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Biomedical subjects

H B Drugeon

Publications and source records attributed to H B Drugeon.

At least 19 recordsLinked to original sources
PubMed2004

[Treatment of exacerbations of chronic obstructive pulmonary disease with pristinamycin].

BACKGROUND: Pristinamycin is a bactericidal antibiotic whose spectrum covers the main respiratory pathogens including S. pneumoniae poorly sensitive to penicillin. It has not yet been evaluated in short course treatment of acute exacerbations of chronic obstructive bronchitis (AECB). METHODS: 476 patients suffering from an AECB were randomised to either a short course of pristinamycin, 3 G daily for 4 days, or conventional treatment with co-amoxiclav (AAC) 2G daily for 8 days. The duration of follow-up was 6 months. RESULTS: The clinical success rate at 21 days was the same in both groups at 87.2% and 87.9%, CI95% [-7.0%, 6.0%], in the protocol population (FEV1<80%). Among the 120 patients in whom a bacterial pathogen was isolated at the time of inclusion a satisfactory bacteriological response was obtained in 84.6% of the PRI patients against 78.2% of the AAC patients. The time to relapse was comparable with a relapse rate of 25% reached in 128 days in the PRI group and 125 days in the AAC group. Treatment related side effects occurred in 9.2% of the PRI group and in 10.6% of the AAC group. CONCLUSION: Pristinamycin 3 G daily for 4 days is as effective and well tolerated as co-amoxiclav 2G daily for 8 days in the treatment of AECB.

Acute Disease↗
PubMed2004

Activity of linezolid against Gram-positive cocci isolated in French hospitals as determined by three in-vitro susceptibility testing methods.

In total, 844 strains of Gram-positive cocci were collected from six university hospitals in France between September 1999 and January 2000. MICs of linezolid were determined: (i) for all strains by agar dilution (method A); (ii) by broth microdilution (method B) for staphylococci and enterococci; (iii) by Etest (method E) for beta-haemolytic streptococci and Streptococcus pneumoniae. Susceptibility to other antibiotics was determined by the disk diffusion method. MIC50 and MIC90 values were identical (2 mg/L) for methicillin-susceptible Staphylococcus aureus (n = 179) by methods A and B. Linezolid was active against methicillin-resistant S. aureus (n = 117), with an MIC90 of 2 mg/L (methods A and B), but with a lower MIC50 of 1 mg/L by method A. Of the 200 coagulase-negative staphylococci, 56.5% were methicillin-resistant and 43.5% were methicillin-susceptible. Linezolid had similar in-vitro activity by methods A and B (MIC50 and MIC90 values of 1-2 mg/L), irrespective of methicillin susceptibility. The MIC90 of linezolid for all enterococci (150 Enterococcus faecalis and 50 Enterococcus faecium) was 2 mg/L by both methods. MICs of linezolid for beta-haemolytic streptococci had a narrow range of 0.5-2 mg/L (method A) and 0.125-2 mg/L (method E). Pneumococci (n = 118), including 67 penicillin G-intermediate and -resistant strains, were all inhibited by linezolid 2 mg/L (MIC90 of 2 mg/L by methods A and E). No strain had an MIC of > 2 mg/L by agar dilution or Etest, or of > 4 mg/L by broth microdilution. Overall, the study confirmed the good in-vitro activity of linezolid and the very narrow range of MICs for Gram-positive cocci susceptible or resistant to other antibiotics, irrespective of the method used.

Acetamides↗
PubMed2001

[Choice of the NaCl concentration for optimizing the detection of methicillin resistance in Staphylococcus using the gel diffusion method].

