Ureaplasma Infection 

Updated: Jul 03, 2019
Author: Ken B Waites, MD; Chief Editor: Michael Stuart Bronze, MD 

Overview

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 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.[1] 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. 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 fastidious organisms.

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 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.[5]

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.[6] 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.[7]

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, 8] 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,[9] and M genitalium has been found rarely via PCR assay[10] . 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. M genitalium can be found more frequently at both urethral and rectal sites of HIV-positive homosexual men than those who are HIV- negative,[11] and M genitalium cervicitis is more common in HIV-positive than in HIV-negative women[12] . 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 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, 13]

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.[14]

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.[15]

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.[16, 17] 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.[5]

M hominis bacteremia has been demonstrated following 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.[18, 19] 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 lung transplant recipients.[20, 21] 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]

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.

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.

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.[5]

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.

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. The organisms can be transmitted venereally and 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, with the exception of 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.

 

Presentation

History

The clinical history of patients with urogenital or extragenital infections caused by Mycoplasma or Ureaplasma species is syndrome-specific, not organism-specific, and, as in the case of M pneumoniae respiratory tract infection, no distinguishing features indicate the microbiologic etiology of these conditions.

Many clinicians are unfamiliar with Mycoplasma and Ureaplasma species as etiologic agents. This unfamiliarity is further complicated by a lack of facilities to diagnose mycoplasmal infections in many clinical settings. Subsequently, identification of these organisms may be achieved only as a last resort, particularly if initial treatment with drugs that are ineffective against Mycoplasma or Ureaplasma species is unsuccessful. The following conditions may be caused by infection with Mycoplasmahominis and/or Ureaplasma species in various patient populations:

  • Urethritis ( Ureaplasma only)
  • Pyelonephritis
  • Cystitis
  • Pelvic inflammatory disease ( M hominis only)
  • Urinary calculi ( Ureaplasma only)
  • Endometritis or chorioamnionitis
  • Infectious arthritis
  • Surgical and nonsurgical wound infections
  • Preterm labor ( Ureaplasma only)
  • Bacteremia
  • Pneumonia
  • Meningitis
  • Hyperammonemia
  • Endocarditis
  • Abscesses

Mycoplasma and Ureaplasma organisms often play minor roles as causes of the above-named conditions, which may be caused by various microorganisms. When present in patients with some of these conditions, such as salpingitis, urethritis, and septic arthritis, one of several etiologic organisms may be present simultaneously.

M genitalium is known to cause male urethritis, female cervicitis, and pelvic inflammatory disease, clinically indistinguishable from these conditions as caused by other microorganisms such as Neisseria gonorrhoeae.[8]

Physical

Rather than listing the many nonspecific historical and clinical findings of various entities that may be associated with infection with Mycoplasma or Ureaplasma species, emphasizing the need to consider these organisms as potential etiologic agents in the conditions named above is more important in order to perform the necessary diagnostic tests and to provide appropriate antimicrobial treatment that provides coverage for them.

Consider a Mycoplasma or Ureaplasma infection when persons with hypogammaglobulinemia present with septic arthritis, chronic pulmonary infection, and any other inflammatory condition or infection that does not respond to antimicrobial treatment that is not likely to be effective against these organisms.

Refer to specific articles on urogenital (eg, Urethritis; Pyelonephritis, Acute; Pyelonephritis, Chronic), obstetric and gynecologic (eg, Pelvic Inflammatory Disease, Endometritis), and neonatal infections (eg, Pneumonia; Meningitis, Bacterial) for additional information regarding history and physical examination findings associated with these conditions.

Physical presentation of M hominis or Ureaplasma infection in neonates includes the following considerations:

  • Neonates, particularly those born preterm, are especially vulnerable to dissemination of infectious organisms (acquired in utero or at birth) in the bloodstream and, ultimately, the central nervous system.

  • Conventional gram-negative and gram-positive bacteria are usually considered the primary culprits of neonatal sepsis; however, when Mycoplasma and Ureaplasma organisms are specifically sought, evidence proves they may be of etiologic significance in neonatal lung disease, bacteremia, and meningitis.

  • As with most neonatal infections, no characteristic signs and symptoms predict the type of organism present. Subtle manifestations, such as temperature instability, blood pressure fluctuations, heart rate, and respiratory efforts, may be the only clues that an infection is present.

