Publications (14)84.23 Total impact
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Article: Lung deposition of continuous and intermittent intravenous ceftazidime in experimental Pseudomonas aeruginosa bronchopneumonia
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ABSTRACT: ObjectiveLung tissue deposition of intravenous ceftazidime administered either continuously or intermittently was compared in ventilated piglets with experimental bronchopneumonia.DesignProspective experimental studyAnimalsEighteen anesthetized and ventilated pigletsInterventionsBronchopneumonia was produced by the intrabronchial inoculation of Pseudomonas aeruginosa characterized by an impaired sensitivity to ceftazidime (MIC 16 mg/l). Ceftazidime was administered either through acontinuous infusion of 90 mg/kg per 24 h after abolus of 30 mg/kg or by an intermittent infusion of 30 mg/kg per 8 h.Measurements and resultsPiglets were killed 24 h after the initiation of continuous ceftazidime (n = 6), and 1 h (peak, n = 6) and 8 h (trough, n = 6) after the third dose following intermittent administration. Lung tissue concentrations of ceftazidime, measured by HPLC, and lung bacterial burden were assessed on multiple postmortem lung specimens. During continuous administration ceftazidime lung tissue concentrations were 9.7 ± 3.8 μg/g. Following intermittent administration peak and trough lung tissue concentrations were, respectively, 7.1 ± 2.4 μg/g and 0.6 ± 1 μg/g. Lung bacterial burden was different after continuous and intermittent administration (median 7.103 vs. 4.102 cfu/g).ConclusionsContinuous infusion of ceftazidime maintained higher tissue concentrations than intermittent administration.Intensive Care Medicine 04/2012; 32(12):2042-2048. · 5.40 Impact Factor -
Article: Mechanical ventilation and lung infection in the genesis of air-space enlargement.
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ABSTRACT: Air-space enlargement may result from mechanical ventilation and/or lung infection. The aim of this study was to assess how mechanical ventilation and lung infection influence the genesis of bronchiolar and alveolar distention. Four groups of piglets were studied: non-ventilated-non-inoculated (controls, n = 5), non-ventilated-inoculated (n = 6), ventilated-non-inoculated (n = 6), and ventilated-inoculated (n = 8) piglets. The respiratory tract of intubated piglets was inoculated with a highly concentrated solution of Escherichia coli. Mechanical ventilation was maintained during 60 hours with a tidal volume of 15 ml/kg and zero positive end-expiratory pressure. After sacrifice by exsanguination, lungs were fixed for histological and lung morphometry analyses. Lung infection was present in all inoculated piglets and in five of the six ventilated-non-inoculated piglets. Mean alveolar and mean bronchiolar areas, measured using an analyzer computer system connected through a high-resolution color camera to an optical microscope, were significantly increased in non-ventilated-inoculated animals (+16% and +11%, respectively, compared to controls), in ventilated-non-inoculated animals (+49% and +49%, respectively, compared to controls), and in ventilated-inoculated animals (+95% and +118%, respectively, compared to controls). Mean alveolar and mean bronchiolar areas significantly correlated with the extension of lung infection (R = 0.50, p < 0.01 and R = 0.67, p < 0.001, respectively). Lung infection induces bronchiolar and alveolar distention. Mechanical ventilation induces secondary lung infection and is associated with further air-space enlargement. The combination of primary lung infection and mechanical ventilation markedly increases air-space enlargement, the degree of which depends on the severity and extension of lung infection.Critical care (London, England) 01/2007; 11(1):R14. · 4.61 Impact Factor -
Article: Lung deposition of continuous and intermittent intravenous ceftazidime in experimental Pseudomonas aeruginosa bronchopneumonia.
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ABSTRACT: Lung tissue deposition of intravenous ceftazidime administered either continuously or intermittently was compared in ventilated piglets with experimental bronchopneumonia. Prospective experimental study Eighteen anesthetized and ventilated piglets Bronchopneumonia was produced by the intrabronchial inoculation of Pseudomonas aeruginosa characterized by an impaired sensitivity to ceftazidime (MIC 16 mg/l). Ceftazidime was administered either through a continuous infusion of 90 mg/kg per 24 h after a bolus of 30 mg/kg or by an intermittent infusion of 30 mg/kg per 8 h. Piglets were killed 24 h after the initiation of continuous ceftazidime (n = 6), and 1 h (peak, n = 6) and 8 h (trough, n = 6) after the third dose following intermittent administration. Lung tissue concentrations of ceftazidime, measured by HPLC, and lung bacterial burden were assessed on multiple postmortem lung specimens. During continuous administration ceftazidime lung tissue concentrations were 9.7 +/- 3.8 microg/g. Following intermittent administration peak and trough lung tissue concentrations were, respectively, 7.1 +/- 2.4 microg/g and 0.6 +/- 1 microg/g. Lung bacterial burden was different after continuous and intermittent administration (median 7.10(3) vs. 4.10(2) cfu/g). Continuous infusion of ceftazidime maintained higher tissue concentrations than intermittent administration.Intensive Care Medicine 01/2007; 32(12):2042-8. · 5.40 Impact Factor -
Article: Novel and innovative strategies to treat ventilator-associated pneumonia: optimizing the duration of therapy and nebulizing antimicrobial agents.
