Department of Neonatology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Inflammation. 2020 Dec;43(6):2202-2208. doi: 10.1007/s10753-020-01287-w.
Clinical studies have confirmed that the use of antibiotics, especially carbapenems, is a high-risk factor for fungal infection in preterm infants. However, it is not entirely clear whether the increased risk for fungal infection is due to the immune differences in preterm infants or antibiotic usage. We found that after newborn rats received antibiotics, they exhibited significantly impaired anti-Candida albicans immunity in comparison with those without treatment, as shown by significantly increased levels of fungal glucan in the peripheral blood, multiple caseous fungal infections in the abdominal cavity, intestinal congestion, ischemia, and a decrease in the number of intestinal villi. Mechanistically, pretreatment with antibiotics diminished antifungal innate immunity by TLR2 and inhibited IL-17A release and neutrophil recruitment, leading to increased susceptibility to fungi. In summary, we demonstrate that antibiotic usage impairs antifungal immunity in neonates and suggest that antifungal prophylaxis may be required after antibiotic treatment in high-risk preterm babies.
临床研究证实，抗生素的使用，尤其是碳青霉烯类抗生素的使用，是早产儿真菌感染的高危因素。然而，真菌感染风险增加的原因是否是由于早产儿的免疫差异还是抗生素的使用，目前还不完全清楚。我们发现，新生大鼠在接受抗生素治疗后，与未接受治疗的大鼠相比，其抗白色念珠菌的免疫力明显受损，表现为外周血中真菌葡聚糖水平显著升高，腹腔内多个干酪样真菌感染，肠道充血、缺血，以及肠绒毛数量减少。从机制上讲，抗生素预处理通过 TLR2 减弱了抗真菌固有免疫，并抑制了 IL-17A 的释放和中性粒细胞的募集，导致对真菌的易感性增加。总之，我们证明抗生素的使用会损害新生儿的抗真菌免疫功能，并提示在高危早产儿中使用抗生素后可能需要进行抗真菌预防。
