Mycoplasma species are the smallest free-living organisms and are unique among prokaryotes in that they lack a cell wall. This feature is largely responsible for their biologic properties, including lack of a Gram stain reaction and nonsusceptibility to many commonly prescribed antimicrobial agents, including beta-lactams. Mycoplasma organisms are usually associated with mucosae. They usually reside extracellularly in the respiratory and urogenital tracts and rarely penetrate the submucosa, except in the case of immunosuppression or instrumentation, when they may invade the bloodstream and disseminate to numerous organs and tissues. Some species also occur as intracellular pathogens.
Among the 17 species isolated from humans, 4 types of organisms are of major concern. Mycoplasma pneumoniae is a well-established pathogen; it is rarely isolated from healthy persons. Mycoplasma hominis and Ureaplasma species, known collectively as the genital mycoplasmal organisms, are generally considered opportunists that cause invasive infections in susceptible populations.
The 2 Ureaplasma biovars, Ureaplasma urealyticum and Ureaplasma parvum, are now designated as separate species. Separation of these species is not possible except via molecular techniques such as polymerase chain reaction (PCR). Therefore, they are now considered together as Ureaplasma species.  U parvum is generally the most common species detected in various clinical specimens but U urealyticum is apparently more pathogenic in conditions such as male urethritis . This differential pathogenicity at the species level has not been shown consistently for other disease conditions. [2, 3, 4]
Serologic studies and PCR have enhanced knowledge of several other fastidious and slow-growing mycoplasmal organisms, including Mycoplasma genitalium, Mycoplasma fermentans, Mycoplasma pirum, and Mycoplasma penetrans, and their possible roles in certain pathologic conditions in humans. Because of their extremely fastidious nature and the lack of reliable means for cultivation on artificial media, detection of these mycoplasmal organisms rests primarily with molecular techniques. Relatively little is known about their importance as human pathogens, with the notable exception of M genitalium, an organism that has been the focus of a considerable number of clinical research studies in recent years. This research and the subsequent data are made possible by the availability of PCR assays, which can detect the presence of these organisms.
Although M hominis and Ureaplasma species are frequently detected in the lower urogenital tracts of healthy adults, they can also produce localized urogenital diseases. In some settings, they can produce infection in extragenital sites, as does M genitalium. Recent studies with PCR assays expanded the understanding of sites of mycoplasmal localization within the human body. The presence of M fermentans was demonstrated in the throats of children with pneumonia and in the synovial fluid of persons with rheumatoid arthritis. M genitalium is found in the lower urogenital tracts of men with urethritis and women with cervicitis and pelvic inflammatory disease. M penetrans is found in the urine of children and homosexual males infected with HIV, but the clinical significance of this is not known.
No credible evidence indicates that mycoplasmal organisms have a role in the pathogenesis of Gulf War syndrome. 
The newest mycoplasmal species to be detected in humans is Mycoplasma amphoriforme, an organism detected in the lower respiratory tract of immunosuppressed persons with chronic bronchitis.  Its true role as a human pathogen has not yet been determined.
In humans, both Mycoplasma and Ureaplasma species may be transmitted by direct contact between hosts (ie, venereally through genital-to-genital or oral-to-genital contact), vertically from mother to offspring (either at birth or in utero), or by nosocomial acquisition through transplanted tissues. Respiratory infections caused primarily by M pneumoniae are usually transmitted through respiratory aerosols.
U urealyticum and M genitalium are causes of nonchlamydial nongonococcal urethritis in men. [1, 7] No evidence indicates that that M hominis causes female urethral syndrome; however, Ureaplasma species may be involved. Ureaplasma organisms have been recovered from an epididymal aspirate from a patient with acute epididymoorchitis, and these organisms may be an infrequent cause of the disease. M hominis has been isolated from the upper urinary tract of patients with symptoms of acute pyelonephritis and may cause approximately 5% of cases.
Mycoplasma species do not cause vaginitis, but they may proliferate in patients with bacterial vaginosis and may contribute to the condition. M hominis has been isolated from the endometria and fallopian tubes of approximately 10% of women with salpingitis; M genitalium may also be involved in pelvic inflammatory disease and cervicitis. Whether Ureaplasma infection causes involuntary infertility remains speculative. Ureaplasma species can cause placental inflammation and may invade the amniotic sac early, causing persistent infection and adverse pregnancy outcomes, including premature birth. M hominis has been isolated from the blood of approximately 10% of women with postpartum or postabortal fever, but not from afebrile women who had abortions or from healthy women who are pregnant. Similar observations have been made for Ureaplasma species.
Colonization of infants by genital mycoplasmal organisms may occur by ascension of the microorganisms from the lower genital tract of the mother at the time of delivery or by direct invasion of the fetus in utero. Congenital pneumonia, bacteremia, meningitis, and death have occurred in infants with very low birth weight due to Ureaplasma or Mycoplasma infection of the lower respiratory tract. In several large studies, chronic lung disease of prematurity or bronchopulmonary dysplasia has also been associated with the presence of Ureaplasma organisms in the lower respiratory tract, presumably because of low-grade inflammation in the airways that causes a prolonged need for supplemental oxygen coupled with barotrauma of mechanical ventilation and oxidant damage due to oxygen administration. 
Experimental infection studies using nonhuman primate models have shown that Ureaplasma in amniotic fluid causes up-regulation of proinflammatory cytokines, leukocytes, and prostaglandins, potentially contributing to premature delivery and fetal lung injury. 
