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Biomedical subjects

J Y Fagon

Publications and source records attributed to J Y Fagon.

At least 37 records · Page 2Linked to original sources
PubMed1996

Severe exacerbations of COPD patients: the role of pulmonary infections.

Infection is usually considered the main cause of acute exacerbation in chronic obstructive pulmonary disease (COPD). However, uncertainty persists concerning the exact role of bacterial and viral infection in this setting because of the confusing and conflicting data on the role of tracheobronchial microflora and the usefulness of antibiotics in treating this disease. Most COPD patients have evidence of lower respiratory tract chronic bacterial colonization during remission periods as well as during acute exacerbations. This is evidenced by using microbiological analysis of secretions, which reflect all the respiratory tract (sputum), the lower respiratory tract (transtracheal aspiration), or the distal respiratory tract (protected specimen brush). Potentially pathogenic organisms can be recovered from the respiratory tract secretions of virtually all patients with COPD at some time during the course of their disease. Absence of difference in isolation of potentially pathogenic organisms between remission periods and acute exacerbations suggests that bacterial infection is probably not the predominant cause of acute exacerbations in COPD. In contrast, data indicate that the association between viral infections and acute exacerbations is clearer than that with bacteria, affecting probably more than 20% of cases. The role of antibiotic therapy in acute exacerbations of COPD remains controversial. (1) Clearly, antibiotic therapy is urgently required in COPD patients with pneumonia. (2) Review of the conflicting results of studies evaluating the role of antibiotic therapy for preventing acute exacerbations suggests that there is no clear-cut rationale for prophylactic treatment of infection for all patients with COPD; it seems, however, that such treatment may be of some use in highly selected patients, such as those with many exacerbations in the winter. (3) Similarly, data are conflicting concerning the curative use of antibiotic therapy, with some studies suggesting acceleration of recovery, prevention of acute deterioration, and longer period of freedom from recurrent exacerbations; conversely many patients recover from exacerbations without resorting to an antibiotic. Unfortunately, no clear data identify patients who could benefit from antibiotic treatment, probably justifying most clinicians' choice to treat acute exacerbations as infectious events.

Acute Disease↗
PubMed1995

Diagnosis and treatment of nosocomial pneumonia in patients in intensive care units.

The optimal management strategy for ventilator-dependent patients who develop symptoms suggestive of lung infection remains controversial. Our personal bias is that using bronchoscopic techniques to obtain protected-brush and bronchoalveolar lavage specimens from the affected area in the lung permits physicians to devise a therapeutic strategy that is superior to one based only on clinical evaluation. These bronchoscopic techniques, when they are performed before new antibiotics are administered, enable physicians to identify most patients who need immediate treatment and to select optimal therapy, in a form that is safe and well tolerated by patients. Furthermore, they frequently permit physicians to withhold antimicrobial treatment from patients without infection, thereby minimizing the risk of emergence of resistant microorganisms in the intensive care unit. Despite many advances in antimicrobial therapy, successful treatment of patients with nosocomial pneumonia remains a complex undertaking, and ultimately further trials will be needed to clarify the optimal duration of treatment and the circumstances in which monotherapy can be safely used.

Aminoglycosides↗
PubMed1995

Nosocomial acquisition of multiresistant Acinetobacter baumannii: risk factors and prognosis.

To identify risk factors for and prognostic indicators of the nosocomial acquisition of multiresistant Acinetobacter baumannii in an intensive care unit, we prospectively studied 40 patients: 13 who were infected with this organism and 27 who were colonized. Isolates were identified by pulsed-field gel electrophoresis; the infected/colonized patients were compared with 348 noninfected, noncolonized patients by logistic regression analysis and with matched historical controls in a cohort study. The severity of illness (evaluated by the APACHE II score; P < .05) and previous infection (P < .001) were retained as independent risk factors for acquiring A. baumannii. Logistic regression analysis selected a high APACHE II score (P < .01) and the acquisition of A. baumannii (P < .01) as factors independently associated with death. The acquisition of A. baumannii was associated not only with high mortality but also with a length of stay on the intensive care unit in excess of that due to the underlying disease alone; specifically, the attributable mortality was 25%, with a risk ratio for death of 2.0 (95% confidence interval, 1.11-3.62), and the duration of stay for infected/colonized patients was 10.3 days longer than that for controls (P < .001).

APACHE↗
PubMed1995

Evaluation of bronchoscopic techniques for the diagnosis of nosocomial pneumonia.

