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Biomedical subjects

B Guery

Publications and source records attributed to B Guery.

At least 19 recordsLinked to original sources

[Quorum sensing: a new clinical target for Pseudomonas aeruginosa?].

Pseudomonas aeruginosa is an opportunistic bacteria causing a wide variety of infections. The bacterial virulence depends on a large panel of cell-associated and extracellular factors. Quorum sensing (QS) allows cell-to-cell communication: sensing the environment, this system coordinates the expression of various genes within the bacterial population. QS is based on an interaction between a small diffusible molecule, an acylhomoserine lactone (AHL), and a transcriptionnal activator. Two QS systems, the las and rhl systems, have been identified in P. aeruginosa. The las system associates the transcriptionnal activator protein LasR and LasI responsible for the synthesis of a specific AHL: C12-HSL. This system was shown to activate the expression of a large number of virulence factors. Similarly, the rhl system associates the transcriptionnal activator protein RhlR with RhlI, which is responsible for the synthesis of another AHL: C4-HSL. Synthesis and secretion of a number of virulence factors are controlled by QS. Utilization of different animals models showed the crucial role of QS in the pathogenesis of P. aeruginosa infections. The discovery of QS has given a new opportunity to treat bacterial infection by another means than growth inhibition. New drugs inhibiting QS were recently discovered: furanone compounds can repress a large number of QS-regulated genes, including numerous P. aeruginosa virulence factor genes. Furanone administration to mice infected with P. aeruginosa significantly reduced lung bacterial load compared with the control group.

Cell Communication↗

Effect of different stabilized preparations of peracetic acid on biofilm.

The effect of three stabilized peracetic acid (PAA) preparations (Bioxal M), with or without surfactants, on an Escherichia coli biofilm model was studied. The biofilm was prepared in glass tubes, and was evaluated indirectly using spectrophotometry. The ability of the products to fix or remove the biofilm was determined by their detergent activity (DA). None of the preparations tested fixed the biofilm. The effect of Bioxal M-1 on the biofilm was equivalent to the control (sterile water). Bioxal M-2 and Bioxal M-3 displayed slightly positive DAs. Non-ionic surfactant improved the DA of the products. Regardless of disinfectant activity, PAA agents display different DAs depending on their formulation. This criterion could be used to select the weakest biofilm-fixing agents. Users should therefore be concerned about the efficiency of the cleaning stage of medical devices. When choosing PAA products, non-fixing ability should be considered in addition to antimicrobial activity.

Biofilms↗

[Pseudomonas aeruginosa and Surfactant-associated Proteins A and D].

Surfactant-associated proteins A and D (SP-A and SP-D) are two pulmonary collectins that bind to bacterial, fungal and viral pathogens and have multiples classes of receptors on pneumocyte and macrophage membrane. They are chemoattractant for phagocytes, enhance uptake and killing of bacteria by macrophages and neutrophils. These molecules also act as activation ligand on macrophages and neutrophils to enhance phagocytosis, resulting in an increased bacterial clearance. Depending on activation of cells by stimuli, SP-A and SP-D modulate production of antimicrobial free radicals by phagocytes and secretion of cytokines. In vivo, SP-A deficient mice infected with Pseudomonas aeruginosa (P. aeruginosa) have decreased bacterial clearance and exacerbated inflammatory response in the lungs. Serious alterations in macrophages and increased production of reactive oxygen species were found in non-infected SP-D deficient mice. Patients with cystic fibrosis are frequently colonized by P. aeruginosa. Decreased levels of SP-A and SP-D have been measured in bronchoalveolar lavage fluid of these patients, as well as patients with acute pneumonia but no chronic lung disease. P. aeruginosa secretes various proteases, among them, elastase and protease IV have been found to degrade SP-A and SP-D and abrogate their immune function. However, further investigations are necessary to examine whether these deficiencies facilitate P. aeruginosa infections or stand as consequences.

Animals↗

[Acute invasive pulmonary aspergillosis in chronic lung disease--a review].

