Ureaplasma Infection

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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 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. 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.

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, 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 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.

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.[1]

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.[8]

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]

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.[9] 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.[5] Production of urease by Ureaplasma species is a mechanism by which these organisms can produce struvite calculi in the urinary tract.[1]

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.

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.

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.

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:

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.[7]

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:

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 or necessary. In both the clinical setting and in the diagnostic laboratory, they are considered Ureaplasma species.

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.

Both M hominis and U urealyticum 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.[10]

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 frozen 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 and if the number of organisms is quantitated. 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 more than 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. 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.

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. Thus far, no PCR assays are approved by the FDA or sold commercially for these organisms. Therefore, the availability of molecular testing is quite limited.

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. Seeking molecular techniques for diagnostic purposes is not usually practical because of the difficulty in their detection and the fact that their role in human disease is not well established. A few research laboratories in the United States are capable of testing for the presence of M genitalium and M fermentans via PCR.

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:

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.

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 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] 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. 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.[11, 12] 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 in several countries, often in patients with prior exposure to these drugs, but the extent to which this occurs in the general population is unknown.[13, 14]

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 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. Erythromycin for Ureaplasma species, 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, 15] No single drug is successful in every instance for eradication of these organisms from the CSF of neonates. Little clinical experience is available with new-generation macrolides such as azithromycin in the treatment of neonatal Ureaplasma infections, and no guidelines for their dosages or use in neonates are available.

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, 16] M fermentans has in vitro susceptibilities comparable to M hominis, demonstrating some degree of 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.[17, 18] Treatment failure has also been described in patients with urethritis in whom M. genitalium was isolated following treatment with levofloxacin. 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]

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

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  Treats mild-to-moderate microbial infections. IV formulation not recommended for children. Does not affect M hominis. No clinical data are available to support dosage or use in neonates.

Clindamycin (Cleocin)

Clinical Context:  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)

Clinical Context:  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)

Clinical Context:  Inhibits DNA gyrase and prevents DNA replication.

Ofloxacin (Floxin)

Clinical Context:  Inhibits DNA gyrase and topoisomerase IV and prevents bacterial DNA replication.

Chloramphenicol (Chloromycetin)

Clinical Context:  Binds to 50S bacterial ribosomal subunits and inhibits bacterial growth by inhibiting protein synthesis.

Minocycline (Dynacin, Minocin)

Clinical Context:  Treats infections caused by susceptible gram-negative and gram-positive organisms. Some M hominis strains and Ureaplasma species maybe resistant.

Class Summary

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

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.

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.

Author

Ken B Waites, MD, Director, UAB Diagnostic Mycoplasma Laboratory, Professor, Department of Pathology, Division of Laboratory Medicine, University of Alabama at Birmingham School of Medicine

Disclosure: Nothing to disclose.

Specialty Editors

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Richard B Brown, MD, FACP, Chief, Division of Infectious Diseases, Baystate Medical Center; Professor, Department of Internal Medicine, Tufts University School of Medicine

Disclosure: Nothing to disclose.

Chief Editor

Michael Stuart Bronze, MD, David Ross Boyd Professor and Chairman, Department of Medicine, Stewart G Wolf Endowed Chair in Internal Medicine, Department of Medicine, University of Oklahoma Health Science Center; Master of the American College of Physicians; Fellow, Infectious Diseases Society of America

Disclosure: Nothing to disclose.

Additional Contributors

Gary L Gorby, MD, Associate Professor, Departments of Internal Medicine and Medical Microbiology and Immunology, Division of Infectious Diseases, Creighton University School of Medicine; Associate Professor of Medicine, University of Nebraska Medical Center; Associate Chair, Omaha Veterans Affairs Medical Center

Disclosure: Nothing to disclose.

References

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  2. Xiao L, Paralanov V, Glass JI, Duffy LB, Robertson JA, Cassell GH, et al. Extensive horizontal gene transfer in ureaplasmas from humans questions the utility of serotyping for diagnostic purposes. J Clin Microbiol. 2011 Aug. 49(8):2818-26. [View Abstract]
  3. Deguchi T, Maeda S, Tamaki M, Yoshida T, Ishiko H, Ito M. Analysis of the gyrA and parC genes of Mycoplasma genitalium detected in first-pass urine of men with non-gonococcal urethritis before and after fluoroquinolone treatment. J Antimicrob Chemother. 2001 Nov. 48(5):742-4. [View Abstract]
  4. Xiao L, Paralanov V, Glass JI, Duffy LB, Robertson JA, Cassell GH. Extensive horizontal gene transfer in ureaplasmas from humans questions the utility of serotyping for diagnostic purposes. J Clin Microbiol. 2011 Aug. 49(8):2818-26. [View Abstract]
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