To compare the usefulness of specimens obtained by bronchoalveolar lavage (BAL) and using a protected specimen brush (PSB) in the diagnosis of nosocomial pneumonia, both procedures were performed via fiberoptic bronchoscopy just after death in a series of 20 ventilated patients who had not developed pneumonia before the terminal phase of their disease and who had no recent changes in antimicrobial therapy. These results were compared with both histologic and microbiologic postmortem lung features in the same area. The total number of bacteria obtained by culture of lung segments and the latters' histologic grade were closely correlated (rho = 0.79, p < 0.0001). PSB and BAL quantitative culture results were strongly correlated with lung tissue values (rho = 0.67 and 0.75, respectively; p < 0.0001). Using discriminative values of > or = 10(3) and > or = 10(4) bacteria/ml to define positive PSB and BAL cultures, respectively, these techniques identified lung segments yielding > or = 10(4) bacteria/g tissue with sensitivities of 82 and 91% and specificities of 89 and 78%, respectively. Moreover, upon direct observation, the percentage of BAL cells containing intracellular bacteria was closely correlated with the total number of bacteria obtained from corresponding lung samples (p < 0.001). These findings indicate that bronchoscopic PSB and BAL samples very reliably identify both qualitatively and quantitatively microorganisms present in lung segments with bacterial pneumonia, even when the infection develops as a superinfection in a patient already receiving antimicrobial treatment for several days.

Aged↗
PubMed1994

Mortality attributable to nosocomial infections in the ICU.

Although a direct relationship between nosocomial infection and mortality in intensive care unit (ICU) patients has not always been demonstrated formally, it is possible to conclude that nosocomial infections increase the risk of death in critically ill patients. A more precise analysis indicates that: 1) this effect is highly probable for pneumonia, doubtful for bacteremia, and uncertain for urinary tract infection; 2) risk increases with duration of stay in the ICU; 3) bacterial etiology modifies the risk; and 4) this effect is stronger in less severely ill patients, probably because the severity of underlying disease remains the most significant factor.

Bacteremia↗
PubMed1993

Characterization of intensive care unit patients using a model based on the presence or absence of organ dysfunctions and/or infection: the ODIN model.

OBJECTIVE: To evaluate the sensitivity, specificity and overall accuracy of a model based on the presence or absence of organ dysfunctions and/or infection (ODIN) to predict the outcome for intensive care unit patients. DESIGN: Prospective study. SETTING: General intensive care unit in a university teaching hospital. PATIENTS: 1070 consecutive, unselected patients. INTERVENTIONS: There were no interventions. MEASUREMENTS AND MAIN RESULTS: We recorded within the first 24 h of admission the presence or absence of dysfunction in 6 organ systems: respiratory, cardiovascular, renal, hematologic, hepatic and neurologic, and/or infection (ODIN) in all patients admitted to our ICU, thus establishing a profile of organ dysfunctions in each patient. Using univariate analysis, a strong correlation was found between the number of ODIN and the death rate (2.6, 9.7, 16.7, 32.3, 64.9, 75.9, 94.4 and 100% for 0, 1, 2, 3, 4, 5, 6 and 7 ODIN, respectively; (p < 0.001). In addition, the highest mortality rates were associated with hepatic (60.8%), hematologic (58.1%) and renal (54.8%) dysfunctions, and the lowest with respiratory dysfunction (36.5%) and infection (38.3%). For taking into account both the number and the type of organ dysfunction, a logistic regression model was then used to calculate individual probabilities of death that depended upon the statistical weight assigned to each ODIN (in the following order of descending severity: cardiovascular, renal, respiratory, neurologic, hematologic, hepatic dysfunctions and infection). The ability of this severity-of-disease classification system to stratify a wide variety of patients prognostically (sensitivity 51.4%, specificity 93.4%, overall accuracy 82.1%) was not different from that of currently used scoring systems. CONCLUSIONS: These findings suggest that determination of the number and the type of organ dysfunctions and infection offers a clear and reliable method for characterizing ICU patients. Before a widespread use, this model requires to be validated in other institutions.

Aged↗
PubMed1993

Nosocomial pneumonia in ventilated patients: a cohort study evaluating attributable mortality and hospital stay.

