Efficacy of temafloxacin in experimental Streptococcus adjacens endocarditis and autoradiographic diffusion pattern of [14C]temafloxacin in cardiac vegetations.
Temafloxacin, a new fluoroquinolone, alone or in combination with tobramycin, was compared with penicillin, tobramycin, and their combination in the therapy of rabbits with endocarditis caused by Streptococcus adjacens GaDT, a new species of nutritionally variant streptococci. Animals were injected intramuscularly for 4 days with temafloxacin (50 mg/kg of body weight twice daily [b.i.d.]) alone or combined with tobramycin (12 mg/kg once daily), with procaine penicillin (150,000 U/kg b.i.d.) alone or combined with tobramycin (12 mg/kg once daily), or with tobramycin (12 mg/kg once daily) alone. Another group of animals was treated with a higher dose of temafloxacin (100 mg/kg b.i.d.). Temafloxacin, penicillin, and tobramycin MICs and MBCs were 1 and 2, 0.015 and 1, and 8 and 16 micrograms/ml, respectively. Time-kill curves showed that the addition of tobramycin to penicillin or temafloxacin increased the killing rate. In vivo, treatment with temafloxacin (50 and 100 mg/kg b.i.d.) alone reduced the bacterial counts in vegetations (3.9 +/- 0.9 and 3.1 +/- 0.8 log10 CFU/g of vegetation) compared with those in the vegetations of control animals (7.5 +/- 0.9 log10 CFU/g of vegetation). This result was similar to that obtained with penicillin alone (4.5 +/- 0.8 log10 CFU/g of vegetation). The combination of temafloxacin (50 mg/kg) and tobramycin was as effective as penicillin plus tobramycin (2.5 +/- 0.3 versus 2.3 +/- 0.4 log10 CFU/g of vegetation, respectively). The autoradiographic pattern of [14C]temafloxacin diffusion into infected cardiac vegetations was studied. Thirty minutes after the end of infusion of 250 microCi of [14C]temafloxacin, the [14C]temafloxacin was homogeneously distributed throughout the vegetations. These data support further evaluation of quinolones in experimental endocarditis.
Cremieux
A C
AC
Hôpital Bichat-Claude Bernard, Institut National de la Santé et de la Recherche Médicale, Unité 13, Paris, France.
Saleh-Mghir
A
A
Vallois
J M
JM
Maziere
B
B
Muffat-Joly
M
M
Devine
C
C
Bouvet
A
A
Pocidalo
J J
JJ
Carbon
C
C
D000818:Animals; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D001345:Autoradiography; D004359:Drug Therapy, Combination; D004697:Endocarditis, Bacterial / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D024841:Fluoroquinolones; D008826:Microbial Sensitivity Tests; D010402:Penicillin G Procaine / Q000097:blood / Q000627:therapeutic use; D015363:Quinolones / Q000097:blood / Q000627:therapeutic use*; D011817:Rabbits; D013290:Streptococcal Infections / Q000188:drug therapy*; D014031:Tobramycin / Q000097:blood / Q000627:therapeutic use
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D015363:Quinolones; D010402:Penicillin G Procaine; C054745:temafloxacin; D014031:Tobramycin