Both M hominis and Ureaplasma species have been isolated from maternal blood, umbilical cord blood, and neonatal blood. Both organisms can invade the cerebrospinal fluid (CSF) and induce pleocytosis. While M fermentans has been detected in pure culture from placentae and amniotic fluid in the presence of inflammation, no studies confirm its occurrence and significance in neonates. 
Both Mycoplasma and Ureaplasma species can cause invasive disease of the joints and respiratory tract with bacteremic dissemination, particularly in persons with antibody deficiencies, indicating the importance of the humoral immune system in host defense against these organisms.  Ureaplasma species are the most common nonbacterial etiologies of infectious arthritis in persons who are hypogammaglobulinemic. M hominis bacteremia has been demonstrated following renal transplantation, trauma, and genitourinary manipulations. This organism has also been found in surgical wound infections, fluids from pericardial effusions, prosthetic valves affected by endocarditis, and subcutaneous abscesses. Both organisms can cause osteomyelitis.
M fermentans, M hominis, and Ureaplasma species can be detected with culture or PCR in the synovial fluid of persons with rheumatoid arthritis. Their precise contribution to this disease is uncertain.  Production of urease by Ureaplasma species is a mechanism by which these organisms can produce struvite calculi in the urinary tract. 
The significance of M fermentans, M penetrans, M pirum, and other mycoplasmal infections in persons also infected with HIV has received a great deal of attention and is a matter of debate. M fermentans has also been detected in adults with an acute influenzalike illness and in the bronchoalveolar lavage fluids of patients with AIDS and pneumonia. Apparently, respiratory tract infection with M fermentans is not necessarily linked with immunodeficiency, but it may behave as an opportunistic respiratory pathogen. 
Ureaplasma species have been isolated from cervicovaginal specimens in 40-80% of women who are asymptomatic and sexually active. M hominis has been isolated from cervicovaginal specimens in 21-53% of women who are asymptomatic and sexually active.  These rates are somewhat lower in males. Only a subgroup of adults who are colonized in the lower urogenital tract develop symptomatic illness from these organisms. Nongonococcal urethritis is the most common sexually transmitted infection. Ureaplasma species and M genitalium may account for a significant portion of cases that are not due to chlamydiae. M genitalium is much less likely to be present in the urogenital tract of asymptomatic persons.
More than 20% of liveborn infants may be colonized by Ureaplasma, and infants born preterm most likely harbor the organisms. Colonization declines after age 3 months. Less than 5% of children and 10% of adults who are not sexually active are colonized with genital mycoplasmal microorganisms. 
Immunosuppression (eg, from antibody deficiency or prematurity) increases the likelihood of developing disseminated disease. Much less is known about the epidemiology of species such as M genitalium and M fermentans. Some organisms, such as M pirum and M penetrans, have been primarily isolated from persons with HIV infection but their significance as pathogens in this population has not been established. 
Although few studies have investigated the geographic distribution of genital mycoplasmal infections, the facts that they (1) are present on mucosal surfaces in so many healthy persons and (2) can be transmitted venereally suggest that variation in prevalence of these organisms in adults is more likely related to behavioral variables such as number of sexual partners and socioeconomic status rather than to geographic or climatic differences.
Assessing morbidity and mortality for diseases specifically caused by genital mycoplasmal infections is difficult because few studies systematically evaluate them and some conditions with which they are involved can be polymicrobial (eg, pelvic inflammatory disease, urethritis). Difficulty in detecting the more fastidious species, such as M genitalium and M fermentans, further complicates such assessments.
In adults with an intact and functional immune system, infections associated with genital mycoplasmal organisms are usually localized and do not result in severe illness, attesting to their relatively low virulence and perceived status as opportunists.
Persons with antibody deficiencies reportedly have developed severe pulmonary infections, destructive arthritis and osteomyelitis associated with subcutaneous abscesses, and other disseminated infections of various organ systems.
Deaths have occurred in neonates with bloodstream invasion by Ureaplasma species and meningitis caused by M hominis; however, in some instances, the organisms spontaneously disappeared from CSF without treatment. 
Sporadic case reports document fatal infections caused by Mycoplasma species of animal origin, including Mycoplasma arginini in immunosuppressed hosts, but these are extremely rare. 
Differences in carriage of genital mycoplasmal organisms and subsequent disease are more likely related to sexual behavior and socioeconomic status than to race. Colonization appears to be more common in African Americans than in whites, but it is not clear whether this is a true racial difference as opposed to a socioeconomic factor.
No obvious sex predilection is reported for infections due to genital mycoplasmal species, except for the differences in urogenital diseases such as salpingitis and endometritis, which are gender-specific. The carriage rate of genital Mycoplasma species in the lower urogenital tract is somewhat greater for females than for males.
Ureaplasma species have been isolated from cervicovaginal specimens in 40-80% of women who are asymptomatic and sexually active, and M hominis has been isolated from cervicovaginal specimens in 21-53% of women who are asymptomatic and sexually active. This prevalence is somewhat lower in males.
M hominis and Ureaplasma species are common commensal inhabitants of the lower genitourinary tract in adolescents and adult men and women who are sexually active. The organisms can be transmitted venereally and vertically from mother to offspring. 
Neonates who acquire the organisms are usually colonized in the upper and sometimes lower respiratory tracts with occasional dissemination to the bloodstream and CSF. Clinically significant infections may ensue in individuals who are sexually active and in neonates but are rare to nonexistent in older children and adolescents who are not sexually active, with the exception of those with immunodeficiencies. 
M fermentans has been recovered from the throats of children with pneumonia; however, the frequency of its occurrence in healthy children is unknown. 
Little is known about the occurrence of other mycoplasmal species in different populations and specific associations with disease.