title: Comparison of six generic vancomycin products for treatment of methicillin-resistant Staphylococcus aureus experimental endocarditis in rabbits.
abstract: Concerns have recently emerged about the potency and the quality of generic vancomycin (VAN) products approved for use in humans, based on experiments in a neutropenic mouse thigh infection model. However, other animal models may be more appropriate to decipher the bactericidal activities of VAN generics in vivo and to predict their efficacy in humans. We aimed to compare the bactericidal activities of six generic VAN products currently used in France (Mylan and Sandoz), Spain (Hospira), Switzerland (Teva), and the United States (Akorn-Strides and American Pharmaceutical Products [APP]) in a rabbit model of aortic valve endocarditis induced by 8 × 10(7) CFU of methicillin-resistant Staphylococcus aureus (MRSA) strain COL (VAN MIC, 1.5 μg/ml). In vitro, there were no significant differences in the time-kill curve studies performed with the six generic VAN products. Ten rabbits in each group were treated with intravenous (i.v.) VAN, 60 mg/kg of body weight twice a day (b.i.d.) for 4 days. Mean peak serum VAN levels, measured 45 min after the last injection, ranged from 35.5 (APP) to 45.9 μg/ml (Teva). Mean trough serum VAN levels, measured 12 h after the last injection, ranged from 2.3 (Hospira) to 9.2 (APP) μg/ml. All generic VAN products were superior to controls (no treatment) in terms of residual organisms in vegetations (P < 0.02 for each comparison) and in the spleen (P < 0.005 for each comparison). Pairwise comparisons of generic VAN products found no significant differences. In conclusion, a stringent MRSA endocarditis model found no significant differences in the bactericidal activities of six generic VAN products currently used in Europe and America.
authors.affiliation: Pontchaillou University Hospital, Rennes, France.
authors.forename: P
authors.initials: P
authors.lastname: Tattevin
authors.forename: A
authors.initials: A
authors.lastname: Saleh-Mghir
authors.forename: B
authors.initials: B
authors.lastname: Davido
authors.forename: I
authors.initials: I
authors.lastname: Ghout
authors.forename: L
authors.initials: L
authors.lastname: Massias
authors.forename: C
authors.initials: C
authors.lastname: Garcia de la Maria
authors.forename: J M
authors.initials: JM
authors.lastname: Miró
authors.forename: C
authors.initials: C
authors.lastname: Perronne
authors.forename: F
authors.initials: F
authors.lastname: Laurent
authors.forename: A C
authors.initials: AC
authors.lastname: Crémieux
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics*; D001021:Aortic Valve / Q000382:microbiology; D000082882:Bicuspid Aortic Valve Disease; D016568:Drugs, Generic / Q000493:pharmacokinetics*; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D006330:Heart Defects, Congenital / Q000188:drug therapy* / Q000382:microbiology; D006349:Heart Valve Diseases / Q000188:drug therapy* / Q000382:microbiology; D006801:Humans; D007275:Injections, Intravenous; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects* / Q000254:growth & development; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013203:Staphylococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013810:Therapeutic Equivalency; D014640:Vancomycin / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D016568:Drugs, Generic; D014640:Vancomycin