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ABSTRACT: Ventilator-associated pneumonia (VAP) is responsible for approximately half of the infections acquired in the intensive care unit (ICU) and represents one of the principal reasons for prescribing antibiotics in this setting. Because unnecessary prolongation of antimicrobial therapy and insufficient dosing of antibiotics at the site of infection in patients with true bacterial infection may lead to the selection of multidrug-resistant microorganisms without improving clinical outcome, efforts to reduce the duration of therapy and optimize pulmonary penetration of antimicrobial agents are warranted. An 8-day regimen can probably be standard for patients with VAP. Possible exceptions to this recommendation include immunosuppressed patients, those whose initial antimicrobial treatment was not appropriate for the causative microorganism(s), and patients whose infection was caused by very difficult-to-treat microorganisms and had no improvement in clinical signs of infection. Nebulizing concentration-dependent antibiotics such as aminoglycosides during mechanical ventilation can markedly increase tissue penetration in foci of pneumonia as compared with intravenous administration. The superiority in terms of pulmonary penetration and antibacterial efficacy of this route of administration was demonstrated in a model of ventilated piglets with and without bronchopneumonia.Seminars in Respiratory and Critical Care Medicine 03/2006; 27(1):82-91. · 2.43 Impact Factor -
Article: Intravenous versus nebulized ceftazidime in ventilated piglets with and without experimental bronchopneumonia: comparative effects of helium and nitrogen.
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ABSTRACT: Lung deposition of intravenous cephalosporins is low. The lung deposition of equivalent doses of ceftazidime administered either intravenously or by ultrasonic nebulization using either nitrogen-oxygen or helium-oxygen as the carrying gas of the aerosol was compared in ventilated piglets with and without experimental bronchopneumonia. Five piglets with noninfected lungs and 5 piglets with Pseudomonas aeruginosa experimental bronchopneumonia received 33 mg/kg ceftazidime intravenously. Ten piglets with noninfected lungs and 10 others with experimental P. aeruginosa bronchopneumonia received 50 mg/kg ceftazidime by ultrasonic nebulization. In each group, the ventilator was operated in half of the animals with a 65%/35% helium-oxygen or nitrogen-oxygen mixture. Animals were killed, and multiple lung specimens were sampled for measuring ceftazidime lung tissue concentrations by high-performance liquid chromatography. As compared with intravenous administration, nebulization of ceftazidime significantly increased lung tissue concentrations (17 +/- 13 vs. 383 +/- 84 microg/g in noninfected piglets and 10 +/- 3 vs. 129 +/- 108 microg/g in piglets with experimental bronchopneumonia; P < 0.001). The use of a 65%/35% helium-oxygen mixture induced a 33% additional increase in lung tissue concentrations in noninfected piglets (576 +/- 141 microg/g; P < 0.001) and no significant change in infected piglets (111 +/- 104 microg/g). Nebulization of ceftazidime induced a 5- to 30-fold increase in lung tissue concentrations as compared with intravenous administration. Using a helium-oxygen mixture as the carrying gas of the aerosol induced a substantial additional increase in lung deposition in noninfected piglets but not in piglets with experimental bronchopneumonia.Anesthesiology 06/2005; 102(5):995-1000. · 5.36 Impact Factor -
Article: Comparative diagnostic performances of auscultation, chest radiography, and lung ultrasonography in acute respiratory distress syndrome.
