In Vitro Susceptibility and Resistance of Mycoplasma genitalium to Nitroimidazoles.
In Vitro Susceptibility and Resistance of Mycoplasma genitalium to Nitroimidazoles.
复制标题
DOI：
10.1128/aac.00006-23
复制
发表时间：
2023-04-18
影响因子：
4.9
通讯作者：
Cichewicz, Robert H.
中科院分区：
文献类型：
--
作者：
Wood, Gwendolyn E.;Kim, Caroline M.;Aguila, Laarni Kendra T.;Cichewicz, Robert H.
生殖道支原体是一种男女性传播的生殖道病原体。由于多西环素疗效不佳，对阿奇霉素和莫西沙星产生耐药性，使得生殖道支原体感染越来越难以治疗。最近的一项临床试验表明，甲硝唑可以提高妇女盆腔炎的治愈率，并在标准强力霉素加头孢曲松治疗的情况下减少生殖器支原体的检出率。由于科学文献缺乏支原体对硝基咪唑的敏感性数据，我们测定了10株生殖支原体对甲硝唑、塞克硝唑和替硝唑的体外敏感性。甲硝唑的mic范围为1.6 ~ 12.5 μg/mL，塞克硝唑为3.1 ~ 12.5 μg/mL，替硝唑为0.8 ~ 6.3 μg/mL。在棋盘肉汤微量稀释试验中，这些药物均与强力霉素无增效作用。在MIC和时间杀伤动力学方面，替硝唑优于甲硝唑和塞克硝唑，并且在浓度低于报道的血清浓度时具有杀菌作用（99.9%）。通过对自发耐药突变体的全基因组测序，发现了与硝基咪唑耐药相关的突变，提示了一种预测的NAD(P) h依赖性黄素单核苷酸（FMN）氧化还原酶还原激活硝基咪唑前药的机制。氧的存在不影响野生型生殖支原体的mic，但一个抗硝基咪唑突变体在厌氧条件下生长有缺陷，这表明耐药突变体在厌氧生殖部位可能存在适应性劣势。需要临床研究来确定硝基咪唑，特别是替硝唑，是否对根除男性和女性生殖器支原体感染有效。
Mycoplasma genitalium is a sexually transmitted reproductive tract pathogen of men and women. M. genitalium infections are increasingly difficult to treat due to poor efficacy of doxycycline and acquired resistance to azithromycin and moxifloxacin. A recent clinical trial suggested that metronidazole may improve cure rates for women with pelvic inflammatory disease and reduced the detection of M. genitalium when included with standard doxycycline plus ceftriaxone treatment. As data regarding susceptibility of mycoplasmas to nitroimidazoles are lacking in the scientific literature, we determined the in vitro susceptibility of 10 M. genitalium strains to metronidazole, secnidazole, and tinidazole. MICs ranged from 1.6 to 12.5 μg/mL for metronidazole, 3.1 to 12.5 μg/mL for secnidazole, and 0.8 to 6.3 μg/mL for tinidazole. None of these agents was synergistic with doxycycline in checkerboard broth microdilution assays. Tinidazole was superior to metronidazole and secnidazole in terms of MIC and time-kill kinetics and was bactericidal (>99.9% killing) at concentrations below reported serum concentrations. Mutations associated with nitroimidazole resistance were identified by whole-genome sequencing of spontaneous resistant mutants, suggesting a mechanism for reductive activation of the nitroimidazole prodrug by a predicted NAD(P)H-dependent flavin mononucleotide (FMN) oxidoreductase. The presence of oxygen did not affect MICs of wild-type M. genitalium, but a nitroimidazole-resistant mutant was defective for growth under anaerobic conditions, suggesting that resistant mutants may have a fitness disadvantage in anaerobic genital sites. Clinical studies are needed to determine if nitroimidazoles, especially tinidazole, are effective for eradicating M. genitalium infections in men and women.
登录
查看更多内容
影响因子：
4.5
作者：
Pereyre S;Sirand-Pugnet P;Beven L;Charron A;Renaudin H;Barré A;Avenaud P;Jacob D;Couloux A;Barbe V;de Daruvar A;Blanchard A;Bébéar C
通讯作者：
Bébéar C
影响因子：
3.6
作者：
Iverson-Cabral, Stefanie L.;Astete, Sabina G.;Totten, Patricia A.
通讯作者：
Totten, Patricia A.
支原体生殖器感染的管理 - 我们可以达到移动的目标吗？
影响因子：
3.7
作者：
Jensen JS;Bradshaw C
通讯作者：
Bradshaw C
影响因子：
6.4
作者：
Horner, Patrick J.;Martin, David H.
通讯作者：
Martin, David H.
影响因子：
3.7
作者：
Panicker, Indu S.;Browning, Glenn F.;Markham, Philip F.
通讯作者：
Markham, Philip F.