INTRODUCTION: Apart from malignancies and solid organ transplant, chronic lung disease, in particular chronic obstructive pulmonary disease (COPD), is a third important predisposing factor for acute invasive pulmonary aspergillosis. STATE OF THE ART: COPD is present in 2% of patients dying from invasive aspergillosis. This opportunistic infection occurs because of an immunodeficiency linked both to altered local immunity and to systemic factors such as long term steroid treatment and malnutrition. In patients whose sputum and/or endotracheal aspirate specimens contain hyphal forms of filamentous Aspergillus, half will have a clinically significant aspergillus infection. Diagnostic tests include serum galactomannan antigen test, serum antibody titre, thoracic CT scan and bronchoalveolar lavage (BAL). The identification of fungal hyphae in BAL fluid by microscopy and/or on culture is critical for a positive diagnosis. The mortality rate for acute invasive pulmonary aspergillosis in chronic lung diseases reaches almost 100%. Antifungal monotherapy is still recommended as a first line treatment. Combined treatment can be used in refractory aspergillosis as a salvage therapy. The question of maintaining, decreasing or interrupting steroid treatment must be considered. PERSPECTIVES: Prospective studies are needed to evaluate a standardised diagnostic strategy such as exists for patients with haematological disease. Whether this will improve prognosis remains to be seen. CONCLUSION: Acute invasive pulmonary aspergillosis complicating chronic lung disease is not rare. Improved diagnosis procedures and recent therapeutic advances may have a positive impact on patient prognosis.

Antifungal Agents↗

Diagnostic and prognostic values of admission procalcitonin levels in community-acquired pneumonia in an intensive care unit.

BACKGROUND: Measurement of procalcitonin (PCT) has been studied for several years in infectious diseases. Some studies have focused on community-acquired pneumonia (CAP) but only one was conducted in critically ill patients hospitalized in an intensive care unit (ICU). PATIENTS AND METHODS: To determine the diagnostic and prognostic role of PCT in patients admitted in an intensive care unit for severe CAP, 110 patients hospitalized in our unit were prospectively studied. Within 48 hours following ICU admission, PCT serum level was measured with a quantitative method above a threshold value of 0.5 ng/ml. RESULTS: Initially focusing on the diagnostic value of PCT, 20% of the patients had a serum PCT level <0.5 ng/ml, 30% between 0.5 ng/ml and 2 ng/ml, and 50%>/=2 ng/ml. Serum PCT level was higher in microbiologically documented CAP (median=4.9 ng/ml vs 1.5 ng/ml if no bacteria were found; p=0.001), but was not predictive of any specific bacterial agent. Concerning the prognostic value, the serum PCT level was higher for bacteremic patients and/or septic shock patients (4.9 ng/ml vs 1.5 ng/ml; p=0.0003). Moreover, PCT levels were increased in patients who developed, during their ICU stay, infection-related complications (septic shock, multiorgan dysfunction, acute respiratory distress syndrome and disseminated intravascular coagulation). Finally, the initial PCT level was significantly higher in patients who died during the ICU stay (5.6 ng/ml vs 1.5 ng/ml; p<0.0001). Such a relationship was not found with C-reactive protein (CRP). CONCLUSION: In ICU patients admitted for severe CAP, initial PCT values could be an interesting predictor for complications and mortality.

Adult↗

[Surgical antimicrobial prophylaxis: compliance to guidelines and impact of targeted information program].

OBJECTIVES: Surgical antimicrobial prophylaxis is used to decrease postoperative wound infection. We assessed the compliance to surgical antimicrobial prophylaxis guidelines in our hospital and the impact of an information program. PATIENTS AND METHODS: Observational study of clean or clean contamined surgery, during two 3-week periods, separated by a targeted information period. The following data were collected prospectively: prophylaxis indication, antimicrobial agent, timing, dose, route and duration of prophylaxis. Chi square test was used for analysis or Fischer test when available. RESULTS: Four hundred seventy-seven patients were enrolled - 270 and 207 for each period respectively. For both periods only 49% of prophylaxis was appropriated. When prophylaxis should be administered - 15 and 13% of patients for each period - it was antibioprophylaxy was strictly adequate with recommandations. The most common error was administration timing. Only the choice of antimicrobial agent was optimized after information period. DISCUSSION: These results are consistent with previous studies. Information program alone have no effect on the good use of antimicrobial for surgical prophylaxis. Only a policy associating organization, restriction and education could improve practices.

Adult↗

Inhaled nitric oxide modulates leukocyte kinetics in the mesenteric venules of endotoxemic rats.

