Teicoplanin and daptomycin bactericidal activities in the presence of albumin or serum under controlled conditions of pH and ionized calcium.
Teicoplanin and daptomycin bactericidal rates (BRs) were measured from standard kill curves in supplemented Mueller-Hinton broth (B), B with 3 g of albumin per dl (BA), B with 50% pooled human serum (BS), and in broth to simulate free concentrations (BF) under controlled physiologic conditions of pH (7.4) and ionized calcium (1.15 to 1.17 mM) against two clinical Staphylococcus aureus strains. Total concentrations of teicoplanin and daptomycin, respectively, were 45 and 12.5 micrograms/ml in B, BA, and BS and 4.5 and 1.25 micrograms/ml in BF. All BRs are reported as log10 CFU per milliliter per hour. There was a trend for the teicoplanin BR to be inhibited by serum for strain 67 (BR in B was -0.26 +/- 0.08 versus a BR in BS of -0.19 +/- 0.08 [P > 0.05]). The teicoplanin BRs for strain 135 were unaffected by the type of medium used (range, -0.17 to -0.20). For both strains, daptomycin BRs were adversely affected by lower concentrations, albumin, and serum. The BR of daptomycin was significantly faster in B (-4.53 +/- 1.92) (P < 0.05) than it was in BF (-0.58 +/- 0.04), BA (-1.68 +/- 0.28), or BS (-1.02 +/- 0.16) against strain 67. BA and BS resulted in BRs more than twice that in BF (P > 0.05). Against strain 135, daptomycin again produced the highest BR in B; however, the BRs in BF, BA, and BS were almost identical, indicating that only free daptomycin was active. After correcting for the influence of protein binding, pH, and ionized calcium, teicoplanin appeared to be inhibited by serum, and daptomycin demonstrated enhanced BRs against different S. aureus strains in the presence of albumin or serum.
College of Pharmacy and Allied Health Professions, Wayne State University, Detroit, Michigan.
K C
KC
Lamp
M J
MJ
Rybak
D000900:Anti-Bacterial Agents / Q000097:blood / Q000494:pharmacology*; D002118:Calcium / Q000097:blood / Q000494:pharmacology*; D003470:Culture Media; D017576:Daptomycin; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000097:blood / Q000494:pharmacology; D012709:Serum Albumin / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*; D017334:Teicoplanin / Q000097:blood / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D003470:Culture Media; D010455:Peptides; D012709:Serum Albumin; D017334:Teicoplanin; D017576:Daptomycin; D002118:Calcium