused by Mycoplasma. Pharmacologic therapies for Mycoplasma pneumonia include either a macrolide (e.g. azithromycin) for 2-5 days, doxycycline for 14 days, or a fluoroquinolone for 14 days. Supportive therapy includes rest, adequate fluid intake, and administration of either non-steroidal anti-inflammatory drugs (NSAIDS) or acetaminophen if needed. Aspirin should be avoided among children.

There is no vaccine against Mycoplasma. There are no preventive measures against Mycoplasma pneumonia. However, avoiding infected individuals helps reduce risk of infection.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Mycoplasma pneumoniae was first described by Hobart A. Reimann in 1938 in a patient with a self-limited “atypical” pneumonia.

• Mycoplasma pneumoniae was first described by Hobart A. Reimann in 1938 in a patient with a self-limited “atypical” pneumonia.^[1]
• In 1943, Reimann first described the phenomenon of cold agglutination.
• The term Mycoplasma is Greek for “fungus-formed” because Mycoplasma was first thought to be a fungus.
• In 1944, Eaton reported Eaton’s agent as the primary cause of atypical pneumonia.^[2] In 1961, M. pneumoniae was discovered to be Eaton’s agent.

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Mycoplasma pneumoniae is transmitted through airborne droplets from person-to-person. M. pneumoniae is primarily an extracellular pathogen that has evolved a specialized attachment organelle for close association with host cells. The organism’s tropism for respiratory epithelial cells and its synthesis of hydrogen peroxide aid in the pathogenesis of Mycoplasma. Additionally, Mycoplasma produces community acquired respiratory distress syndrome (CARDS) toxin, a unique virulence factor which activates the host’s inflammatory pathways and airway dysfunction.

• Mycoplasma is thought to be exclusively a human pathogen.^[1]
• Mycoplasma pneumoniae is transmitted through airborne droplets from person-to-person.
• Incubation period ranges from 1 to 4 weeks.^[1]

• M. pneumoniae is primarily an extracellular pathogen that has evolved a specialized attachment organelle for close association with host cells.^[1]
• M. pneumoniae’s uses sialoglycoproteins or sialoglycolipid receptors for attachment.
• The close association between M. pneumoniae and the host cells prevents the bacterium from being eliminated by the host’s mucociliary clearance mechanisms.
• Following attachment, Mycoplasma uses adhesion proteins to adhere to the host cell. Adhesion proteins include P1 and P30.
• Once adhered to the mucosa of a host organism, M. pneumonia extracts nutrients, grows and is then able to undergo binary fission to reproduce.
• Mycoplasma damages the respiratory epithelial cells at the base of cilia, activating the innate immune response and producing local cytotoxic effects.^[1]
• While M. pneumoniae primarily lives on the surface of the respiratory epithelial cells, it has also been shown to invade tissues and replicate intracellularly.
• The endocytosis of M. pneumoniae by the host cells could aid in the establishment of a latent or chronic disease state, facilitate the bacterium in evading an immune response, or interfere with the efficacy of certain drug therapies.^[1]
• M. pneumoniae has the following features which aid in its pathogenesis:^[1]

• Tropism for respiratory epithelial cells
• Production of hydrogen peroxide, which results in the production of reactive oxygen species and subsequent damage to the respiratory tract and membranes of red blood cells

• Attachment sites include the upper and lower respiratory tract, causing pharyngitis, bronchitis and pneumonia.
• Pneumonia results from the host’s production of macrophages, immunoglobulins (IgA, IgG, and IgM).

• M. pneumoniae produces community acquired respiratory distress syndrome (CARDS) toxin, a unique virulence factor.^[1]
• The CARDS toxin most likely aids in the colonization and pathogenic pathways of M. pneumoniae, leading to activation of cytokines, inflammation, and airway dysfunction.^[1]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Mycoplasma pneumonia is caused by Mycoplasma pneumoniae, a very small bacterium that lacks cell wall and periplasmic space. On Gram-stain, Mycoplasma stains pink, i.e. it is Gram-negative by staining. However, it is structurally different from other Gram-negative organisms because it lacks a cell wall.

