Mycoplasma Infections (Mycoplasma pneumoniae)


Mycoplasma species are the smallest free-living organisms. These organisms are unique among prokaryotes in that they lack a cell wall, a feature largely responsible for their biologic properties such as their lack of a reaction to Gram stain and their lack of susceptibility to many commonly prescribed antimicrobial agents, including beta-lactams. Mycoplasmal organisms are usually associated with mucosal surfaces, residing extracellularly in the respiratory and urogenital tracts. They rarely penetrate the submucosa, except in the case of immunosuppression or instrumentation, when they may invade the bloodstream and disseminate to different organs and tissues throughout the body.

Although scientists have isolated at least 17 species of Mycoplasma from humans, 4 types of organisms are responsible for most clinically significant infections that may come to the attention of practicing physicians. These species are Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma genitalium, and Ureaplasma species. The focus of this article is infections caused by M pneumoniae; articles on Ureaplasma infections (eg, Ureaplasma Infection) and genital mycoplasmal infections contain discussions of infections caused by other mycoplasmal species.


M pneumoniae is perhaps best known as the cause of community-acquired walking or atypical pneumonia, but the most frequent clinical syndrome caused by this organism is actually tracheobronchitis or bronchiolitis, often accompanied by upper respiratory tract manifestations. Pneumonia develops in only 5-10% of persons who are infected. Acute pharyngitis may also occur. [1Recent evidence has also implicated M pneumoniae with prolonged ventilator course and hypoxemia in adults with suspected ventilator-associated pneumonia. However, the presence of other microorganisms in many of these patients makes it difficult to assess the true role of M pneumoniae as a causative pathogen in this setting. [2]

After inhalation of respiratory aerosols, the organism attaches to host epithelial cells in the respiratory tract. The P1 adhesin and other accessory proteins mediate attachment, followed by induction of ciliostasis, local inflammation that consists primarily of perivascular and peribronchial infiltration of mononuclear leukocytes, and tissue destruction that may be mediated by liberation of hydrogen peroxide. Recently, M pneumoniae has been shown to produce an exotoxin that is also believed to play a major role in the damage to the respiratory epithelium that occurs during acute infection. [3This toxin, named the community-acquired respiratory disease toxin (CARDS) is an ADP-ribosylating and vacuolating cytotoxin similar to pertussis toxin. [4]

Evidence from animal models of M pneumoniae infection have proven that recombinant CARDS toxin results in significant pulmonary inflammation, release of proinflammatory cytokines, and airway dysfunction. [5Variation in CARDS toxin production among M pneumoniae strains may be correlated with the range of severity of pulmonary disease observed among patients. [4The organism also has the ability to exist and possibly replicate intracellularly, which may contribute to chronicity of illness and difficult eradication. [1Additionally, acute mycoplasmal respiratory tract infection may be associated with exacerbations of chronic bronchitis and asthma. [6More extensive information on the pathogenesis of mycoplasmal respiratory infections is available in review articles and book chapters. [716]

Spread of infection throughout households is common, although person-to-person transmission is slower than for many other common bacterial respiratory tract infections; close contact appears necessary. The mean incubation period is 20-23 days. The organism may persist in the respiratory tract for several months, and sometimes for years in patients who are immunosuppressed, after initial infection. [8]



United States

Researchers estimate that more than 2 million cases of M pneumoniae infections occur annually. M pneumoniae causes approximately 20% of community-acquired pneumonias that require hospitalization and an even greater proportion of those that do not require hospitalization. M pneumoniae may exist endemically in large urban areas. Epidemics occur every 3-7 years, with the incidence varying considerably from year to year. Slow spread throughout households is common, with a mean incubation period of 20-23 days. Disease tends to not be seasonal, except for a slight increase in late summer and early fall. [1]


M pneumoniae infections occur both endemically and in cyclic epidemics in Japan and several European countries, similar to what occurs in the United States. Less information is available for tropical or polar countries; however, based on seroprevalence studies, the disease also occurs in these regions, suggesting that climate and geography are not important determinants in the epidemiology of M pneumoniae infections. [1]


As the term walking pneumonia implies, the great majority of M pneumoniae respiratory tract infections are mild and self-limited, although administration of antimicrobials hastens clinical resolution. Hospitalization is sometimes necessary, but recovery is almost always complete and without sequelae. Studies have indicated that M pneumoniae is second only to Streptococcus pneumoniae as a cause of bacterial pneumonia that requires hospitalization in elderly adults. [9Subclinical infections may occur in 20% of adults infected with M pneumoniae, suggesting that some degree of immunity may contribute to the failure of clinical symptoms in some instances. [1]

