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H B Drugeon

Publications and source records attributed to H B Drugeon.

At least 37 records · Page 2Linked to original sources
PubMed1994

In vivo bactericidal activities of ciprofloxacin and pefloxacin in an experimental model of Serratia marcescens endocarditis.

The critical concentrations of pefloxacin and ciprofloxacin in serum, corresponding to the lowest concentration in serum able to achieve a 2-log-unit reduction in the CFU in vegetations after a 24-h exposure at a steady-state concentration obtained by a continuous intravenous infusion, were determined in an experimental model of Serratia marcescens endocarditis in rabbits. In vitro data showed that the MICs of ciprofloxacin and pefloxacin were 0.06 and 0.25 mg/liter, respectively. The killing curves indicated a maximum killing rate at a concentration four times that of the MICs. In vivo, the critical concentrations of pefloxacin and ciprofloxacin in serum were 0.4 and 0.24 mg/liter, respectively, corresponding to a concentration of four times the MICs.

Animals↗
PubMed1994

Comparison of phenotypic methods and DNA hybridization for detection of methicillin-resistant Staphylococcus aureus.

One hundred thirty-eight Staphylococcus aureus isolates from patients with severe staphylococcal infections were collected in 15 French hospitals. Detection of the mec gene was performed by dot blot hybridization with a specific DNA probe. Dot blot results were used to characterize the isolates as methicillin susceptible (77 isolates) or resistant (61 isolates). The isolates were screened for methicillin resistance by an agar spread method on Mueller-Hinton plates containing oxacillin (2 and 10 micrograms/ml) and were incubated at 37 degrees C, with 10(8) CFU as the inoculum. MICs of oxacillin and methicillin were determined by the agar dilution method on Mueller-Hinton plates without NaCl, by using 10(5) CFU per spot, after 24 and 48h of incubation at 30 or 37 degrees C. Moderately elevated MICs were found for 20 isolates (14.5%). The mec gene was detected in six (30%) of the isolates expressing a low level of resistance to methicillin and/or oxacillin. As determined by comparison with probe hybridization results, the spread plate method with oxacillin at 2 micrograms/ml was more sensitive (sensitivity, 100%) and specific (specificity, 100%) than agar dilution with either methicillin or oxacillin in identifying methicillin resistance or susceptibility. Determinations of methicillin and oxacillin MICs by the agar dilution method had a specificity of 99 to 100% depending on the conditions of incubation, but the sensitivity was below 85% whatever the duration or temperature of incubation.

DNA, Bacterial↗
PubMed1994

[A simple method for the determination of the class of expression of methicillin resistance].

Four stable classes of phenotypic expression in methicillin resistant Staphylococcus aureus were described: three of them showed heterogeneous resistance. The fourth was homogeneous. Methicillin resistance depend on the gene mecA encoding an altered penicillin-binding protein. The phenotypic expression was controlled by chromosomic factors (fem and aux genes) and was modified by test conditions: (temperature - pH - NaCl 4%). The conventional method for determination of these different classes was the population analysis method using methicillin as antibiotic indicator. This fastidious method cannot use in routine laboratory. In this work, the authors developed a common method using the diffusion agar method. Four antibiotic disks (methicillin 2.5, 15, 100 micrograms oxacillin 30 micrograms) and three incubation temperatures (30 - 35 - 40 degrees C). The determination of the phenotypic classes could be an epidemiologic marker for the survey of epidemic MRSA in hospital.

Bacteriological Techniques↗
PubMed1993

[Mechanisms of adhesion of Staphylococci to biomaterials: effect of fusidic acid].