The detection of oxacillin resistance is evaluated by the disk diffusion method in a collection of 374 Staphylococcus sp strains. The disk diffusion assay is performed with 5-microgram oxacillin disk and a 10(8) CFU/mL inoculum on Mueller-Hinton agar plates supplemented with 2 or 5% NaCl and incubated at 37 degrees C for 24 h. Strains are considered resistant in accordance to the French recommendations (any growth around the disk is observed). The detection of mecA gene is performed by PCR almost for resistant and discordant strains. Results are concordant for 246 of 256 Staphylococcus aureus strains (182 susceptible and 64 resistant strains) and for 105 of 118 S. epidermidis isolates tested (37 susceptible and 68 resistant strains). Six mecA-negative strains (3 S. aureus and 3 S. epidermidis) give false resistant results on agar with 2 and 5% NaCl. Seventeen isolates are discordant on 5% NaCl: 7 mecA-negative S. aureus strains are susceptible on 2% NaCl agar but resistant at 5% (3% false-positive results), 10 mecA-positive S. epidermidis strains are resistant on 2% NaCl agar but susceptible at 5% NaCl (5% false-negative results). The detection of meticillin resistance is improved on agar supplemented with 2% NaCl.

Agar↗
PubMed2000

Comparison of the in vitro activities of rifapentine and rifampicin against Mycobacterium tuberculosis complex.

The in vitro activity of rifapentine for 44 clinical isolates of Mycobacterium tuberculosis complex was compared with that of rifampicin using the Bactec radiometric method and the absolute concentration method for susceptibility testing. Twenty-nine M. tuberculosis, 11 Mycobacterium bovis and four Mycobacterium africanum strains were studied. Control tests showed that rifapentine was stable for 14 days in 7H9 broth and for 3 weeks in 7H10 agar medium. The 44 M. tuberculosis complex strains were more susceptible to rifapentine than to rifampicin, irrespective of the testing method. In the radiometric system, the MIC50 and MIC90 of rifapentine for M. tuberculosis complex strains were one or two two-fold dilutions lower than those of rifampicin (0.06-0.125 mg/L versus 0.25 mg/L, respectively). By the absolute concentration method, the MIC50 and MIC90 of rifapentine for M. tuberculosis complex strains were two two-fold dilutions lower than those of rifampicin (0.125-0.25 mg/L versus 0.5-1 mg/L, respectively). The MIC90 of rifapentine for the 44 M. tuberculosis complex strains was always 0.25 mg/L, irrespective of the method used, but the radiometric method was more reliable and more reproducible than the agar 7H10 method.

Agar↗
PubMed2000

In vitro activity of the new ketolide telithromycin compared with those of macrolides against Streptococcus pyogenes: influences of resistance mechanisms and methodological factors.

One hundred and seven clinical isolates of Streptococcus pyogenes, 80 susceptible to macrolides and 27 resistant to erythromycin A (MIC >0.5 microgram/ml), were examined. The erythromycin A-lincomycin double-disk test assigned 7 resistant strains to the M-phenotype, 8 to the inducible macrolide, lincosamide, and streptogramin B resistance (iMLS(B)) phenotype, and 12 to the constitutive MLS(B) resistance (cMLS(B)) phenotype. MICs of erythromycin A, clarithromycin, azithromycin, roxithromycin, and clindamycin were determined by a broth microdilution method. MICs of telithromycin were determined by three different methods (broth microdilution, agar dilution, and E-test methods) in an ambient air atmosphere and in a 5 to 6% CO(2) atmosphere. Erythromycin A resistance genes were investigated by PCR in the 27 erythromycin A-resistant isolates. MICs of erythromycin A and clindamycin showed six groups of resistant strains, groups A to F. iMLS(B) strains (A, B, and D groups) are characterized by two distinct patterns of resistance correlated with genotypic results. A- and B-group strains were moderately resistant to 14- and 15-membered ring macrolides and highly susceptible to telithromycin. All A- and B-group isolates harbored erm TR gene, D-group strains, highly resistant to macrolides and intermediately resistant to telithromycin (MICs, 1 to 16 microgram/ml), were all characterized by having the ermB gene. All M-phenotype isolates (C group), resistant to 14- and 15-membered ring macrolides and susceptible to clindamycin and telithromycin, harbored the mefA gene. All cMLS(B) strains (E and F groups) with high level of resistance to macrolides, lincosamide, and telithromycin had the ermB gene. The effect of 5 to 6% CO(2) was remarkable on resistant strains, by increasing MICs of telithromycin from 1 to 6 twofold dilutions against D-E- and F-group isolates.