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ABSTRACT: Lung auscultation and bedside chest radiography are routinely used to assess the respiratory condition of ventilated patients with acute respiratory distress syndrome (ARDS). Clinical experience suggests that the diagnostic accuracy of these procedures is poor. This prospective study of 32 patients with ARDS and 10 healthy volunteers was performed to compare the diagnostic accuracy of auscultation, bedside chest radiography, and lung ultrasonography with that of thoracic computed tomography. Three pathologic entities were evaluated in 384 lung regions (12 per patient): pleural effusion, alveolar consolidation, and alveolar-interstitial syndrome. Auscultation had a diagnostic accuracy of 61% for pleural effusion, 36% for alveolar consolidation, and 55% for alveolar-interstitial syndrome. Bedside chest radiography had a diagnostic accuracy of 47% for pleural effusion, 75% for alveolar consolidation, and 72% for alveolar-interstitial syndrome. Lung ultrasonography had a diagnostic accuracy of 93% for pleural effusion, 97% for alveolar consolidation, and 95% for alveolar-interstitial syndrome. Lung ultrasonography, in contrast to auscultation and chest radiography, could quantify the extent of lung injury. Interobserver agreement for the ultrasound findings as assessed by the kappa statistic was satisfactory: 0.74, 0.77, and 0.73 for detection of alveolar-interstitial syndrome, alveolar consolidation, and pleural effusion, respectively. At the bedside, lung ultrasonography is highly sensitive, specific, and reproducible for diagnosing the main lung pathologic entities in patients with ARDS and can be considered an attractive alternative to bedside chest radiography and thoracic computed tomography.Anesthesiology 02/2004; 100(1):9-15. · 5.36 Impact Factor -
Article: Experimental ventilator-associated pneumonia: distribution of lung infection and consequences for lung aeration.
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ABSTRACT: Ventilator-associated pneumonia (VAP) has been described in humans and in experimental animals. The most severe lesions are located in dependent lung segments along a sterno-vertebral axis, however the cephalocaudal distribution of lung infection remains unknown. We used an experimental model to evaluate the distribution of lung infection, considering its anteroposterior and cephalocaudal gradient, and its impact on lung aeration. Ten healthy domestic piglets were anesthetized, paralyzed and mechanically ventilated for 59 hours in the prone position. At the end of the experiment they were sacrificed and their lungs were fixed. Six segments were analyzed: a non-dependant (ND) and a dependant (D) segment of the upper (UL), middle (ML) and lower (LL) lobes. The presence of healthy lung or of histological infectious lesions was analyzed with a semi-quantitative method. The regional distribution of lung infection was compared between upper, middle and lower lobes, as well as between dependant and non-dependant regions. The presence of infectious lesions was correlated with measurements of lung aeration. Nine of the ten piglets developed VAP. Infectious lesions were distributed along a sterno-vertebral and a cephalocaudal gradient; the lower and middle lobes were more frequently infected than the upper lobes. There was an inverse correlation (R= - 0.902) between the development of lung lesions and lung aeration. In conclusion, VAP was a frequent complication in healthy mechanically ventilated piglets, showing an anteroposterior as well as a cephalocaudal gradient. As expected, development of lung infection was accompanied by a corresponding loss of aeration.Brazilian Journal of Infectious Diseases 07/2003; 7(3):216-23. · 1.00 Impact Factor -
Article: Lack of lung tissue and systemic accumulation after consecutive daily aerosols of amikacin in ventilated piglets with healthy lungs.
Anesthesiology 05/2003; 98(4):1016-9. · 5.36 Impact Factor -
Article: Lack of Lung Tissue and Systemic Accumulation after Consecutive Daily Aerosols of Amikacin in Ventilated Piglets with Healthy Lungs
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ABSTRACT: An abstract is unavailable. This article is available as HTML full text and PDF.Anesthesiology 03/2003; 98(4):1016-1019. · 5.36 Impact Factor -
Article: Lung deposition and efficiency of nebulized amikacin during Escherichia coli pneumonia in ventilated piglets.
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ABSTRACT: Lung tissue deposition and antibacterial efficiency of nebulized and intravenous amikacin (AMK) were compared in anesthetized and ventilated piglets suffering from a bronchopneumonia produced by the intrabronchial inoculation of Escherichia coli. AMK was administered 24 hours after the inoculation either through an ultrasonic nebulizer (45 mg x kg-1, n = 10) or by intravenous infusion (15 mg x kg-1, n = 8). Piglets were killed 1 hour after a second AMK administration performed 24 hours after the first one, and lung tissue concentrations of AMK and lung bacterial burden were assessed on multiple lung specimens. The amount of nebulized AMK reaching the tracheobronchial tree represented 38 +/- 6% of the initial nebulizer AMK charge. After nebulization, AMK lung tissue concentrations were 3- to 30-fold higher than after intravenous administration and were influenced by the severity of lung lesions: 188 +/- 175 microg x g-1 in lung segments with mild bronchopneumonia versus 40 +/- 65 microg x g-1 in lung segments with severe bronchopneumonia (p < 0.01). Lung bacterial burden was significantly lower in the aerosol group than in the intravenous group (median = 0 colony forming units. g-1 versus median = 5 x 10(2) colony forming units x g-1, p < 0.001). In conclusion, the deposition of AMK in infected lung parenchyma and the efficiency of bacterial killing were greater after nebulization than after intravenous administration.American Journal of Respiratory and Critical Care Medicine 11/2002; 166(10):1375-81. · 11.08 Impact Factor -
Article: Influence of lung aeration on pulmonary concentrations of nebulized and intravenous amikacin in ventilated piglets with severe bronchopneumonia.