  • Consider Mycoplasma and Ureaplasma species if signs and symptoms of infection are present; if the neonate does not respond to beta-lactam drugs; and if cultures from blood, the lower respiratory tract, and CSF do not reveal a more common microbiological etiology.

  • Radiographic evidence of pneumonitis in the absence of a proven bacterial or viral etiology and mononuclear or polymorphonuclear pleocytosis of CSF with a negative Gram stain and culture result are consistent with infection associated with M hominis or Ureaplasma species.

Causes

The Ureaplasma genus now is subdivided into 2 species: U urealyticum and U parvum. For clinical purposes, separating infections caused by the different 2 species is not possible without molecular testing, nor is it necessary. In both the clinical setting and in the diagnostic laboratory, they are usually considered Ureaplasma species.

 

DDx

Diagnostic Considerations

Ureaplasma infections of the urogenital tract and systemic sites may be similar to infections caused by other bacteria and can only be distinguished by appropriate laboratory testing. Specifically, urogenital infections may mimic infections due to gonococci, chlamydiae, or other genital mycoplasmal species.

Differential Diagnoses

 

Workup

Laboratory Studies

Perform diagnostic tests for Mycoplasma and Ureaplasma species when a patient presents with a clinical condition known to be caused by or associated with these organisms and when more common etiologies are excluded. The correct microbiological diagnosis takes on greater importance in patients who are immunosuppressed and at greater risk for disseminated infection and a poor outcome.

Culture

Obtain culture results.

M hominis and Ureaplasma species can be detected in culture using specialized media and techniques within 2-5 days. These organisms can also be detected by PCR assays. M genitalium requires a PCR assay due to its slow growth and fastidious nature.

Specialized culture media and growth conditions are necessary, and most hospital-based laboratories do not offer these services on site, with the exception of some of the larger tertiary care university hospitals. Regional or national microbiology reference laboratories usually offer these cultures. Routine bacterial cultures are not sufficient to recover M hominis and cannot detect Ureaplasma species. Detailed laboratory procedures for detection and characterization of genital Mycoplasma and Ureaplasma infections can be found in reference texts.[22]

Specimens can be collected in a specialized liquid transport system, a growth medium designed for mycoplasmal organisms (eg, 10-B broth), or some of the common transport systems for Chlamydia species or other bacteria and viruses and shipped to a reference laboratory for testing if necessary. Preventing desiccation and protecting the specimen from adverse temperature extremes is essential if the organisms are to remain viable.

In men, urethral swabs are preferred over urine samples for detection of genital mycoplasmal infections because the organisms are cell associated. Use Dacron polyester swabs with plastic shafts, not wooden cotton-tipped swabs, because the latter may inhibit growth of Mycoplasma and Ureaplasma organisms. Prostatic secretions, semen, and urinary calculi can also be cultured.

For females, urine, cervical swabs, or vaginal swabs are acceptable. Avoid specimens contaminated by lubricants or antiseptics. Urine samples from females are most useful when obtained by catheter or suprapubic aspiration. Endometrial tissue, tubal samples, or pouch of Douglas fluid can be obtained to confirm a mycoplasmal etiology for pelvic inflammatory disease or postpartum fever. For women with clinical amnionitis, culture amniotic fluid, blood, and placenta.

Culture of nasopharyngeal, throat, and endotracheal secretions from neonates is appropriate, especially if their birth weight is less than 1500 g and they have clinical, radiographic, laboratory, or other evidence of pneumonia.

Extragenital or extrapulmonary specimens submitted for culture should reflect the site of infection and disease process. Sterile fluids, including synovial fluid, peritoneal fluid, pericardial fluid, CSF, and blood, are suitable for culture. Bone chips from patients with chronic osteomyelitis without a proven bacterial etiology are also appropriate for culture, as are wound aspirates and tissue collected after biopsy or autopsy. Successful isolation of M hominis and Ureaplasma species from blood can be achieved by inoculating 5-10 mL directly into liquid mycoplasmal growth medium in at least a 1:10 ratio. Smaller volumes can be used for neonates or children.

Proper specimen collection and handling

Proper specimen collection and handling are of utmost importance in detecting these fastidious organisms. Inquiring about the services of a suitable reference laboratory and maintaining the appropriate specimen transport medium in clinical facilities is worthwhile if Mycoplasma or Ureaplasma infections are frequently encountered. Numerous references describe the optimum conditions for specimen collection, handling, and detecting these organisms in culture.[22] Obtain specific instructions from the laboratory when testing is performed.

