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Jean-Yves Fagon

Publications and source records attributed to Jean-Yves Fagon.

At least 19 recordsLinked to original sources
PubMed2007

Early predictors for infection recurrence and death in patients with ventilator-associated pneumonia.

OBJECTIVE: Early recognition of predictors of unfavorable evolution of ventilator-associated pneumonia (VAP) might prompt therapeutic measures that might improve outcome. The objective of this study was to describe resolution of VAP variables and to determine early predictors of VAP recurrence and death. DESIGN AND SETTING: Description of the natural course of VAP resolution and multivariable analyses of predictors of VAP recurrence and death by day 28 after VAP onset based on the 401 patients included in the PNEUMA trial, a multiple-center, randomized study comparing 8 vs. 15 days of antibiotics for microbiologically proven VAP. Every patient included in that trial had received appropriate empirical antibiotics. MEASUREMENTS AND MAIN RESULTS: By day 28 after VAP onset, 27% of patients had VAP recurrence and 18% had died. On day 8 after VAP onset, predictors of VAP recurrence included intensive care unit admission Simplified Acute Physiology Score II (odds ratio [OR], 1.02), radiologic score (OR, 1.17), temperature (OR, 1.34), nonfermenting Gram-negative bacilli (OR, 2.00) or methicillin-resistant Staphylococcus aureus (OR, 2.50) as pathogens responsible for VAP, and mechanical ventilation dependency (OR, 2.08). Day 8 predictors of 28-day death were age (OR, 1.06), female sex (OR, 2.30), Sepsis-Related Organ Failure Assessment score (OR, 1.26), and nonfermenting Gram-negative bacilli (OR, 2.83) as pathogens responsible for VAP. However, the duration of antimicrobial therapy (8 vs. 15 days) was not associated with any of the studied adverse outcomes. CONCLUSIONS: For patients benefiting from appropriate empirical antibiotics for VAP, early predictors of infection recurrence or death included demographic characteristics, such as age or female sex, disease severity at VAP onset, nonfermenting Gram-negative bacilli or methicillin-resistant S. aureus as VAP-causative pathogens, prolonged mechanical ventilation dependency, persistent fever, and severity of lung injury. Future studies should attempt to determine whether specific diagnostic or therapeutic strategies could markedly improve VAP outcomes when early criteria for treatment failure are present.

APACHE↗
PubMed2006

Impact of piperacillin resistance on the outcome of Pseudomonas ventilator-associated pneumonia.

BACKGROUND: The impact of antibiotic resistance on the outcome of infections due to Gram-negative bacilli, especially Pseudomonas, remains highly controversial. STUDY OBJECTIVE, DESIGN, AND PATIENTS: We evaluated the impact of piperacillin resistance on the outcomes of Pseudomonas aeruginosa ventilator-associated pneumonia (VAP) for patients who had received appropriate empiric antibiotics before enrollment in the PNEUMA trial, a multicenter randomized study comparing 8 vs 15 days of antibiotics. RESULTS: Despite similar characteristics at intensive care unit (ICU) admission, patients infected with piperacillin-resistant Pseudomonas strains were more acutely ill at VAP onset and had a higher 28-day mortality rate (37 vs 19%; P = 0.04) than those with piperacillin-susceptible Pseudomonas VAP. Factors associated with 28-day mortality retained by multivariable analysis were: age (OR: 1.07; 95% CI: 1.03-1.12); female gender (OR: 4.00; 95% CI: 1.41-11.11); severe underlying comorbidities (OR: 2.73; 95% CI: 1.02-7.33); and SOFA score (OR: 1.17; 95% CI: 1.03-1.32), but piperacillin resistance did not reach statistical significance (OR: 2.00; 95% CI: 0.72-5.61). The VAP recurrence rates, either superinfection or relapse, and durations of mechanical ventilation and ICU stay did not differ as a function of Pseudomonas-resistance status. CONCLUSIONS: For patients with Pseudomonas VAP benefiting from appropriate empiric antibiotics, piperacillin resistance was associated with increased disease severity at VAP onset and higher 28-day crude mortality; however, after controlling for confounders, piperacillin-resistance was no longer significantly associated with 28-day mortality. The VAP recurrence rates and durations of ICU stay and mechanical ventilation did not differ for susceptible and resistant strains.