The production of slime, adherence to plastics and hydrophobicity are factors which regulate the colonisation of biomaterials by Staphylococci. The influence of fusidic acid on these 3 factors was studied by using 3 pairs of pathogenic strains of S. aureus and S. epidermidis. Each pair presented differences in the expression of one or several of these factors. The influence of fusidic acid was initially studied by determining the expression of these factors by these strains cultured in the presence of 0.03 mg/l and 0.5 mg/l of antibiotic. Hydrophobicity was measured by the Bath-test method, slime was detected by Trypan blue staining after fixation with Carnoy's fixative and adherence was determined on polystyrene. The variations observed were generally minor, except for S. epidermidis, high slime produces, which showed a reduced production. Using this collection of strains, we then selected mutants resistant to 2 micrograms/ml of fusidic acid. This resistance induced a reduction in the 3 colonisation factors and it can be proposed that strains resistant to fusidic acid have a lesser capacity to colonise than sensitive strains. The bacteria adhere to and colonise the majority of surfaces proposed to them [3, 7, 10]. This was the case for biomaterials used in medicine, whose number and diversity (catheters, prostheses) are continually increasing. Apart from thrombosis, the major complication is the development of infection. Coagulase positive or negative Staphylococci are very frequently responsible for this type of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacterial Adhesion↗
PubMed1991

[Bactericide activity of cefadroxil comparated with amoxicillin-clavulanic acid, cefaclor and josamycin].

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.

Amoxicillin↗
PubMed1991

[Bactericidal effect of cefadroxil, amoxicillin alone or in combination with clavulanic acid in sera of healthy volunteers].

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.

Amoxicillin↗
PubMed1990

Determination of optimal dosage regimen for amikacin in healthy volunteers by study of pharmacokinetics and bactericidal activity.

The pharmacokinetics and serum killing curves of amikacin, which was administered by a 30-minute intravenous infusion of single doses of 7.5 mg/kg and then 15 mg/kg, were investigated in six healthy volunteers who received the two doses in a crossover study with a washout period of 20 days. The serum killing curves were determined for four bacterial species: Escherichia coli, Serratia marcescens, Enterobacter cloacae, and Pseudomonas aeruginosa. All strains were serum resistant, and the bactericidal activity was analyzed by separating the early phase (first 5 h) and the late phase (24 h) of the killing curve. For the early phase, the bactericidal activity was evaluated by correlating an index of surviving bacteria with amikacin concentrations. This methodology allowed determination of two parameters: the maximal effective concentration and the lowest effective concentration. For the late phase, the threshold values separating bacteriostatic and bactericidal activities were lower than 10 mg/liter for each strain. The concentration dependence of amikacin bactericidal activity was confirmed for Escherichia coli and Enterobacter cloacae and, to a lesser extent, for Serratia marcescens and Pseudomonas aeruginosa. Correlation of these data with amikacin pharmacokinetic data in volunteers indicated that a daily dose of 15 mg/kg may be effective in the treatment of Escherichia coli and Enterobacter cloacae infections. For Pseudomonas aeruginosa and Serratia marcescens, the partially time-dependent activity probably necessitates two daily administrations and combination with another antibiotic.

Adult↗
PubMed1990

A new approach to optimal antibiotic dosage regimen by coupling pharmacokinetics and killing curve parameters.

Antibiotic therapy is directed against bacteria responsible for infectious pathology which are able to resist treatment mainly when the dosage is misadapted. The choice of the initial dosage regimen actually takes into account toxicological, bacteriological and pharmacokinetic parameters. The determination of the classical bacteriological data is performed in vitro using fixed drug concentrations that are far from human therapy conditions, and moreover the efficiency is not well defined. The estimation of the pharmacokinetic parameters is realized in animals, healthy subjects or ill patients but takes into account only the drug disposition without correspondence with the kinetics of the antibiotic effect on the bacteria. Thus, each type of evaluation is made independently from the others without any correlation between the observed phenomena. It appears, therefore, interesting to propose a new approach including pharmacokinetic and bacteriological data to enable approximation of drug efficacy. The coupled evaluation of individual pharmacokinetic estimation and the killing curve determinations of an antibiotic will allow this type of development. On the basis of these data, a preliminary profile of the optimal dosage would be possible. This methodology has been applied to three antibiotics: teicoplanin, amikacin and ofloxacin and demonstrates a time- or dose-dependent activity, with interesting possibilities for optimization of dosage.

Amikacin↗
PubMed1989

Evaluation of pefloxacin, ofloxacin and ciprofloxacin in the treatment of thirty-nine cases of chronic osteomyelitis.