M. pneumoniae is the bacterium responsible for Mycoplasma pneumonia, an atypical pneumonia common in children and young adults.

• Bacteria; Firmicutes; Mollicutes; Mycoplasmatales; Mycoplasmataceae; Mycoplasma pneumoniae
• The term Mycoplasma (“mykes”, meaning fungus and “plasma”, meaning formed) is derived from the fungal-like growth of some mycoplasma species.^[1]

• Mycoplasma is the smallest self-replicating organism. They are bacteria that lack a cell wall and periplasmic space, have reduced genomes, and limited metabolic activity.^[2][3]
• Mycoplasma pneumoniae cells have an elongated shape that is approximately 1-2 µm in length and 0.1–0.2 µm in width.
• The extremely small cell size means they are incapable of being examined by light microscopy; a stereomicroscope is required for viewing the morphology of M. pneumoniae colonies, which are usually less than 100 µm in length. The inability to synthesize a peptidoglycan cell wall is due to the absence of genes encoding its formation and results in an increased importance in maintenance of osmotic stability to avoid desiccation. The lack of a cell wall also calls for increased support of the cell membrane, which includes a rigid cytoskeleton composed of an intricate protein network and, potentially, an extracellular capsule to facilitate adherence to the host cell.^[1]
• M. pneumoniae are the only bacterial cells that possess cholesterol in their cell membrane (obtained from the host) and possess more genes that encode for membrane lipoprotein variations than other mycoplasmas, which are thought to be associated with its parasitic lifestyle. M. pneumoniae cells also possess an attachment organelle, which is used in the gliding motility of the organism by an unknown mechanism.^[2]
• The absence of a peptidoglycan cell wall results in resistance to many antibacterial agents. The persistence of M. pneumoniae infections even after treatment is associated with its ability to mimic host cell surface composition.
• On Gram-stain, Mycoplasma stains pink, i.e. it is Gram-negative by staining. However, it is structurally different from other Gram-negative organisms because it lacks a cell wall.

• Sequencing of the M. pneumoniae genome in 1996 revealed it is 816,394 bp (approximately 800 kb) in size. The genome contains 687 genes that encode for proteins, of which about 56.6% code for essential metabolic enzymes; notably those involved in glycolysis and organic acid fermentation.^[2][4]
• M. pneumoniae is consequently very susceptible to loss of enzymatic function by gene mutations, as the only buffering systems against functional loss by point mutations are for maintenance of the pentose phosphate pathway and nucleotide metabolism.^[4]
• Loss of function in other pathways is suggested to be compensated by host cell metabolism.^[4]
• In addition to the potential for loss of pathway function, the reduced genome of M. pneumoniae outright lacks a number of pathways, including the TCA cycle, respiratory electron transport chain, and biosynthesis pathways for amino acids, fatty acids, cholesterol and purines and pyrimidines.^[2][4]
• These limitations make M. pneumoniae dependent upon import systems to acquire essential building blocks from their host or the environment that cannot be obtained through glycolytic pathways.^[2][4]
• Along with energy costly protein and RNA production, a large portion of energy metabolism is exerted to maintain proton gradients (up to 80%) due to the high surface area to volume ratio of M. pneumoniae cells. Only 12 – 29% of energy metabolism is directed at cell growth, which is unusually low for bacterial cells, and is thought to be an adaptation of its parasitic lifestyle.^[4] Unlike other bacteria, M. pneumoniae uses the codon UGA to code for tryptophan rather than using it as a stop codon.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Mycoplasma pneumonia must be differentiated from other causes of pneumonia, chest pain, and cough, such as other infectious causes, aspiration pneumonia, pneumonitis, lung abscess, empyema, COPD exacerbation, asthma, interstitial lung disease, cardiac diseases, and malignancies.

