Pharmacokinetics of Teicoplanin in Patients Undergoing Continuous Ambulatory Peritoneal Dialysis

Abstract

Objective To achieve concentrations of teicoplanin in serum and dialysate within the therapeutic range in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Design Pharmacokinetic study. Setting A tertiary-care hospital. Patients Eight hospitalized anuric patients undergoing CAPD. Interventions One single dose of 10 mg/kg teicoplanin was administered intravenously, and blood and dialysate were sampled at regular time intervals for 48 hours post drug infusion. Concentrations of teicoplanin were determined by microbiological assay. Results Teicoplanin serum levels above 10 μg/mL, the level desired to treat systemic infections, were detected for 24 hours after administration. All dialysate concentrations were very low. Teicoplanin presented two phases of elimination: an early first phase and a late second phase. Mean maximum serum concentration was 75.56 μg/mL, mean half-life (t°) of the early elimination was 3.34 hours, mean t° of the late elimination was 61.68 hours, mean area under the serum-concentration–time curve was 1491.92 mg·hr/L, mean clearance rate was 10.68 mL/minute, mean apparent volume of distribution was 0.80 L/kg, and mean volume of distribution at steady state was 0.22 L/kg. Mean dialysate excretion was 3.16% and mean peritoneal clearance rate was 0.023 mL/minute. Conclusions Based on the time period with the achieved serum levels and on the prolonged t°, it is proposed that teicoplanin might be administered at 10 mg/kg every 24 hours for the therapy of systemic infections in patients undergoing CAPD. However, its intravenous administration should be avoided in the treatment of peritonitis, because the achieved dialysate concentrations were very low.

Current concepts and future strategies in the antimicrobial therapy of emerging Gram-positive spontaneous bacterial peritonitis

“…Furthermore, the minimum inhibitory concentration (MIC) of vancomycin appears to be shifting upwards in some institutions, a phenomenon known as MIC creep; and, where the MIC increase occurs, treatment failure is common[ 53 , 54 ]. Teicoplanin MIC creep has also been described; but, regardless, when it is administered intravenously it does not achieve therapeutic concentration in the ascitic fluid[ 55 ].…”

The empirical antibiotic treatment of nosocomial spontaneous bacterial peritonitis: Results of a randomized, controlled clinical trial

“…On the other hand, when teicoplanin was administered intravenously (IV) at 10 mg/kg of body weight, low concentrations were achieved in peritoneal fluid. (18) Linezolid cannot be used in the majority of patients with cirrhosis and bacterial infections because of thrombocytopenia. Daptomycin is a lipopeptide that is highly effective against MDR Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci.…”

“…As for glycopeptides, there are some concerns owing to a high rate of vancomycin‐resistant Enterococci in patients with cirrhosis and nosocomial infections and the potential risk of nephrotoxicity. On the other hand, when teicoplanin was administered intravenously (IV) at 10 mg/kg of body weight, low concentrations were achieved in peritoneal fluid . Linezolid cannot be used in the majority of patients with cirrhosis and bacterial infections because of thrombocytopenia.…”

Nosocomial spontaneous bacterial peritonitis: discussing a specific infection treatment algorithm

“…Currently, glycopeptides, which for years have been the chief antibiotic for MDR Gram-positive cocci infections, give concerns owing to a high rate of vancomycin-resistant enterococci (VRE), the potential risk of nephrotoxicity and an increase in the mean minimum inhibitory concentration (MIC) of vancomycin in clinical isolates (a phenomenon known as MIC creep), besides when teicoplanin is administered intravenously at 10 mg/kg of body weight, low concentrations are achieved in peritoneal fluid (5). These observations seem to be confirmed by the Randomized Clinical Trial of Piano et al (2), who demonstrated high efficacy of daptomycin combined to meropenem for the treatment of N-SBP.…”