Increased killing of staphylococci and streptococci by daptomycin compared with cefazolin and vancomycin in an in vitro peritoneal dialysate model.
Peritoneal dialysate fluid (PDF) is a bacteriostatic medium that compromises the antibacterial activity of cell wall-active agents. By use of an in vitro static model, methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible S. aureus (MSSA), methicillin-susceptible Staphylococcus epidermidis (MSSE), and Streptococcus sanguis were exposed to daptomycin at concentrations of 10, 30, and 100 mg/liter, cefazolin at 125 mg/liter, and vancomycin at 25 mg/liter in cation-adjusted Mueller-Hinton Broth or Todd Hewitt Broth (for S. sanguis) and PDF at pHs of 5.5 and 7.4. The pH had no effect on antibacterial activity. Neither cefazolin nor vancomycin produced a bactericidal or a bacteriostatic effect versus MRSA, MSSA, MSSE, or S. sanguis in PDF, while all concentrations of daptomycin were bactericidal against all organisms in PDF. Daptomycin did not exhibit concentration-dependent activity in PDF. Daptomycin appears to be a promising agent for use in peritoneal dialysis-associated peritonitis, producing bacterial kill to a greater extent and at a higher rate than cefazolin or vancomycin in PDF.
Hermsen
Elizabeth D
ED
Department of Experimental and Clinical Pharmacology, The University of Minnesota College of Pharmacy, Minneapolis, Minnesota 55455, USA.
Hovde
Laurie B
LB
Hotchkiss
John R
JR
Rotschafer
John C
JC
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002437:Cefazolin / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology*; D015169:Colony Count, Microbial; D017576:Daptomycin / Q000494:pharmacology*; D015314:Dialysis Solutions; D006863:Hydrogen-Ion Concentration; D016106:Methicillin Resistance; D010530:Peritoneal Dialysis / Q000009:adverse effects*; D010538:Peritonitis / Q000209:etiology / Q000382:microbiology*; D011485:Protein Binding; D013210:Staphylococcus / Q000187:drug effects*; D013291:Streptococcus / Q000187:drug effects*; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D015314:Dialysis Solutions; D014640:Vancomycin; D002437:Cefazolin; D017576:Daptomycin