Aged↗
PubMed2006

Renal failure in septic shock: predictive value of Doppler-based renal arterial resistive index.

OBJECTIVE: Because acute renal failure (ARF) is frequent in septic shock, an early marker of ARF could impact on management of such patients. High renal arterial resistive index (RI) is associated with parenchymatous renal failure. We assessed whether Doppler-measured RI on day 1 (D1) of septic shock can predict ARF. DESIGN: Prospective descriptive clinical study. SETTING: A 20-bed medical intensive care unit in a university hospital. PATIENTS: All patients with septic shock, excluding those with chronic renal failure (serum creatinine >120 micromol/l). MEASUREMENTS AND RESULTS: RI was determined during the first 24 h (D1) following vasopressor introduction, concomitant with recording of: age, SAPS II, mean arterial pressure, arterial lactate, catecholamine (dose and type), urine output and serum creatinine. ARF was diagnosed according to the RIFLE classification. RI measurement was possible for 35 of 37 included patients. On day 5 (D5), 17 patients were without ARF (RIFLE-0 or R) and 18 patients were classified as having ARF (RIFLE-I or F). On D1, RI was higher in these latter 18 patients (0.77+/-0.08 vs. 0.68+/-0.08, p<0.001). They also had higher SAPS II and arterial lactate concentration. RI >0.74 on D1 had a positive likelihood ratio of 3.3 (95% CI 1.1-35) for developing ARF on D5. RI correlated inversely with mean arterial pressure (rho=-0.48, p=0.006) but not with catecholamine type or dose or with lactate concentration. CONCLUSION: Doppler-based determination of RI on D1 in septic shock patients may help identify those who will develop ARF.

Acute Kidney Injury↗
PubMed2006

Phosphodiesterase 4 inhibitors modulate beta2-adrenoceptor agonist-induced human airway hyperresponsiveness.

Chronic exposure of human isolated bronchi to beta2-adrenergic agonists, especially fenoterol, potentiates smooth muscle contraction in response to endothelin-1 (ET-1), a peptide implicated in chronic inflammatory airway diseases. 5'-Cyclic adenosine monophosphate (cAMP) pathways are involved in fenoterol-induced hyperresponsiveness. The present study investigated whether chronic elevation of intracellular cAMP by other pathways than beta2-adrenoceptor stimulation provokes bronchial hyperresponsiveness. Samples from eighteen human bronchi were sensitized to ET-1 by prolonged incubation with 0.1 microM fenoterol (15 h, 21 degrees C), or, under similar conditions, were incubated with a selective type-3 phosphodiesterase inhibitor (1 microM siguazodan), two selective type-4 phosphodiesterase inhibitors (0.1 microM rolipram and 0.1 microM cilomilast), a combination of fenoterol and rolipram (0.1 microM each) or of fenoterol and cilomilast (0.1 microM each). Rolipram and cilomilast, but not siguazodan, induced hyperresponsiveness (p < 0.01 and p < 0.05 vs. paired controls, respectively) similar to the fenoterol effect. Fenoterol-induced bronchial hyperresponsiveness was significantly enhanced by coincubation with cilomilast (p < 0.05 vs. fenoterol alone) but not with rolipram. Our results suggest that prolonged activation of intracellular cAMP through phosphodiesterase 4 inhibition induces hyperresponsiveness to ET-1 in human isolated bronchi. However, differences in subcellular localization of phosphodiesterase 4 may provoke divergent responsiveness patterns when human bronchi are continuously exposed to selective phosphodiesterase inhibitors with or without beta2-adrenergic agonists.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed2006

Diagnosis and treatment of ventilator-associated pneumonia: fiberoptic bronchoscopy with bronchoalveolar lavage is essential.

