Evaluation of in vitro interaction of daptomycin with gentamicin or beta-lactam antibiotics against Staphylococcus aureus and Enterococci by FIC index and timed-kill curves.
The interactions of daptomycin with gentamicin and 5 beta-lactam agents were determined by checkerboard and timed-kill studies. Eighty isolates were tested by checkerboard: 20 each of methicillin-resistant Staphylococcus aureus (MRSA), methicillin-susceptible Staphylococcus aureus (MSSA), vancomycin-susceptible Enterococcus faecalis (VSEF) and vancomycin-resistant enterococci (VRE). Time kill curves were performed on 8 selected isolates: 2 each of MRSA, MSSA, VSEF and VRE. Checkerboard results showed highest frequency of synergistic effects against VSEF (35-75%) with daptomycin combined with ceftriaxone, cefepime or imipenem; a modest effect with most combinations against VRE and MRSA (5-20%); and indifference with daptomycin and most agents against MSSA (0-5%); except with daptomycin with oxacillin where 10-20% synergy was observed. Synergistic interaction was confirmed by time kill studies in seven of ten isolates where checkerboard suggested synergy. A bactericidal effect was exerted in 5/7 synergistic combinations. The in vitro data suggest that daptomycin combined with other antibiotics may be microbiologically beneficial and not antagonistic.
Snydman
D R
DR
Tufts-New England Medical Center, 750 Washington St., Boston, MA 02111, USA. dsnydman@Tufts-nemc.org
McDermott
L A
LA
Jacobus
N V
NV
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017576:Daptomycin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D004357:Drug Synergism; D016983:Enterococcus / Q000187:drug effects* / Q000302:isolation & purification; D005839:Gentamicins / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D047090:beta-Lactams / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D047090:beta-Lactams; D017576:Daptomycin