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ABSTRACT: Pulmonary concentrations of aminoglycosides administered intravenously are usually low in the infected lung parenchyma. Nebulization represents an alternative to increase pulmonary concentrations, although the obstruction of bronchioles by purulent plugs may impair lung deposition by decreasing lung aeration. An experimental bronchopneumonia was induced in anesthetized piglets by inoculating lower lobes with a suspension of 10(6) cfu/ml Escherichia coli. After 24 h of mechanical ventilation, 7 animals received two intravenous injections of 15 mg/kg amikacin, and 11 animals received two nebulizations of 40 mg/kg amikacin at 24-h intervals. One hour following the second administration, animals were killed, and multiple lung specimens were sampled for assessing amikacin pulmonary concentrations and quantifying lung aeration on histologic sections. Thirty-eight percent of the nebulized amikacin (15 mg/kg) reached the tracheobronchial tree. Amikacin pulmonary concentrations were always higher after nebulization than after intravenous administration, decreased with the extension of parenchymal infection, and were significantly influenced by lung aeration: 197 +/- 165 versus 6 +/- 5 microg/g in lung segments with focal bronchopneumonia (P = 0.03), 40 +/- 62 versus 5 +/- 3 microg/g in lung segments with confluent bronchopneumonia (P = 0.001), 18 +/- 7 versus 7 +/- 4 microg/g in lung segments with lung aeration of 30% or less, and 65 +/- 9 versus 2 +/- 3 microg/g in lung segments with lung aeration of 50% or more. In a porcine model of severe bronchopneumonia, the nebulization of amikacin provided 3-30 times higher pulmonary concentrations than the intravenous administration of an equivalent dose. The greater the lung aeration, the higher were the amikacin pulmonary concentrations found in the infected lung segments.Anesthesiology 08/2002; 97(1):199-206. · 5.36 Impact Factor -
Article: Influence of Lung Aeration on Pulmonary Concentrations of Nebulized and Intravenous Amikacin in Ventilated Piglets with Severe Bronchopneumonia
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ABSTRACT: Background: Pulmonary concentrations of aminoglycosides administered intravenously are usually low in the infected lung parenchyma. Nebulization represents an alternative to increase pulmonary concentrations, although the obstruction of bronchioles by purulent plugs may impair lung deposition by decreasing lung aeration.Anesthesiology 06/2002; 97(1):199-206. · 5.36 Impact Factor -
Article: Selecting the right level of positive end-expiratory pressure in patients with acute respiratory distress syndrome.
American Journal of Respiratory and Critical Care Medicine 05/2002; 165(8):1182-6. · 11.08 Impact Factor -
Article: Lung tissue concentrations of nebulized amikacin during mechanical ventilation in piglets with healthy lungs.
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ABSTRACT: The tissue concentration of aminoglycosides in lung parenchyma is the main determinant of bactericidal efficiency. The aim of the study was to compare the lung deposition of amikacin administered either by an ultrasonic nebulizer or by intravenous infusion during mechanical ventilation. Eighteen healthy ventilated piglets received a single daily dose of amikacin by intravenous infusion (15 mg. kg(-1)) and 18 by aerosol (1 g in 12 ml). The amount of aerosolized amikacin reaching the tracheobronchial tree represented 40 +/- 5% of the initial dose with an aerodynamic size distribution showing 50% of particles ranging between 0.5 and 5 microm mass median diameter. Animals were killed at different time intervals after the second dose. Tissue concentrations of amikacin were determined on cryomixed multiple lung specimen by an immunoenzymatic method. The lung concentrations of nebulized amikacin, peaking at 208 +/- 76 microg. g(-1), were more than 10-fold higher than the lung concentrations of intravenous amikacin and were homogeneously distributed throughout the lung parenchyma. Amikacin plasma concentrations lower than 5 mmol. l(-1) were measured after the sixth hour after the nebulization. In conclusion, the ultrasonic nebulization of amikacin resulted in high tissue concentrations, far above the minimal inhibitory concentrations of most gram-negative strains.American Journal of Respiratory and Critical Care Medicine 02/2002; 165(2):171-5. · 11.08 Impact Factor
Top co-authors
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Institutions
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2002–2007
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Hôpital La Pitié Salpêtrière – Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix"
Paris, Ile-de-France, France -
invivo-AFDIAR
USA
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2004
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Université Pierre et Marie Curie Paris 6
Paris, Ile-de-France, France
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