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H Drugeon

Publications and source records attributed to H Drugeon.

At least 19 recordsLinked to original sources
PubMed2006

Biological cost of fluoroquinolone resistance in Escherichia coli implicated in polyclonal infection.

Polyclonal Escherichia coli strains were isolated in a transplanted patient who experienced successive septic shocks. Fluoroquinolone susceptible and resistant strains were corresponding to different PFGE fragment profiles. The gyrA S83L mutation was associated with a reduction in biological fitness. Resistant strain was selected by a long-term single use of ofloxacin.

Drug Resistance, Bacterial↗
PubMed2006

[Clinical aspects and management of patients with tuberculous meningitis. Retrospective analysis from 1994 to 2005].

Tuberculous meningitis remains a devastating disease with poor prognosis in terms of mortality or invalidating after-effects. Eighteen cases of tuberculous meningitis, occurred between 1994 and 2005, were re-examined retrospectively. Among the 18 patients, 13 were aged from 14 to 64 years, and 5 were older than 64. There was no gender dominance. Factors of risk were identified in 7 patients. British Medical Research Council staging was III in 9 patients, II in 2 patients and I in 7 patients. Protein and glucose levels in the cerebrospinal fluid sample were very variable ranging from 0.4 to 10.7 g/L and 0.4 to 3.7 mmol/L respectively. The cellular reaction was also very variable ranging from 0 to 250 elements, mostly lymphocytes. Antituberculous treatment was given to 15 patients, associated with corticosteroid therapy for 9 patients. Among the 18 patients, 11 died within 1 year, 4 were treated for a recurrence occurring up to 6 years after the diagnosis, 1 presented important neuropsychic after-effects and 2 patients survived without after-effects with a time ranging between 6 months and 1 year. The deceased patients were significantly older than the others. The risk of mortality was 4.5-fold greater among stage III patients than among stage I and II patients. The use of corticosteroids significantly reduced the risk of death.

Adolescent↗
PubMed2005

[Efficacy and safety of extended-release clarithromycin (5-day short-course) vs telithromycin, in acute bacterial exacerbation of chronic bronchitis].

BACKGROUND: The extended-release formulation of clarithromycin (CLA-ER) allows using this macrolide as a single daily dose. The purpose of this study was to evaluate the efficacy and safety of the CLA-ER formulation (500 mgx2) vs telithromycin (TELI) (400 mgx2) as a short course 5-day treatment, once a day, in patients with AECB. METHOD: This randomized double-blind study was conducted in patients with AECB without severe airflow limitation (FEV1>35%), with sputum purulence (mandatory criterion), and with either increased sputum volume or increased dyspnea, or both (Anthonisen criteria I or II). RESULTS: Three hundred sixty-two patients were assessed (62.6 years of age+/-12.9, men: 58.8%) positive culture on inclusion for 53.8%, with Haemophilus influenzae (N=57), Moraxella catarrhalis (N=42), and Streptococcus pneumoniae (N=41). In the per protocol population, the clinical success rate at day 8 was 97% (161/166) vs 97% (146/151), 97.5% CI=[-4.12 -4.71], the clinical cure rate at day 30 was 78% (129/166) versus 77% (116/151), P=0.85, and mean time without recurrence was 62 days versus 61 days (P=0.51), in CLA-ER and TELI groups, respectively. Fourteen patients in the CLA-ER group (8.2%) and 20 patients in the TELI group (12.4%) experienced at least one treatment-related adverse event (P=0.21), upon which gastrointestinal events were the most commonly reported treatment-related ones. CONCLUSION: CLA-ER (1000 mg once a day) for 5 days is at least as effective as telithromycin in the treatment of AECB without severe airflow limitation and is well tolerated.

Aged↗
PubMed2005

[Vaccination failure: case report of Haemophilus influenzae b meningitis in a 14-month-old child].

BACKGROUND: The generalization of the vaccination against H. influenzae b (Hib), according to its integration in the French vaccinal calendar, led to the incidence decrease of the purulent meningitis with Hib in young children, which became a so rare event. CASE REPORT: We described the case of a 14-months-old child showing a bacterial purulent meningitis with Hib, despite of a well driven vaccination. DISCUSSION: The epidemiology of bacterial meningitis was upset by the generalization of the anti-H. influenzae b vaccination. The use of combined vaccines specially reduced the incidence and the gravity of this pathology. Nevertheless, in spite of the excellent vaccinal coverage, the limited but real persistence of epiglottis or meningitis due to H. influenzae b should keep in mind of the biologists and the clinicians. Indeed, the chronic nasopharyngal carriage, the existence of not vaccinated or not answering people allow to consider the persistent risk of H. influenzae b bacterial meningitis.

