Dextranase enhances antibiotic efficacy in experimental viridans streptococcal endocarditis.
In endocarditis, exopolysaccharide production by viridans streptococci has been associated with delayed antimicrobial efficacy in cardiac vegetations. We compared the efficacies of temafloxacin alone and in combination with dextranase, an enzyme capable of hydrolyzing 20 to 90% of the bacterial glycocalyx, in a rabbit model of endocarditis. In in vivo experiments, rabbits were infected intravenously with 10(8) 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 effective 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.
Mghir
A S
AS
Institut National de la Santé et de la Recherche Médicale Unité 13, Hôpital Claude-Bernard Bichat, Paris, France.
Cremieux
A C
AC
Jambou
R
R
Muffat-Joly
M
M
Pocidalo
J J
JJ
Carbon
C
C
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000890:Anti-Infective Agents / Q000627:therapeutic use; D003910:Dextranase / Q000494:pharmacology / Q000627:therapeutic use*; D004357:Drug Synergism; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D024841:Fluoroquinolones; D008070:Lipopolysaccharides / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D008854:Microscopy, Electron; D015363:Quinolones / Q000627:therapeutic use; D011817:Rabbits; D013290:Streptococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013298:Streptococcus sanguis / Q000187:drug effects / Q000378:metabolism
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D008070:Lipopolysaccharides; D015363:Quinolones; C054745:temafloxacin; D003910:Dextranase