Espersen, F.

Comparison of pharmacodynamics of azithromycin and erythromycin in vitro and in vivo (Article)

1998-01-01T00:00:00Z

In this study, we determined the efficacy of various dosing regimens for erythromycin and azithromycin against four pneumococci with different susceptibilities to penicillin in an in vitro pharmacokinetic model and in a mouse peritonitis model. The MIC was 0.03 microg/ml, and the 50% effective doses (determined after one dose) of both drugs were comparable for the four pneumococcal strains and were in the range of 1.83 to 6.22 mg/kg. Dosing experiments with mice, using regimens for azithromycin of one to eight doses/6 h, showed the one-dose regimen to give the best result; of the pharmacodynamic parameters tested (the maximum drug concentration in serum [Cmax], the times that the drug concentration in serum remained above the MIC and above the concentration required for maximum killing, and the area under the concentration time curve), Cmax was the best predictor of outcome. The bacterial counts in mouse blood or peritoneal fluid during the first 24 h after challenge were not correlated to survival of the mice. The serum concentration profiles obtained with mice for the different dosing regimens were simulated in the in vitro pharmacokinetic model. Here as well, the one-dose regimen of azithromycin showed the best result. However, the killing curves in vivo in mouse blood and peritoneal fluid and in the vitro pharmacokinetic model were not similar. The in vitro killing curves showed a decrease of 2 log10 within 2 and 3 h for azithromycin and erythromycin, respectively whereas the in vivo killing curves showed a bacteriostatic effect for both drugs. It is concluded that the results in terms of predictive pharmacodynamic parameters are comparable for the in vitro and in vivo models and that high initial concentrations of azithromycin favor a good outcome.

Staphylococcus aureus carriage and infections among patients in four haemo- and peritoneal-dialysis centres in Denmark. The Danish Study Group of Peritonitis in Dialysis (DASPID) (Article)

1996-08-01T00:00:00Z

A three-month prospective surveillance study was undertaken in four dialysis centres to establish the prevalence of Staphylococcus aureus carriage in a Danish population of patients on haemodialysis (HD) or on continuous ambulatory peritoneal dialysis (CAPD). General data such as sex, age, diagnosis, number of months in dialysis, hospital and ward were registered on a precoded form. Standardized nose and four skin swabs (axillae, groins, perineum) were performed on the first day of the survey. After one and two months, nose swabs were collected. Infections were registered and cultures were sent for phage-typing together with the S. aureus strains isolated from the swabs; 59.5% of HD patients and 51.2% of CAPD patients carried S. aureus. Permanent carriage was most frequent (P < 0.00009), primarily in the nose (44.0 and 34.9%, respectively in HD and CAPD). Skin carriage alone was rare (2.4 and 4.7%). Approximately one third (36.6 and 40.7%) of infections were caused by S. aureus. Although diabetics were not significantly more frequent carriers (60.5%) than non-diabetics (55.0%), the incidence of infection was much higher (26.3% vs. 10.3%, P = 0.004). In CAPD, peritonitis and tunnel/exit-site infections predominated (81.4%), often caused by S. aureus (34.8%). More than two thirds of the infections in HD patients were related to intravascular catheterization. The most serious infection was septicaemia, in all cases due to S. aureus. S aureus infections occurred significantly more frequently among carriers (P = 0.005), and more than half the patients were infected by the same or possibly the same strain as they carried in the nose or on skin. Different regimens for the elimination of S. aureus carriage in dialysis patients are discussed. A policy for risk assessment of patients should be developed, and the elimination of S. aureus carriage before dialysis should be encouraged. Controlled trials comparing the cost-effectiveness of recommended regimens to eliminate carriage in HD/CAPD patients are needed. Nose swabs are reliable indicators of carriage in dialysis patients.

Evaluation of Methods for the Detection of Nasal Carriage of Staphylococcus Aureus (Article)

1994-01-01T00:00:00Z