Recent evidence suggests that M pneumoniae disease is sometimes much more severe than appreciated, even in otherwise healthy children and adults. [6Severe disease is more common in persons with underlying disease or immunosuppression. Detection of CARDS toxin or antitoxin antibodies in bronchoalveolar lavage fluid obtained from persons with suspected ventilator-associated pneumonias in association with prolonged ventilator course and hypoxemia suggest this organism may be of considerable significance among trauma patients in intensive care units. [2]

Children with sickle cell disease and functional asplenia may be at greater risk for severe respiratory tract disease due to M pneumoniae. While reports describe fatal cases of mycoplasmal pneumonia, the overall mortality rate is extremely low, probably less than 0.1%.


No racial predilection is apparent.


Available studies indicate no sexual predilection for M pneumoniae disease.


M pneumoniae has long been associated with pneumonias in children aged 5-9 years, adolescents, and young adults. Infection is particularly common among college students and military recruits who are likely to live together in close proximity. M pneumoniae may be the most common agent causing bacterial pneumonia in such populations.

In recent years, M pneumoniae infection has been common in persons older than 65 years, accounting for as much as 15% of community-acquired pneumonia cases in persons in this age group.

The common misconception that M pneumoniae disease is rare among very young populations and among older adults has led to physician failure to consider the organism in the differential diagnoses of respiratory tract infections in persons in these age groups. Physicians should always consider M pneumoniae as a cause of pneumonia in persons of all ages, including children younger than 5 years. Although M pneumoniae disease in infants is somewhat uncommon, when it is present, it can be severe. 



Typical symptoms can develop and persist over weeks to months and include flulike manifestations.

Symptoms may include the following:

  • Generalized aches and pains

  • Fever (usually ≤ 102°F)

  • Cough - Usually nonproductive

  • Sore throat (nonexudative pharyngitis)

  • Headache/myalgias

  • Chills but not rigors

  • Nasal congestion with coryza

  • Earache

  • General malaise

In very young children, upper respiratory tract manifestations may predominate, whereas in older children and adults, lower respiratory tract symptoms are more likely.


Physical findings can be quite variable. Patients typically do not appear toxic or severely ill, but some abnormalities may be apparent in a significant proportion of cases.

Physical findings include the following:

  • Oropharyngeal inflammation

  • Cervical adenopathy - Usually absent

  • Erythematous tympanic membranes

  • Conjunctivitis

  • Maculopapular or urticarial rash

Chest auscultation in patients with pneumonia may demonstrate localized rhonchi and scattered moist rales, generally involving multiple lobes of the lung and sometimes accompanied by wheezes, with no signs of consolidation, egophony, or bronchial breathing.

In many persons, chest auscultative and percussive abnormalities are minimal to absent.

Extrapulmonary manifestations may occur in a minority of persons (see Complications). [6]


This is a bacterial infection caused by M pneumoniae.


Differential Diagnoses


Medical Care

Ambulatory care versus hospitalization

The choice of outpatient management versus hospitalization for persons with community-acquired pneumonia depends on the clinical syndrome and not the organism, largely because the microbiologic diagnosis is often unavailable when the physician must make these decisions.

Professional organizations of physicians and managed care organizations have developed management algorithms that include decision trees for diagnostic studies and management, including specifications of antimicrobial agents to be used. These guidelines vary somewhat, but, in general, the decision to hospitalize a patient depends on an assessment of the following:

  • The person's ability to tolerate and comply with oral medication

  • Whether the patient appears hypoxic or toxic to the extent that the physician suspects a bacteremic pneumonia

  • Whether the person is immunosuppressed

Relatively few patients with M pneumoniae pneumonia require hospitalization based on these criteria.

Antimicrobial therapy

Experts formerly believed that mycoplasmal respiratory tract infections were entirely self-limited and that antimicrobial treatment was not indicated.

Appropriate antimicrobial therapy shortens the symptomatic period and hastens radiological resolution of pneumonia and recovery, even though patients may shed organisms for several weeks.

When treating community-acquired pneumonia, physicians usually must provide empiric coverage for several different bacterial agents that may be responsible because the microbiologic diagnosis is seldom available at the initiation of treatment. Fortunately, many of the drugs of choice for treating M pneumoniae provide broad-spectrum coverage for other organisms.


