Impact of quinupristin/dalfopristin (RP59500) on the faecal microflora in healthy volunteers

Abstract

The effect of 5 days' administration of quinupristin/dalfopristin (RP59500) on the faecal microflora was evaluated in healthy volunteers. Twenty healthy volunteers received 7.5 mg/kg of quinupristin/dalfopristin infused over 1 h twice daily for 5 days and four received a matched placebo. Faecal samples were collected before, during and after treatment (days -1/-2, 6, 8, 14/15, 35 ± 2, 60 ± 4, 90 ± 4). In the treated volunteers, anaerobes, including sporulating and Gram-negative bacteria, decreased slightly during treatment, whereas numbers of enterococci and Enterobacteriaceae increased significantly (P < 0.01). Counts of anaerobes and enterococci resistant to erythromycin or to quinupristin/dalfopristin increased significantly (P < 0.01) during treatment and returned slowly to their baseline levels after the end of treatment. Mean faecal antibiotic concentrations reached 291 ± 184 and 42 ± 22 μg/g of faeces for quinupristin and dalfopristin, respectively, by the fifth day of treatment. Counts of yeasts were not influenced significantly by the treatment. No emergence of glycopeptide-resistant enterococci, Staphylococcus aureus, Pseudomonas aeruginosa or Clostridium difficile was observed. No episode of diarrhoea was reported. In conclusion, quinupristin/dalfopristin administration was associated with a temporary shift towards resistance of the endogenous flora and a temporary increase in counts of enterobacteria and enteroccocci. However, no decrease in colonization resistance towards exogenous potentially pathogenic bacteria was observed and the observed modifications disappeared within 12 weeks after the end of quinupristin/dalfopristin administration.