Haemophilus Vaccines↗
PubMed2005

Correlation of agar dilution and VITEK2 system for detection of resistance to macrolides, lincosamides and pristinamycin among Staphylococcus aureus and Staphylococcus epidermidis: association with genotypes.

The performance of the VITEK2 system was evaluated against the agar dilution reference procedure for testing susceptibility of Staphylococcus aureus and Staphylococcus epidermidis to macrolides, lincosamides and streptogramins (MLS). Eighty clinical isolates were selected according to their resistance phenotype and genotype. Results for erythromycin and clindamycin showed 100% agreement; results for lincomycin showed agreement of 78%, with one very major error and 17 minor errors; and results for pristinamycin showed agreement of 46%, with one major error and 43 minor errors. Most isolates resistant to lincomycin and streptogramin A (L SgAr phenotype) were falsely susceptible to lincomycin, and intermediately-resistant or resistant to pristinamycin, with the VITEK2 system. No resistance gene was detected. Most (80%) isolates resistant constitutively to MLS (MLS(r)BC phenotype) were falsely intermediately-resistant to pristinamycin with the VITEK2 system. The erm(A) gene was more common than erm(C) in MLS(r)BC strains. Resistance to pristinamycin alone (SgA SgB PTr phenotype), or associated with either lincomycin resistance (L SgA SgB PTr phenotype) or constitutive MLS(B) resistance (MLS(BC) SgA PTr phenotype), was well-characterised without discordant results. Resistance to pristinamycin was always associated with resistance to streptogramin A, encoded by the vga(A), vga(B), vgb(A) and vat(A) genes in association with the erm(A) or erm(C) genes.

Agar↗
PubMed2004

[An example of simulation for a better understanding of PK/PD relationship of antibiotics].

The interpretation of PK/PD indices is specific to each class of antibiotics. In order to illustrate this, we developed a multidisciplinary tutorial program based on simulation of clinical cases. Three drugs were included in this software: tobramycin, vancomycin and azithromycin. From the dosage regimen proposed by the user, the model simulates a plotting of antibiotic plasma concentrations vs. time (tobramycin, vancomycin and azithromycin) and tissue concentrations (azithromycin). Peak and trough concentrations are calculated at steady-state. A commentary is provided to evaluate the efficacy of treatment and to assist the user in improving his prescription of tobramycin or vancomycin. T(> MIC) (time the concentration remains above the MIC) and AUC(24) (area under the concentration-time curve) are calculated in plasma and tissues for azithromycin. In order to create a link between theoretical pharmacokinetics and clinical practice, we propose this model as a simulation of antibiotic monitoring. We put the emphasis on interactivity and simulation, leading to applied reasoning and decision making. It illustrates (i) the influence of pharmacokinetic parameters, location of infection and bactericidal kinetics on the use of three different classes of antibiotics, (ii) the role of route of administration, dosing and intervals between administrations on therapeutic response and (iii) the influence of erratic administrations on clinical efficacy.

Anti-Bacterial Agents↗
PubMed2003

[Should we screen for colonization to control the spread of multidrug resistant bacteria?].

Should we screen for colonization to control the spread of multidrug-resistant bacteria? A multidrug-resistant bacteria surveillance program was performed in 1999 at Laënnec Hospital (Nantes, France). After a 3-year period, the results permit us to determine the strategy to strengthen their spread. In 2001, Staphylococcus aureus resistant to methicillin represented 45% of the 202 multidrug-resistant bacteria isolated. The global incidence rate per 100 admissions remained stable between 1999 and 2001 (0.42%), but those of infections acquired in our institution decreased significantly from 0.27% in 1999 to 0.18% in 2001 (P < 0.05), particularly in medical care units (P < 0.04). In spite of this surveillance program and hygiene trainings, the global incidence remained stable during the study period, even if our action contributed to decrease the incidence of S. aureus resistant to methicillin acquired in our institution. Isolation precautions and screening for colonization policy in intensive care units are not sufficient to control the spread of MRB at hospital level. They should be strengthened by procedures for the transfer of infected or colonized patients and by antibiotic use control.

Cross Infection↗
PubMed2003

In vitro antibacterial activity of moxifloxacin against hospital isolates: a multicentre study.

