Pharmacokinetic and bacteriological study of cefadroxil-salicylate and josamycin-salicylate drug regimens.

Eye, nose, throat and bronchopulmonary infections are frequently associated with inflammatory symptoms. This often leads the clinician to prescribe a combination of an anti-inflammatory and an antibiotic. Cefadroxil and josamycin are among the antibiotics most frequently used in these infections, and they are often combined with acetylsalicylic acid in various pharmaceutical formulations. The study of possible pharmacokinetic and bacteriological interactions was performed in healthy volunteers who received in a crossover protocol each of the two antibiotics, either alone or combined with acetylsalicylic acid or lysine acetylsalicylate. No marked pharmacokinetic interaction was noted except an increase in the AUC for plasma concentrations of cefadroxil when combined with a salicylate. A greater uniformity of kinetic profiles was seen with cefadroxil than with josamycin. Lastly, with the exception of one strain, the salicylates did not alter the antibacterial activity of cefadroxil.

[Adherence properties and production of slime by staphylococci: relation to pathogenicity]. / Propriétés d'adhérence et production de slime des staphylocoques: relation avec la pathogénicité.

Among the S. aureus 25/39 are non producing slime and non adherent isolates. These results did not allow a correlation between these properties and pathogenesis. Several different phenotyping systems (biotyping, phage typing, serotyping, antibiotic susceptibility profiling, and plasmid pattern analysis) have been used in an attempt to identify strains of CNS. There is still a need however, for a simple, rapid, and cost effective method of distinguishing true pathogens from simple contaminants. Our results suggest that testing isolates for slime positivity and for adherence property may fulfill this task.

Pefloxacin in the treatment of bone infections associated with foreign material.

Thirteen patients with bone infection caused by Staphylococcus aureus, Pseudomonas aeruginosa, Serratia marcescens or Escherichia coli in association with implanted foreign material were treated with pefloxacin 400 mg 12-hourly for up to six months. Satisfactory results, with fistula closure and eradication of the infecting bacteria, were achieved in nine patients, who have been followed up for four to seven years. Treatment failed in two patients, with re-isolation of the infecting bacteria (P. aeruginosa; Ser. marcescens) which showed reduced sensitivity to pefloxacin. Primary failure (failure to close of the fistula and re-isolation of bacteria sensitive to pefloxacin) occurred in one patient, who achieved a satisfactory result later after removal of foreign material. Relapse after treatment occurred in one patient. Eight patients suffered migrating arthralgia (without signs of arthritis) but this did not interfere with the treatment, which was generally well tolerated.

[Effect of fibronectin on the adhesion of staphylococci and interaction with pefloxacin's anti-adherence properties]. / Rôle de la fibronectine sur l'adhésion des staphylocoques et interaction avec les propriétés anti-adhérentielles de la péfloxacine.

Fibronectin (Fn) is recognized for its ability to mediate Staphylococcus aureus (SA) adhesion. The number of Fn receptors is dependent on the phase of growth, and type of media. Furthermore, it was of interest to examine SA and Staphylococcus epidermidis (SE) adherence to porcine Fn (IBF 10 ng/ml) immobilized on tissue culture plates. The aim of our study was to examine if removal of FN receptors by growing bacteria in an antibiotic containing medium decreased the ability to adhere and of pefloxacin (P) anti-adhesive properties were medium dependent. As SE usually lack Fn binding capabilities, it seemed of interest to investigate if the effects of subinhibitory concentrations of P were modified by medium or Fn. We found: a) For SA: whether Fn coated onto plastic substrata promoted adherence of strains, P's anti-adhesive properties were saved, non medium or phase of growth dependent. b) For SE: adherence properties were decreased if Fn was coated onto plates. P's anti-adhesive properties were not modified and non medium dependent. The number of Fn receptors on clinical isolates of SA correlates with the invasiveness of the isolates. As P reduced the binding of SA to Fn coated plates, this observation may have important implications for antimicrobial prophylaxis.

[Bactericide activity of cefadroxil comparated with amoxicillin-clavulanic acid, cefaclor and josamycin]. / Activité bactéricide du céfadroxil comparée à celle de l'amoxicilline-acide clavulanique, du céfaclor et de la josamycine.

