Temporal impacts of topical ceftazidime and tobramycin-vancomycin mixtures on the ocular surface microbiota in rabbits

Abstract

Antibiotics are one of the important factors that can alter the diversity and composition of ocular surface microbiota. At present, there are a few studies about the antibiotic effect on ocular surface microbiota, including its time-dependent changes. However, these limited studies have revealed various results, and more experiments are required. In this study, we used 16 S rRNA sequencing method to investigate the effects of topical ceftazidime and tobramycin-vancomycin mixtures on the ocular surface microbiota and the temporal changes of the microbiota after discontinuing antibiotic treatment in rabbits. Seventeen healthy rabbits were treated with 5% ceftazidime and a mixture of 0.3% tobramycin-5% vancomycin (CTV) eye drops on one eye four times a day for 7 days. Swab samples of conjunctiva sacs were collected before antibiotic treatment (D0), 12 h after the last antibiotic treatment (D8) and two further time points on Day 15 (D15) and Day 30 (D30). We found that the species diversity of the ocular surface microbiota increased significantly at D8 and was restored at D15, namely, one week after antibiotic cessation. The community structure of the ocular surface microbiota changed after treatment with CTV but recovered at D30. At D8, the relative abundances of 13 bacterial phyla of the initial top 20 phyla and 11 bacterial genera of the initial top 20 genera were significantly different from the relative abundances of the phyla and genera at D0. Furthermore, the relative abundance of the dominant phylum Epsilonbacteraeota obviously decreased, while Proteobacteria and Bacteroidetes markedly increased. For dominant genera, the relative abundance of Helicobacter notably decreased, while Acinetobacter and Pasteurella greatly increased. Thirteen altered bacterial phyla and 7 of 11 altered bacterial genera recovered to preantibiotic levels at D30. In addition, there was a group of nondominant and rare bacteria enriched at D8, and most of them were restored at D30. In conclusion, the species diversity, community structure and composition of the ocular surface microbiota changed greatly after exposure to CTV, but they tended to be restored within weeks after discontinuing antibiotic treatment.