Bactericidal effect of pefloxacin and fosfomycin against Pseudomonas aeruginosa in a rabbit endocarditis model with pharmacokinetics of pefloxacin in humans simulated in vivo.
The bactericidal activity of pefloxacin and fosfomycin alone and in combination against Pseudomonas aeruginosa was evaluated in an experimental rabbit endocarditis model after 24 h of treatment. Two strains with intermediate susceptibility to pefloxacin and good susceptibility to fosfomycin were tested. The serum kinetics obtained during administration of 400 mg every 12 h in humans were simulated in the animals using computer-controlled variable-flow infusion. Fosfomycin was administered as a continuous infusion at a constant flow, allowing a steady-state concentration of 47.4 +/- 11.9 mg/ml to be reached in serum. In valvular vegetations, pefloxacin was less bactericidal than fosfomycin, and in combination treatment, it reduced (but did not abolish) the bactericidal effect of fosfomycin. The duration of the pretreatment interval (12-48 h) had a negative effect on the bactericidal activity of both drugs, especially that of fosfomycin.
Bugnon
D
D
Laboratoire d'Antibiologie Clinique et Expérimentale de la Faculté de Médecine de Nantes, France.
Potel
G
G
Xiong
Y Q
YQ
Caillon
J
J
Navas
D
D
Gras
C
C
Kergueris
M F
MF
Le Conte
P
P
Jehl
F
F
Baron
D
D
Drugeon
H
H
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D004697:Endocarditis, Bacterial / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D005578:Fosfomycin / Q000494:pharmacology* / Q000627:therapeutic use; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D015366:Pefloxacin / Q000494:pharmacology* / Q000627:therapeutic use; D011552:Pseudomonas Infections / Q000175:diagnosis / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D011817:Rabbits; D011897:Random Allocation; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D015366:Pefloxacin; D005578:Fosfomycin