Serologic studies

Serologic studies are not useful for evaluating genital mycoplasmal infections and none is commercially available in the United States.

Molecular techniques

Molecular techniques such as the PCR assay are available from research or reference laboratories using published methods or their own internally developed protocols. FDA-approved molecular tests are commercially available for detection of M genitalium, but not for M hominis or Ureaplasma species. Therefore, the availability of molecular testing is quite limited for these organisms.

Molecular techniques such as PCR are not required when culture is available for M hominis and Ureaplasma species, although it should be acknowledged that PCR assays may be inherently more sensitive for detection of small numbers of organisms in clinical material. Fastidious slow-growing mycoplasmal species, such as M genitalium and M fermentans, may cause clinically significant illnesses in the respiratory tract, urogenital tract, or other sites. Their presence can be reliably detected only by molecular techniques such as the PCR assay.

Imaging Studies

Imaging studies are not usually performed as part of a workup for uncomplicated infections due to Mycoplasma or Ureaplasma. Exceptions include persons who are immunosuppressed and have apparent septic arthritis or suspected pulmonary infection and neonates with clinical evidence of pneumonitis or chronic lung disease of prematurity. In each of these instances, genital Mycoplasma species may be involved.

CT scanning

Case reports describe neonates with congenital infections in whom intracranial calcifications and necrosis consistent with congenital cytomegalovirus infection were observed, yet the only infectious organism detected was M hominis; thus, in neonates with unexplained neurologic abnormalities and CSF pleocytosis, CT scanning of the head may be useful to further characterize the intracranial pathologic effects.

Radiography

Radiographic features typical of neonatal pneumonitis caused by chlamydiae and other pathogens are associated with congenital Ureaplasma infection. Infants who are culture-positive in the lower respiratory tract for Ureaplasma species develop radiographic lung findings consistent with bronchopulmonary dysplasia more rapidly than neonates with negative cultures.

Procedures

Specimen collection

Collection of adequate culture specimens from the infected site is of utmost importance if the microbiological diagnosis of an infection due to Mycoplasma or Ureaplasma species is to be determined because none of the clinical manifestations or other laboratory tests is definitive.

Collection techniques include the following:

  • Lumbar puncture to obtain CSF

  • Arthrocentesis to obtain synovial fluid

  • Tracheal aspiration to obtain lower respiratory tract secretions or tissues

  • Lung biopsy to obtain lower respiratory tract secretions or tissues

  • Bronchoalveolar lavage to obtain lower respiratory tract secretions or tissues

  • Nasopharyngeal aspiration to obtain respiratory secretions in neonates who are not intubated

  • Blood collection to detect bacteremia

  • Urethral or cervicovaginal swabs to detect urethritis or pelvic inflammatory disease.

The nature of the procedure reflects the infection suspected.

Severity of illness dictates the extent to which invasive procedures (eg, lumbar puncture, bronchoalveolar lavage, lung biopsy) are necessary.

 

Treatment

Medical Care

Successful treatment hinges on promptly considering Mycoplasma and Ureaplasma species as potential etiologic agents, performing proper diagnostic tests for their detection, and providing appropriate antimicrobial coverage.

Although persons who are immunosuppressed (eg, those with antibody deficiencies) are rarely encountered in some practices, such individuals may have a disproportionately high frequency of serious infections caused by Mycoplasma and Ureaplasma species; therefore, always consider these organisms in the patient's differential diagnosis.

Handle medical treatment according to the patient involved, the presence of underlying disease or immunodeficiency, and whether the infection is localized or disseminated. Key to providing pathogen-specific management is obtaining adequate material for microbiologic diagnosis and properly handling this material once it is collected.

Choose general treatment guidelines for conditions such as acute salpingitis, endometritis, pyelonephritis, urethritis, septic arthritis, neonatal pneumonia, and other conditions associated with or attributed to genital Mycoplasma species according to standard care practices for the various clinical syndromes.

Other than providing specific antimicrobial agents to cover Mycoplasma and Ureaplasma species, no other unique aspects to the management of these conditions are beneficial.

Note that Mycoplasma and Ureaplasma organisms are often opportunists and may be present simultaneously with other pathogens in many of the above-described conditions. Treatment decisions should reflect this possibility.