Anti-Bacterial Agents↗
PubMed1999

Relative potential for selection of fluoroquinolone-resistant Streptococcus pneumoniae strains by levofloxacin: comparison with ciprofloxacin, sparfloxacin and ofloxacin.

The aim of this study was to evaluate the relative potential of levofloxacin to select for resistance in Streptococcus pneumoniae in comparison with ciprofloxacin, sparfloxacin and ofloxacin. Two S. pneumoniae strains were studied; HBD 153 (parental strain, serotype 3) and HBD 964 (selected from the parental strain in an experimental mouse peritonitis infection model). MICs for the two strains were, respectively: 2 and 2 mg/L for ciprofloxacin; 2 and 4 mg/L for ofloxacin; 0.5 and 1 mg/L for sparfloxacin; 2 and 2 mg/L for levofloxacin. In-vitro, with 4 x MIC as the selection concentration, no mutant was obtained with strain HBD 153 (mutation frequency < 10(-8). With HBD 964, the mutation frequency was 9 x 10(-7) for ofloxacin, 10(-7) for ciprofloxacin, 4 x 10(-5) for sparfloxacin and < 10(-8) for levofloxacin. In an immunosuppressed mouse peritonitis model (20 mice per dose), the S. pneumoniae strains were studied with sc doses of ciprofloxacin, sparfloxacin and ofloxacin at 50 mg/kg od, and with sc levofloxacin at a dose of 10 and 50 mg/kg od, or 10 and 50 mg/kg bid. The MICs for strains isolated after antibiotic treatment and the mutation frequencies at 4 x MIC were determined. Against HBD 153, sparfloxacin was the most active treatment, followed by levofloxacin 10 mg/kg and 50 mg/kg bid, but strains identical to HBD 964 (showing a resistant variant at 4 x MIC) were selected by sparfloxacin. Against HBD 964, levofloxacin (10 mg/kg and 50 mg/kg) was the most active drug. Highly resistant mutants were selected by ofloxacin and ciprofloxacin, but not by sparfloxacin and levofloxacin. In conclusion, the relative potential of levofloxacin to select for fluoroquinolone-resistant S. pneumoniae is lower than that of ciprofloxacin, ofloxacin and sparfloxacin both in vitro and in vivo.

Anti-Infective Agents↗
PubMed1999

Inactivation of Mycobacterium tuberculosis for DNA typing analysis.

DNA fingerprinting analysis of Mycobacterium tuberculosis is used for epidemiological studies and the control of laboratory cross-contamination. Because standardized procedures are not entirely safe for mycobacteriology laboratory staff, the paper proposes a new technique for the processing of specimens. The technique ensures the inactivation of M. tuberculosis before DNA extraction without the loss of DNA integrity. The control of inactivated cultures should be rigorous and should involve the use of two different culture media incubated for at least 4 months.

Bacterial Typing Techniques↗
PubMed1998

In vivo simulation of human pharmacokinetics in the rabbit.

The evaluation of drugs in vivo is often based on experimental models using small animals such as mice, rats and rabbits. However, these models could be improved to correspond more closely to the human situation if the pharmacokinetics of the drugs tested in animals were similar to that observed in humans. The use of a computer-controlled pump allowing an adequate flow of tobramycin and amikacin to be infused into rabbits enabled us to simulate the human pharmacokinetics of these antibiotics in vivo in this study. The function defining the rate of infusion required to perform the simulation of an intravenous bolus was first determined generally and symbolically for linear pharmacokinetic models independently from the number of compartments involved. The practical simulation of a decreasing monoexponential serum profile with a half-life of 2 h (one-compartment model for the human pharmacokinetics of aminoglycosides) was then studied for tobramycin and amikacin on the basis of a two-compartment model in the animal. The kinetics obtained had an apparent elimination half-life of 1.97 and 1.86 h, respectively. Linearity of the semilogarithmic regressions of the profiles obtained was quite sound. Finally, an a posteriori analysis of the pharmacokinetic model and its parameters is proposed on the basis of the results obtained after simulation.

