Pristinamycin

Three genes encoding AfsK, AfsR, AfsS homologues inStreptomyces pristinaespiraliswere studied, respectively, to investigate regulatory role of AfsKRS system for pristinamycin biosynthesis. Transcription change and gene inactivation analysis indicated that these genes had active transcription and positive regulation for the improvement of pristinamycin production inS. pristinaespiralis. The analysis of AfsKRS-defective mutagenesis indicated that there might be a positive correlation between the product ofafsKand pristinamycin I biosynthesis, and a negative correlation to pristinamycin II biosynthesis. However, bothafsRandafsSmight have negative correlation to pristinamycin I production and positive correlation to pristinamycin II production. The effects on pristinamycin production of AfsKRS disruptants by protein kinase inhibitor K252a indicated that AfsR, both not AfsK and AfsS, was the inhibition target of K252a inS. pristinaespiralis, and AfsR should serve as a pleiotropic regulator to have differential regulation on biosynthesis of pristinamycin I and II components. Based on above study, it might be deduced that different signal transduction patterns via AfsK, AfsR, AfsS of AfsKRS system should be involved in respective regulation for biosynthesis of pristinamycin I and II inS. pristinaespiralis. In conclusion, the investigation could give some valuable clues for exploring furtherly regulatory function of AfsKRS system inS. pristinaespiralis.

Osteoarticular infections with Gram positive bacteria present an increasing challenge in an era of multidrug-resistant organisms. Prolonged intravenous antibiotic treatment is often required, with associated risks, costs and difficulties with administration; a safe, effective oral option would be ideal for this indication. Pristinamycin, an oral streptogramin antibiotic with bactericidal activity against Gram positive organisms including methicillin-resistant Staphylococcus aureus, has been used for over 50 years in Europe for the treatment of osteoarticular infections. We review the published evidence for the treatment of native bone and prosthesis-related osteoarticular infections with pristinamycin.

High levels of macrolide resistance and increasing fluoroquinolone resistance are found in Mycoplasma genitalium in many countries. We evaluated pristinamycin for macrolide-resistant M. genitalium in a sexual health center in Australia. Microbiologic cure was determined by M. genitalium-specific 16S PCR 14-90 days after treatment began. Of 114 persons treated with pristinamycin, infection was cured in 85 (75%). This percentage did not change when pristinamycin was given at daily doses of 2 g or 4 g or at 3 g combined with 200 mg doxycycline. In infections with higher pretreatment bacterial load, treatment was twice as likely to fail for each 1 log10increase in bacterial load. Gastrointestinal side effects occurred in 7% of patients. Pristinamycin at maximum oral dose, or combined with doxycycline, cured 75% of macrolide-resistant M. genitalium infections. Pristinamycin is well-tolerated and remains an option where fluoroquinolones have failed or cannot be used.