Differential diagnosis for Mycoplasma pneumonia includes the following:

• Other causes of bacterial pneumonia
• Viral pneumonia
• Fungal pneumonia
• Pneumocystis pneumonia
• Aspiration pneumonia
• Tuberculosis
• Chlamydia infection (including C. trachomatis, C. psittaci, and C. pneumoniae)
• Empyema
• Lung abscess
• Bronchiectasis
• COPD exacerbation
• Asthma
• Interstitial lung disease
• Lung tumor
• Pulmonary embolism
• Pneumothorax
• Hemothorax
• Epiglottitis
• Croup
• Respiratory distress syndrome
• Atelectasis
• Congestive heart failure
• Myocardial infarction
• Pericarditis
• Endocarditis
• Myocarditis
• Cardiomyopathy
• Lymphoma
• Leukemia
• Sarcoidosis

Mycoplasma pneumonia must be differentiated from other diseases that cause atypical pneumonia such as Q fever and legionella

Disease	Prominent clinical features	Lab findings	Chest X-ray
Q fever	Q fever is characterized by abrupt onset of fever, myalgia, headache, and other constitutional symptoms. Cough is the most prominent respiratory symptom and it is usually dry.[1] Cough is associated with dyspnea and pleuritic chest pain.	Antibody detection using indirect immunofluorescence (IIF) is the preferred method for diagnosis. PCR can be used if IIF is negative, or very early once disease is suspected. C. burnetii does not grow on ordinary blood cultures, but can be cultivated on special media such as embryonated eggs or cell culture. A two-to-three fold increase in AST and ALT is seen in most patients.
Mycoplasma pneumonia	Mycoplasma pneumonia can be asymptomatic. Headache, nausea, and malaise usually precede the onset of symptoms.[1] Cough is intractable and nonproductive.	Postitve Coombs test Leukocytosis Thrombocytosis
Legionellosis	Legionellosis is characterized by cough that is slightly productive.[1] Constitutional symptoms such as chills, myalgia, and arthralgia. Gastrointestinal symptoms such as diarrhea, nausea, and vomiting.	Labs are nonspecific for diagnosing legionellosis Renal and hepatic dysfunction Thrombocytopenia and leukocytosis Hyponatremia
Chlamydia pneumonia	There are no specific clinical features of chlamydia pneumonia. Symptoms appear gradually. Chlamydia infection is usually associated with upper respiratory tract symptoms (pharyngitis, sinusitis, etc). It might be associated with extrapulmonary maifestations such as meningitis and Guillain-Barre syndrome.[1]	Chlamydia pneumonia is usually associated with normal WBC count. Diagnosed with the presence of antichlamydial antibody (through complement fixation or direct immunofluoroscence) or direct antigen detection.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

In the USA, the incidence of Mycoplasma pneumonia is approximately 600 per 100,000 individuals.^[1] Patients younger than 40 years of age (especially between 5 and 20 years of age) are more commonly affected with Mycoplasma pneumonia.^[1] In contrast, Mycoplasma pneumonia is less common (but still incident) among children < 5 years of age or adults > 40-60 years of age. There is no gender predilection to the development of Mycoplasma pneumonia. The incidence of Mycoplasma pneumonia is higher in regions with temperate climate during the Summer and Fall.^[2]

• In the USA, the incidence of Mycoplasma pneumonia is approximately 600 per 100,000 individuals.^[1]
• It is estimated that approximately 2 million cases of M. pneumoniae infection occur annually and account for approximately 100,000 hospitalizations.^[1]
• Mycoplasma pneumonia accounts for approximately 1% to 20% of cases of community-acquired pneumonia.^[3]

• Patients younger than 40 years of age are more commonly affected with Mycoplasma pneumonia.^[1]
• Mycoplasma pneumonia is especially common among individuals between 5 and 20 years of age.^[1]
• Mycoplasma pneumonia is less common (but still incident) among children < 5 years of age or adults > 40-60 years of age.

