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Published on: January 22, 2021
Increased killing of staphylococci and streptococci by daptomycin compared with cefazolin and vancomycin in an in
Elizabeth D Hermsen1, Laurie B Hovde, John R Hotchkiss
1Department of Experimental and Clinical Pharmacology, The University of Minnesota College of Pharmacy, Minneapolis, Minnesota 55455, USA.
Abstract:
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.
Insights
Daptomycin demonstrated bactericidal activity against common pathogens in peritoneal dialysis fluid (PDF), outperforming cefazolin and vancomycin. This suggests daptomycin
Area of Science:
- Microbiology
- Pharmacology
- Nephrology
Background:
- Peritoneal dialysate fluid (PDF) can inhibit antibacterial activity, posing challenges for treating infections in patients undergoing peritoneal dialysis.
- Common pathogens in peritoneal dialysis-associated peritonitis include Staphylococcus aureus (both methicillin-resistant [MRSA] and susceptible [MSSA]) and Staphylococcus epidermidis (MSSE).
- The efficacy of standard antibiotics like cefazolin and vancomycin may be compromised in the PDF environment.
Purpose of the Study:
- To evaluate the in vitro antibacterial activity of daptomycin, cefazolin, and vancomycin against key pathogens in PDF.
- To compare the efficacy of these antibiotics in PDF at different pH levels (5.5 and 7.4).
- To determine if daptomycin is a suitable agent for treating peritoneal dialysis-associated peritonitis.
Main Methods:
- An in vitro static model was used to expose MRSA, MSSA, MSSE, and Streptococcus sanguis to daptomycin (10, 30, 100 mg/liter), cefazolin (125 mg/liter), and vancomycin (25 mg/liter).
- Antibiotic activity was tested in both cation-adjusted Mueller-Hinton Broth and PDF at pH 5.5 and 7.4.
- Bactericidal and bacteriostatic effects were assessed for each antibiotic and organism combination.
Main Results:
- Neither cefazolin nor vancomycin showed bactericidal or bacteriostatic effects against the tested organisms in PDF.
- All tested concentrations of daptomycin exhibited bactericidal activity against all tested organisms in PDF.
- The pH of the PDF did not influence the antibacterial activity of the tested agents.
Conclusions:
- Daptomycin demonstrates significant bactericidal activity in PDF, unlike cefazolin and vancomycin.
- Daptomycin shows promise as an effective agent for treating peritoneal dialysis-associated peritonitis.
- Daptomycin offers a potential therapeutic advantage due to its potent bacterial kill rate and extent in the PDF environment.
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