Jean-Christophe Dubus

Aix-Marseille Université, Marseille, Provence-Alpes-Cote d'Azur, France

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Publications (28)72.74 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Clinical isolates of Pseudomonas aeruginosa exhibiting high-level resistance to carbapenems were recovered from a French patient with cystic fibrosis (CF) who had not received carbapenem therapy. This study was conducted to investigate the molecular mechanism conferring the carbapenem-resistant phenotype in clinical isolates of P. aeruginosa recovered from the same CF patient chronically colonised since 2005. Investigation of imipenem resistance of P. aeruginosa strain_02 isolated in May 2011 showed no carbapenemase activity. However, amplification and sequencing of the oprD porin gene revealed disruption of this gene by an insertion sequence (IS) element of 1337bp that contained a novel transposase of 1227bp (ISPa46) bordered by two terminal imperfect inverted repeats of 28bp, which was associated with carbapenem resistance. Retrospective analysis of five additional strains of P. aeruginosa isolated before May 2011 from the same patient revealed that all isolates were likely to be the same clone by multilocus sequence typing analysis (ST540/551), but one of the five isolates was imipenem-susceptible. Although it was possible to demonstrate the presence of ISPa46 in all strains by PCR, this IS was transposed in the oprD gene only for imipenem-resistant isolates. Therefore, this study reports a novel IS element (ISPa46) in P. aeruginosa clinical isolates of a CF patient in Marseille, France, that was associated with carbapenem resistance and was selected in the absence of carbapenem treatment.
    International journal of antimicrobial agents 07/2013; · 3.03 Impact Factor
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    ABSTRACT: Abstract Background: The use of valved holding chambers (VHCs) with pressurized metered dose inhalers (pMDIs) is reported to reduce the oral deposition of inhaled drugs and to facilitate the handling of these devices by patients, especially children. Although the number of commercially available VHCs is increasing, the correct choice of VHC in clinical practice is important, because VHCs are not equally effective regarding medication delivery. Hence, we aimed to evaluate the use of three small-volume VHCs-Vortex(®), AeroChamber(®) Plus (ACP), and Able Spacer™ (AS)-along with a commercial pMDI containing a combination of beclomethasone and formoterol (Innovair(®)) frequently used by asthma patients. Methods: Evaluation of the delivered dose of both drugs and analysis of particle size distribution of aerosols emitted for the inhaler were performed using the Next Generation Impactor with and without the tested VHCs. Results: The VHCs retained significant quantities of both drugs and dramatically reduced the quantity of drugs deposited in the throat of the impactor, indicating that particles with large size were preferably retained in the VHCs. Interestingly, although the delivered dose of both drugs was reduced by the use of VHCs, the use of the Vortex and the ACP resulted in comparable fine particle doses (FPDs) to that obtained when the pMDI was used alone, whereas the AS VHC significantly reduced the FPDs of both drugs. This may be due to the fact that, unlike the AS VHC, the Vortex and the ACP VHCs are made of antistatic materials that minimize the electrostatic interaction with emitted aerosols, enhancing medication delivery. Conclusion: The Vortex and the ACP VHCs present interesting advantages over the AS VHC to be used with Innovair pMDI. However, these results are based on an in vitro evaluation and need to be validated in an in vivo study in order to clinically assess the performance of these VHCs.
    Journal of Aerosol Medicine and Pulmonary Drug Delivery 10/2012; · 2.89 Impact Factor
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    ABSTRACT: The emergence of multidrug-resistant Gram-negative bacteria that cause nosocomial infections is a growing problem worldwide. Colistin was first introduced in 1952 and was used until the early 1980s for the treatment of infections caused by Gram-negative bacilli. In vitro, colistin has demonstrated excellent activity against various Gram-negative rod-shaped bacteria, including multidrug-resistant Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae. Recent clinical findings regarding colistin activity, pharmacokinetic properties, clinical uses, emerging resistance, toxicities and combination therapy have been reviewed. Recent approaches to the use of colistin in combination with other antibiotics hold promise for increased antibacterial efficacy. It is probable that colistin will be the 'last-line' therapeutic drug against multidrug-resistant Gram-negative pathogens in the 21st century.
