In Vitro Drug Sensitivity of Ureaplasma Species and Mycoplasma Hominis and the Mechanism of Resistance to Quinolones: A Single-center Retrospective Study

  Objective  The aim of this study was to summarize and analyze the in vitro antimicrobial susceptibility of Ureaplasma species and Mycoplasma hominis and the mechanisms responsible for resistance to quinolones.

  Methods  The clinical data of Ureaplasma species and Mycoplasma hominis detected by in vitro culture from September 2012 to April 2017 in Peking Union Medical College Hospital were retrospectively collected and analyzed; their characteristics of antimicrobial susceptibility were also analyzed combined with the information about the patients and species identification. According to the drug-resistance characteristics of quinolone, the target genes were amplified and sequenced by PCR, and the sequencing results were translated into protein sequences. The mutations in DNA gyrase(GyrA/GyrB) and topoisomerase Ⅳ (ParC/ParE) that were related to quinolones resistance were detected by comparing sequences in the NCBI database.

  Results  In vitro sensitivity to antibiotics of Ureaplasma species mixed with Mycoplasma hominis was significantly lower than that of Ureaplasma species or Mycoplasma hominis alone. Compared to Mycoplasma hominis, Ureaplasma species was less susceptible to quinolones, tetracycline, josamycin, and primycin, except for macrolides, but the difference was not statistically significant (all P > 0.05). In addition, the susceptibility of Ureaplasma species to azithromycin, erythromycin, clarithromycin, and ofloxacin in female patients was lower than that in male patients (all P < 0.05). Ureaplasma parvum were more susceptible than Ureaplasma urealyticum to most antibiotics, especially tetracycline (98.48% vs. 72.73%; 25.75% discrepancy, P < 0.05). Moreover, twenty-one mutations from sequences of GyrA, GyrB, ParC, and ParE were determined. The mutation in ParC with S83L substitution was the most frequent, 96.22% (51/53); mutations of A136T substitution in ParC, R448K substitution in ParE, and L176F in GyrA combined with S83L in ParC were also detected. This study also found six novel mutations that have not been reported:L540F, R718W, Q767E, S789N, M828I, and I831T amino acid substitutions in ParC protein.

  Conclusions  The in vitro antimicrobial susceptibility of Ureaplasma species or Mycoplasma hominis is associated with genus, and the in vitro sensitivity of Ureaplasma species to antibiotics is correlated with species and genders of patients. Sole S83L substitution in ParC might be the major mechanism of resistance to quinolones of Ureaplasma species, while the possible function of the six novel mutations remains further studies.