PURPOSE: Although nosocomial pneumonia is a common problem in intubated and ventilated patients, previous studies have not clearly demonstrated that nosocomial pneumonia actually results in increased mortality or prolongs hospitalization of these patients. In an attempt to answer these questions, we have performed a cohort study in which patients who developed nosocomial pneumonia and control subjects were carefully matched for the severity of underlying illness and other important variables. PATIENTS AND METHODS: Case patients were 48 ventilated patients with nosocomial pneumonia identified on the basis of results of protected specimen brush quantitative culture and identification of intracellular organisms in cells recovered by bronchoalveolar lavage. For matching cases and their respective controls, the following variables were used: age (+/- 5 years), Simplified Acute Physiologic Score (+/- 3 points), indication for ventilatory support, date of admission, and duration of exposure to risk. RESULTS: Successful matching was achieved for 222 of 240 (92.5%) variables. The mortality rate in cases was 26 of 48 (54.2%) compared with 13 of 48 (27.1%) in controls. The attributable mortality was 27.1% (95% confidence interval [CI], 8.3% to 45.9%; p < 0.01) and the risk ratio for death was 2.0 (95% CI, 1.61 to 2.49). The mean length of stay was 34 days for cases and 21 days for controls (p < 0.02). In the case of pneumonia due to Pseudomonas or Acinetobacter species, the mortality rate was 71.4%, the attributable mortality was 42.8% (95% CI, 14.5% to 69.0%), and the risk ratio was 2.50 (95% CI, 1.31 to 4.61). CONCLUSION: Pneumonias occurring in ventilated patients, especially those due to Pseudomonas or Acinetobacter species, are associated with considerable mortality in excess of that resulting from the underlying disease alone, and significantly prolong the length of stay in the intensive care unit.

Acinetobacter Infections↗
PubMed1993

Analysis of vancomycin entry into pulmonary lining fluid by bronchoalveolar lavage in critically ill patients.

Vancomycin penetration into the fluid lining the epithelial surface of the lower respiratory tract was studied by performing fiberoptic bronchoscopy with bronchoalveolar lavage on 14 critically ill, ventilated patients who had received the drug for at least 5 days. The apparent volume of epithelial lining fluid (ELF) recovered by bronchoalveolar lavage was determined by using urea as an endogenous marker. Vancomycin levels in ELF ranged from 0.4 to 8.1 micrograms/ml (mean, 4.5 micrograms/ml), while the mean simultaneous level of the drug in plasma was 24 micrograms/ml (range, 9 to 37.4 micrograms/ml). There was a significant relationship (r = 0.64, P < 0.02) between vancomycin levels in plasma and those in ELF, with a correlation whose slope (0.15) indicated that the blood-to-ELF ratio of drug penetration was 6:1. Using the albumin concentration in ELF as a marker of lung inflammation, we found that vancomycin penetration was higher in patients with ELF albumin values of > or = 3.4 mg/ml than in patients with normal values (< 3.4 mg/ml) (P < 0.02). These results suggest that the vancomycin distribution includes the ELF of the lower respiratory tract at a concentration that is dependent upon the levels in blood and the alveolar capillary membrane protein permeability. These concentrations were well above the MICs for most staphylococci and enterococci.

Aged↗
PubMed1993

High levels of interleukin-8 in the blood and alveolar spaces of patients with pneumonia and adult respiratory distress syndrome.

There is ample experimental evidence that polymorphonuclear neutrophils (PMN) play a critical role in the pathogenesis of the adult respiratory distress syndrome (ARDS). Since interleukin-8 (IL-8) is a strong chemotactic factor for PMN, we measured IL-8 levels in plasma and bronchoalveolar lavage (BAL) fluid of 18 patients, 12 with ARDS and 6 with severe pneumonia uncomplicated by ARDS, all of whom had an increased number of PMN in BAL fluid. Seven healthy subjects served as controls. We found elevated levels of IL-8 in the alveolar spaces of all patients tested. Elevated BAL IL-8 levels were related to a fatal outcome and the presence of shock and correlated with a general clinical severity index (simplified acute physiological score). BAL fluid levels of IL-8 were significantly higher in patients with ARDS than in patients with pneumonia. In plasma, IL-8 levels were increased similarly in all patients and did not correlate with survival or the presence of shock. The BAL fluid-to-plasma ratio of IL-8 was significantly greater than that of tumor necrosis factor alpha, indicating higher local production of IL-8. Moreover, the presence of a primed subpopulation of blood PMN with respect to H2O2 production indicates that IL-8 may contribute to the neutrophil-mediated process in the pathogenesis of ARDS and pneumonia.

Adult↗
PubMed1993

Follow-up protected specimen brushes to assess treatment in nosocomial pneumonia.

