- Author: Ken B Waites, MD; Chief Editor: Michael Stuart Bronze, MD more...
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. Recent 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.
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. This toxin, named the community-acquired respiratory disease toxin (CARDS) is an ADP-ribosylating and vacuolating cytotoxin similar to pertussis toxin.
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. Variation in CARDS toxin production among M pneumoniae strains may be correlated with the range of severity of pulmonary disease observed among patients. The organism also has the ability to exist and possibly replicate intracellularly, which may contribute to chronicity of illness and difficult eradication. Additionally, acute mycoplasmal respiratory tract infection may be associated with exacerbations of chronic bronchitis and asthma. More extensive information on the pathogenesis of mycoplasmal respiratory infections is available in review articles and book chapters.[7, 1, 6]
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.
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.
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.
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. 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.
Recent evidence suggests that M pneumoniae disease is sometimes much more severe than appreciated, even in otherwise healthy children and adults. 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.
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.
Muir MT, Cohn SM, Louden C, Kannan TR, Baseman JB. Novel toxin assays implicate Mycoplasma pneumoniae in prolonged ventilator course and hypoxemia. Chest. 2011 Feb. 139(2):305-10. [Medline].
Kannan TR, Provenzano D, Wright JR, Baseman JB. Identification and characterization of human surfactant protein A binding protein of Mycoplasma pneumoniae. Infect Immun. 2005 May. 73(5):2828-34. [Medline].
Techasaensiri C, Tagliabue C, Cagle M, Iranpour P, Katz K, Kannan TR. Variation in colonization, ADP-ribosylating and vacuolating cytotoxin, and pulmonary disease severity among mycoplasma pneumoniae strains. Am J Respir Crit Care Med. 2010 Sep 15. 182(6):797-804. [Medline].
Hardy RD, Coalson JJ, Peters J, Chaparro A, Techasaensiri C, Cantwell AM. Analysis of pulmonary inflammation and function in the mouse and baboon after exposure to Mycoplasma pneumoniae CARDS toxin. PLoS One. 2009. 4(10):e7562. [Medline].
Talkington DF, Waites KB, Schwartz S, Besser RE. Emerging from obscurity: Understanding pulmonary and extrapulmonary syndromes, pathogenesis, and epidemiology of human Mycoplasma pneumoniae infections. Scheld WM, Craig WA, Hughes JM, eds. Emerging Infections. Washington, DC: ASM Press; 2001. Vol 5: 57-84.
Foy HM. Infections caused by Mycoplasma pneumoniae and possible carrier state in different populations of patients. Clin Infect Dis. 1993 Aug. 17 Suppl 1:S37-46. [Medline].
Marston BJ, Plouffe JF, File TM Jr, et al. Incidence of community-acquired pneumonia requiring hospitalization. Results of a population-based active surveillance Study in Ohio. The Community-Based Pneumonia Incidence Study Group. Arch Intern Med. 1997 Aug 11-25. 157(15):1709-18. [Medline].
Waites KB. New concepts of Mycoplasma pneumoniae infections in children. Pediatr Pulmonol. 2003 Oct. 36(4):267-78. [Medline].
Cunha BA. The atypical pneumonias: clinical diagnosis and importance. Clin Microbiol Infect. 2006 May. 12 Suppl 3:12-24. [Medline].
Cunha BA. Pneumonia Essentials. 3rd ed. Royal Oak, MI: Physicians Press; 2010.
Cunha BA. Liver involvement with Mycoplasma pneumoniae community-acquired pneumonia. J Clin Microbiol. Jul/2003. 41(7):3456-7. [Medline].
Parchuri S, Cunha BA. Mycoplasma pneumoniae community-acquired pneumonia: Diagnostic usefulness of the agglutination-dissociation test. Infect Dis Pract. 2006. 30:550-1.
Talkington DF, Shott S, Fallon MT, Schwartz SB, Thacker WL. Analysis of eight commercial enzyme immunoassay tests for detection of antibodies to Mycoplasma pneumoniae in human serum. Clin Diagn Lab Immunol. 2004 Sep. 11(5):862-7. [Medline].
Beersma MF, Dirven K, van Dam AP, Templeton KE, Claas EC, Goossens H. Evaluation of 12 commercial tests and the complement fixation test for Mycoplasma pneumoniae-specific immunoglobulin G (IgG) and IgM antibodies, with PCR used as the "gold standard". J Clin Microbiol. 2005 May. 43(5):2277-85. [Medline].
Winchell JM, Thurman KA, Mitchell SL, Thacker WL, Fields BS. Evaluation of three real-time PCR assays for detection of Mycoplasma pneumoniae in an outbreak investigation. J Clin Microbiol. 2008 Sep. 46(9):3116-8. [Medline].
Liu Y, Ye X, Zhang H, Xu X, Li W, Zhu D, et al. Antimicrobial susceptibility of Mycoplasma pneumoniae isolates and molecular analysis of macrolide-resistant strains from Shanghai, China. Antimicrob Agents Chemother. 2009 May. 53(5):2160-2. [Medline]. [Full Text].
Li X, Atkinson TP, Hagood J, Makris C, Duffy LB, Waites KB. Emerging macrolide resistance in Mycoplasma pneumoniae in children: detection and characterization of resistant isolates. Pediatr Infect Dis J. 2009 Aug. 28(8):693-6. [Medline].
Peuchant O, Ménard A, Renaudin H, Morozumi M, Ubukata K, Bébéar CM, et al. Increased macrolide resistance of Mycoplasma pneumoniae in France directly detected in clinical specimens by real-time PCR and melting curve analysis. J Antimicrob Chemother. 2009 Jul. 64(1):52-8. [Medline].
Wolff BJ, Thacker WL, Schwartz SB, Winchell JM. Detection of macrolide resistance in Mycoplasma pneumoniae by real-time PCR and high-resolution melt analysis. Antimicrob Agents Chemother. 2008 Oct. 52(10):3542-9. [Medline]. [Full Text].
Suzuki S, Yamazaki T, Narita M, et al. Clinical evaluation of macrolide-resistant Mycoplasma pneumoniae. Antimicrob Agents Chemother. 2006 Feb. 50(2):709-12. [Medline].
Klausner JD, Passaro D, Rosenberg J, et al. Enhanced control of an outbreak of Mycoplasma pneumoniae pneumonia with azithromycin prophylaxis. J Infect Dis. 1998 Jan. 177(1):161-6. [Medline].
Ou G, Liu Y, Tang Y, You X, Zeng Y, Xiao J, et al. In vitro subminimum inhibitory concentrations of macrolide antibiotics induce macrolide resistance in Mycoplasma pneumoniae. Hippokratia. 2015 Jan-Mar. 19 (1):57-62. [Medline].