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

Abstract

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.