OBJECTIVE: To evaluate the in vitro antibacterial activity of moxifloxacinin in comparison to that of other fluoroquinolones (ciprofloxacin, ofloxacin and trovafloxacin). METHODS: A total of 2,196 strains was collected in 11 French hospitals in 1998. Minimum inhibitory concentrations (MICs) (mg/L) were determined by agar dilution and agar diffusion was performed with 5-microg discs. Internal quality control was carried out with genetically defined strains. RESULTS: MIC50s and MIC90s of moxifloxacin against nalidixic acid (NAL)-susceptible Enterobacteriaceae (n = 663) were 0.12 and 0.5. As for other quinolones, the activity of moxifloxacin (4-32) was reduced against NAL-intermediate and NAL-resistant strains (n = 222). MIC50s and MIC90s of moxifloxacin were 2 and 4 for ciprofloxacin-susceptible P. aeruginosa (n = 128); moxifloxacin had no activity against ciprofloxacin-resistant strains (n = 56). The activity of moxifloxacin was maintained against NAL-susceptible A. baumannii (n = 11; 0.032-0.125), but reduced against NAL-resistant strains (n = 30; 16-32). H. influenzae (n = 97) and M. catarrhalis (n = 40) were inhibited by low concentrations (0.03-0.06 and 0.06-0.25, respectively). Moxifloxacin had better activity (0.06-0.12) than other tested quinolones against methicillin-susceptible S. aureus strains (n = 110); ciprofloxacin-resistant strains (n = 85) (2-8) were usually methicillin-resistant. Moxifloxacin was moderately active against enterococci (n = 149) (E. faecalis: 0.5-16; E. faecium: 2-4). Streptococci (n = 194) and pneumococci (n = 136), including 70 penicillin G-intermediate or G-resistant strains, were inhibited by low concentrations (0.25-0.5 for each species). Based on the regression curve, tentative zone diameter breakpoints could be > or =21 and <18 mm for MIC breakpoints of < or =1 and >2 mg/L, respectively. CONCLUSIONS: While retaining activity against Enterobacteriaceae, moxifloxacin was moderately active against P. aeruginosa. Its activity was inferior to that of ciprofloxacin for these species. This study confirmed the comparatively high in vitro activity of moxifloxacin against Gram-positive cocci and other pathogens isolated from community-acquired respiratory tract infections.

Anti-Infective Agents↗
PubMed1997

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.

Animals↗
PubMed1997

Adaptive resistance of Pseudomonas aeruginosa induced by aminoglycosides and killing kinetics in a rabbit endocarditis model.

Adaptive resistance following the first exposure to aminoglycosides is a recently described in vitro phenomenon in Pseudomonas aeruginosa and other aerobic gram-negative bacilli. We investigated the in vivo relevance of adaptive resistance in P. aeruginosa following a single dose of amikacin in the experimental rabbit endocarditis model. Rabbits with P. aeruginosa endocarditis received either no therapy (control) or a single intravenous (i.v.) dose of amikacin (80 mg/kg of body weight) at 24 h postinfection, after which they were sacrificed at 5, 8, 12, 16, or 24 h postdose. Excised aortic vegetations were subsequently exposed ex vivo to amikacin at 2.5, 5, 10 or 20 times the MIC for 90 min. In vivo adaptive resistance was identified when amikacin-induced pseudomonal killing within excised aortic vegetations was less in animals receiving single-dose amikacin in vivo than in vegetations from control animals not receiving amikacin in vivo. Maximal adaptive resistance occurred between 8 and 16 h after the in vivo amikacin dose, with complete refractoriness to ex vivo killing by amikacin seen at 12 h postdose. By 24 h postdose, bacteria within excised vegetations had partially recovered their initial amikacin susceptibility. In a parallel treatment study, we demonstrated that amikacin given once daily (but not twice daily) at a total dose of 80 mg/kg i.v. for 1-day treatment significantly reduced pseudomonal densities within aortic vegetations versus those in untreated controls. When therapy was continued for 3 days with the same total daily dose (80 mg/kg/day), amikacin given once or twice daily significantly reduced intravegetation pseudomonal densities versus those in controls. However, amikacin given once daily was still more effective than the twice-daily regimen. These data confirm the induction of aminoglycoside adaptive resistance in vivo and further support the advantages of once-daily aminoglycoside dosing regimens in the treatment of serious pseudomonal infections.

Amikacin↗
PubMed1996

The effect of rifampicin on adaptive resistance of Pseudomonas aeruginosa to aminoglycosides.

Using the dynamic chequerboard technique, we confirmed that rifampicin produces a synergistic bactericidal effect when combined with amikacin or netilmicin. Adaptive resistance was suppressed when rifampicin was added to aminoglycoside after, but not during, first exposure to amikacin or netilmicin. The effect of rifampicin on adaptive resistance could account for the synergy between rifampicin and aminoglycosides.

Adaptation, Physiological↗
PubMed1996

Influence of pH on adaptive resistance of Pseudomonas aeruginosa to aminoglycosides and their postantibiotic effects.