    Expert Review of Anticancer Therapy 08/2012; 10(8):917-34. · 3.22 Impact Factor
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    ABSTRACT: Spacer devices are used to optimize airway aerosol deposition from pressurized metered-dose inhalers (pMDI). The in vitro performance of the combination fluticasone/salmeterol pMDI alone and con- nected to 3 different valved holding chambers (VHC) was compared by measuring impactor entry port (“throat”) deposition and fine particle dose (FPD) of each medication. Salmeterol (SX) and Fluticasone (FP) throat deposition was reduced over 90 % by all VHC compared to pMDI alone (p < 0,001). The FPD obtained from pMDI alone and connected to VHCs Vortex®, AeroChamber Plus® and Able Spacer® for Salmeterol (25 μg nominal dose) were 12.2 ± 0.7, 12.5 ± 0.5, 11.6 ± 0.8, and 7.9 ± 0.9 μg, respectively. For Fluticasone (125 μg nominal dose) the FPD were 42.5 ± 2.6, 36.3 ± 3.1, 39.8 ± 2.4, and 22.8 ± 3.5 μg, respec- tively. There were no statistical differences in FPD between devices, except for AbleSpacer® that delivered a lower FPD for both drugs (p < 0.001).
    LATIN AMERICAN JOURNAL OF PHARMACY 06/2012; 31(6):877-82. · 0.24 Impact Factor
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    ABSTRACT: We report the case of a 6-year-old boy who had Kawasaki disease resistant to intravenous immunoglobulin and systemic steroids. Because of an uncontrolled disease course, with significant lesions of the coronary arteries, anti-CD20 treatment was used. Rapid clinical, biological, and cardiac improvement was observed. The patient tolerated the treatment well.
    The Journal of pediatrics 02/2012; 160(5):875-6. · 4.02 Impact Factor
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    ABSTRACT: Mycobacterium chimaera is a recently described species within the Mycobacterium avium complex. Its pathogenicity in respiratory tract infection remains disputed. It has never been isolated during cystic fibrosis respiratory tract infection. An 11-year-old boy of Asian ethnicity who was born on Réunion Island presented to our hospital with cystic fibrosis after a decline in his respiratory function over the course of seven years. We found that the decline in his respiratory function was correlated with the persistent presence of a Mycobacterium avium complex organism further identified as M. chimaera. Using sequencing-based methods of identification, we observed that M. chimaera organisms contributed equally to respiratory tract infections in patients with cystic fibrosis when compared with M. avium subsp. hominissuis isolates. We believe that M. chimaera should be regarded as an emerging opportunistic respiratory pathogen in patients with cystic fibrosis, including young children, and that its detection warrants long-lasting appropriate anti-mycobacterial treatment to eradicate it.
    Journal of Medical Case Reports 09/2011; 5:473.
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    ABSTRACT: Jet nebulizers are commonly used to administer aerosolized tobramycin to CF patients. The aim of this study was to assess the performance of disposable jet nebulizers as an alternative to reusable nebulizers such as the Pari LC Plus. From a survey conducted in 49 CF centers in France, 18 disposable jet nebulizer systems were selected. An in vitro study was performed with 20 jet nebulizer/air source combinations (18 disposable and 2 reusable) to determine their performance with tobramycin solution (300 mg/5 mL). A scintigraphic deposition study in baboons was performed to validate the in vitro data. In vitro and in vivo results correlated. There was no overall relationship between the compressed air source and nebulizer performance, but the nebulizer interface was responsible for significantly different results. None of the disposable nebulizers tested in this study can be recommended as an alternative to the Pari LC Plus nebulizer for tobramycin.
    Journal of cystic fibrosis: official journal of the European Cystic Fibrosis Society 11/2010; 10(2):86-92. · 3.19 Impact Factor
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    ABSTRACT: Respiratory tract infections are the major causes of morbidity and mortality in patients with cystic fibrosis. Nocardia are rarely implicated in these infections and few reports of the involvement of this species are found in the literature. We describe a case of lung infection followed by chronic colonization of trimethoprim and sulfamethoxazole resistant Nocardia farcinica in a patient with cystic fibrosis. The chronic colonization of this uncommon bacterium in patients with cystic fibrosis was proved using a newly developed real-time polymerase chain reaction assay, which indicates that this bacterium, despite treatment, is difficult to eradicate. Our case report confirms that this organism can be recovered in persons with cystic fibrosis. Its eradication is necessary especially if the patient is to undergo lung transplantation.