OBJECTIVE: to determine whether inhaled nitric oxide (NO) would alter leukocyte kinetics in the septic microvasculature. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Male Sprague Dawley rats. INTERVENTIONS: Rats were treated with either saline or endotoxin (10 mg/kg, iv) and then allowed to breathe either air or air plus NO (10 ppm). MEASUREMENTS AND MAIN RESULTS: After a 4-hr period, rolling, firm adhesion, and emigration of leukocytes and endothelial dysfunction were monitored in mesenteric venules by using intravital videomicroscopy. Compared with controls, endotoxemic rats exhibited a profound influx in mesenteric venule rolling leukocytes (55+/-17 vs. 70+/-19 leukocytes/min; p < .05), associated with a reduction of leukocyte rolling velocity (83+/-14 vs. 34+/-3 microm/sec; p < .05). In endotoxemic rats, venular endothelium leukocyte firm adhesion (1.15+/-0.32 vs. 4.08+/-0.96 leukocytes/ 100 microm; p < .05) and emigration (0.84+/-0.47 vs. 4.23+/-1.2 leukocytes/100 microm; p < .05) increased compared with controls. Inhaled NO had no effect on leukocyte kinetics in control rats. Inhaled NO significantly attenuated endotoxin-induced venular endothelium leukocyte adhesion (4.08+/-0.96 vs. 1.86+/-0.76 leukocytes/100 microm; p < .05) and emigration (4.23+/-1.2 vs. 1.68+/-0.72 leukocytes/100 microm; p < .05). Compared with control rats, macromolecular (FITC-dextran) vascular leakage, expressed as the perivenular/intravenular fluorescence intensity ratio, increased in endotoxemic rats (0.56+/-0.02 vs. 0.81+/-0.05; p < .01). Endotoxin-induced macromolecular vascular leakage increases were partially prevented by inhaled NO (0.66+/-0.01 vs. 0.56+/-0.02; p < .05). CONCLUSION: These observations suggest that inhaled NO reduces leukocyte adhesion and the degree of vascular permeability dysfunction in mesenteric venule of endotoxemic rats.

Administration, Inhalation↗

Escherichia coli endotoxin reduces cytochrome aa3 redox status in pig skeletal muscle.

OBJECTIVE: To assess the effect of endotoxin on cytochrome aa3 (Caa3) redox status in a controlled blood flow preparation of pig isolated hindlimb, at a constant oxygen delivery (Do2limb) (constant flow period) and during progressive ischemia (decreasing flow period). DESIGN: Randomized, controlled experimental study. SETTING: University hospital experimental laboratory. SUBJECTS: Ten piglets. INTERVENTIONS: Hindlimb blood flow was restricted to the femoral vessels. The arterial femoral blood flow coming from the carotid artery was controlled by a roller occlusive pump. The femoral venous blood flow was returned to the jugular vein. During the first 100 mins, the hindlimb blood flow was maintained at a normal level and then decreased stepwise. Animals were randomized to receive 150 microg/kg endotoxin lipopolysaccharide (LPS; n = 5) or saline (control; n = 5). MEASUREMENTS AND MAIN RESULTS: Hindlimb muscle Caa3 redox status was monitored by near-infrared spectroscopy. Hindlimb Do2limb and oxygen consumption (Vo2limb) were calculated. In the LPS group, a rapid reduction of Caa3 redox status was observed after LPS administration, whereas the hindlimb blood flow remained normal with no change in Do2limb and Vo2limb. A progressive simultaneous decrease in Do2limb and Vo2limb was observed during the decreasing flow period with no further reduction in Caa3 redox status. In the control group, no change was observed in Caa3, Do2limb, or Vo2limb during the constant flow period. During the decreasing flow period, Caa3 redox status was reduced as Do2limb and Vo2limb decreased. CONCLUSION: Our results suggest that endotoxin may induce a reduction of Caa3 redox status independently of Do2 and Vo2.

Animals↗

Inhaled NO reduces leukocyte-endothelial cell interactions and myocardial dysfunction in endotoxemic rats.

Inhaled nitric oxide (NO) has been shown to have some protective effect in the peripheral distal inflamed vasculature. The objective of the study was to determine whether inhaled NO would reduce endotoxin-induced leukocyte activation and myocardial contractile dysfunction. Rats were treated with either saline or endotoxin (10 mg/kg iv) and then allowed to breathe (4 h) either air or air plus NO (10 ppm). In endotoxemic rats, mesenteric venular endothelium leukocyte firm adhesion increased compared with control rats (1.15 +/- 0.32 vs. 4.08 +/- 0.96 leukocytes/100 microm; P < 0.05). Inhaled NO significantly attenuated endotoxin-induced venular endothelium leukocyte adhesion (4.08 +/- 0.96 vs. 1.86 +/- 0.76 leukocytes/100 microm; P < 0.05) and FITC-conjugated anti-intercellular adhesion molecule-1 fluorescence intensity. Endotoxin-induced myocardial dysfunction and leukocyte content increases were reduced in inhaled NO-treated rats. These observations suggest that inhaled NO reduces the degree of cardiovascular dysfunction and inflammation in endotoxemic rats.

