Azithromycin Reduces the Production of α-hemolysin and Biofilm Formation in Staphylococcus aureus

Staphylococcus aureus causes a broad range of life-threatening diseases in humans. This bacterium produces a large number of extracellular virulence factors that are closely associated with specific diseases which are controlled by quorum sensing. In this study, we show that azithromycin was active against methicillin-resistant Staphylococcus aureus (MRSA) strains with MICs ranged from 32 to 64 μg/mL. Azithromycin at subinhibitory concentration, markedly reduced the production of α-hemolysin at (1/16MIC, 1/8MIC) and biofilm formation at (1/16MIC, 1/8MIC), respectively. The results indicated that sub-inhibitory concentrations of azithromycin decreased the production of α-hemolysin and biofilm formation in MRSA in a dose-dependent manner. Therefore, azithromycin may be useful in the treatment of α-hemolysin producing and biofilm formation MRSA infections.     

阿奇霉素联合糖皮质激素治疗重症支原体肺炎患儿的临床效果分析

目的:分析阿奇霉素联合糖皮质激素治疗重症支原体肺炎患儿的临床效果及安全性。方法:选择112例重症支原体肺炎患儿并通过抽签法分为对照组与观察组,每组各56例。对照组予以阿奇霉素治疗,观察组在对照组基础上加用糖皮质激素治疗。观察并比较两组患儿治疗前后血沉(ESR)、血清乳酸脱氢酶(LDH)、同工酶MB(CK-MB)、肌酸激酶(CK)、谷草转氨酶(AST)、C反应蛋白(CRP)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)水平、CD4~+及CD8~+,临床疗效及不良反应的发生情况。结果:观察组有效率为96.4%,显著高于对照组(82.1%),差异有统计学意义(P0.05)。治疗后,两组ESR、血清LDH、CK-MB、CK、AST、CRP、IL-6、TNF-α水平及CD8~+均较治疗前显著降低,且观察组以上指标均明显低于对照组;两组CD4~+均较治疗前明显上升,且观察组显著高于对照组,差异均有统计学意义(P0.05)。观察组退热、咳嗽缓解、肺部湿啰音消失时间均明显短于对照组(P0.05)。两组不良反应的发生情况比较差异无统计学意义(P0.05)。结论:阿奇霉素联合糖皮质激素治疗小儿重症支原体肺炎的临床效果明显优于单用阿奇霉素治疗,可有效减轻心肌损伤和炎症反应,并提高患儿免疫功能,且安全性高。     

In silico investigation of pro-arrhythmic effects of azithromycin on the human ventricle

The macrolide antibiotic azithromycin (AZM) is widely used for respiratory infections and has been suggested to be a possible treatment for the Coronavirus Disease of 2019 (COVID-19). However, AZM-associated QT interval prolongation and arrhythmias have been reported. Integrated mechanistic information on AZM actions on human ventricular excitation and conduction is lacking. Therefore, this study was undertaken to investigate the actions of AZM on ventricular cell and tissue electrical activity. The O'Hara- Virag-Varro-Rudy dynamic (ORd) model of human ventricular cells was modified to incorporate experimental data on the concentration-dependent actions of AZM on multiple ion channels, including I_Na, I_CaL, I_Kr, I_Ks, I_K1 and I_NaL in both acute and chronic exposure conditions. In the single cell model, AZM prolonged the action potential duration (APD) in a concentration-dependent manner, which was predominantly attributable to I_Kr reduction in the acute condition and potentiated I_NaL in the chronic condition. High concentrations of AZM also increased action potential (AP) triangulation (determined as an increased difference between APD₃₀ and APD₉₀) which is a marker of arrhythmia risk. In the chronic condition, the potentiated I_NaL caused a modest intracellular Na ⁺ concentration accumulation at fast pacing rates. At the 1D tissue level, the AZM-prolonged APD at the cellular level was reflected by an increased QT interval in the simulated pseudo-ECG, consistent with clinical observations. Additionally, AZM reduced the conduction velocity (CV) of APs in the acute condition due to a reduced I_Na, and it augmented the transmural APD dispersion of the ventricular tissue, which is also pro-arrhythmic. Such actions were markedly augmented when the effects of chronic exposure of AZM were also considered, or with additional I_Kr block, as may occur with concurrent use of other medications. This study provides insights into the ionic mechanisms by which high concentrations of AZM may modulate ventricular electrophysiology and susceptibility to arrhythmia.