    Journal of Medical Case Reports 03/2010; 4:84.
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    ABSTRACT: Systematic flexible bronchoscopy is advocated in the initial management of childhood pulmonary tuberculosis. Our aim was to describe and to compare the systematic flexible bronchoscopy findings of 53 children (6.5 + or - 4.4 years; 52.8% boys) with active pulmonary tuberculosis to their initial clinical and radiological (chest x-ray, n=53; CT, n=45) features in an 11-year retrospective study. Flexible bronchoscopy was normal in 51% of cases. A severe tracheobronchial involvement (extrinsic compression >50% or obstructive endoluminal mass >25% of the lumen) was found in 10 patients. Flexible bronchoscopy guided therapy in 13 cases (steroids n=12, bronchoscopic extraction of a granuloma n=1) and permitted isolation of Mycobacterium tuberculosis in three patients (5.7%). No useful information was obtained by flexible bronchoscopy in 73.5% of cases. No correlation was found between flexible bronchoscopy findings and clinical features or x-ray findings. Conversely, a strong correlation was found between severe bronchoscopic involvement and tracheobronchial luminal narrowing on CT. The CT negative predictive value was 100% (95% CI 91% to 100%). Based on CT results, flexible bronchoscopy could have been avoided in about 60% of our patients. Flexible bronchoscopy remains a very relevant tool in the diagnostic and therapeutic management of childhood pulmonary tuberculosis but resulted in treatment modification or microbiological proof in a minority of our patients. We propose that flexible bronchoscopy in children with pulmonary tuberculosis be limited to those who show tracheobronchial luminal narrowing on an initial CT scan.
    Archives of Disease in Childhood 02/2010; 95(2):125-9. · 3.05 Impact Factor
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    ABSTRACT: BACKGROUND: Systematic flexible bronchoscopy (FB) is advocated in the initial management of childhood pulmonary tuberculosis. METHODS: Our aim was to describe and to compare the systematic FB findings of 53 children (6.5 +/- 4.4 years; 52.8% boys) with active pulmonary tuberculosis to their initial clinical and radiological (chest X-Ray, n=53; computerized tomography (CT), n=45) features in a 11-year retrospective study. RESULTS: FB was normal in 51% of the cases. A severe tracheobronchial involvement (extrinsic compression >50% or obstructive endoluminal mass >25% of the lumen) was found in 10 patients. FB guided therapy in 13 cases (steroids n=12, bronchoscopic extraction of a granuloma n=1) and permitted to isolate Mycobacterium tuberculosis in 3 patients (5.7%). No useful information was obtained by FB in 73.5% of the cases. No correlation was found between FB findings and clinical features or X-Ray findings. Conversely, a strong correlation was found between severe bronchoscopic involvement and tracheobronchial luminal narrowing on CT. CT negative predictive value was 100% (95% confidence interval = 91-100%). Based upon CT results, FB could have been avoided in about 60% of our patients. CONCLUSIONS: FB remains a very relevant tool in the diagnostic and therapeutic management of childhood pulmonary tuberculosis but resulted in treatment modification or microbiological proof in a minority of our patients. We propose that FB in children with pulmonary tuberculosis might be limited to those who show tracheobronchial luminal narrowing on an initial CT scan.
