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. [29] 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. [29, 30, 31] 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. [32, 33] In a 2016 US study, the rate of resistance to levofloxacin was 6% for U parvum and 5% for U urealyticum. [29]
Most clinical trials for treatment of genitourinary infections focus primarily on other pathogens, such as C trachomatis, Neisseria gonorrhoeae, and/or M genitalium. Few studies include microbiologic data specific to Ureaplasma species or M hominis, 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 relative 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, 34] 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. [35] 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, except for 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, 36] 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.
Azithromycin has historically 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 and continue to spread. [37, 38] 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. [39]
The US Centers for Disease Control and Prevention 2021 Sexually Transmitted Infection Guidelines [26] specify that due to the high rates of macrolide resistance, a single 1-g dose of azithromycin should not be used. Two-stage therapy approaches, ideally using resistance-guided therapy made possible by molecular-based tests for macrolide-resistance mutations are recommended. Resistance tests for mutations in 23S ribosomal RNA that confer macrolide resistance are available only through specialized reference laboratories. Doxycycline is provided as initial empiric therapy, which reduces the organism load and facilitates organism clearance, followed by macrolide-susceptible infections treated with high-dose azithromycin.
Macrolide-resistant infections are treated with moxifloxacin. If M genitalium resistance testing is available and shows the infection to be macrolide susceptible, use doxycycline 100 mg orally 2 times/day for 7 days, followed by azithromycin 1 g orally initial dose, followed by 500 mg orally once daily for 3 additional days (2.5 g total). If macrolide-resistant, use doxycycline 100 mg orally 2 times/day for 7 days followed by moxifloxacin 400 mg orally once daily for 7 days. If M genitalium resistance testing is not available and the organism is detected by an FDA-cleared molecular-based test use doxycycline100 mg orally 2 times/day for 7 days, followed by moxifloxacin 400 mg orally once daily for 7 days.
In vitro susceptibility testing for macrolides, quinolones, and tetracyclines is available for M hominis and Ureaplasma species through specialized reference laboratories and is recommended in the case of clinical treatment failure or any systemic infection in a normally sterile body site in a person who is immunosuppressed.
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. Has been used to treat M. genitalium but acquired resistance and treatment failures have made it necessary for guidelines for its use to be revised.
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.
