Mycoplasma genitalium, Ureaplasma spp. and Mycoplasma hominis: human urogenital mycoplasmas

Mycoplasma genitalium is a sexually transmitted organism. The urogenital tract is the primary site of M. genitalium infection but asymptomatic rectal carriage is reported. M. genitalium is responsible for urethritis in men and for cervicitis, pelvic inflammatory disease, preterm birth and spontaneous abortion in women.

Ureaplasma urealyticum, Ureaplasma parvum (referred to hereafter as Ureaplasma spp.), and Mycoplasma hominis are microorganisms that reside, as commensals, in the lower urogenital tract but can be responsible for urogenital infections. M. hominis is an agent of endometritis and salpingitis in women, and Ureaplasma spp., mainly U. urealyticum, may be responsible for urethritis in men. These microorganisms can also be involved in reproductive disorders, neonatal infections, and extra-genital infections in immunocompromised patients.

Laboratory diagnosis of infections is based on direct methods either by culture or nucleic acid amplification tests (NAATs) according to the species and the type of specimen. Culture is well adapted to species like Ureaplasma spp. and M. hominis, which can be isolated easily and rapidly from urogenital specimens leading to quantitative results and allowing susceptibility testing from isolates. PCR can also be performed to increase the sensitivity of detection in specimens from extra-genital sites or from normally sterile body fluids or tissues. In contrast, culture is not adapted for the detection of the extremely fastidious M. genitalium species. The M. genitalium detection is only obtained by NAATs, using either in-house PCR or commercially available diagnostic tests.

Three families of antibiotics, tetracyclines, fluoroquinolones, and macrolides have potential activity against these bacteria.

genitalium is susceptible to tetracyclines in vitro but therapeutic failures are reported in two-third cases even though there is no documented specific acquired resistance. Macrolide-resistant clinical isolates of M. genitalium were reported a few years ago and are now spreading in several countries. All resistant isolates harbor a point mutation at position 2058 or 2059 (Escherichia coli numbering) in the domain V of the 23S rRNA gene. The prevalence of macrolide resistance in M. genitalium is ranging between 20 and 30% in France, but is over 40% in several European countries, Australia and the USA. Molecular methods were developed to detect macrolide resistance directly in urogenital clinical specimens and some of them are commercially available. Moxifloxacin, a fluoroquinolone, is the second-line treatment but treatment failures have also been reported. Mutations associated with fluoroquinolone resistance were described in the parC or gyrA genes in more than 10% of M. genitalium-infected patients in Sweden, Germany, the USA and Australia and in up to 47% of M. genitalium-infected patients in Japan. In France, 7% of patients are infected with fluoroquinolone-resistant M. genitalium. Because only rare other registered antibiotics can be used as third-line treatment, M. genitalium infections may become untreatable in certain circumstances.
hominis and Ureaplasma spp. are susceptible to tetracyclines but acquired tetracycline resistance is ranging between 10 and 15%. This resistance is associated with the acquisition of the tet(M) gene, encoding the Tet(M) protein which protects the ribosome from the action of tetracyclines and confers high-level resistance to all tetracyclines. Acquired resistance to fluoroquinolones is associated with mutations in the gyrA, gyrB, parC and parE genes. The prevalence of resistance remains below 3% for these species. Only a very few cases of acquired resistance to macrolides have been reported for clinical isolates of M. hominis and Ureaplasma spp..