    Archives of Disease in Childhood 10/2009; · 3.05 Impact Factor
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    ABSTRACT: Staphylococcus aureus is a major human pathogen responsible for a variety of nosocomial and community-acquired infections. Recent reports show that the prevalence of Methicillin-Resistant S. aureus (MRSA) infections in cystic fibrosis (CF) patients is increasing. In 2006 in Marseille, France, we have detected an atypical MRSA strain with a specific antibiotic susceptibility profile and a unique growth phenotype. Because of the clinical importance of the spread of such strain among CF patients we decided to sequence the genome of one representative isolate (strain CF-Marseille) to compare this to the published genome sequences. We also conducted a retrospective epidemiological analysis on all S. aureus isolated from 2002 to 2007 in CF patients from our institution. CF-Marseille is multidrug resistant, has a hetero-Glycopeptide-Intermediate resistance S. aureus phenotype, grows on Cepacia agar with intense orange pigmentation and has a thickened cell wall. Phylogenetic analyses using Complete Genome Hybridization and Multi Locus VNTR Assay showed that CF-Marseille was closely related to strain Mu50, representing vancomycin-resistant S. aureus. Analysis of CF-Marseille shows a similar core genome to that of previously sequenced MRSA strains but with a different genomic organization due to the presence of specific mobile genetic elements i.e. a new SCCmec type IV mosaic cassette that has integrated the pUB110 plasmid, and a new phage closely related to phiETA3. Moreover this phage could be seen by electron microscopy when mobilized with several antibiotics commonly used in CF patients including, tobramycin, ciprofloxacin, cotrimoxazole, or imipenem. Phylogenetic analysis of phenotypically similar h-GISA in our study also suggests that CF patients are colonized by polyclonal populations of MRSA that represents an incredible reservoir for lateral gene transfer. In conclusion, we demonstrated the emergence and spreading of a new isolate of MRSA in CF patients in Marseille, France, that has probably been selected in the airways by antibiotic pressure. Antibiotic-mediated phage induction may result in high-frequency transfer and the unintended consequence of promoting the spread of virulence and/or antibiotic resistance determinants. The emergence of well-adapted MRSA is worrying in such population chronically colonized and receiving many antibiotics and represents a model for emergence of uncontrollable super bugs in a specific niche. This article was reviewed by Eric Bapteste, Pierre Pontarotti, and Igor Zhulin. For the full reviews, please go to the Reviewers' comments section.
    Biology Direct 02/2009; 4:1. · 2.72 Impact Factor
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    ABSTRACT: Cystic fibrosis afflicted lungs support the growth of many bacteria rarely implicated in other cases of human infections. We report the isolation and identification, by 16S rRNA amplification and sequencing, of two emerging pathogens resistant to colistin, Brevundimonas diminuta and Ochrobactrum anthropi, in a 17-year-old woman with cystic fibrosis and pneumonia. The patient eventually responded well to a 2-week regime of imipenem and tobramycin. Our results clearly re-emphasize the emergence of new colistin-resistant pathogens in patients with cystic fibrosis.
    Journal of Medical Case Reports 01/2009; 2:373.
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    ABSTRACT: The objective of this observational study was to estimate influenza vaccination coverage for the 2005/2006 season in cystic fibrosis (CF) patients consulting at or hospitalized in 12 CF care centers. Data from 518 CF patients >6 months of age (children: 64.9%) were analyzed: 79.9% were vaccinated. The vaccination coverage was 85.6% in children, 69.4% in adults and 44.4% in transplanted patients. General practitioners vaccinated 67.9% of the patients. "Lack of time" reason was reported by 24.7% non-vaccinated patients. In France, influenza vaccination coverage in CF patients meets the National Health objective (> or =75% by 2008), but could be improved in adults and transplanted patients.
    Vaccine 09/2008; 26(44):5612-8. · 3.49 Impact Factor
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    Emerging Infectious Diseases 07/2008; 14(6):993-5. · 6.79 Impact Factor
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    Smart Zeidan, Jean-Christophe Dubus, Hervé Dutau, Pascal de Lagausie
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    ABSTRACT: We report the first case in the literature of thoracoscopic bronchial reimplantation in 5 month-old boy. The child was born with congenital cystic adenomatoid malformation of the right lower lobe associated with lower intralobar pulmonary sequestration diagnosed prenatally. An iatrogenic middle lobar bronchus injury was detected per-operatively during thoracoscopic lobectomy. Management and follow-up were exposed.