Amikacin↗
PubMed1998

Diagnosis of extrapulmonary tuberculosis by a commercial polymerase chain reaction kit.

The Roche Amplicor Mycobacterium tuberculosis PCR test was compared with mycobacterial culture for direct detection of M. tuberculosis in extrapulmonary specimens. From January 1995 to October 1996, 124 clinical specimens from 112 patients were assessed, including 47 body fluids, 61 tissue specimens and 16 abscesses. The sensitivity and specificity of Amplicor PCR compared to culture were 63.6% and 93.1% respectively. Analysis of 7 PCR-positive, culture-negative specimens confirmed that all were from patients with recently diagnosed tuberculosis under treatment. Eight specimens were PCR negative-culture positive, including a pleural fluid containing inhibitory substances. On acid-fast bacilli (AFB) smear-negative specimens, sensitivity and specificity were 53 and 100% respectively. The best results for Amplicor PCR were obtained with abscesses and biopsies. It is concluded that this test, highly specific for the diagnosis of tuberculosis, is at least as sensitive on extrapulmonary specimens as on smear-negative respiratory specimens.

Abscess↗
PubMed1997

Pharmacokinetics and pharmacodynamics of two oral forms of cefuroxime axetil.

Cefuroxime axetil is a cefuroxime ester that can be administered by mouth. Two dosage forms (tablets and granules) have been developed for oral administration. We evaluated the pharmacokinetics and pharmacodynamics of these forms in an open cross-over study involving 12 healthy volunteers receiving single doses of 250 mg. The bioavailability of the two forms was different, the observed peak concentration and time-concentration curve values of the tablet form being, respectively, 39 and 27% higher than those of the granule form. However, ex vivo studies of serum bactericidal activity against Streptococcus pneumoniae showed no significant differences between the two formulations. This is in keeping with the fact that the bactericidal activity of samples from only six subjects gave evaluable data for Haemophilus influenzae; although small differences were found between the two formulations, further investigations are required. The pharmacodynamic approach is becoming an essential element in determining the equivalence of antibiotic dosage forms.

Administration, Oral↗
PubMed1995

[Critical serum concentration of antibiotics. A therapeutic tool and means of comparative evaluation].

It is difficult to predict the clinical activity of antibiotics solely on the basis of in vitro data. Experimental models measuring the relationship between serum concentration and in vivo activity are essential for comparing the activity of different compounds currently available. The critical serum concentration can be used to compare the intrinsic activity of antibiotics on a given bacterial strain. When compared with the minimal inhibiting concentration measured in vitro, "activity loss" can be determined for each antibiotic placed in contact with bacteria in an infected tissue. The relevance of this therapeutic tool in comparison with other methods is discussed.

Animals↗
PubMed1994

Teaching individualized antibiotic dosage regimens by means of two computer-assisted learning programs.

We developed two multidisciplinary tutorial programs (TOBRA-DIDACT and VANCO-DIDACT) for teaching the basic principles of antibiotic drug monitoring by simulation of repeated administrations to fictitious patients whose physio-pathologic characteristics were pre-defined in the programs. To illustrate the two types of bactericidal kinetics, we have chosen one time-dependent (vancomycin) and one concentration-dependent (tobramycin) antibiotic. These computer-assisted programs operate on an interactive mode. In each of them, three main steps are connected: (1) Various types of clinical cases are submitted to the student: for each of them, case report includes clinical characteristics, location of infection, bacterial strain and minimal bactericidal concentration. These data must be taken into account during the following steps. (2) The student has to establish the treatment schedule: route of administration, dose for each injection, intervals between injections and duration of infusion. (3) The result of the dosage scheme proposed by the student is represented by a simulation of plotting antibiotic plasma concentrations vs. time during the first 4 days of treatment. These curves are obtained by a monoexponential (TOBRA-DIDACT) or biexponential (VANCO-DIDACT) pharmacokinetic model. Peak and trough concentrations are calculated at steady-state. An expert system provides a commentary with each result to evaluate the efficacy of the treatment and to assist the student in improving his prescription. TOBRA-DIDACT and VANCO-DIDACT illustrate the influence of age, obesity, renal impairment, location of infection and bacterial strain on antibiotic therapy. They also show the role of route of administration, dosing and intervals between injections on therapeutic response.(ABSTRACT TRUNCATED AT 250 WORDS)

