Fifty-two healthy adult male and female volunteers were enrolled in this double-blind study to determine the maximum tolerated dose, characterize the pharmacokinetics, and obtain serum bactericidal activity (SBA) data for intravenous dalbavancin. Subjects were assigned to single-or multiple-dose groups and randomized to receive dalbavancin or placebo intravenously over 30 min. Doses started at 140 mg in the single-dose group and with a 300-mg loading dose (LD), followed by six daily 30-mg maintenance doses (MDs), in the multipledose cohort and escalated to a 1,120-mg single dose and a 1,000-mg LD and 100-mg MD regimen. Plasma, urine, and skin blister fluid aspirate drug concentrations were measured, and pharmacokinetic parameters were determined via noncompartmental methods. SBA against methicillin-resistant Staphylococcus aureus (MRSA) was determined at several time points. Adverse events and changes from the baseline for laboratory data, electrocardiograms, audiologic assessments, physical examinations, and vital signs were assessed. Concentrations increased in proportion to the dose. Steady-state concentrations were achieved by day 3 with the 10:1 LD-MD regimen. The half-life averaged 181 h, and the mean volume of distribution and clearance were 9.75 liters and 0.0473 liters/h, respectively. Mean values were similar in all groups and in males and females. The portion of the dose excreted renally averaged 33.5%. Bactericidal activity was demonstrated in serum at 7 days in all subjects receiving single doses of >500 mg. All doses were well tolerated. Dose-limiting toxicity was not encountered. No changes in auditory or vestibular function occurred. The long half-life and maintenance of SBA against MRSA for 1 week suggest that weekly dosing may be feasible.

The selection of a novel weekly dalbavancin dosage regimen was based on pharmacokinetic and pharmacodynamic data from humans and an animal model of infection. The results from the granuloma pouch model of infection suggested that dalbavancin concentrations >/=5 mg/L are necessary for extended in vivo activity. Serum bactericidal activity assessments demonstrated that dalbavancin serum concentrations of approximately 20 mg/L were bactericidal upon two-fold dilution. These data, coupled with simulations based on the pharmacokinetic profile derived from a clinical study in healthy volunteers, were used to design the weekly regimen studied in the initial efficacy trial. This efficacy study showed that a two-dose weekly regimen was well tolerated and associated with a higher clinical response rate than the comparator regimens. The data collectively support the further study of dalbavancin as a once-weekly regimen for the treatment of infections caused by Gram-positive bacteria.

Orthopaedic joint replacement is generally considered 'clean' surgery characterized by a low incidence of infection. In recent years the use of a clean theatre environment, high local concentrations of antibiotic in the cement and systemic antibiotic prophylaxis have been recognized as important measures to reduce infection rates significantly, and this has been supported by clinical trials. Staphylococcus aureus and Staphylococcus epidermidis cause at least half of all orthopaedic surgical infections. Gram-negative bacilli are involved to a much lesser extent (10-30%). First- and second-generation cephalosporins are currently considered by most authors as standard prophylaxis in elective orthopaedic surgery. In the light of the increasing incidence of methicillin resistance in coagulase-positive and -negative staphylococci, it is becoming more important for antibiotics to act efficiently against such organisms if they are to be of value in prophylaxis in orthopaedic surgery. A combined, single-dose of vancomycin/gentamicin has been used successfully in an open, controlled study in patients undergoing total joint arthroplasty but, given the disadvantages associated with the use of vancomycin, teicoplanin may be an alternative choice in such procedures. This review analyses four comparative trials of the efficacy and safety of teicoplanin, two with cefamandole, one with cefuroxime and one with cephazolin, as prophylaxis in orthopaedic total joint replacement surgery.

Teicoplanin (8-10 mg/kg) administered intravenously or intramuscularly once daily after a loading-dose regimen of 15-20 mg/kg per day appears to be an effective and well tolerated treatment for Gram-positive infections in neonates.

A multicentre, comparative, randomized study was performed to compare the efficacy and tolerability of two antibiotic regimens in the treatment of peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients: teicoplanin plus tobramycin versus cephalothin plus tobramycin. After informed consent had been obtained, 68 patients were randomized prospectively to receive either teicoplanin plus tobramycin or cephalothin plus tobramycin. Patients were followed throughout the study and for up to 4 weeks after the end of treatment, when clinical and microbiological parameters were assessed again. The incidence of clinical failure was 4.6 times higher in the cephalothin plus tobramycin group than in the teicoplanin plus tobramycin group (7/28 versus 2/37; P < 0.05). There was no significant difference in bacterial eradication between the two groups. Local and systemic tolerability were good for both regimens. The study shows that teicoplanin plus tobramycin is more effective than cephalothin plus tobramycin and might become a 'first-line' treatment for peritonitis in CAPD patients.