Plasma and Lung Tissue Pharmacokinetics of Ceftaroline Fosamil in Patients Undergoing Cardiac Surgery with Cardiopulmonary Bypass: an In Vivo Microdialysis Study.

Ceftaroline fosamil, a fifth-generation cephalosporin antibiotic with activity against methicillin-resistant Staphylococcus aureus (MRSA), is currently approved for the treatment of pneumonia and complicated skin and soft tissue infections. However, pharmacokinetics data on free lung tissue concentrations in critical patient populations are lacking. The aim of this study was to evaluate the pharmacokinetics of the high-dose regimen of ceftaroline in plasma and lung tissue in cardiac surgery patients during intermittent and continuous administration. Nine patients undergoing elective cardiac surgery on cardiopulmonary bypass were included in this study and randomly assigned to intermittent or continuous administration. Eighteen hundred milligrams of ceftaroline fosamil was administered intravenously as either 600 mg over 2 h every 8 h (q8h) (intermittent group) or 600 mg over 2 h (loading dose) plus 1,200 mg over 22 h (continuous group). Interstitial lung tissue concentrations were measured by in vivo microdialysis. Relevant pharmacokinetics parameters were calculated for each group. Plasma exposure levels during intermittent and continuous administration were comparable to those of previously published studies and did not differ significantly between the two groups. In vivo microdialysis demonstrated reliable and adequate penetration of ceftaroline into lung tissue during intermittent and continuous administration. The steady-state area under the concentration-time curve from 0 to 8 h (AUCss 0-8) and the ratio of AUCSS 0-8 in lung tissue and AUC in plasma (AUClung/plasma) were descriptively higher in the continuous group. Continuous administration of ceftaroline fosamil achieved a significantly higher proportion of time for which the free drug concentration remained above 4 times the minimal inhibitory concentration (MIC) during the dosing interval (% fT>4xMIC) than intermittent administration for pathogens with a MIC of 1 mg/liter. Ceftaroline showed adequate penetration into interstitial lung tissue of critically ill patients undergoing major cardiothoracic surgery, supporting its use for pneumonia caused by susceptible pathogens.

Hemodynamic effects of Vernakalant in cardio-surgical ICU-patients treated for recent-onset postoperative atrial fibrillation.

Postoperative atrial fibrillation (POAF) is one of the most frequent complications after cardiothoracic surgery and a predictor for postoperative mortality and prolonged ICU-stay. Current guidelines suggest the multi-channel inhibitor Vernakalant as a treatment option for rhythm control. However, rare cases of severe hypotension and cardiogenic shock following drug administration have been reported. To elucidate the impact of Vernakalant on hemodynamics, we included ten ICU patients developing POAF after elective cardiac surgery, all of them awake and breathing spontaneously, in this prospective trial. Patients received the recommended dosage of Vernakalant and were clinically observed and monitored (heart rate, invasive blood pressure, pulse oximetry, central venous pressure) in 1-minute-intervals for 20 minutes before- and 120 minutes after the first dose of Vernakalant. The median time from the end of surgery until occurrence of POAF amounted up to 52.8 [45.9-77.4] hours, it took 3.5 [1.2-10.1] hours from occurrence of POAF until the first application of Vernakalant. All patients received catecholamine support with epinephrine that was held steady and not dynamic throughout the observational phase. We noted stable hemodynamic conditions, with a trend towards a reduction in heart rate throughout the 120 minutes after drug administration. In 7 patients (70%), conversion to sustained sinus rhythm (SR) occurred within 8.0 minutes [6.0-9.0]. No serious adverse events (SAEs) were noted during the observation period. In this prospective trial in ICU-patients showing POAF after cardiac surgery, intravenous Vernakalant did not induce clinically relevant negative effects on patients' hemodynamics but resulted in conversion to sustained SR after a median of 8.0 minutes in 7 out of ten patients.

Microbial risk and removal--a utility perspective.

In this paper the results of a sampling programme, undertaken as part of the EU MicroRisk project, are described. This project was undertaken to ascertain the occurrence of pathogens and indicators in the River Thames and their subsequent removal through a treatment works. Appropriate physico-chemical surrogates, as determined by statistical correlation are proposed for the microorganisms identified in the raw water. This study shows that under normal raw water conditions the treatment works is able to remove microbial contamination with a significant margin of safety.

Sports related injuries: incidence, management and prevention.

The incidence of injury related to various sports is reviewed according to sport, area of injury, number of participants and hours per week spent at the sport. Organized sports accounted for fewer injuries than unsupervised recreational activities like tree climbing, skateboarding and running. The knee is the most commonly injured site. Sensitivity to patients' commitment to their sport is necessary: sometimes instead of rest, they can substitute a less hazardous form of exercise. Principles of prevention involve proper familiarity with the sport, proper equipment and proper conditioning.

Northern health service in Canada.

The current state and future development of Canada's North present significant medical problems. The medical facilities available at present are inadequate and, although they are improving rapidly, they must keep pace with the coming expansion of the North. Arctic regions of other northern countries do not show the great discrepancies in health standards that Canada's North does in comparison to her southern areas. To improve the situation adequate communication, transportation, personnel and facilities are needed. It is proposed that residents in hospital training programs work for a period in the North to supplement recommendations of the Hall Commission in this connection and to broaden their own training.