In vitro activity of thiamphenicol against drug-susceptible and drug-resistant strains of Mycoplasma genitalium

Objectives 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. Methods 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. Results 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. Conclusions 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.