Pefloxacin in rabbits: protein binding, extravascular diffusion, urinary excretion and bactericidal effect in experimental endocarditis

Abstract

The serum protein binding, extravascular diffusion and urinary excretion of pefloxacin were studied in rabbits. The effect of furosemide on the urinary excretion of pefloxacin was investigated. In an experimental model of Escherichia coli endocarditis, diffusion into heart valves and infected vegetations and bactericidal effect of pefloxacin were also studied. We observed a serum protein binding of 25%. Extravascular concentrations found were within the range of the minimal inhibitory concentrations for most susceptible strains. Pefloxacin appeared to be reabsorbed by renal tubules (fractional excretion: 61 +/- 21%). Furosemide significantly increased the renal excretion of pefloxacin through a tubular process. We observed a good penetration of pefloxacin into normal heart valves and infected vegetations. Pefloxacin reduced the colony counts in infected vegetations after seven im injections of the drug (given as 15 mg/kg/12 h).

Correlates of Therapeutic Efficacy in Experimental Methicillin-Resistant <i>Staphylococcus aureus</i> Endocarditis

“…As expected with its long half-life (-3-4 h) and terminal elimination phase in rabbits [6], pre-dosing (trough) pefloxacin serum levels were usually in excess of the MBC of MRSA-173. In contrast, no predosing serum samples from vancomycin-treated animals contained detectable levels of this agent.…”

Single daily dosing of antibiotics: importance of in vitro killing rate, serum half-life, and protein binding

“…This model of experimental endocarditis was previously used, among other purposes, to evaluate the relationship between the bacterial titer and the antibiotic level in the infected site (3,4,17,23) when repeated doses of antibiotics were given. For this study, we decided to use a single dose of each drug in order to simplify the approach of the 25 ,ug/ml).…”

“…E. coli CB 1496, used to induce experimental endocarditis, was isolated from the blood of a patient with infective endocarditis. This strain was resistant to rabbit serum and was used in previous studies (3,4,11,17,23 Mueller-Hinton broth dilution technique, with an inoculum of 105 CFU/ml in mid-exponential phase of growth. The MIC was defined as the lowest concentration of the drug which produced no visible growth after an 18-h incubation.…”

“…The animals were kept in individual cages and allowed free access to food and water throughout the experiment. Left ventricular endocarditis was induced as previously described (3,23,25). Twenty-four hours after a polyethylene catheter was inserted through the aortic valve, each rabbit was injected in the marginal ear vein with a 1-ml suspension containing 107 E. coli (CB 1496).…”

Efficacy of pefloxacin-fosfomycin in experimental endocarditis caused by methicillin-resistant Staphylococcus aureus

“…At present there are few satisfactory alternatives to vancomycin for therapy of endocarditis caused by these organisms (21). Among the fluoroquinolones which have shown promising activity against MRSA (5,17,23,25), pefloxacin appears to be an attractive option for treatment of endocarditis because of excellent penetration into cardiac valve tissue (6,8), long serum half-life (16), and feasibility of administration by both oral and parenteral routes. Although pefloxacin has been effective in some experimental MRSA infections (19,22), the emergence of resistance to pefloxacin among staphylococci has been noted both in vitro (3) and in vivo (27).…”