    Pediatric Surgery International 06/2008; 24(5):629-31. · 1.22 Impact Factor
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    ABSTRACT: There is strong evidence that culture-based methods detect only a small proportion of bacteria present in the respiratory tracts of cystic fibrosis (CF) patients. Standard microbiological culture and phenotypic identification of bacteria in sputa from CF patients have been compared to molecular methods by the use of 16S rDNA amplification, cloning and sequencing. Twenty-five sputa from CF patients were cultured that yield 33 isolates (13 species) known to be pathogens during CF. For molecular cloning, 760 clones were sequenced (7.2+/-3.9 species/sputum), and 53 different bacterial species were identified including 16 species of anaerobes (30%). Discrepancies between culture and molecular data were numerous and demonstrate that accurate identification remains challenging. New or emerging bacteria not or rarely reported in CF patients were detected including Dolosigranulum pigrum, Dialister pneumosintes, and Inquilinus limosus. Our results demonstrate the complex microbial community in sputa from CF patients, especially anaerobic bacteria that are probably an underestimated cause of CF lung pathology. Metagenomic analysis is urgently needed to better understand those complex communities in CF pulmonary infections.
    PLoS ONE 02/2008; 3(8):e2908. · 3.73 Impact Factor
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    ABSTRACT: Repeated disinfection of a nebulizer may modify its performance. During 60 cycles of disinfection with the Nuk steam sterilizer (120 nebulizations), the median volume diameter of tobramycin or colistin, nebulization time and various parameters correlated with the membrane weight of the e-Flow rapid are not modified. Results are similar when tap or purified water is used for washing and disinfection.
    Journal of Cystic Fibrosis 08/2007; 6(4):309-10. · 2.87 Impact Factor
  • Vaccine 07/2007; 25(25):4755-6. · 3.49 Impact Factor
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    ABSTRACT: This randomised cross-over pilot study was undertaken in 10 cystic fibrosis children aged 10 to 63 months to describe lung absorption of tobramycin delivered by the PariLC+/PariTurboboyN (Pari GmbH) and the disposable NL9M/AtomisorBoxPlus (Diffusion Technique Française) nebulising systems. Each child inhaled 300 mg tobramycin delivered with one or the other apparatus via a facemask in two separate and standardised sessions. Urine was collected for 6 h. Tobramycin concentrations determined by immunoprecipitation were expressed in mg per g of creatinine and compared by a Wilcoxon test for matched pairs. The influences of age, weight and Brasfield score on this parameter were evaluated by correlation tests, and those of sex, previous nebulisation treatment, and crying or coughing were evaluated by Student's t-test. The amount of tobramycin measured in urines was low and variable. Median values for urinary tobramycin concentration were 47.6 mg/g (14.9-79.6) with the PariLC+ and 42.6 mg/g (6.3-112.8) with the NL9M (p=0.6). PariLC+ delivered tobramycin in 22 min and NL9M in 12 min (p=0.005). Crying or coughing dramatically reduced the amount of tobramycin collected. This pilot study shows that evaluation of nebulisers based on tobramycin renal excretion is feasible in young children with cystic fibrosis.
    Journal of Cystic Fibrosis 05/2007; 6(2):137-43. · 2.87 Impact Factor
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    ABSTRACT: An 11-year-old girl was referred to our institution with complete obstruction of the left main stem bronchus by an endoluminal mass and was successfully treated by a combination of laser and mechanical debulking. Coring of the mass both allowed histological diagnosis (inflammatory myofibroblastic tumour) and definitive treatment with no recurrence after 3 years of follow-up. This case report emphasizes the major role of interventional bronchoscopy in the management of tumoural obstruction in children in whom benign conditions are frequent. Interventional bronchoscopy, which is minimally invasive when compared to surgery, in the vast majority of cases allows a precise diagnosis as it provides large samples of tissue removed during coring; in some cases it can be curative by itself and preserves lung parenchyma and function.
    Respiration 05/2007; 76(4):444-8. · 2.62 Impact Factor

Publication Stats

301 Citations
72.74 Total Impact Points

Institutions

  • 2012–2013
    • Aix-Marseille Université
      • Unité de Recherche sur les maladies Infectieuses et Tropicales Emergentes (UM 63 UMR_S 1095 UMR 7278 URMITE)
      Marseille, Provence-Alpes-Cote d'Azur, France
  • 2010
    • Institut de Recherche sur les Phénomènes Hors Equilibre
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2007–2010
    • University of Tours
      Tours, Centre, France
  • 2008
    • Centre Hospitalier Universitaire de Toulouse
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2003–2007
    • Assistance Publique Hôpitaux de Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France