Betalactamase-producing organisms are responsible for an increasing number of ENT and lower respiratory tract infections. Or cephalosporins and the combination of amoxicillin with the beta-lactamase inhibitor clavulanic acid are alternatives to ampicillin therapy. The killing activity of cefadroxil on the organisms most often responsible for ENT and respiratory infections was evaluated in vitro using a viable bacteria count method, comparatively with cefaclor, josamycin, and amoxicillin-clavulanic acid. Killing activity was found to be time-dependent for all the antimicrobial agents studied. Cefadroxil exhibited the same bactericidal effect on Streptococcus pyogenes and S. pneumoniae than the other agents. Haemophilus influenzae and an increasing number of Pneumococcus strains were resistant to josamycin which is therefore not appropriate for first-line therapy. As compared with amoxicillin and amoxicillin-clavulanic acid, cefadroxil was less active on H. influenzae and more active on Staphylococcus aureus. Production of beta-lactamase failed to influence the killing activity of cefadroxil. These bacteriologic data, together with results of pharmacologic studies (long half-life and good penetration within tissues) can explain the clinical successes obtained with cefadroxil in ENT and lower respiratory tract infections.

[Bactericidal effect of cefadroxil, amoxicillin alone or in combination with clavulanic acid in sera of healthy volunteers]. / Etude de l'activité bactéricide du céfadroxil, de l'amoxicilline seule ou associée à l'acide clavulanique, à partir de sérums de volontaires sains.

Determination of minimal inhibitory concentrations (MICs) provides data on the susceptibility or resistance of a bacteria; however, in susceptible bacteria this parameter is not predictive of effectiveness of the antimicrobial agent. Bactericidal activities of cefadroxil, of amoxicillin, and of the amoxicillin-clavulanic acid combination on bacteria commonly found in ENT and lower respiratory tract disease were studied comparatively. The antibiotics were given by the oral route to six healthy volunteers. With beta-lactamase-producing and non-beta-lactamase-producing strains of Escherichia coli, amoxicillin produced MICs consistent with susceptibility but failed to exhibit a bactericidal effect, whereas cefadroxil was bactericidal. Combination of amoxicillin with an inhibitor did not modify this activity on E. coli and failed to produce a bactericidal effect on Klebsiella pneumoniae similar to that seen with cefadroxil. Amoxicillin with and without clavulanic acid exhibited comparable effectiveness on Streptococcus pyogenes and S. Pneumoniae. The bactericidal effect of cefadroxil on S. pneumoniae was of similar magnitude but shorter duration than that of amoxicillin. Cefadroxil and the amoxicillin-clavulanic acid combination had similar bactericidal effects against Staphylococcus aureus. These antibiotics exhibited a time-dependent effect on Gram positive microorganisms. These pharmacodynamic data, together with measures of bactericidal activity, may be very helpful for selecting the appropriate antibiotic and dosage.

[Kinetics of pefloxacin diffusion in human bone tissue following a single infusion of 800 mg. Evaluation of an extraction technic using chloroform]. / Cinétique de la diffusion de la péfloxacine dans le tissu osseux humain après perfusion unique de 800 mg. Evaluation de la technique d'extraction par le chloroforme.

A better understanding of the pharmacokinetics of pefloxacin in human bone is warranted by the efficacy of this drug in the treatment of bone and joint infections. Surgical bone samples were taken at 30 mn, 1h, 6h, 12h and 24 h after the administration of a single 800 mg intravenous dose of pefloxacin over 1 hour for 26 patients who underwent surgery in an orthopedic surgery ward. Drug concentration was measured by a microbiological method (extraction of the antibiotic in buffer or with chloroform). Up until the 24th hour, in 25/26 cases, the bone levels were superior to 2 mg/l (the critical concentration of pefloxacin) in cortical as well as in spongy bone. Our study reveals a good diffusion of pefloxacin in bone, results which support the idea that this antibiotic may be prophylactically effective in orthopedic surgery.

[Contribution of bacterial detachment by enzymatic or physical methods to the diagnosis of foreign material infections and chronic osteomyelitis]. / Apport des méthodes de décrochage enzymatique ou physique des bactéries au diagnostic des infections sur matériel étranger et des ostéomyélites chroniques.

Bacterial adhesion is a crucial factor in the pathogenicity of numerous bacterial species. This property plays such a great role in infections of foreign material that removal of the material is the only effective therapy. The electron microscopy studies performed by Christensen have demonstrated that infected foreign material harbors bacteria which are often coated with slime and therefore escape detection by conventional microbiological methods. in view of these properties, enzymatic or physical detachment of adherent bacteria was attempted. 231 specimens from a variety of materials (catheters, heart valves, drains, bone biopsies) which yielded negative results after 15 days culture in Schaedler medium were either exposed to trypsin or sonicated. Among catheter specimens, 44.7% yielded positive bacteriologic results; pathogens recovered included 8.3% micrococci, 5.1% nongroupable streptococci, 1.7% group D streptococci, 2.9% Enterobacteria, and 23.3% coagulase-negative staphylococci. Among the bone specimens, the improvement in yield was 64.7%; except in one case, the pathogens recovered were consistent with previously initiated treatments. This bacterial detachment method should be studied in a larger number of specimens to determine its diagnostic value as compared with conventional techniques.