In endocarditis, exopolysaccharide production by viridans streptococci has been associated with delayed antimicrobial efficacy in cardiac vegetations. We compared the eflicacies of temafloxacin alone and in combination with dextranase, an enzyme capable of hydrolyzing 20 to 90%o of the bacterial glycocalyx, in a rabbit model of endocarditis. In in vivo experiments, rabbits were infected intravenously with 108 Streptococcus sanguis organisms and were treated 6 days later with temafloxacin (50 mg/kg of body weight intramuscularly twice a day) alone or combined with dextranase (1,000 U per rabbit per day intravenously). After 4 days of treatment (day 11), the animals were sacrificed and vegetations were quantitatively cultured. For ex vivo experiments, rabbits were infected as stated above and, on day 11, vegetations were excised aseptically and incubated in vitro in rabbit serum alone (control) or with temafloxacin or temafloxacin plus dextranase at concentrations similar to peak levels in plasma. In vitro, dextranase alone had no antimicrobial effect. In vivo and ex vivo, temafloxacin combined with dextranase was more elfective than temafloxacin alone (P < 0.05). Our results suggest that dextranase is able to increase the effects of temafloxacin by reducing the amount of bacterial glycocalyx in infected vegetations, as confirmed in vitro by electron microscopy showing a markedly reduced amount of glycocalyx and a more clearly visible fibrin matrix.Previous studies have suggested that the difficulty in curing endocarditis could be due to heterogeneous diffusion of some antibiotics into fibrin vegetations (5) or to the reduced metabolic activity of organisms inside vegetations, especially the older ones (11,12,14). However, other factors may account for the difficulty in curing endocarditis, among them the secretion of exopolysaccharide by some organisms inside vegetations.Viridans streptococci still represent a major cause of native valve endocarditis. These streptococci are known to produce an exopolysaccharide (glycocalyx) composed predominantly of dextran in the human mouth and have been shown to produce dextran in experimental cardiac vegetations (18). This production is strain dependent and can be quantified by histochemical techniques (18) or tryptophan quantitative assay (9). Glycocalyx-producing strains form larger vegetations (18). Also, the presence of glycocalyx surrounding viridans streptococci within cardiac vegetations adversely affects penicillin efficacy (8,20). Experimental vegetations infected by exopolysaccharide-producing strains of viridans streptococci are more difficult to sterilize than those infected by exopolysaccharide-deficient strains (20). Moreover, combining penicillin with dextranase, an enzyme capable of hydrolyzing 20 to 90% of the bacterial glycocalyx, has been shown to facilitate sterilization of experimental vegetations infected with a glycocalyx-producing strain of Streptococcus sanguis (8).Glycocalyx could alter the efficacy of penicillin by increasing the size of the vegetat...
Prosthesis infections are difficult to cure. Infection with methicillin-resistant staphylococci is becoming more common in patients with orthopedic implants. Using a recently developed model of methicillin-resistant Staphylococcus aureus (MRSA) infection of a knee prosthesis, we compared the efficacies of teicoplanin and vancomycin. [14C]teicoplanin diffusion in this model was also studied by autoradiography. A partial knee replacement was performed with a silicone implant fitting into the intramedullary canal of the tibia, and 107 CFU of MRSA was injected into the knee. Treatment with teicoplanin or vancomycin (20 or 60 mg/kg of body weight, respectively, given intramuscularly twice daily) was started 7 days after inoculation and was continued for 7 days. The teicoplanin and vancomycin MICs for MRSA were 1 μg/ml. Mean peak and trough levels in serum were 39.1 and 23.5 μg/ml, respectively, for teicoplanin and 34.4 and 18.5 μg/ml, respectively, for vancomycin. Fifteen days after the end of therapy, the animals were killed and their tibias were removed, pulverized, and quantitatively cultured. Teicoplanin and vancomycin significantly reduced (P < 0.05) the bacterial density (2.7 ± 1.3 and 3.3 ± 1.6 log10 CFU/g of bone, respectively) compared to those for the controls (5.04 ± 1.4 log10 CFU/g of bone). The bacterial covents of teicoplanin- and vancomycin-treated rabbits were comparable. The [14C]teicoplanin autoradiographic diffusion patterns in rabbits with prostheses, two of which were uninfected and two of which were infected, were studied 15 days after inoculation. Sixty minutes after the end of an infusion of 250 μCi of [14C]teicoplanin, autoradiography showed that in the infected animals, the highest levels of radioactivity were located around the prosthesis and in the periosteum, bone marrow, and trabecular bone. Radioactivity was less intense in epiphyseal disk cartilage, femoral cartilage, articular ligaments, and muscles and was weak in compact bone. A similar distribution pattern was seen in uninfected rabbits. Thus, teicoplanin may represent an effective alternative therapy for the treatment of these infections.
Using a new rabbit model of methicillin-susceptible Staphylococcus aureus knee prosthesis infection, we compared the efficacies of sparfloxacin (50 mg/kg of body weight subcutaneously, twice a day) and pefloxacin (50 mg/kg subcutaneously, twice a day). A partial knee replacement was performed with a silicone implant fitted into the intramedullary canal of the tibia, and 5 x 10(7) CFU of methicillin-susceptible S. aureus was injected into the knee. The 7-day treatment regimen was started 15 days later. The MICs and MBCs of sparfloxacin and pefloxacin were, respectively, 0.06 and 0.25 microgram/ml (MIC) and 0.25 and 1 microgram/ml (MBC). The peak levels of sparfloxacin and pefloxacin in serum were 3.6 and 21 micrograms/ml, respectively. Three weeks after the end of treatment, animals were sacrificed and tibias were removed, pulverized, and quantitatively cultured. In contrast to pefloxacin (3.61 +/- 1.64 log10 CFU/g of bone), sparfloxacin significantly reduced the bacterial density (2.12 +/- 1.1 log10 CFU/g of bone) (P = 0.01) in comparison with the level in controls (4.59 +/- 1.21 log10 CFU/g of bone), without selection of resistant variants. Sparfloxacin was significantly more effective than pefloxacin (P = 0.025). The autoradiographic pattern of [14C]sparfloxacin diffusion was studied in noninfected animals with prostheses and in infected animals 15 days after inoculation. Sixty minutes after completion of infusion of 250 microCi of [14C]sparfloxacin, in infected animals the highest levels of radioactivity were detected around the prosthesis, in femoral cartilage, and in articular ligaments. Radioactivity was slightly less intense in bone marrow and muscles and was very weak in compact bone. The distribution of sparfloxacin in uninfected rabbits was similar. Thus, sparfloxacin may represent a valid alternative therapy in these infections provided that it is carefully monitored for potential side effects.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.