Ureaplasma Infection

Updated: Nov 14, 2022
  • Author: Ken B Waites, MD; Chief Editor: Michael Stuart Bronze, MD  more...
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Overview

Practice Essentials

Ureaplasma urealyticum and Ureaplasma parvum are common commensal organisms found in the lower urogenital tracts of many healthy sexually active adults. Mycoplasma hominis may also be found in this population, but at lower frequencies, quite often in association with ureaplasmas. Mycoplasma genitalium is even less common in healthy asymptomatic hosts. All these organisms can produce urogenital infections in men and women and can be transmitted venereally between individuals and vertically from mother to offspring. Persons who are immunosuppressed due to congenital antibody deficiencies, iatrogenically following organ transplantation, or because they are extremely preterm neonates may be susceptible to disseminated infection.

Since these organisms require highly specialized conditions for culture in vitro and because molecular-based detection is not widely available (except for M genitalium), clinicians must be aware of the clinical syndromes with which these organisms have been associated and have a high level of suspicion prompting them to order the appropriate diagnostic tests from reference laboratories. Treatment is often empiric but ideally should be based on a microbiological diagnosis proving their presence. While tetracyclines, macrolides, lincosamides, and quinolones have historically been used for treatment of infections due to these organisms, acquired resistance is now well documented and varies according to drug, organism, and patient population. In vitro susceptibility testing and molecular resistance testing may be useful to guide therapy, especially for disseminated infections if available. 

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Background

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 usually are 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. [1] U parvum generally is 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, Mycoplasma amphoriforme, and their possible roles in certain pathologic conditions in humans. 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.

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Pathophysiology

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, particularly in immunosuppressed hosts, 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 arthritisM 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 and has been implicated as a possible cause of male urethritis. [5]  No credible evidence indicates that mycoplasmal organisms have a role in the pathogenesis of Gulf War syndrome. [6]

The newest mycoplasmal species to be detected in humans is Mycoplasma amphoriforme, an organism initially detected in the lower respiratory tract of immunosuppressed persons with chronic bronchitis. [7] Its true role as a human pathogen has not yet been determined, but evidence of person-to-person transmission is accumulating, as well as the possibility that it causes illness in immunocompetent persons. [8]

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, 9] No evidence indicates that that M hominis causes female urethral syndrome; however, Ureaplasma species may be involved. M hominis and Ureaplasma species have not been detected via culture of prostatic biopsy samples from patients with chronic abacterial prostatitis, [10] and M genitalium has been found rarely via PCR assay. [11]  Ureaplasma species and M genitalium have been recovered from epididymis from patients with acute epididymoorchitis and 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 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. M genitalium can be found more frequently at both urethral and rectal sites of HIV-positive homosexual men than those who are HIV- negative, [12] and M genitalium cervicitis is more common in HIV-positive than in HIV-negative women. [13]  

Whether Ureaplasma infection causes involuntary infertility remains speculative, but some infertility specialists recommend testing infertile women and their sexual partners for ureaplasmas and treating them if positive. 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 M hominis 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. [1, 14]

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. [15]

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. [1] Although few studies have investigated the role of M genitalium infection in adverse pregnancy outcomes and neonatal diseases, recent evidence suggests that this mycoplasma can play a role in spontaneous abortion and preterm birth. [16, 17]

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. [18, 19] Ureaplasma species are the most common nonbacterial etiologies of infectious arthritis in persons who are hypogammaglobulinemic. 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. [6]

M hominis bacteremia has been demonstrated after renal transplantation, trauma, and genitourinary manipulations. This organism has also been found in the lower respiratory tract of persons with pneumonia, surgical wound infections, fluids from pericardial effusions, prosthetic valves affected by endocarditis, and abscesses in various locations, including the brain. Both organisms can cause osteomyelitis and meningitis. [20, 21] Ureaplasma species have also been associated with culture-negative endocarditis. Production of urease by Ureaplasma species is a mechanism by which these organisms can produce struvite calculi in the urinary tract. [1] Ureaplasma species and M hominis have been shown to cause systemic and sometimes fatal infections leading to hyperammonemia in immunosuppressed transplant recipients. [22, 23, 24]  Disseminated urogenital Mycoplasma and Ureaplasma infections outside the neonatal period are most often associated with a defect in humoral immunity and very rarely occur in hosts with a normally functioning immune system.

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. [1]

 

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Epidemiology

Frequency

United States

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. [1] 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, occurring in about 1% to 6.4% of men and women in the general population. However, it has a much higher prevalence (sometimes exceeding 20%) in persons with urogenital symptoms and in those who attend clinics providing sexual health services. [25]  

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. [1]

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. [1]

International

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.

Mortality/Morbidity

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. Fatal cases of hyperammonemia in lung transplant recipients who had systemic infections with M hominis and Ureaplasma species are now well known. [22, 23]

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. [1]

Sporadic case reports document fatal infections caused by Mycoplasma species of animal origin, including Mycoplasma arginini in immunosuppressed hosts, but these are extremely rare. [6]

Race

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.

Sex

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. Most people who are colonized with the genital mycoplasmas do not develop clinical illnesses.

Age

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. Larger numbers of sexual contacts may result in greater likelihood of colonization and disease with these organisms which can be transmitted venereally as well as vertically from mother to offspring. [1]

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, except for those with immunodeficiencies. [1]

M fermentans has been recovered from the throats of children with pneumonia; however, the frequency of its occurrence in healthy children is unknown. [1]

Little is known about the occurrence of other mycoplasmal species in different populations and specific associations with disease.

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Prognosis

Mycoplasma hominis, Mycoplasma genitaliumUreaplasma parvum, and Ureaplasma urealyticum are fairly low-grade pathogens that usually cause severe illness only in immunosuppressed hosts. This can include persons with congenital antibody deficiencies, persons undergoing iatrogenic immunosuppression following organ transplantation, and preterm neonates. Treatment with the proper antimicrobial agents will usually clear mucosal infections such as urethritis in normal hosts, but systemic infections in immunosuppressed hosts can be extremely difficult to eradicate and may evolve into chronic conditions in which the organisms and symptoms return once antimicrobial agents are discontinued. 

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Patient Education

Patients who are shown by culture or molecular-based testing to have an infection known to be caused by M hominis, M genitalium, U urealyticum, or U parvum should receive appropriate antimicrobial treatment. Clinical infection should be distinguished from colonization, and other causes of illness should be excluded before assuming it is due to one of the genital mycoplasmas. Sexually active men and women may have long-term asymptomatic colonization in the urethra and vagina that cannot be eradicated with multiple courses of antimicrobials and should be told this. Abstinence from sexual relations can help prevent recurrence once an infection is eradicated. All sexual partners of persons proven to be infected should be treated with the same antimicrobial, especially if the causative organism is M genitalium. There are no recommendations for screening or treating asymptomatic persons who have a positive culture or molecular-based test for these organisms. [26]  There also is no justification in treatment of any clinical condition not known to be associated with the presence of the genital mycoplasmas, even in the setting of a positive laboratory test indicating their presence.

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