Review of Medical Microbiology and Immunology, 13th Edition

23. Mycoplasmas



Mycoplasma pneumoniae

Self-Assessment Questions

Summaries of Organisms

Practice Questions: USMLE & Course Examinations


Mycoplasmas are a group of very small, wall-less organisms, of which Mycoplasma pneumoniae is the major pathogen.



M. pneumoniae causes “atypical” pneumonia.

Important Properties

Mycoplasmas are the smallest free-living organisms; many are as small as 0.3 mm in diameter. Their most striking feature is the absence of a cell wall.1

Consequently, mycoplasmas stain poorly with Gram stain, and antibiotics that inhibit cell wall (peptidoglycan) synthesis (e.g., penicillins and cephalosporins) are ineffective. Their outer surface is a flexible cell membrane; hence these organisms can assume a variety of shapes. Theirs the only bacterial membrane that contains cholesterol, a sterol usually found in eukaryotic cell membranes.

Mycoplasmas can be grown in the laboratory on artificial media, but they have complex nutritional requirements, including several lipids. They grow slowly and require at least 1 week to form a visible colony. The colony frequently has a characteristic “fried-egg” shape, with a raised center and a thinner outer edge.

Pathogenesis & Epidemiology

M. pneumoniae, a pathogen only for humans, is transmitted by respiratory droplets. In the lungs, the organism is rod-shaped, with a tapered tip that contains specific proteins that serve as the point of attachment to the respiratory epithelium. The respiratory mucosa is not invaded, but ciliary motion is inhibited and necrosis of the epithelium occurs. The mechanism by which M. pneumoniae causes inflammation is uncertain. It does produce hydrogen peroxide, which contributes to the damage to the respiratory tract cells.

M. pneumoniae has only one serotype and is antigenically distinct from other species of Mycoplasma. Immunity is incomplete, and second episodes of disease can occur. During M. pneumoniae infection, autoantibodies are produced against red cells (cold agglutinins) and brain, lung, and liver cells. These antibodies may be involved in some of the extrapulmonary manifestations of infection.

M. pneumoniae infections occur worldwide, with an increased incidence in the winter. This organism is the most frequent cause of pneumonia in young adults and is responsible for outbreaks in groups with close contacts such as families, military personnel, and college students. It is estimated that only 10% of infected individuals actually get pneumonia. Mycoplasma pneumonia accounts for about 5% to 10% of all community-acquired pneumonia.

Clinical Findings

Mycoplasma pneumonia is the most common type of atypical pneumonia. It was formerly called primary atypical pneumonia. (Atypical pneumonia is also caused by Legionella pneumophila [Legionnaires’ disease], Chlamydia pneumoniae, Chlamydia psittaci [psittacosis], Coxiella burnetii [Q fever], and viruses such as such as influenza virus and adenovirus. The term atypical means that a causative bacterium cannot be isolated on routine media in the diagnostic laboratory or that the disease does not resemble pneumococcal pneumonia.) The onset of Mycoplasma pneumonia is gradual, usually beginning with a nonproductive cough, sore throat, or earache. Small amounts of whitish, nonbloody sputum are produced. Constitutional symptoms of fever, headache, malaise, and myalgias are pronounced. The paucity of findings on chest examination is in marked contrast to the prominence of the infiltrates seen on the patient’s chest X-ray. The disease resolves spontaneously in 10 to 14 days. In addition to pneumonia, M. pneumoniae also causes bronchitis.

The extrapulmonary manifestations include Stevens-Johnson syndrome, erythema multiforme, Raynaud’s phenomenon, cardiac arrhythmias, arthralgias, hemolytic anemia, and neurologic manifestations such as Guillain-Barré syndrome.

Laboratory Diagnosis

Diagnosis is usually not made by culturing sputum samples; it takes at least 1 week for colonies to appear on special media. Culture on regular media reveals only normal flora.

Serologic testing is the mainstay of diagnosis. A cold-agglutinin titer of 1:128 or higher is indicative of recent infection. Cold agglutinins are IgM autoantibodies against type O red blood cells that agglutinate these cells at 4°C but not at 37°C. However, only half of patients with Mycoplasma pneumonia will be positive for cold agglutinins. The test is nonspecific; false-positive results occur in influenza virus and adenovirus infections. The diagnosis of M. pneumoniae infection can be confirmed by a fourfold or greater rise in specific antibody titer in the complement fixation test.


The treatment of choice is either a macrolide, such as erythromycin or azithromycin, or a tetracycline, such as doxycycline. The fluoroquinolone levofloxacin is also effective. These drugs can shorten the duration of symptoms, although, as mentioned earlier, the disease resolves spontaneously. Penicillins and cephalosporins are inactive because the organism has no cell wall.


There is no vaccine or other specific preventive measure.

Other Mycoplasmas

Mycoplasma hominis has been implicated as an infrequent cause of pelvic inflammatory disease. Ureaplasma urealyticum may cause approximately 20% of cases of nongonococcal urethritis. Ureaplasmas can be distinguished from mycoplasmas by their ability to produce the enzyme urease, which degrades urea to ammonia and carbon dioxide.


1Mycoplasma pneumoniae is an important cause of atypical pneumonia. Regarding this organism, which one of the following is the most accurate?

(A) Amoxicillin is the drug of choice for pneumonia caused by this organism.

(B) Antibody in a patient’s serum will agglutinate human red blood cells at 4°C, but not at 37°C.

(C) Gram stain of the sputum reveals small gram-negative rods.

(D) It is an obligate intracellular parasite that can only grow within human cells in the clinical laboratory.

(E) People with cystic fibrosis are predisposed to pneumonia caused by this organism.

2. Which one of the following is the drug of choice for atypical pneumonia caused by M. pneumoniae?

(A) Amoxicillin

(B) Azithromycin

(C) Ceftriaxone

(D) Gentamicin

(E) Vancomycin


1. (B)

2. (B)


Brief summaries of the organisms described in this chapter begin on page 663. Please consult these summaries for a rapid review of the essential material.


Questions on the topics discussed in this chapter can be found in the Clinical Bacteriology section of PART XIII: USMLE (National Board) Practice Questions starting on page 693. Also see PART XIV: USMLE (National Board) Practice Examination starting on page 731.

1Other types of bacteria, in the presence of penicillin, can exist in a wall-less state called an “L form” but can resynthesize their cell walls when penicillin is removed.

If you find an error or have any questions, please email us at Thank you!