 

Medication

Medication Summary

An oral tetracycline administered for at least 7 days historically has been the drug of choice for urogenital infections due to M hominis, but resistance due to ribosomal modification now occurs in 20-40% of isolates. A survey performed in several states between 2000 and 2004 detected tetracycline resistance in 45% of Ureaplasma isolates, indicating that the susceptibility of these organisms can no longer be assumed.[1] However, a 2016 US study reported that only 1 of 202 U parvum isolates were resistant to doxycycline.[23] The degree of resistance may vary according to geographic area, patient population, and previous exposure to antimicrobial agents.

If tetracyclines are relied upon as first-line drugs, consider alternative agents in the event of treatment failures. In vitro susceptibility testing is sometimes indicated for Mycoplasma and Ureaplasma species recovered from a normally sterile body site, from hosts who are immunocompromised, or from persons who have not responded to initial treatment. Minimal inhibitory concentrations (MICs) for doxycycline are typically lower than those of tetracycline against these organisms.

Clindamycin is an alternative treatment for tetracycline-resistant M hominis but is much less effective against Ureaplasma species. Clindamycin resistance among M hominis isolates appears to be extremely rare, with only a few reported cases. Macrolides, fluoroquinolones, or tetracyclines are the DOCs for Ureaplasma infections. Although tetracycline resistance is described in Ureaplasma species, high-level erythromycin resistance is uncommon, although it has been described in the United States and elsewhere due to ribosomal modification.[24, 25, 23] A single 1-g dose of azithromycin is approved for treatment of urethritis due to Chlamydia trachomatis and works as well clinically as 7 days of doxycycline in persons with urethritis due to Ureaplasma species.

Clarithromycin, although active against Ureaplasma species in vitro at concentrations comparable to or lower than erythromycin, has not been approved for use in the treatment of urogenital infections. M hominis is resistant to 14- and 15-membered macrolides, including erythromycin, azithromycin, and clarithromycin. Despite apparent in vitro susceptibility of Ureaplasma species to tetracycline or erythromycin, treatment of vaginal organisms with these agents is not always successful.

Fluoroquinolones are useful alternatives for treatment of certain infections caused by M hominis or Ureaplasma species within the urogenital tract and in some extragenital locations. Activity of quinolones is not affected by tetracycline resistance, making these drugs attractive alternatives for tetracycline-resistant M hominis or Ureaplasma infections. Levofloxacin and moxifloxacin have the greatest in vitro potency. In general, M hominis is more susceptible to quinolones in vitro than Ureaplasma species based on MICs. Fluoroquinolone resistance among M hominis and Ureaplasma species has been reported, often in patients with prior exposure to these drugs, and especially in immunosuppressed persons..[26, 27] In a 2016 US study, the rate of resistance to levofloxacin was 6% for U parvum and 5% for U urealyticum.[23]

Most clinical trials for treatment of genitourinary infections focus primarily on other pathogens, such as C trachomatis and Neisseria gonorrhoeae. Few studies include microbiologic data specific to genital Mycoplasma species, and no systematic comparative evaluations have been performed on treatment regimens for extragenital infections in adults or infections in neonates.

Treatment recommendations, including dosage and duration of therapy, are based largely on in vitro susceptibility data, outcomes of treatment trials evaluating clinical response to syndromes such as pelvic inflammatory disease and urethritis that may be due to genital Mycoplasma, and individual case reports. For infections such as urethritis that may be transmitted venereally, sexual contacts of the index case should also receive treatment.

Experience with Mycoplasma or Ureaplasma infections in patients who are immunocompromised, especially those with hypogammaglobulinemia (who have been studied most extensively), demonstrates that although Mycoplasma species are primarily noninvasive mucosal pathogens in healthy hosts, they have the capacity to produce destructive and progressive disease. Infections may be caused by resistant organisms refractory to antimicrobial therapy and may require prolonged administration of a combination of intravenous antimicrobials for several weeks or even months, intravenous immunoglobulin, and antisera prepared specifically against the infecting species. Even with aggressive therapy, relapses are likely. Repeat cultures of affected sites may be necessary to gauge in vivo response to treatment.

Isolation of M hominis or Ureaplasma species from neonatal pericardial fluid; pleural fluid; tracheal aspirate in association with respiratory disease; abscess material; CSF from those with pleocytosis, progressive hydrocephalus, or other neurologic abnormality; or blood justifies specific treatment in neonates who are critically ill when no other verifiable microbiologic etiologies of the clinical condition are apparent. Whether treatment should be given for a positive CSF culture in neonates when inflammation or other evidence of clinical illness is not observed should be handled on a case-by-case basis. Monitoring the patient, repeating the lumbar puncture, and reexamining for inflammation and organisms may be appropriate before initiating treatment because some cases may resolve spontaneously without intervention.