To prospectively determine the bacteriologic and clinical efficacy of antimicrobial therapy for nosocomial bacterial pneumonia selected based upon information provided by cultures of protected specimen brush (PSB) samples obtained during bronchoscopy, 76 consecutive patients with ventilator-associated pneumonia were studied using follow-up quantitative PSB cultures obtained after 3 days of treatment. Of the 173 microorganisms initially present in the PSB samples, only 11 (6%) were not eradicated by antimicrobial therapy, including three recovered at high (> or = 10(3) cfu/ml) concentrations. Thirty-two emerging pathogens, including nine at high concentrations, were also detected; 26 of them (81%) were resistant to the initial antibiotics administered. Of the 76 patients included in the study, cultures of follow-up PSB samples identified 51 in whom the infection site in the lung was completely sterilized, 16 with low-grade infection, and only nine with persistent high-grade infection. Analysis of clinical outcome within the 15 days after the initiation of antimicrobial therapy demonstrated clinical improvement in 62 of 67 (93%) patients in whom the site of infection was contained by treatment as compared with four of 9 (44%) patients with persistent high-grade infection (p < 0.01). These data suggest that appropriate antimicrobial therapy for ventilator-associated pneumonia results in the control of the initial infection in 88% of the patients. However, an early superinfection caused by multiresistant pathogens can occur in a small subset of these patients. When follow-up PSB cultures were negative, an improved outcome was noted.

Adolescent↗
PubMed1993

Evaluation of clinical judgment in the identification and treatment of nosocomial pneumonia in ventilated patients.

To evaluate the accuracy of clinical judgment in the diagnosis and treatment of nosocomial pneumonia in ventilated patients, we studied 84 patients suspected of having nosocomial pneumonia because of the presence of a new pulmonary infiltrate and purulent tracheal secretions. We prospectively evaluated the accuracy of diagnostic predictions and therapeutic plans independently formulated by a team of physicians aware of all clinical, radiologic and laboratory data, including the results of Gram-stained bronchial aspirates. Definite (n = 51) or probable (n = 33) diagnoses could be established in all patients by strict histopathologic and/or bacteriologic criteria. Only 27/84 patients were diagnosed as having pneumonia. Organisms responsible for pneumonias were identified by quantitative cultures of samples obtained using a protected specimen brush or pleural fluid cultures. Four hundred eight predictions were made for the 84 studied patients. Clinical diagnoses for patients subsequently diagnosed as having pneumonia were accurate in 81/131 cases (62 percent). Furthermore, only 43/131 (33 percent) therapeutic plans proposed for these patients represented effective therapy. Common causes of inappropriate treatment included failure to diagnose pneumonia (50 plans), failure to effectively treat highly resistant organisms (21 plans), and failure to treat all organisms in cases of polymicrobial pneumonia (14 plans). Therapeutic plans formulated for patients without pneumonia included the unnecessary use of antibiotics in 45/277 cases (16 percent). These findings indicate that the use of clinical criteria alone does not permit the accurate diagnosis of nosocomial pneumonia in ventilated patients, and commonly results in inappropriate or inadequate antibiotic therapy for these patients.

Bacterial Infections↗
PubMed1993

Pilot study of cardiopulmonary risk from pentoxifylline in adult respiratory distress syndrome.

Neutrophils and cytokines are directly involved in the pathophysiology of adult respiratory distress syndrome (ARDS). Pentoxifylline (PTX) has been shown in vitro to protect against the inflammatory effects of neutrophils and cytokines. The same protective effects have been demonstrated on animal models of lung injury. These results suggested that PTX might be useful in patients with ARDS. The cardiopulmonary effects of large doses of PTX were evaluated in a pilot study performed in six patients with severe ARDS. PTX was administered with an initial 1-mg/kg bolus, followed by infusion of 1.5 mg/kg/h over 6 h. No significant change was observed in the gas exchange and hemodynamic parameters, except for a 10 percent increase in the heart rate during the infusion period. Our results demonstrate that large doses of PTX induced only minor hemodynamic changes without worsening in pulmonary gas exchange. Further studies are warranted to evaluate human safety and ultimately the effectiveness of PTX in the treatment of ARDS.

Aged↗
PubMed1992

Procedures for the diagnosis of pneumonia in ICU patients.

The optimal technique for diagnosing nosocomial bacterial pneumonia in critically ill patients cared for in the intensive care unit remains unclear, especially in the subgroup of patients requiring mechanical ventilation. An important advance has been the development of the protected specimen brush technique. Secretions obtained using this technique and evaluated by quantitative cultures are useful in distinguishing patients with and without pneumonia. However, this procedure has important limitations in that results are not available immediately, and in that a few false negative of false positive results may occur. Bronchoalveolar lavage has been suggested to be of value in establishing the diagnosis of pneumonia, because the cells and liquid recovered can be examined microscopically immediately after the procedure and are also suitable for quantitative culture. Microscopic identification of bacteria within cells recovered by lavage may provide a sensitive and specific means for the early and rapid diagnosis of pneumonia in this setting. The lavage technique can also be conveniently incorporated into a protocol along with quantitative culture of samples obtained using the protected specimen brush. This combination will probably improve the overall accuracy of diagnosis while allowing the administration of prompt empiric antimicrobial therapy in most patients with pneumonia.

Bacteriological Techniques↗