From October 1983 to October 1986, 39 patients with chronic osteomyelitis (of at least two month's duration) were treated with either pefloxacin (n = 15), ofloxacin (n = 17), or ciprofloxacin (n = 7). The length of treatment ranged from 3 to 6 months; follow-up examinations were performed up until July 1988. The infecting bacterial strains (19 Staphylococcus aureus, 2 Staphylococcus epidermidis, 10 Escherichia coli, 8 Pseudomonas aeruginosa) were all sensitive to the quinolone prescribed. Twenty-nine of the 38 evaluable patients had a satisfactory outcome at follow-up examinations 14 to 48 months after the end of treatment. Fourteen of the 21 patients with gram-positive bacterial infections responded satisfactorily, as did 15 of the 17 patients infected by gram-negative bacteria. Nine cases of failure were observed (2 for pefloxacin, 4 for ofloxacin, 3 for ciprofloxacin). The infecting bacteria were Staphylococcus aureus in six cases (3 on ofloxacin, 3 on ciprofloxacin). The infecting bacteria were Staphylococcus aureus in six cases (3 on ofloxacin, 3 on ciprofloxacin), and Staphylococcus epidermidis (ofloxacin), Escherichia coli (pefloxacin), and Pseudomonas aeruginosa (pefloxacin) in one case each. In all these cases, local conditions (presence of a foreign body in 5 cases, sequestra in 3, and post-radiotherapy necrosis in 1) could have been responsible for treatment failure. Tolerance was good; adverse effects observed in the pefloxacin and ofloxacin groups disappeared after treatment was ended. Bone levels varied but were always superior to the MIC for the pathogen. In view of the satisfactory results, the possibility of oral administration, and the good tolerance, these quinolones should be considered as alternative agents for the treatment of chronic osteomyelitis.

Administration, Oral↗
PubMed1989

New mechanism for methicillin resistance in Staphylococcus aureus: clinical isolates that lack the PBP 2a gene and contain normal penicillin-binding proteins with modified penicillin-binding capacity.

Seventeen clinical isolates of Staphylococcus aureus (from the United States and Europe) selected for low (borderline)-level methicillin resistance (MIC of methicillin, 2 to 4 micrograms/ml; MIC of oxacillin, 0.5 to 8 micrograms/ml) were examined for their mechanisms of resistance. Five strains were typical of heterogeneous S. aureus: they gave positive reactions with a DNA probe specific for mec and contained a small fraction (10(-6] of highly resistant cells (MIC, greater than 100 micrograms/ml). The rest of the 12 strains were homogeneous with respect to their methicillin resistance: the MIC of methicillin for all cells was 2 to 4 micrograms/ml, and no cells for which MICs were 50 micrograms/ml or higher were detectable (less than 10(-9]. None of these strains reacted with the mec-specific DNA probe. One representative strain of each group was characterized in more detail. Strain CDC-1, prototype of heterogeneous methicillin-resistant S. aureus, contained penicillin-binding protein (PBP) 2a; its DNA could transform a methicillin-susceptible and novobiocin-resistant recipient to methicillin resistance with ca. 35% linkage to Novr. Introduction of the "factor X" determinant (K. Murakami and A. Tomasz, J. Bacteriol. 171:874-879, 1989) converted strain CDC-1 to high, homogeneous resistance. Strain CDC-6, prototype of the second group of isolates, showed completely homogeneous MICs of methicillin, oxacillin, and cefotaxime. The strain contained modified "normal" PBPs: PBPs 1 and 2 showed low drug reactivity (and/or cellular amounts), and PBP 4 was present in elevated amounts. No PBP 2a could be detected. DNA isolated from strain CDC-6 could transform the methicillin-susceptible and novobiocin-resistant strain to methicillin resistance in a multistep fashion, but this resistance showed no genetic linkage to the Nov marker. We suggest that staphylococci with borderline resistance may contain at least three different classes of mechanism: heterogeneous, methicillin-resistant S. aureus, PBPs of modified drug reactivities, and the previously reported hyperproduction of beta-lactamase (L.K. McDougal and C. Thornsberry, J. Clin Microbiol. 23:832-839, 1986).

