e Increasing antimicrobial resistance reduces treatment options for implant-associated infections caused by methicillin-resistant Staphylococcus aureus (MRSA). We evaluated the activity of fosfomycin alone and in combination with vancomycin, daptomycin, rifampin, and tigecycline against MRSA (ATCC 43300) in a foreign-body (implantable cage) infection model. The MICs of the individual agents were as follows: fosfomycin, 1 g/ml; daptomycin, 0.125 g/ml; vancomycin, 1 g/ml; rifampin, 0.04 g/ ml; and tigecycline, 0.125 g/ml. Microcalorimetry showed synergistic activity of fosfomycin and rifampin at subinhibitory concentrations against planktonic and biofilm MRSA. In time-kill curves, fosfomycin exhibited time-dependent activity against MRSA with a reduction of 2.5 log 10 CFU/ml at 128 ؋ the MIC. In the animal model, planktonic bacteria in cage fluid were reduced by <1 log 10 CFU/ml with fosfomycin and tigecycline, 1.7 log 10 with daptomycin, 2.2 log 10 with fosfomycin-tigecycline and fosfomycin-vancomycin, 3.8 log 10 with fosfomycin-daptomycin, and >6.0 log 10 with daptomycin-rifampin and fosfomycin-rifampin. Daptomycin-rifampin cured 67% of cage-associated infections and fosfomycin-rifampin cured 83%, whereas all single drugs (fosfomycin, daptomycin, and tigecycline) and rifampin-free fosfomycin combinations showed no cure of MRSA cageassociated infections. No emergence of fosfomycin resistance was observed in animals; however, a 4-fold increase in fosfomycin MIC (from 2 to 16 g/ml) occurred in the fosfomycin-vancomycin group. In summary, the highest eradication of MRSA cageassociated infections was achieved with fosfomycin in combination with rifampin (83%). Fosfomycin may be used in combination with rifampin against MRSA implant-associated infections, but it cannot replace rifampin as an antibiofilm agent.
BackgroundInsulin resistance is frequent in human immunodeficiency virus (HIV) infection and may be related to antiretroviral therapy. Cytokines secreted by adipose tissue (adipokines) are linked to insulin sensitivity. The present study is aimed to assess the prevalence of insulin resistance (IR) and its association with several adipokines, in a non-diabetic Romanian cohort of men and women with HIV-1 infection, undergoing combination antiretroviral therapy (cART).MethodsA cross-sectional study was conducted in an unselected sample of 89 HIV-1-positive, non-diabetic patients undergoing stable cART for at least 6 months. Metabolic parameters were measured, including fasting plasma insulin, and circulating adiponectin, leptin, resistin, tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) levels. Insulin resistance was estimated by measuring the Quantitative Insulin Sensitivity Check Index (QUICKI), using a cut-off value of 0.33. A linear regression model was fitted to QUICKI to test the association of IR and adipokines levels.ResultsA total of 89 patients (aged 18–65, median: 28 years) including 51 men (57.3%) and 38 women (42.7%) were included in the study. Fifty nine patients (66.3%) were diagnosed with IR based on QUICKI values lower than the cut-off point. IR prevalence was 72.5% in men and 57.6% in women. The presence of the IR was not influenced by either the time of the HIV diagnosis or by the duration of cART. Decreased adiponectin and increased serum triglycerides were associated with increased IR in men (R=0.43, p=0.007). Hyperleptinemia in women was demonstrated to be associated with the presence of IR (R=0.33, p=0.03).ConclusionsGiven the significant prevalence of the IR in our young non-diabetic cohort with HIV infection undergoing antiretroviral therapy reported in our study and the consecutive risk of diabetes and cardiovascular events, we suggest that the IR management should be a central component of HIV-infection therapeutic strategy. As adipokines play major roles in regulating glucose homeostasis with levels varying according to the sex, we suggest that further studies investigating adipokines should base their analyses on gender differences.
Despite the encouraging improvement in mean-age-at-diagnosis 2 years after PP implementation, other indicators showed a failure to maintain the improvements. A systematic screening program would be the most reliable method to reinforce the PPs.
In Romania, HSV-2 seroprevalence was higher in women than men, and was within European limits and lower than that in Africa and the USA. In contrast, HSV-1 seroprevalence was generally higher than that previously recorded in similarly aged populations in Western Europe.
Risk of type 1 diabetes at 3 years is high for initially multiple and single Ab+ IT and multiple Ab+ NT. Genetic predisposition, age, and male sex are significant risk factors for development of Ab+ in twins.
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