Skovmand Sofie, Nørgaard Christina, Salado-Rasmussen Kirsten, Jensen Jørgen Skov
Department of Bacteria, Parasites and Fungi, Statens Serum Institut, Artillerivej 5 Copenhagen 2300, Denmark.
Department of Dermato-Venereology, Bispebjerg University Hospital, Copenhagen, Denmark.
J Antimicrob Chemother. 2025 Aug 6. doi: 10.1093/jac/dkaf272.
Mycoplasma genitalium causes a range of urogenital infections. It is inherently resistant to beta-lactam antibiotics, and the first and second-line treatments recommended are azithromycin and moxifloxacin, respectively. However, resistance towards these drugs is rising, and third-line treatment options exhibit cure rates between 40% and 80%. Thiamphenicol, a chloramphenicol analogue, is excreted unchanged in the urine in high concentrations and has previously successfully treated uncomplicated gonorrhoea. This study aimed to test the in vitro activity of thiamphenicol in a collection of M. genitalium strains with various resistance patterns and to exclude antagonism between thiamphenicol and doxycycline.
Fifty-three strains of M. genitalium were tested for macrolide resistance mutations in the 23S rRNA gene and quinolone resistance-associated mutations in the parC gene. MICs of thiamphenicol, doxycycline, azithromycin, and moxifloxacin were determined using Vero cell cultures followed by quantitative PCR. A chequerboard analysis was performed to exclude antagonism between thiamphenicol and doxycycline in four isolates of M. genitalium.
The thiamphenicol MICs ranged from 1 to 64 mg/L with a median of 8 mg/L, and 94% (n = 50) of the strains had a thiamphenicol MIC ≤ 16 mg/L. Resistance to macrolides, quinolones, and dual-class resistance did not affect the MIC levels of thiamphenicol. The chequerboard analysis excluded antagonism in all four isolates and indicated a synergistic effect in one isolate.
Our study offered encouraging results on the therapeutic potential of thiamphenicol for M. genitalium infections. The possible synergistic relationship between thiamphenicol and doxycycline encourages further studies.
生殖支原体可引起一系列泌尿生殖系统感染。它对β-内酰胺类抗生素具有固有抗性，推荐的一线和二线治疗药物分别是阿奇霉素和莫西沙星。然而，对这些药物的耐药性正在上升，三线治疗方案的治愈率在40%至80%之间。甲砜霉素是一种氯霉素类似物，以高浓度原形经尿液排泄，此前已成功治疗非复杂性淋病。本研究旨在测试甲砜霉素对一组具有不同耐药模式的生殖支原体菌株的体外活性，并排除甲砜霉素与多西环素之间的拮抗作用。
对53株生殖支原体进行23S rRNA基因大环内酯类耐药突变和parC基因喹诺酮类耐药相关突变检测。采用Vero细胞培养及定量PCR法测定甲砜霉素、多西环素、阿奇霉素和莫西沙星的最低抑菌浓度（MIC）。对4株生殖支原体进行棋盘分析，以排除甲砜霉素与多西环素之间的拮抗作用。
甲砜霉素的MIC范围为1至64mg/L，中位数为8mg/L，94%（n = 50）的菌株甲砜霉素MIC≤16mg/L。对大环内酯类、喹诺酮类的耐药性及双重耐药性均不影响甲砜霉素的MIC水平。棋盘分析排除了所有4株菌中的拮抗作用，并显示其中1株菌有协同效应。
我们的研究为甲砜霉素治疗生殖支原体感染的潜力提供了令人鼓舞的结果。甲砜霉素与多西环素之间可能的协同关系值得进一步研究。