Administration, Inhalation↗

Predisposing factors for nosocomial pneumonia in patients receiving mechanical ventilation and requiring tracheotomy.

STUDY OBJECTIVES: To assess the incidence of nosocomial pneumonia (NP) after tracheotomy in an ICU population and to determine NP risk factors during the ICU stay, particularly on the day of tracheotomy. DESIGN: A retrospective study using prospectively collected data. SETTING: A 16-bed multidisciplinary ICU. PATIENTS: One hundred thirty-five patients requiring tracheotomy for mechanical ventilation (MV) weaning. RESULTS: The mean (+/- SD) duration of MV before tracheotomy was 17.8 +/-13.4 days. Thirty-seven cases of NP occurred in 35 patients (25.9%), 8.7+/-7.3 days after the tracheotomy procedure. NP cases were classified as early NP (n = 19) if they occurred within 5 days after the procedure (mean, 2.7+/-1.1 days), and as late NP (n = 18) if they occurred beyond the fifth day (mean, 14.4+/-6.1 days). Multivariate analysis identified the following three independent factors associated with early NP: the presence of positive endotracheal aspirates (EAs) with pathogen levels of > or =10(5) cfu/mL (p = 0.0001); hyperthermia (temperature, > or =38.3 degrees C; p = 0.002) on the day of tracheotomy; and the continuation of sedation beyond 24 h after the tracheotomy (p = 0. 0001). Accountable pathogens of early NP were present in EA on the day of tracheotomy (p = 0.001). Cases of late NP were significantly associated with the duration of sedation before the procedure (p = 0. 002) and with hyperthermia (temperature, > or =38.3 degrees C) on the day of tracheotomy (p = 0.0005). The ICU admitting diagnosis, previous NP, duration of administration of antimicrobial agents and MV before tracheotomy, indication for tracheotomy, PO(2)/fraction of inspired oxygen ratio, and use of steroids on the day of the procedure were not associated with the occurrence of NP. The mortality rate of our population was 33.3%, and NP increased this percentage to 54.3%. CONCLUSIONS: Our results could suggest that tracheotomy should be delayed in mechanically ventilated patients with bronchial colonization and hyperthermia, when sedation cannot be discontinued after the procedure, to prevent occurrence of early NP.

Adult↗

Epidemiological features and prognosis of severe community-acquired pneumococcal pneumonia.

OBJECTIVE: To describe risk factors of severe pneumococcal community-acquired pneumonia and to study variables influencing outcome. DESIGN: Retrospective (1987-1992) and prospective (1993-1995) study. SETTING: Three participating ICUs from primary care hospitals. PATIENTS: Five hundred and five patients (mean age: 63 +/- 17 years) with severe community-acquired pneumonia (CAP). Three groups of patients were defined: pneumococcal CAP (group 1), CAP with microbial diagnosis other than Streptococcus pneumoniae (group 2), CAP from group 2 and CAP without microbial diagnosis (group 3). MEASUREMENTS AND RESULTS: Admission data and data on the disease's course were recorded. The mean Simplified Acute Physiologic Score (SAPS) was 12.5 +/- 5.4. On admission 288 (57 %) patients were mechanically ventilated (mv) and 82 (16.2 %) required inotropic support. A microbial diagnosis was established for 309 (61.2%) patients. S. pneumoniae was isolated in 137 (27.1%) patients. Severe pneumococcal CAP was independently associated with male sex (p = 0.01), lack of antibiotics use before admission (p = 0.0001), non-aspiration pneumonia (p = 0.01) and septic shock (p = 0.0001). The overall mortality rate was 27.5 % (29.2 % in group 1). In patients with severe pneumococcal CAP, multivariate analysis showed that leukopenia less than 3,500/mm3 (p = 0.0004), age over 65 years (p = 0.01), septic shock (p = 0.01), sepsis related complications (p = 0.0001), ICU complications (p = 0.001) and inadequacy of antimicrobial therapy (p = 0.002) worsened the prognosis. CONCLUSIONS: Few features facilitate the identification of pneumococcal CAP on ICU admission. The prognosis is mostly related to severity of illness (leukopenia, septic shock) while comorbidities do not seem to influence outcome. Sepsis-related disorders, ICU complications and adequate antimicrobial chemotherapy are the major variables affecting the outcome during an ICU stay.

