Practice Essentials
Mycoplasma pneumoniae is a common respiratory pathogen that can cause both upper and lower respiratory tract infections in children and adults, with a wide range of severity from mild to life-threatening. It is a leading cause of community-acquired pneumonia (CAP) in school-aged children. In addition to respiratory symptoms, M pneumoniae infections also can present with extrapulmonary manifestations affecting multiple organ systems and have been associated with the development or exacerbation of asthma. [1]
Diagnosing M pneumoniae infections traditionally involved serological tests, but molecular-based tests such as polymerase chain reaction (PCR) have become more commonly used due to their higher sensitivity and specificity. These tests have revolutionized the diagnosis of M pneumoniae, allowing for more accurate and rapid detection of the pathogen.
One concerning aspect of M pneumoniae infections is the emergence of clinically significant acquired resistance to macrolide antibiotics, a common treatment for these infections. This resistance has become a global issue, complicating treatment options for healthcare providers.
During the COVID-19 pandemic, the incidence of M pneumoniae infections, like many other respiratory infections, decreased significantly. However, as the pandemic subsided, cases of M pneumoniae infections began to rise once again. Data in 2024 suggest that the rate of macrolide resistance in M pneumoniae isolates is lower than before the pandemic, offering hope for better treatment outcomes.
Overall, early and accurate diagnosis, along with appropriate antibiotic treatment, is crucial in managing M pneumoniae infections and reducing associated complications. Understanding the epidemiology, resistance patterns, and changing trends in M pneumoniae infections is essential for effective management of these respiratory illnesses. [2]
Background
Mycoplasma species are the smallest free-living organisms. They 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 usually are 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, four types of organisms are responsible for most clinically significant infections that may come to the attention of practicing physicians. These species are M pneumoniae, M hominis, M genitalium, and Ureaplasma species. This article is focused on 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 only one of several bacterial pathogens that cause CAPs with overlapping clinical presentations. It is impractical and even impossible to identify a microbiologic etiology in an ambulatory care setting or even a hospital setting when empiric antimicrobial treatment should be begun in a timely manner. Therefore, various professional organizations have published guidelines for diagnosis and management of CAP that are updated at periodic intervals taking into account changes in epidemiology of likely microbial causes and emergence of acquired antimicrobial resistance.
The American Thoracic Society (ATS) has joined with the Infectious Diseases Society of America (IDSA) to publish a guideline for adults, whereas the Pediatric Infectious Diseases Society (PIDSA) has joined with the IDSA to publish guidelines for children. The ATS/IDSA guidelines published in 2019 do not address laboratory testing or specific antimicrobial treatment directed at M pneumoniae, nor do they address the issue of treatment failures due to macrolide resistance. However, these guidlines for CAP, including moderate or severe illness, all incorporate macrolides, doxycycline, and/or fluoroquinolones into their recommendations. These antimicrobial agents should provide adequate coverage for M pneumoniae infections except for some of those that may be due to macrolide-resistant organisms. [3]
The PIDS/IDSA guidelines for CAP in children published in 2011 [4] recommend testing for M pneumoniae if laboratory results can be available within a clinically relevant timeframe. The guidelines were published prior to the widespread availablity of FDA-cleared automated commercial PCRs to detect M pneumoniae. The recommendations advise primary treatment with a macrolide, with levofloxacin as a secondary choice, even though they do not specifically address the issue of clinically significant macrolide resistance in M pneumoniae. There have been reports of successful treatment of children with macrolide-resistant M pneumoniae infections with levlfloxacin. [5]
Pathophysiology
M pneumoniae perhaps is best known as the cause of community-acquired walking or atypical pneumonia, but the most frequent clinical syndrome caused by this organism actually is tracheobronchitis or bronchiolitis, often accompanied by upper respiratory tract manifestations. Pneumonia develops in only 5-10% of persons who are infected. Acute pharyngitis also may occur. [5] M pneumoniae has been implicated 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. [6]
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. M pneumoniae has been shown to produce an exotoxin that also is believed to play a major role in the damage to the respiratory epithelium that occurs during acute infection. [7] This toxin, named the community-acquired respiratory disease toxin (CARDS) is an ADP-ribosylating and vacuolating cytotoxin similar to pertussis toxin. [8]
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. [9] Variation in CARDS toxin production among M pneumoniae strains may be correlated with the range of severity of pulmonary disease observed among patients. [8] The organism also has the ability to exist and possibly replicate intracellularly, which may contribute to chronicity of illness and difficult eradication. [5] Additionally, acute mycoplasmal respiratory tract infection may be associated with exacerbations of chronic bronchitis and asthma. [10] More extensive information on the pathogenesis of mycoplasmal respiratory infections is available in review articles and book chapters. [5, 10, 11]
Epidemiology
Frequency
United States
Researchers estimate that more than 2 million cases of M pneumoniae infections occur annually. M pneumoniae causes approximately 20% of CAPs that require hospitalization and an even greater proportion of those that do not require hospitalization. M pneumoniae may exist endemically in large urban areas. Disease tends not to be seasonal, except for a slight increase in late summer and early fall. [5] Epidemics occur every 3-7 years, with the incidence varying considerably from year to year. 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. [12]
Climate factors may be important in the spread of M pneumoniae. Analysis of the pattern of M pneumoniae pneumonia cases in Japan suggests that higher temperature and relative humidity are associated with higher rates of pneumonia, perhaps through effects on persistence of aerosols. [13]
International
M pneumoniae infections occur both endemically and in cyclic epidemics in Japan and several European countries, similar to the pattern seen 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. [5]
Mortality/Morbidity
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 sometimes is necessary, but recovery almost always is complete and without sequelae. Studies have indicated that M pneumoniae is second only to Streptococcus pneumoniae (S pneumoniae) as a cause of bacterial pneumonia that requires hospitalization in elderly adults. [14] Subclinical 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. [5]
Recent evidence suggests that M pneumoniae disease sometimes is much more severe than appreciated, even in otherwise healthy children and adults. [10] Severe 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. [6]
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%.
Race
No racial predilection is apparent.
Sex
Available studies indicate no sexual predilection for M pneumoniae disease.
Age
M pneumoniae long has 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. Please see Pediatric Mycoplasma Infections.
Infection caused by M pneumoniae has been common in persons older than 65 years, accounting for as much as 15% of CAP 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 always should 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. [15]
Prognosis
Most patients with respiratory infections caused by M pneumoniae will respond to oral antimicrobial treatment in an outpatient setting. [2] Elderly persons, very young infants, and persons with iimmunodeficiencies may have a harder time recovering and eradicating the organism. In some instances chronic infection can ensue. Additionally, there are some reports of fulminant and ultimately fatal cases of M pneumoniae infection in otherwise healthy persons.