• There is no gender predilection to the development of Mycoplasma pneumonia.^[1]

• The incidence of Mycoplasma pneumonia is higher in regions with temperate climate.^[2]
• The incidence of Mycoplasma pneumonia is higher in Summer and Fall (between June and November).^[2]

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Risk factors in the development of Mycoplasma pneumonia include age between 5-40 years, living in closed communities (healthcare settings, prisoners, military, college students), active lung disease, immunocompromised status, history of sickle cell disease, active smoking, and living in regions with temperate climates.

Risk factors in the development of Mycoplasma pneumonia include the following:

• Individuals between 5 and 40 years of age

• Mycoplasma pneumonia is less common (but still incident) among children < 5 years of age or adults > 40-60 years of age.
• Elderly individuals are at increased risk of developing Mycoplasma pneumonia-related complications.

• Individuals in closed communities

• Healthcare setting
• Prisoners
• Military
• College dormitories

• Active smoking status
• Active lung disease
• Patients with sickle cell disease
• Immunocompromised status
• Living in regions with temperate climates (especially during Summer and Fall)

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Following transmission, Mycoplasma incubation period is approximately 1 to 4 weeks. During this time, the patient remains asymptomatic. Onset of symptoms can be gradual and subacute. If left untreated, Mycoplasma pneumonia slowly progresses, and patients typically report high-grade fever and a persistent cough. While the disease can persist for weeks or months, it is frequently mild and self-resolving. In children < 5 years of age, the infection may run subclinical, mild, and non-pneumonia courses. Complications of Mycoplasma pneumonia include otitis, hemolytic anemia, asthma exacerbation, bronchiectasis, Swyer-James syndrome (post-infectious obliterative bronchiolitis), acute kidney injury, Guillain-Barré syndrome, Stevens-Johnson syndrome, pericarditis, myocarditis, transverse myelitis, or meningoencephalitis. Prognosis is usually good, and the majority of patients recover completely even without antimicrobial therapy. Elderly individuals and patients with sickle cell disease and other immunocompromised patients are at increased risk of developing complications of Mycoplasma pneumonia.

• Following transmission, Mycoplasma incubation period is approximately 1 to 4 weeks. During this time, the patient remains asymptomatic.^[1]

• Onset of symptoms can be gradual and subacute. If left untreated, Mycoplasma pneumonia slowly progresses, and patients typically report high-grade fever and a persistent cough.^[1]
• While the disease can persist for weeks or months, it is frequently mild and self-resolving. The organism may persist for several weeks in the oropharynx despite resolution of clinical symptoms.^[1]

• Younger patients often manifest with different clinical characteristics than patients over 5 years old.^[1]
• The infection may run subclinical, mild, and non-pneumonia courses.
• Infections in younger patients are often characterized by coryza and wheezing without concomitant fever, and sometimes include diarrhea and vomiting.
• Persistent cough is common during convalescence.^[1]

Complications of Mycoplasma pneumonia include:^[1][2]

• Hemolytic anemia
• Asthma exacerbation
• Acute kidney injury
• Guillain-Barré syndrome
• Erythema multiforme, Stevens-Johnson syndrome, or toxic epidermal necrolysis
• Encephalitis or meningoencephalitis
• Transverse myelitis
• Arthropathy
• Pericarditis
• Myocarditis
• Bronchiectasis
• Swyer-James syndrome (post-infectious obliterative bronchiolitis)
• Bullous myringitis (possible)

• Prognosis is usually good, and the majority of patients recover completely even without antimicrobial therapy.^[1]
• Elderly individuals and patients with sickle cell disease and other immunocompromised patients are at increased risk of developing complications of Mycoplasma pneumonia.^[1]