Medication Summary

Oral erythromycin or one of the newer macrolides such as azithromycin or clarithromycin have long been the DOC for mycoplasmal respiratory tract infections. Tetracycline and its analogues are also active. Clindamycin is effective in vitro, but limited reports suggest it may not be active in vivo and thus is not considered a first-line treatment. Fluoroquinolones such as levofloxacin or moxifloxacin exhibit bactericidal antimycoplasmal activity but are generally less potent in vitro than macrolides against M pneumoniae. Their advantage lies in the fact that they are active against all classes of bacteria that produce clinically similar respiratory tract infections, including macrolide-resistant S pneumoniae. As would be predicted by the lack of a cell wall, none of the beta-lactams is effective in vitro or in vivo against M pneumoniae, and neither are the sulfonamides or trimethoprim. [1]

Mycoplasma species are slow-growing organisms that have the capacity to reside intracellularly; thus, respiratory tract infections are expected to respond better to longer treatment courses than might be offered for other types of infections. Although physicians typically prescribe most treatment regimens (ie, both oral and parenteral) for 7-10 days, a 14- to 21-day course of oral therapy with most agents is also appropriate. A 5-day course of oral azithromycin is approved for the treatment of community-acquired M pneumoniae pneumonia. Clinical data indicate that this duration of treatment is of comparable efficacy to a 10-day course of erythromycin. Other drugs, including fluoroquinolones, have been approved for the treatment of mycoplasmal respiratory infections with shorter courses because of their favorable pharmacokinetics and tolerability.

In addition to the administration of antimicrobials for the management of M pneumoniae infections, other measures (eg, cough suppressants, antipyretics, analgesics) should be administered as needed to relieve headaches and other systemic symptoms. Because extrapulmonary manifestations are often diagnosed late in the course of disease, the benefit of early treatment is unknown.

Since 2000, macrolide-resistant M pneumoniae caused by point mutations in domain V of 23S ribosomal RNA has emerged in Asia and has now been reported in Europe and North America. Recent surveillance conducted primarily in pediatric populations has documented resistance rates of 46%-93% in Japan, 69%-97% in China, 12.3%-23% in Taiwan, 61.3% in South Korea, 30% in Israel, 9.8% in France, and 8.2% in the United States.

Macrolide resistance has also been documented in adults, but to a lesser extent. Selection of resistance during macrolide therapy has been documented in children in France, Italy, and Israel.

While there are no apparent differences in initial presentation to distinguish a patient with macrolide-resistant M pneumoniae, when such infections occur, they are often clinically significant, resulting in prolonged fever, coughing, longer hospital stays, or worsening findings on chest radiographs compared with persons with infections caused by susceptible strains. [18192021]

The spread of macrolide resistance has led to development of real-time PCR-based assays to detect resistance genes directly in clinical specimens since cultures and conventional susceptibility tests require many more time. [211920In view of the increasing spread of macrolide resistance, clinicians are advised to monitor patient outcomes and to consider using alternative antimicrobial agents (eg, minocycline, doxycycline, tigecycline, fluoroquinolones) if an initial treatment with a macrolide is unsuccessful. [22]


Class Summary

Therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting.

Erythromycin (E-Mycin, Ery-Tab, E.E.S.)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections.

In children, age, weight, and severity of infection determine proper dosage. When bid dosing desired, half-total daily dose may be taken q12h. For more severe infections, double the dose.

Clarithromycin (Biaxin, Biaxin XL)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Azithromycin (Zithromax)

Semisynthetic antibiotic belonging to the macrolide subgroup of azalides and is similar in structure to erythromycin. Inhibits protein synthesis in bacterial cells by binding to the 50S subunit of bacterial ribosomes. Action generally is bacteriostatic but can be bactericidal in high concentrations or against susceptible organisms.

Doxycycline (Vibramycin)

Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Minocycline (Minocin)

Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria.

Levofloxacin (Levaquin)

Inhibits A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.

Moxifloxacin (Avelox)

Inhibits A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.

Gemifloxacin (Factive)

Inhibits DNA gyrase and topoisomerase IV, resulting in inhibition of bacterial DNA replication and transcription.

Telithromycin (Ketek)

Blocks bacterial protein synthesis by binding to domains II and V of 23s rRNA of the 50S ribosomal subunit.