Efficacies of Vancomycin, Arbekacin, and GentamicinAlone or in Combination against Methicillin-Resistant Staphylococcus aureus in an In Vitro InfectiveEndocarditisModel

Abstract

We adopted an in vitro infective endocarditis model (IVIEM) to compare the efficacy of vancomycin (VAN), arbekacin (ABK), and gentamicin (GEN) alone or in combination. Using two strains of clinically isolated methicillin-resistant Staphylococcus aureus, one GEN susceptible (GS171) and one GEN resistant (GR153), fibrin clots were prepared and suspended in the IVIEM. Antibiotics were given as boluses every 6 h (q6h), q12h, or q24h or by continuous infusion with VAN, q12h or q24h with ABK, and q8h or q24h with GEN. For combination treatment, VAN q12h plus ABK q24h and VAN q12h plus GEN q24h were given. Fibrin clots were removed from each model at 0, 8, 24, 32, 48, and 72 h, and the bacterial densities were determined. The number of colonies within the fibrin clot was significantly decreased in all study groups compared with control groups (P < 0.001). When VAN and ABK were administered alone, the number of colonies was significantly lower in GS171 than in GR153 by 8 h after administration (P ‫؍‬ 0.02) and was lowest in GS171 when ABK was administered q12h (P ‫؍‬ 0.01). At 72 h, ABK or VAN alone produced equivalent bacterial reductions regardless of dosing frequency and GEN resistance. In GR153, VAN plus ABK showed an additive effect till 24 h, although VAN plus GEN showed indifference. Our data suggest that ABK could be used as an alternative to VAN in GEN-resistant staphylococcal endocarditis. An additive effect was seen when VAN and ABK were used together in GEN-resistant strains until 24 h; however, further studies are warranted for the clinical application of this combination.

The Efficacy and Safety of Arbekacin and Vancomycin for the Treatment in Skin and Soft Tissue MRSA Infection: Preliminary Study

“…Arbekacin is a derivative of aminoglycoside dibekacin, and it has been reported with a good in vitro activity against MRSA [19, 20]. …”

“…Lee et al reported that an arbekacin based combination therapy can substitute glycopeptide antibiotics for the treatment of MRSA or hetero-VISA infections, and the study concluded that there was no difference in the clinical efficacy between arbekacin and vancomycin [20]. …”

Once-Daily Gentamicin Administration for Community-Associated Methicillin ResistantStaphylococcus aureusin anin vitroPharmacodynamic Model: Preliminary Reports for the Advantages for Optimizing Pharmacodynamic Index

“…GEN was administered via syringes connected to the central compartment. The simulated GEN regimens were as follows: 80 mg every 8 hours (q8h, peak concentration 5 mg/L, half-life 2 hours) and 240 mg every 24 hours (q24h, peak concentration 15 mg/L, half-life 2 hours) 4,20. Before starting the experiment, 10 minutes passed before reaching the equilibrium of GEN concentration between central and peripheral compartment.…”

Drug–Drug Combinations

“…The earlier work from the Rybak group (Palmer and Rybak 1996 ;LaPlante and Rybak 2004 ;Tsuji and Rybak 2005 ) showed essentially no difference between the resistant and susceptible strains that they studied. Lee et al employed the SEV model to show that vancomycin killing was enhanced by arbekacin and gentamicin whether or not the strain was susceptible to gentamicin (Lee et al 2003 ), although the killing at 72 h was not greater than that with arbekacin alone. Recently, the novel combination of trimethoprimsulfamethoxazole with daptomycin has been shown to synergistic with daptomycin in the SEV model against strains of S. aureus with reduced susceptibility to daptomycin (Steed et al 2010 ).…”