RESUMO
Carbapenem resistant Acinetobacter baumannii has emerged as one of the most difficult to treat nosocomial bacterial infections in recent years. It was one of the major causes of secondary infections in Covid-19 patients in developing countries. The polycationic polypeptide antibiotic colistin is used as a last resort drug to treat carbapenem resistant A. baumannii infections. Therefore, resistance to colistin is considered as a serious medical threat. The purpose of this study was to assess the current status of colistin resistance in Pakistan, a country where carbapenem resistant A. bumannii infections are endemic, to understand the impact of colistin resistance on virulence in mice and to assess alternative strategies to treat such infections. Out of 150 isolates collected from five hospitals in Pakistan during 2019-20, 84% were carbapenem resistant and 7.3% were additionally resistant to colistin. There were two isolates resistant to all tested antibiotics and 83% of colistin resistant isolates were susceptible to only tetracycline family drugs doxycycline and minocycline. Doxycycline exhibited a synergetic bactericidal effect with colistin even in colistin resistant isolates. Exposure of A. baumannii 17978 to sub inhibitory concentrations of colistin identified novel point mutations associated with colistin resistance. Colistin tolerance acquired independent of mutations in lpxA, lpxB, lpxC, lpxD, and pmrAB supressed the proinflammatory immune response in epithelial cells and the virulence in a mouse infection model. Moreover, the oral administration of water extract of Saussuria lappa, although not showing antimicrobial activity against A. baumannii in vitro, lowered the number of colonizing bacteria in liver, spleen and lung of the mouse model and also lowered the levels of neutrophils and interleukin 8 in mice. Our findings suggest that the S. lappa extract exhibits an immunomodulatory effect with potential to reduce and cure systemic infections by both opaque and translucent colony variants of A. baumannii.
RESUMO
OBJECTIVE: To find any difference in the fasting lipid profile in patients with history of ischaemic heart disease (IHD) and established atherosclerotic plaques on angiography and in subjects with no known history of IHD. STUDY DESIGN: Observational, cross-sectional study. PLACE AND DURATION OF STUDY: Immunology Department of University of Health Sciences, Lahore, from January 2007 to January 2009. METHODOLOGY: In this study, 200 male subjects, between 40 and 60 years of age were recruited. Serum cholesterol and triglycerides were determined by enzymatic CHOD-PAP and GPO-PAP calorimetric method, HDL-C by accelerator selective detergent method and LDL-C by direct homogeneous enzymatic method. Serum ox-LDL contents were determined by using quantitative sandwich enzyme immuno-assay kits. RESULTS: The total serum cholesterol, triglyceride and LDL-C levels were within the normal range in control and patient groups whereas HDL-C levels were significantly higher in the control group compared to the patient group (p = 0.001). A significant difference (p = 0.001) for HDL-C levels was observed between smokers and non-smokers. Serum ox-LDL levels were higher in patient group as compared to the control group but the difference was not statistically significant. CONCLUSION: The significantly lower HDL levels in patient group with normal cholesterol, LDL and triglyceride levels may suggest low HDL-C has a greater role in IHD. Raising plasma HDL-cholesterol through weight loss, healthy diet, increased physical activity and by proper pharmacotherapy is, therefore, a legitimate therapeutic target for the optimal prevention of CHD in native population.