Adaptive resistance to aminoglycosides in Pseudomonas aeruginosa and other gram-negative bacilli is usually induced by the initial exposure to the drug. We investigated the influence of pH on the adaptive resistance of a clinical P. aeruginosa strain to aminoglycosides in vitro and on their postantibiotic effects. For adaptive resistance, the first-exposure concentrations of both amikacin and netilmicin were one, two, four, and eight times the MIC of each drug and the second-exposure concentrations were two times the MIC of each drug. Adaptive resistance was greater and more prolonged with higher initial aminoglycoside concentrations, and the bactericidal effects of the aminoglycosides were concentration dependent at pH 7.4. At pH 6.5, the killing rates of amikacin and netilmicin were far lower than those observed at pH 7.4. At pH 5.5, amikacin and netilmicin exerted practically no bactericidal effect on the P. aeruginosa strain used. However, with media at pH 5.5 and 6.5, adaptive resistance of P. aeruginosa preexposed to amikacin and netilmicin was also clearly exhibited, with the degree of adaptive resistance depending on the bactericidal effects of both drugs on nonpreexposed controls. Maximal adaptive resistance occurred between 0 and 4 h after preexposure. The postantibiotic effects of amikacin and netilmicin against the P. aeruginosa strain were shown to be concentration dependent and were reduced at acidic pHs. No changes in outer and inner membrane proteins occurred during the adaptive-resistance interval.

Adaptation, Physiological↗
PubMed1996

In vivo antibacterial effects of simulated human serum profiles of once-daily versus thrice-daily dosing of amikacin in a Serratia marcescens endocarditis experimental model.

Once-daily dosage of aminoglycosides is currently under consideration. The lower toxicity of this regimen has been clearly established, but there are conflicting experimental and clinical data concerning its efficacy. It is inadvisable to optimize human therapy by extrapolation from experimental studies since animal and human pharmacokinetics differ. The simulation of human pharmacokinetics in experimental infectious models would seem to offer a more rational approach. We used computer-controlled infusion of amikacin at a variable flow rate to simulate human pharmacokinetics in a Serratia marcescens rabbit endocarditis model and to compare two therapeutic regimens (once-daily versus thrice-daily doses). The doses corresponded to simulations of 15 and 30 mg/kg of body weight per day in humans, and antibacterial activity was measured in vegetations (Veg) after 24 h of treatment. The results show that the dose corresponding to 15 mg/kg/day failed to produce a significant reduction of CFU (6.8 +/- 0.9 and 6.4 +/- 0.8 log10 CFU/g of Veg, respectively, for once-daily and thrice-daily doses versus 7.6 +/- 1.0 for controls). A significant reduction was observed only for the dose corresponding to 30 mg/kg/day in humans (5.2 +/- 1.5 and 5.4 +/- 1.1 log10 CFU/g of Veg, respectively, for the two regimens). With this model, the efficacy of amikacin was similar for both regimens after 24 h of treatment simulating human pharmacokinetics.

Amikacin↗
PubMed1996

Importance of penicillinase production for activity of penicillin alone or in combination with sulbactam in experimental endocarditis due to methicillin-resistant Staphylococcus aureus.

The activity of penicillin, alone and in combination with sulbactam, against a heterogeneously methicillin-resistant, penicillinase-producing clinical isolate of Staphylococcus aureus and its penicillinase-negative derivative was investigated in vitro and in a rabbit experimental endocarditis model. Penicillin was significantly more effective than vancomycin against the penicillinase-negative derivative in vivo (P < 0.001), and it sterilized 25% of the vegetations. The combination of penicillin and sulbactam exhibited an in vivo synergistic effect on the penicillinase-producing strain (P < 0.01) but did not produce any advantage over treatment with vancomycin, even when a high dose of sulbactam was used (100 mg/kg of body weight every 6 h). This combination was significantly less effective against the penicillinase-producing strain than was penicillin alone against the penicillinase-negative derivative (P < 0.03). In addition, the most resistant subpopulation of the surviving bacteria, which grew on agar containing 16 micrograms of methicillin per ml, was detected in 5 of 6 animals treated with penicillin and a high dose of sulbactam against the penicillinase-producing strain compared with only 1 of 12 animals treated with penicillin alone against the penicillinase-negative derivative (P < 0.01). We conclude that penicillin is highly effective against penicillinase-negative methicillin-resistant S. aureus and that penicillinase production, rather than methicillin resistance, appears to be the limiting factor for the activity of the penicillin-sulbactam combination against penicillinase-producing, methicillin-resistant S. aureus.

Animals↗