The management of patients suspected of having ventilator-associated pneumonia (VAP) requires a strategy for diagnosis and treatment that is designated to: (1) identify patients with true lung bacterial infection; (2) determine the pathogen(s) responsible for pneumonia; (3) permit early selection of appropriate antimicrobial therapy; and (4) avoid indiscriminate administration of antibiotics. The use of bronchoscopic techniques to obtain bronchoalveolar lavage (BAL) specimens from the affected area in the lung allows definition of a strategy superior to that based exclusively on clinical evaluation. When BAL is performed before introduction of new antibiotics, it enables physicians to identify patients who need immediate treatment and help to select initial antibiotic therapy (with the results of direct examination of BAL liquid) and to withhold, deescalate, and/or optimize treatment (when the results of quantitative cultures are available), in a manner that is safe and well tolerated by patients. This strategy, based on clinical and bacteriological evaluation, prevents resorting to broad-spectrum drug coverage in all patients who develop signs and symptoms suggestive of pneumonia, thus minimizing the emergence of resistant flora, and redirects the search for another infection site.

Anti-Bacterial Agents↗
PubMed2006

Elevated growth-arrest-specific protein 6 plasma levels in patients with severe sepsis.

OBJECTIVE: Growth-arrest-specific protein 6 (Gas6), an intracellular protein released by apoptotic cells, has been detected in normal plasma. As the Gas6 system has been implicated in mouse susceptibility to sepsis, and as leukocyte apoptosis is thought to play a major role in the physiopathology of human severe sepsis, we studied Gas6 plasma levels and possibly related variables in patients with severe sepsis. DESIGN: Matched case-control study. SETTING: Adult intensive care unit in a university hospital. PATIENTS: Thirty patients with severe sepsis, 30 patients with organ failure not related to infection, and 30 healthy subjects matched for age and gender. INTERVENTIONS: Blood draw. MEASUREMENTS AND MAIN RESULTS: Gas6 plasma levels were quantified using enzyme-linked immunosorbent assay. Whole-blood gas6 messenger RNA levels were measured by quantitative real-time polymerase chain reaction. Gas6 plasma levels were elevated (110 ng/mL [75, 139]; median values [interquartile range]) in severe sepsis patients compared with organ failure patients (85 ng/mL [56, 101]) and healthy subjects (54 ng/mL [49, 68]). In patients with severe sepsis, this increase correlated with the Acute Physiology and Chronic Health Evaluation II severity score, the organ failure Organ Dysfunction and Infection (ODIN) score, and the existence of a septic shock. Gas6 messenger RNA levels were increased in patients with severe sepsis and correlated specifically with the monocyte count. CONCLUSIONS: In severe sepsis, the recently described anti-apoptotic protein Gas6 was found at high levels in plasma and correlated well with the degree of organ dysfunction.

APACHE↗
PubMed2006

Acute respiratory failure in the elderly.

With the current epidemiology of a growing advanced-age population and the specificities of critical illness in elderly patients, studies on this topic are appropriate. We need more clinical trials and evaluations of diagnostic and management procedures applied in the elderly, as well as studies designed to identify prognostic factors for inhospital mortality or mortality in the intensive care unit in the elderly. Studies evaluating long-term outcomes, including quality of life and costs, are also needed to try to define realistic goals for patients, families and physicians.

Acute Disease↗
PubMed2005

beta2-Adrenoceptor agonist modulates endothelin-1 receptors in human isolated bronchi.