Bacterial Proteins↗
PubMed1989

[Bactericidal effect of daptomycin (LY 146032) compared with vancomycine and teicoplanin against gram-positive bacteria].

Daptomycin (LY 146032) is a semi-synthetic antibiotic whose structure consists of a cyclic peptide with a lipophilic chain. It inhibits synthesis of the bacterial wall differently than vancomycin and teicoplanin. The bactericidal activity of daptomycin was compared with that of vancomycin and of teicoplanin with regard to 54 Gram positive strains of bacteria: (S. aureus meti S and meti R; S. epidermidis meti S and meti R; E. faecalis, E. faecium, and Corynebacterium group JK). Vancomycin and teicoplanin have the same slow and time-dependent bactericidal activity. The activity of daptomycin is different: rapid and concentration-dependent, similar to that of the aminoglycosides. In the case of the Corynebacteria, however, the activity of daptomycin is comparable to that of vancomycin and of teicoplanin slow and time-dependent.

Anti-Bacterial Agents↗
PubMed1988

[Theoretical bases for the combination of ceftazidime with other antibiotics. Synergism research].

Combinations of antibiotics have always been difficult to study, and the available methods often give discordant results making interpretation uneasy in the absence of in vitro-in vivo correlations. By studying the bactericidal effects of combinations a better definition of interactions between two antibiotics can be obtained if the concept of dominance is taken into account. Ceftazidime, a time-dependent antibiotic, acts synergistically with aminoglycosides, notably against moderately sensitive strains. This synergistic effect results from acceleration of the early bacterial kill and from blockage of the late regrowths. With quinolones, the synergistic effect does not result from blockage of late regrowths. However, the significance of these results needs to be confirmed by clinical trials.

Aminoglycosides↗
PubMed1988

[Kinetics of ofloxacin-amoxicillin and ofloxacin-clavulanic acid combinations against pathogenic bacteria of the respiratory tract].

Ofloxacin exhibit a good activity against the pathogen bacteria of the respiratory tract, except for S. pneumoniae. Its use is interesting because it has a good diffusion into respiratory tissues. However, the combination with an another antibiotic was necessary to spread the activity spectrum and to prevent the resistant variants. By the new killing curve checkerboard method, these 2 combinations are studied against 8 strains: 4 H. influenzae (2 beta-lactamase producers), 2 S. pneumoniae and 2 K. pneumoniae, at 0, 2, 4, 6 and 24 hours, a viable bacteria counting is executed by a microdilution method and is subcultured with a Steers-type multiple inoculator. With K. pneumoniae, ofloxacin has a dose dependent bactericidal activity which is maximum at 1 mg/l, While augmentin has a time-dependent activity. In the combination the synergy is rare. With H. influenzae, the results are the same; the bactericidal activity is less rapid but it is better than the ones with amoxicillin and clavulanic acid. With S. pneumoniae, the 2 antibiotics have the same activity. No antagonism is observed. And the antibiotic which has a better bactericidal activity determine the viable bacteria count.

Amoxicillin↗
PubMed1988

[Experimental Enterobacter cloacae endocarditis treated with gentamicin. Predictive value of the in vitro bactericidal rate].

The predictive value of in vitro time-kill curve was tested on an Enterobacter cloacae endocarditis experimental model. The antibiotic studied was gentamicin. Despite a similar MIC, 2 Enterobacter cloacae strains exhibited very different time-kill curves in vitro. This difference was found being predictive of efficacy on the in vivo model, 24 hours after a single injection of gentamicin.

Animals↗
PubMed1988

[Kinetics of pefloxacin diffusion in human bone tissue following a single infusion of 800 mg. Evaluation of an extraction technic using chloroform].

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.

Bone and Bones↗
PubMed1987

Actinomycosis of the gallbladder due to Actinomyces naeslundii.

We report two cases of actinomycosis of the gallbladder due to Actinomyces naeslundii. Both patients presented with acute cholecystitis. After cholecystectomy with the removal of gallstones each patient made an uneventful recovery. The literature on cholecystitis due to Actinomyces is reviewed.

Actinomyces↗