♦ BACKGROUND: Peritonitis is a major problem among patients on peritoneal dialysis (PD). The influence of diverse PD fluids on the activity of frequently used antibiotics has been insufficiently investigated. Thus, the present study set out to investigate the impact of different PD fluids on the activity of cefepime, ciprofloxacin, ertapenem, meropenem, and tobramycin against Escherichia coli. ♦ METHODS: Time-kill curves in 4 different PD fluids (Dianeal PDG4, Extraneal, Nutrineal PD4 and Physioneal 40, all Baxter Healthcare Corp., Deerfield, IL, USA) were performed over 24 hours with 4 different concentrations (1 × minimum inhibitory concentration [MIC], 4 × MIC, 8 × MIC, 30 × MIC) of each antibiotic evaluated and without antibiotics as control. Cation-adjusted Mueller Hinton broth (CA-MHB) was used as comparator solution. ♦ RESULTS: In all PD fluids investigated, bacterial growth and antimicrobial activity of all antibiotics tested was significantly reduced compared with the CA-MHB comparator solution. Except at high concentrations of 30 × MIC, cefepime, ertapenem and meropenem demonstrated a strongly reduced activity in all PD fluids investigated. Ciprofloxacin and tobramycin were highly active and bactericidal in all PD fluids and demonstrated dose-dependent activity. ♦ CONCLUSION: The antimicrobial activity of cefepime, ertapenem and meropenem is limited or even nullified in certain PD fluids in vitro, whereas ciprofloxacin and tobramycin show excellent activity. The choice of PD fluids can impact the activity of antimicrobial agents and might influence microbiological outcome. Further studies are required to verify the clinical relevance of our findings.