介绍他汀类药物的巨大多效性作用吸引了许多研究人员选择它们作为对抗细菌感染的潜在候选者。他汀类药物对细菌病原体的作用仍有争议。进行这项研究是为了评估和比较常用他汀类药物对我们三级医院使用痰液作为样本最常见的引起呼吸道感染的细菌病原体的抗菌作用。材料与方法本研究在我院微生物实验室进行。药物包括阿托伐他汀,瑞舒伐他汀,和辛伐他汀以纯形式购自SigmaAldrich。使用二甲基亚砜(DMSO)作为所有三种药物的溶剂。使用的阳性对照是庆大霉素和阿莫西林的革兰氏阴性和革兰氏阳性细菌,分别。分析了过去12个月入住呼吸重症监护病房的患者的痰液样本的所有培养和敏感性结果。最常见的细菌病原体金黄色葡萄球菌,肺炎克雷伯菌,从痰标本中分离出的肺炎链球菌用于我们的研究。采用琼脂杯扩散法和肉汤稀释法两种方法研究了他汀类药物的抑菌效果。计算并分析药物的抑制区和最小抑制浓度。使用GraphPadPrism软件版本10.2.0进行统计分析。使用单向ANOVA检验来确定不同他汀类药物和抗生素组之间是否存在任何统计学差异。使用非配对t检验来确定他汀类药物之间的统计学差异。结果与讨论对于琼脂杯扩散法,我们的结果表明,所有三种他汀类药物阿托伐他汀都缺乏抗菌活性,瑞舒伐他汀,和辛伐他汀对抗所有三种细菌菌株金黄色葡萄球菌,肺炎克雷伯菌,和肺炎链球菌过夜孵育后琼脂杯法浓度为3.125μg/ml,6.25μg/ml,12.5μg/ml,25μg/ml和50μg/ml,分别。对于阿托伐他汀的所有系列稀释液,观察到的抑制区小于4mm(抗性),瑞舒伐他汀,还有辛伐他汀.对于肉汤稀释法,方差分析结果显示,与阿托伐他汀和瑞舒伐他汀相比,阿莫西林和庆大霉素具有较高的微生物生长抑制活性(p值<0.005).统计上,尽管与生理盐水和瑞舒伐他汀相比,阿托伐他汀显示出显著的抗菌活性,这被认为没有临床意义,因为与使用的对照相比,阿托伐他汀显示的抗菌活性非常微不足道,并且与药物的系列稀释度不一致.结论阿托伐他汀,瑞舒伐他汀,和辛伐他汀缺乏对从痰标本中分离出的所有三种细菌菌株的抗菌活性:金黄色葡萄球菌,肺炎克雷伯菌,和肺炎链球菌。因此,他汀类药物作为呼吸道感染的抗菌药物的应用有限.
Introduction The vast
pleiotropic effect of statins has intrigued many researchers to select them as potential candidates against bacterial infections. The role of statins against bacterial pathogens remains debatable. This study was undertaken to evaluate and compare the antibacterial effect of commonly available statins against the most frequently isolated bacterial pathogens causing respiratory tract infections in our tertiary care hospital using sputum as a sample. Materials and methods The study was conducted in the Microbiology Laboratory of our hospital. Drugs including atorvastatin, rosuvastatin, and simvastatin were purchased in pure form from Sigma Aldrich. Dimethylsulfoxide (DMSO) was used as a solvent for all three drugs. The positive controls used were gentamycin and amoxicillin for Gram-negative and Gram-positive bacteria, respectively. Data regarding all the culture and sensitivity results of sputum samples of patients admitted to the Respiratory Intensive Care Unit over the past 12 months were analyzed. The most common bacterial pathogens Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus pneumoniae isolated from sputum specimens were taken for our study. The antibacterial effect of statins was studied using two methods: the agar cup diffusion method and the broth dilution method. The zone of inhibition and minimum inhibitory concentration of the drugs were calculated and analyzed. Statistical analysis was performed using GraphPad Prism software version 10.2.0. A one-way ANOVA test was used to determine if there was any statistical difference between the different statins and antibiotic groups. An unpaired t-test was used to determine the statistical difference between the statins. Results and discussion For the agar cup diffusion method, our results displayed a lack of antibacterial activity of all three statins atorvastatin, rosuvastatin, and simvastatin against all three bacterial strains Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus pneumoniae after overnight incubation by agar cup method at concentrations of 3.125 μg/ml, 6.25 μg/ml, 12.5 μg/ml, 25 μg/ml and 50 μg/ml, respectively. The zone of inhibition observed was less than 4 mm (resistant) for all the serial dilutions of atorvastatin, rosuvastatin, and simvastatin. For the broth dilution method, the ANOVA test showed amoxicillin and gentamicin to have high statistically significant microbial growth inhibitory activity (p-value < 0.005) compared to atorvastatin and rosuvastatin. Statistically, though atorvastatin showed significant antimicrobial activity compared to normal saline and rosuvastatin, this was not considered clinically significant as the antimicrobial activity shown by atorvastatin was very negligible compared to the controls used and did not correspond to the serial dilutions of the drug. Conclusion Atorvastatin, rosuvastatin, and simvastatin lacked antibacterial activity against all three bacterial strains isolated from sputum specimens: Staphylococcus aureus, Klebsiella pneumoniae, and Streptococcus pneumoniae. Hence, the use of statins as an antimicrobial drug for respiratory tract infections has limited applications.