Anti-Bacterial Agents↗
PubMed1994

[Microbiologic criteria of the choice of antibiotic for antibiotic prophylaxis in surgery].

The choice of an antibiotic for antimicrobial prophylaxis is based on microbiological, pharmacokinetic, chemical and pharmacodynamic parameters. The knowledge of the bacterial flora allows the identification of bacteria which could be responsible for postsurgical infections. These floras are complex and their equilibrium can be modified by various factors, such as hospitalization, co-existing disease, medico-surgical procedure, administration of antibiotics, which cause the selection of the so-called hospital-bacteria feared by therapists. The infection will develop according to the quantity of bacteria that have been introduced and to their virulence, which is often altered by local factors, especially the biomaterials. The knowledge of pharmacodynamic parameters such as bactericidal activity, postantibiotic effect, activity on virulence factors (bacterial adhesion), allows the refinement of the choice of the antibiotic and the optimization of its posology.

Anti-Bacterial Agents↗
PubMed1994

In-vitro antibacterial activity of fusidic acid alone and in combination with other antibiotics against methicillin-sensitive and -resistant Staphylococcus aureus.

The activity of fusidic acid alone and in combination with gentamicin, oxacillin, rifampicin, fosfomycin and ciprofloxacin was investigated against 36 strains of Staphylococcus aureus. The fusidic acid MIC50 of 0.06 mg/L and MIC90 of 0.125 mg/L were determined for 36 strains. Bactericidal activity of fusidic acid was confirmed. Several types of interaction were observed with other antibiotics: dominant effect of fusidic acid over gentamicin; synergy with rifampicin for three or four strains; indifference or dominance with oxacillin, indifference with vancomycin, indifference or dominance with fosfomycin, and indifference with ciprofloxacin. Antagonism was seen with only one strain, following exposure to fusidic acid and rifampicin.

Ciprofloxacin↗
PubMed1994

Pharmacokinetics, toxicity, and efficacy of liposomal capreomycin in disseminated Mycobacterium avium beige mouse model.

Capreomycin was incorporated into multilamellar vesicles of pure dipalmitoylphosphatidylcholine. The pharmacokinetics and nephrotoxicity of capreomycin in the free and liposomal forms were studied in normal mice. The efficacies of the two forms were evaluated by using the Mycobacterium avium complex beige mouse model. Approximately 10(7) viable M. avium cells were injected intravenously. Seven days later, treatment with either liposomal or free capreomycin at 60 or 120 mg/kg of body weight was administered daily for 5 days. Mice were sacrificed 5 days after the end of treatment, and the viable bacteria in liver, spleen, lungs, and blood were counted. After 5 days of treatment with dosages of 60 or 120 mg/kg/day, the level of blood urea nitrogen increased in the group treated with free capreomycin but not in the group treated with liposomal capreomycin. After intravenous injection of 120 mg/kg, liposomes enhanced the diffusion of capreomycin in the spleen, lungs, and kidneys and increased the half-life in serum. The 120-mg/kg dose of liposomal capreomycin significantly reduced the number of viable mycobacteria in the liver, spleen, and blood compared with those in the controls. Although these results are promising, further studies are needed to assess the efficacy of liposomal capreomycin for the treatment of M. avium complex infections.

Animals↗