Parenteral tetracyclines are used most often to treat neonatal meningitis caused by either M hominis or Ureaplasma species, despite contraindications. Macrolides for Ureaplasma species and clindamycin for M hominis are alternatives. Treatment of ureaplasmal respiratory infections in neonates with erythromycin or azithromycin may be effective in eradicating the organisms from the lower airways, but treatment failures are known to occur.[1, 28] If possible, erythromycin should be avoided in neonates because of an association with pyloric stenosis. Azithromycin is a reasonable alternative to erythromycin in neonates with Ureaplasma respiratory tract infections. In a small study of preterm infants, azithromycin effectively eradicated Ureaplasma from the respiratory tract.[29] No single drug is successful in every instance for eradication of these organisms from the CSF of neonates.

Drugs such as the aminoglycosides and chloramphenicol sometimes demonstrate activity against genital mycoplasmas in vitro. However, their toxicities and the availability of better agents means they are not normally considered as suitable antimycoplasmal agents, with the exception of occasional use of chloramphenicol for treatment of systemic infections in neonates caused by M hominis or Ureaplasma species in the setting of tetracycline resistance or clinical failure with other agents.

Overall treatment alternatives for neonates are the same as for urogenital and systemic mycoplasmal infections in adults, with appropriate dosage modifications based on weight, except that the intravenous route should be used for serious systemic infections. Duration of treatment and drug dosages for neonatal mycoplasmal infections have not been evaluated critically, but a minimum duration of 10-14 days is suggested based on experience in individual cases when microbiologic follow-up care has been assessed.[1, 30] M fermentans has in vitro susceptibilities comparable to M hominis, demonstrating resistance to macrolides and susceptibility to clindamycin, but little clinical data are available to guide therapeutic choices for this mycoplasma.

M genitalium is usually susceptible in vitro to tetracyclines, macrolides, and fluoroquinolones. Azithromycin has been recommended as a treatment for M genitalium urethritis in view of clinical failures with the tetracyclines, which appear to be less active overall. However, several reports of azithromycin treatment failure with documentation of elevated MICs to this drug have been reported.[31, 32] Treatment failure has also been described in patients with urethritis in whom M. genitalium was isolated following treatment with levofloxacin or moxifloxacin. Mutations in the gyrA and parC genes of M genitalium, and more recently in gyrB and parE, have been detected by molecular methods in M genitalium.[3] Minocycline appears to be more effective than tetracycline or doxycycline against M genitalium and has been clinically successful in the treatment of multidrug-resistant M genitalium genitourinary infections.[33]

Antimicrobial agents

Class Summary

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Erythromycin (E.E.S., E-Mycin, Eryc)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Does not affect M hominis.

Clarithromycin (Biaxin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Does not affect M hominis. No data support use in urogenital infections.

Azithromycin (Zithromax)

Treats mild-to-moderate microbial infections. Does not affect M hominis. Has been used to successfully treat Ureaplasma lower respiratory tract infection in neonates.

Clindamycin (Cleocin)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest. Does not affect Ureaplasma.

Doxycycline (Vibramycin, Bio-Tab, Doryx)

Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Some M hominis strains and Ureaplasma species may be resistant.

Levofloxacin (Levaquin)

Inhibits DNA gyrase and prevents DNA replication. Active against most M hominis, M genitalium, and Ureaplasma species.

Ofloxacin (Floxin)

Inhibits DNA gyrase and topoisomerase IV and prevents bacterial DNA replication. Active against most M hominis, M genitalium, and Ureaplasma isolates.

Chloramphenicol (Chloromycetin)

Binds to 50S bacterial ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis. Has been used to successfully treat Mycoplasma and Ureaplasma neonatal meningitis.

Minocycline (Dynacin, Minocin)

Treats infections caused by susceptible gram-negative and gram-positive organisms. Some M hominis strains and Ureaplasma species maybe resistant. Has been used to successfully treat multidrug-resistant M genitalium infections.

Moxifloxacin (Avelox, Moxifloxacin Systemic)

Inhibits DNA gyrase and prevents DNA replication. Active against most M hominis, M genitalium, and Ureaplasma isolates. More potent against these organisms than levofloxacin.

