Single-dose daptomycin pharmacokinetics in chronic haemodialysis patients.
ABSTRACT Daptomycin has concentration-dependent antibacterial activity against Gram-positive bacteria. Its use is increasing in haemodialysis units. The manufacturer recommends a 4-6-mg/kg dose administered every 48 hrs for patients receiving haemodialysis. However, there are no published data about daptomycin pharmacokinetics and clearance during haemodialysis. The recommended dosing regimen would conflict with asymmetric thrice-weekly haemodialysis, which yields two ~44-hr and one ~68-hr interdialytic periods. This is the first study to evaluate daptomycin pharmacokinetics in haemodialysis patients, assess the extent of daptomycin dialytic removal and model serum concentrations at 44 and 68 hrs.
Six otherwise healthy subjects on chronic haemodialysis (55.3 +/- 16.1 years old, three females, 66.2 +/- 14.2 kg) received a single 6-mg/kg dose of daptomycin post-haemodialysis infused over 30 minutes. Serial blood samples were collected for ~44 hrs (pre-next haemodialysis) and throughout the subsequent haemodialysis session with a high permeability haemodialyser. Individual pharmacokinetic parameters determined by compartmental analysis were used to model trough serum concentrations at 44 and 68 hrs with 6-, 8- and 10-mg/kg post-haemodialysis doses.
The haemodialysis session in this trial yielded mean urea and daptomycin reduction ratios of 79.6 +/- 5.8% and 57.6 +/- 9.2%, respectively. Daptomycin half-life was 19.4 +/- 6.5 and 3.8 +/- 1.1 hrs 'off' and 'on haemodialysis', respectively, with minimal rebound 1 hr post-haemodialysis. All modelled trough concentrations at 44 and 68 hrs at all doses exceed typical minimum inhibitory concentration (MIC(90)) values for Staphylococcus aureus and Enterococcus faecalis.
Daptomycin serum concentrations declined by ~50% after a 4-hr haemodialysis session with a high permeability haemodialyser. A 6-mg/kg i.v. post-haemodialysis thrice-weekly dose should result in sufficient pre-haemodialysis daptomycin serum concentrations even after a 68-hr interdialytic period.
Article: [Daptomycin in diabetic patients].[Show abstract] [Hide abstract]
ABSTRACT: In diabetic patients, there is a high prevalence of skin or nasal carriage of Staphylococcus aureus, which is associated with an increased risk of local or systemic infections and consequently with greater morbidity and mortality. The microorganisms causing most infections in diabetic ulcers and diabetic foot are S. aureus and Streptococcus pyogenes, although chronic diabetic foot infections are generally polymicrobial, including Pseudomonas aeruginosa and enterobacteria. The present article describes experience with daptomycin in the treatment of the most frequent infectious complications in diabetic patients. The Cubicin Outcomes Registry and Experience (CORE) registry contains information on 60 patients with skin and soft tissue infections treated with daptomycin, with a success rate of 83%. Other recent studies comparing daptomycin with vancomycin or semi-synthetic penicillins have also shown the efficacy and safety of daptomycin with cure rates of between 70% and 80%. In the European version of the CORE registry, the EUROCORE, diabetic patients who developed bacteremia or endocarditis due to Gram-positive pathogens and who received daptomycin showed success rates of 76.8% and 72%, respectively. No significant differences were found in a study comparing daptomycin or standard therapy with vancomycin in methicillin-resistant S. aureus (MRSA) or antistaphylococcal penicillin in methicillin-susceptible S. aureus (MSSA) in diabetic patients with bacteremia or endocarditis. Because of its rapid bactericidal action and scarce adverse effects, daptomycin is an attractive antimicrobial agent in the treatment of Gram-positive infections in diabetic patients, whether in monotherapy or in association with other agents.Enfermedades Infecciosas y Microbiología Clínica 02/2012; 30 Suppl 1:54-8. · 1.48 Impact Factor
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ABSTRACT: Gram-positive cocci are the most common cause of bloodstream infections in hemodialysis patients, with Staphylococcus aureus and coagulase-negative staphylococci causing most infections. Management of these infections often is complicated by limited vascular access options, as well as an increasing prevalence of drug-resistant bacteria in hemodialysis centers, including the emergence of strains of methicillin-resistant S aureus with vancomycin heteroresistance and increasing rates of vancomycin-resistant enterococci, both of which have limited antibiotic treatment options. This article describes the management of these infections based on the organism and its susceptibility profile, including catheter management, antibiotic lock therapies, and systemic antibiotic choices. Although coagulase-negative staphylococci bacteremia often may be managed with preservation of the catheter, antibiotic lock therapy, and intravenous antibiotics, this is rarely the case with S aureus bacteremia because of frequent relapse and the risk of complications, including endocarditis. Enterococcal bacteremia requires more individualization of care, but catheters are less likely to be salvaged, especially when vancomycin-resistant Enterococcus is the causative organism. Finally, strong infection control policies in the hemodialysis unit, conversion from catheter to arteriovenous access when possible, and appropriate use of antibiotics are essential factors in the prevention of these bloodstream infections.American Journal of Kidney Diseases 02/2011; 57(4):624-40. · 5.29 Impact Factor
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ABSTRACT: Daptomycin is a cyclic lipopeptide that is effective in the treatment of Gram-positive infections, including those caused by multiresistant pathogens. This drug has rapid bactericidal action and low nephrotoxicity. Patients with severe renal failure show a dicrease in its renal clearance and an increase in the elimination half-life. The recommended dose in patients with creatinine clearance (CrCl) < 30 ml/min is 4 mg/kg/48 h in skin and soft tissue infections and is 6 mg/kg/48 h in bacteremia and right endocarditis. Pharmacokinetic studies and data from the CORE Registry have allowed improved the dosing regimen in patients under hemodialysis, peritoneal dialysis and other extrarenal depuration techniques. Patients with a CrCl < 30 ml/ min have rates of efficacy ranging between 69.2% and 96%, these rates being similar to or lower than those observed in patients with a CrCl > 30 ml/min. Patients under hemodialysis may have higher rates of clinical failure. This article presents the preliminary results of the EUCORE in Spain. The presence of renal failure at the start of daptomycin therapy is not associated with an increase in the rates of severe adverse effects. Daptomycin has a good safety and efficacy profile for the treatment of infections in patients with chronic renal insufficiency. The consensus documents of distinct societies have incorporated the use of daptomycin in the treatment of bacteremia due to methicillin-resistant Staphylococcus aureus in patients with renal insufficiency.Enfermedades Infecciosas y Microbiología Clínica 02/2012; 30 Suppl 1:38-42. · 1.48 Impact Factor