Chronic exposure of human isolated bronchi to beta(2)-adrenergic agonists, especially fenoterol, potentiates smooth muscle contraction in response to endothelin-1 (ET-1), a peptide implicated in chronic inflammatory airway diseases. Our objective was to determine whether ET-1 receptors ETA and ETB are involved in fenoterol enhancement. Twenty-two human bronchi were sensitized to ET-1 by prolonged incubation with 0.1 microM fenoterol (15 h, 21 degrees C). Removing the epithelium after fenoterol incubation limited the maximal contraction (0.10+/-0.36 g without epithelium versus 1.18+/-0.22 with, n=8, P=0.04). After 15 h incubation, 14 and 8 paired rings were fixed, respectively, for immunolabeling of bronchial ETA and ETB receptors, and to determine the mRNA expression levels using real-time quantitative reverse transcription polymerase chain reaction. ETA and ETB receptor mRNA expressions were 1.27- +/- 0.14-fold (not significant) and 2.24- +/- 0.28-fold (P<0.01) higher, respectively, in fenoterol-treated bronchi than in paired controls. Fenoterol incubation significantly increased epithelial ETA and ETB receptor labeling intensity scores (P=0.001 and P=0.002, respectively, versus controls), and enhanced the diffuse localization of ETA receptors on the epithelial cells (P=0.002 versus controls), but did not change the ETB-receptor immunolabeling intensity on airway smooth muscle. We conclude that fenoterol-induced sensitization of human isolated bronchi involves epithelial ETA and ETB receptors, which suggests perturbation of the epithelial regulation of airway smooth muscle contraction in response to ET-1.

Adrenergic beta-Agonists↗
PubMed2005

A randomized double-blind trial of iseganan in prevention of ventilator-associated pneumonia.

RATIONALE: Iseganan, an antimicrobial peptide, is active against aerobic and anaerobic gram-positive and gram-negative bacteria as well as fungi and yeasts. The drug has shown little resistance in vitro and to be safe and well tolerated in 800 patients with cancer treated for up to 6 wk. OBJECTIVES: To determine the efficacy of iseganan for the prevention of ventilator-associated pneumonia (VAP). METHODS: Mechanically ventilated patients in the United States and Europe were randomized to oral topical iseganan or placebo (1:1) and treated six times per day while intubated for up to 14 d. Patients were eligible if randomized within 24 h of intubation and estimated to survive and remain mechanically ventilated for 48 h or more. The primary efficacy endpoint of the study was VAP measured among survivors at Day 14. MEASUREMENTS AND MAIN RESULTS: A total of 709 patients were randomized and received at least one dose of study drug. The two groups were comparable at baseline except iseganan-treated patients were, on average, 3 yr older. The rate of VAP among survivors at Day 14 was 16% (45/282) in patients treated with iseganan and 20% (57/284) in those treated with placebo (p = 0.145). Mortality at Day 14 was 22.1% (80/362) in the iseganan group compared with 18.2% (63/347) in the placebo group (p = 0.206). No pattern of excess adverse events in the iseganan group compared with placebo was observed. CONCLUSIONS: Iseganan is not effective in improving outcome in patients on prolonged mechanical ventilation.

Administration, Oral↗
PubMed2005

Antimicrobial treatment of hospital-acquired pneumonia.

This article highlights the importance of providing adequate empirical antibiotic therapy for hospital-acquired pneumonia and avoiding the excessive use of antibiotics. To meet these goals, a strategy for the management of suspected ventilator-associated pneumonia should include obtaining reliable pulmonary specimens for direct microscope examination and cultures before new antibiotics are administered.

Anti-Bacterial Agents↗
PubMed2005

High prevalence of respiratory viral infections in patients hospitalized in an intensive care unit for acute respiratory infections as detected by nucleic acid-based assays.

Forty-seven bronchoalveolar lavages (BAL) were obtained from 41 patients with acute pneumonia attending an intensive care unit. By molecular diagnosis, 30% of total BAL and 63% of bacteria-negative BAL were positive for respiratory viruses. Molecular detection allows for high-rate detection of respiratory viral infections in adult patients suffering from severe pneumonia.

Acute Disease↗