Evaluation of the microbiota-sparing properties of the anti-staphylococcal antibiotic afabicin.

BACKGROUND: Antibiotic use is associated with collateral damage to the healthy microbiota. Afabicin is a first-in-class prodrug inhibitor of the FabI enzyme that, when converted to the pharmacologically active agent afabicin desphosphono, demonstrates a staphylococcal-specific spectrum of activity. An expected benefit of highly targeted antibiotics such as afabicin is microbiome preservation. OBJECTIVES: To compare the effects of oral treatment with afabicin and standard-of-care antibiotics upon the murine gut microbiota, and to assess the effects of oral afabicin treatment on the human gut microbiota. METHODS: Gut microbiota effects of a 10 day oral course of afabicin treatment were monitored in mice and compared with clindamycin, linezolid and moxifloxacin at human-equivalent dose levels using 16S rDNA sequencing. Further, the gut microbiota of healthy volunteers was longitudinally assessed across 20 days of oral treatment with afabicin 240 mg twice daily. RESULTS: Afabicin treatment did not significantly alter gut microbiota diversity (Shannon H index) or richness (rarefied Chao1) in mice. Only limited changes to taxonomic abundances were observed in afabicin-treated animals. In contrast, clindamycin, linezolid and moxifloxacin each caused extensive dysbiosis in the murine model. In humans, afabicin treatment was not associated with alterations in Shannon H or rarefied Chao1 indices, nor relative taxonomic abundances, supporting the findings from the animal model. CONCLUSIONS: Oral treatment with afabicin is associated with preservation of the gut microbiota in mice and healthy subjects.

Efficacy and safety of the probiotic Lactobacillus paracasei LP-33 in allergic rhinitis: a double-blind, randomized, placebo-controlled trial (GA2LEN Study).

BACKGROUND/OBJECTIVES: An imbalance between Th1 and Th2 cells is involved in allergic rhinitis (AR) that may be improved by probiotics. To test the efficacy of the probiotic Lactobacillus paracasei subsp. paracasei LP-33, a double-blind, placebo-controlled, randomized trial was carried out in patients with AR to grass pollen treated with loratadine and presenting altered quality of life. SUBJECTS/METHODS: Subjects with persistent AR, symptomatic during the grass pollen season, and a positive skin test or specific immunoglobulin E to grass pollens were included by general practitioners (GPs). All received loratadine for 5 weeks. The primary end point was the improvement in Rhinitis Quality of Life (RQLQ) global score at the fifth week of LP-33 consumption compared with placebo (in addition to loratadine). Secondary end points included nasal and ocular symptoms (individual and total symptom scores), visual analogue scale and time of first exacerbation of the symptoms when loratadine was stopped. RESULTS: A total of 425 subjects were included. Using intent-to-treat analysis, the RQLQ global score decreased significantly more in the LP-33 group than in the placebo group (P=0.0255, difference=-0.286 (95% confidence interval (CI): -0.536; -0.035)). No significant differences were noted for the change of the rhinitis total symptom score 5 global score between groups (P=0.1288, difference=-0.452 (95% CI: -1.036; 0.132)). Significant differences in ocular symptoms (RQLQ) were observed between groups (P=0.0029, difference=-0.4087 (95% CI: -0.6768; -0.1407)). CONCLUSIONS: This study performed by GPs shows that LP-33 improves the quality of life of subjects with persistent AR who are currently being treated with an oral H1-antihistamine. Whereas nasal symptoms had not changed, ocular symptoms had consistently improved.