Compatibility of fosfomycin with different commercial peritoneal dialysis solutions

M Kussmann,A Baumann,W Poeppl,G Reznicek,S Hauer,P Pichler,M Wiesholzer,H Burgmann,M Zeitlinger

doi:10.1007/s10096-017-3051-3

Abstract

For treatment of peritoneal dialysis-related peritonitis, intraperitoneal administration of antibiotics remains the preferable route. For home-based therapy, patients are commonly supplied with peritoneal dialysis fluids already containing antimicrobial agents. The present study set out to investigate the compatibility of fosfomycin with different peritoneal dialysis fluids, namely, Extraneal®, Nutrineal®, Physioneal® 1.36% and Physioneal® 2.27%, under varying storage conditions. The peritoneal dialysis fluid bags including 4 g fosfomycin were stored over 14 days at refrigeration temperature (6°C) and room temperature (25°C) and over 24 h at body temperature (37°C). Drug concentrations over time were determined by using high-performance liquid chromatography coupled to a mass spectrometer. In addition, drug activity was assessed by a disk diffusion method, diluent stability by visual inspection and drug adsorption by comparison of the measured and calculated concentrations. Blank peritoneal dialysis fluids and deionized water were used as comparator solutions. Fosfomycin was stable in all peritoneal dialysis fluids and at each storage condition investigated over the whole study period. The remaining drug concentrations ranged between 94% and 104% of the respective initial concentrations. No significant drug adsorption was observed for any peritoneal dialysis fluid at any storage condition. No relevant reduction of antimicrobial activity was observed. Fosfomycin is compatible with Extraneal®, Nutrineal® and Physioneal® for up to two weeks at refrigeration or room temperature and may be used for home-based therapy. No dose adjustment is needed due to adsorption or degradation.

Highlights

Peritoneal dialysis-related peritonitis (PDRP) remains a common and serious complication of peritoneal dialysis (PD) which may result in peritoneal membrane failure and conversion to long-term hemodialysis [1]
Defined as a decomposition of ≤10% compared to the initial concentration, fosfomycin was stable in all peritoneal dialysis fluids (PDF) and at each storage condition investigated over the whole study period
Drug concentrations were determined by the use of a microbiological assay and fosfomycin was found to be stable at room temperature over 24 h

Summary

Introduction

Peritoneal dialysis-related peritonitis (PDRP) remains a common and serious complication of peritoneal dialysis (PD) which may result in peritoneal membrane failure and conversion to long-term hemodialysis [1]. The most common pathogens isolated from patients with PDRP are mainly gram positive cocci like Staphylococci or Streptococci, and gram negative bacteria like Escherichia coli or Pseudomonas aeruginosa are frequently detected [2,3,4]. Empirical antimicrobial regimens for treatment of PDRP should cover both gram positive and gram negative bacteria in consideration of center-specific resistance patterns [1]. For home-based therapy of PDRP, patients are commonly supplied with PDFs already containing antimicrobial agents. These PDF bags are warmed up to body temperature by a heating plate at home directly before administration [1, 6]. Fosfomycin is a bactericidal agent with longstanding clinical use in a wide range of

Methods

Results

Conclusion