 

Follow-up

Deterrence/Prevention

Because of the frequency with which genital Mycoplasma and Ureaplasma organisms are carried in the lower urogenital tract in persons who are asymptomatic and sexually active, use of barrier protection methods (eg, condoms) is of little benefit because the organisms most often act as opportunistic normal florae. In cases of U urealyticum or M genitalium urogenital infections, sexual partners should also undergo treatment.

Delivery of infants by cesarean delivery has not prevented colonization in the lower respiratory tract because acquisition of the organisms can occur in utero by ascending infection, even through intact fetal membranes.

Although no systematic studies have been performed, the epidemiology of these organisms suggests that persons who are sexually inactive do not usually harbor them and, therefore, cannot be expected to develop clinically significant infections. Abstinence may prevent spread of the organisms among adolescents and adults.

 

Questions & Answers

Overview

What is Ureaplasma?

What is the pathophysiology of Ureaplasma infection?

How are Ureaplasma species transmitted?

Which clinical conditions are caused by Ureaplasma infection?

Which clinical conditions in women may be caused by Ureaplasma infection?

How are Ureaplasma infections transmitted to infants, and what conditions do they cause?

What does Ureaplasma in amniotic fluid cause?

Where have Ureaplasma species been isolated in pregnant women and fetuses?

Which invasive diseases are caused by Mycoplasma and Ureaplasma species?

What is the significance of mycoplasmal infections in persons with HIV infection?

What is the prevalence of Ureaplasma infection in the US?

What factors affect the prevalence of Ureaplasma infection?

What is the mortality and morbidity associated with Ureaplasma infection?

How does the prevalence of Ureaplasma infection vary by race?

How does the prevalence of Ureaplasma infection vary by sex?

How does the prevalence of Ureaplasma infection vary by age?

Presentation

What clinical history is characteristic of Ureaplasma infection?

Which clinical conditions are caused by Ureaplasma infections?

Why is it important to consider an Ureaplasma etiology in the differential diagnoses of genitourinary infection?

When should Mycoplasma or Ureaplasma infection be considered?

What is the physical presentation of Ureaplasma infection in neonates?

How are Ureaplasma species differentiated?

DDX

How are Ureaplasma infections diagnosed?

What are the differential diagnoses for Ureaplasma Infection?

Workup

What is the role of lab testing in the evaluation of Ureaplasma infection?

What is the role of cultures in the evaluation for Ureaplasma infection?

How are culture specimens collected for the evaluation of Ureaplasma infection?

What cultures are indicated for the evaluation of Ureaplasma infection in neonates?

What is the role of extragenital or extrapulmonary culture specimens in the evaluation of Ureaplasma infection?

What is the proper specimen handling for evaluation of Ureaplasma infection?

What is the role of serologic studies in the workup of Ureaplasma infection?

What is the role of PCR assay in the evaluation of Ureaplasma infection?

What is the role of imaging studies in the workup of Ureaplasma infection?

What is the role of CT scanning in the workup of Ureaplasma infection?

Which radiographic findings are characteristic of Ureaplasma infection in infants?

What is the indication for specimen collection for culture in the workup of Ureaplasma infection?

What specimen collection techniques are used in the evaluation of Ureaplasma infection?

Treatment

What is the basis for treatment selection in Ureaplasma infection?

What comorbidities should be considered in the differential diagnosis of Ureaplasma infection?

How are Ureaplasma infections managed?

What are the treatment options for conditions attributed to genital Mycoplasma species or Ureaplasma infection?

What are considerations regarding the treatment of Ureaplasma infection?

Medications

What is the role of tetracycline in the treatment of Ureaplasma infection?

What is the role of clindamycin in the treatment of Ureaplasma infection?

What is the efficacy of clarithromycin in the treatment of Ureaplasma infection?

What is the role of fluoroquinolones in the treatment of Ureaplasma infection?

Have many clinical trials been conducted for Ureaplasma infections?

What is the basis for the treatment recommendations for Ureaplasma infection?

What has been learned from treatment of Ureaplasma infections in immunocompromised patients?

What are the treatment options for neonates with Ureaplasma infection?

How is neonatal Ureaplasma meningitis treated?

What is the efficacy of aminoglycosides and chloramphenicol for the treatment of Ureaplasma infection?

What are the treatment alternatives for neonates with Ureaplasma infection?

What are the treatment options for Mycoplasma genitalium urethritis?

Which medications in the drug class Antimicrobial agents are used in the treatment of Ureaplasma Infection?

Follow-up

How are Ureaplasma infections prevented?