Rifampicin reduces plasma concentration of linezolid in patients with infective endocarditis

BACKGROUND\nOBJECTIVES\nPATIENTS AND METHODS\nRESULTS\nCONCLUSIONS\nLinezolid in combination with rifampicin has been used in treatment of infective endocarditis especially for patients infected with staphylococci.\nBecause rifampicin has been reported to reduce the plasma concentration of linezolid, the present study aimed to characterize the population pharmacokinetics of linezolid for the purpose of quantifying an effect of rifampicin cotreatment. In addition, the possibility of compensation by dosage adjustments was evaluated.\nPharmacokinetic measurements were performed in 62 patients treated with linezolid for left-sided infective endocarditis in the Partial Oral Endocarditis Treatment (POET) trial. Fifteen patients were cotreated with rifampicin. A total of 437 linezolid plasma concentrations were obtained. The pharmacokinetic data were adequately described by a one-compartment model with first-order absorption and first-order elimination.\nWe demonstrated a substantial increase of linezolid clearance by 150% (95% CI: 78%-251%), when combined with rifampicin. The final model was evaluated by goodness-of-fit plots showing an acceptable fit, and a visual predictive check validated the model. Model-based dosing simulations showed that rifampicin cotreatment decreased the PTA of linezolid from 94.3% to 34.9% and from 52.7% to 3.5% for MICs of 2 mg/L and 4 mg/L, respectively.\nA substantial interaction between linezolid and rifampicin was detected in patients with infective endocarditis, and the interaction was stronger than previously reported. Model-based simulations showed that increasing the linezolid dose might compensate without increasing the risk of adverse effects to the same degree.Pharmacolog

Association of neighborhood characteristics with incidence of out-of-hospital cardiac arrest and rates of bystander-initiated CPR: Implications for community-based education intervention

Objective A 10-fold regional variation in survival after out-of-hospital cardiac arrest (OHCA) has been reported in the United States, which partly relates to variability in bystander cardiopulmonary resuscitation (CPR) rates. In order for resources to be focused on areas of greatest need, we conducted a geospatial analysis of variation of CPR rates. Methods Using 2010–2011 data from Durham, Mecklenburg, and Wake counties in North Carolina participating in the Cardiac Arrest Registry to Enhance Survival (CARES) program, we included all patients with OHCA for whom resuscitation was attempted. Geocoded data and logistic regression modeling were used to assess incidence of OHCA and patterns of bystander CPR according to census tracts and factors associated herewith. Results In total, 1466 patients were included (median age, 65 years [interquartile range 25]; 63.4% men). Bystander CPR by a layperson was initiated in 37.9% of these patients. High-incidence OHCA areas were characterized partly by higher population densities and higher percentages of black race as well as lower levels of education and income. Low rates of bystander CPR were associated with population composition (percent black: OR, 3.73; 95% CI, 2.00–6.97 per 1% increment in black patients; percent elderly: 3.25; 1.41–7.48 per 1% increment in elderly patients; percent living in poverty: 1.77, 1.16–2.71 per 1% increase in patients living in poverty). Conclusions In 3 counties in North Carolina, areas with low rates of bystander CPR can be identified using geospatial data, and education efforts can be targeted to improve recognition of cardiac arrest and to augment bystander CPR rates