Ecological Effect of Solithromycin on Normal Human Oropharyngeal and Intestinal Microbiota

Abstract

Solithromycin is a new fluoroketolide. The purpose of the present study was to investigate the effect of orally administered solithromycin on the human oropharyngeal and intestinal microbiota. Thirteen healthy volunteers (median age, 27.3 years) received oral solithromycin at 800 mg on day 1 followed by 400 mg daily on days 2 to 7. Fecal and saliva samples were collected at baseline and on days 2, 5, 7, 9, 14, and 21 for pharmacokinetic and microbiological analyses. Plasma samples were collected predose on days 2, 5, and 7 as proof of exposure, and solithromycin concentration ranges were 21.9 to 258 ng/ml, 18.0 to 386 ng/ml, and 16.9 to 417 ng/ml, respectively. The solithromycin concentrations in feces were 15.8 to 65.4 mg/kg, 24.5 to 82.7 mg/kg, 21.4 to 82.7 mg/kg, 12.1 to 72.4 mg/kg, 0.2 to 25.6 mg/kg, and 0 to 0.5 mg/kg on days 2, 5, 7, 9, 14, and 21, respectively. The numbers of enterobacteria and enterococci decreased and were normalized on day 14. The numbers of lactobacilli and bifidobacteria decreased from day 2 to day 14 and were normalized on day 21. The clostridia decreased on days 2, 7, and 14 and were normalized on day 21. No Clostridium difficile strains or toxins were detected during the study period. The number of Bacteroides strains was not significantly changed. The solithromycin concentrations in saliva were 0 to 1.2 mg/liter, 0 to 0.5 mg/liter, 0 to 0.5 mg/liter, and 0 to 0.1 mg/liter on days 2, 5, 7, and 9, respectively. The numbers of streptococci decreased on day 2 and were normalized on day 5. The numbers of lactobacilli, prevotellae, fusobacteria, and leptotrichiae decreased from day 2 and were normalized on day 21.

Leptotrichia species in human infections II

“…They were also recovered from oral plaque of guinea pigs [21] and feces of piglets [54], dental plaque from healthy individuals, plaque and saliva from patients with various types of caries, gingivitis, chronic periodontitis, and peri-implantitis [23,25–27,34,35,37,38,44,45,47,49,52,59,60,62,66–69,91,94], decayed tooth surfaces and discordant caries from intact enamel surfaces [53]. Leptotrichia species were also isolated from bronchoalveolar lavage fluid, and patients with leukocytosis, hypoxemia, and dyspnea [24].…”

“…The concept that Leptotrichia infections are opportunistic is further supported in the current review. Leptotrichia species, primarily oral commensals, have been associated with infections, particularly in immunocompromised hosts (Table 2) [4,9,13–17,24,30,32,46,55,74,78,97], but occasionally in immunocompetent persons [5,11,12,24,33,60,74,78,85]. …”

“…A few Leptotrichia species were related to 88 incidences of various cancers [4–7,9–11,13–15,17–19,22,28,33,40,57,60,61,66,74,80,87,91], of which 43 cases had neutropenia, sepsis, and fever [4–7,9,10,12–15,17,22,24,33,87], 14 had transplant issues [4,9,10,13,16,17,22,33], 14 mucositis [4,7,9,13–15,17,22,87], 12 various lesions (6, 11, 27, 32, 37, 44, 56 64, 99), and five pneumonia [5,9,11,24,33]. The suspected port of Leptotrichia entry included mucositis, abscesses, wound infections, gingivitis, diverticulitis, peritonitis, neutropenic sepsis, and ulcers (Table 2).…”

“…Leptotrichia species were reported in close association with fungi, including species of Saccharomyces , Aspergillus, Zygosaccharomyces , Pichia, Saccharomycopsis , Talaromyces, Eurotium , Fomitopsis, Trichosporon , Candida albicans , C. parapsilosis , and C. tropicalis , and other species from liquor [39], gastric fluid [16], the saliva of HIV patients [46], sputum [50], blood, and saliva [60] (Table 2). The importance of these associations remains unknown.…”