APACHE↗

Effect of hospital-acquired ventilator-associated pneumonia on mortality of severe community-acquired pneumonia.

PURPOSE: The purpose of this article is to evaluate, using two pairwise case-control studies, attributable mortality linked to hospital-acquired ventilator-associated pneumonia (HA-VAP) complicating the intensive care unit (ICU) stay of patients exhibiting severe community-acquired pneumonia (CAP). MATERIALS AND METHODS: Over an 11-year period, 498 patients with severe CAP were collected. Among them, 43 exhibited HA-VAP. In a first case-control study, these patients were matched with control on the basis of six confounding variables known to be general ICU prognosis factors. In a second case-control study, six variables specifically linked to CAP prognosis were used for matching. RESULTS: In the two case-control studies, each case patient was matched with one control patient. In the first analysis, success of matching was achieved in 198 of 258 (77%) variables used for matching. In the second analysis, matching was successful for 242 of 258 (94%) confounding variables used. Eighteen patients died, compared with, respectively, 6 (P = .003) and 7 (P = .01) controls. Attributable mortality of HA-VAP was similar in the two pairwise analyses, respectively, 28% (risk ratio = 3.0; 95% confidence interval, 1.32 to 6.82) and 26% (risk ratio = 2.57; 95% confidence interval, 1.2 to 5.52). CONCLUSION: When confounding factors were controlled, HA-VAP appeared to increase mortality of severe CAP requiring ICU admission.

Aged↗

Community-acquired pneumonia in the intensive care unit: epidemiological and prognosis data in older people.

OBJECTIVES: To compare epidemiological data, etiology, and prognosis of severe community-acquired pneumonia (CAP) in the intensive care unit (ICU) according to age (< or > or = 65 years) and to determine prognostic factors of CAP in older people. DESIGN: A retrospective (1987-1992) and prospective (1993-95) multicenter study. SETTING: Six ICUs in the north of France. PATIENTS: Five hundred five patients admitted to an ICU for severe CAP. MEASUREMENTS: Patient characteristics were compared with regard to age. Prognosis of CAP in older patients was studied by stepwise discriminant analysis. RESULTS: Two hundred seventy-eight patients (55%) were aged 65 years or older. Comparison of epidemiological data between older and younger patients revealed a higher prevalence of women (38% vs 29%), more severe underlying comorbidities (anticipated death within 5 years: 59% vs 26%), and more frequent chronic respiratory insufficiency (48% vs 33%) in the older patients. In this study group, 224 organisms were isolated from 172 patients (62%); those identified most frequently were Gram-negative bacilli (34%), S. pneumoniae (32%), and Staphylococcus sp. (19%). Compared with younger patients, no significant differences in bacteriological data were observed. However, crude and attributable mortality rates were significantly higher in the older patients (33% vs 21% and 30% vs 19%, respectively). Prognosis analysis identified four independent predictors of mortality in the older patients: initial septic shock (relative risk (RR) = 3), sepsis-related complications (RR = 4.3), hospital-acquired lower respiratory tract superinfections (RR = 2), and nonspecific pneumonia-related complications (RR = 2.8). CONCLUSION: The bacterial etiology provides some approaches to empirical therapy for older patients with severe community-acquired pneumonia. In addition, the inappropriateness of withholding intensive care for reasons of age alone is emphasized.

Age Factors↗

Inhaled NO preadministration modulates local and remote ischemia-reperfusion organ injury in a rat model.

Inhaled nitric oxide (iNO) has been shown to have a protective effect in lung ischemia-reperfusion (I/R)-induced injuries. We studied the role of iNO (10 parts/million for 4 h) administered before I/R. In an isolated perfused lung preparation, iNO decreased the extravascular albumin accumulation from 2,059 +/- 522 to 615 +/- 105 microl and prevented the increase in lung wet-to-dry weight ratio. To study the mechanisms of this prevention, we evaluated the role of nitric oxide (NO) transport and lung exposure with matched experiments by using either lungs or blood of animals exposed to iNO and blood or lungs of naive animals. iNO-exposed blood with naive lungs did not limit the extravascular albumin accumulation (2,561 +/- 397 microl), but iNO-exposed lungs showed a leak not significantly different from the group in which both lungs and blood were iNO exposed (855 +/- 224 vs. 615 +/- 105 microl). An improvement in heart I/R left ventricular developed pressure in the animals exposed to iNO showed that blood-transported NO was, however, sufficient to trigger remote organ endothelium and reduce the consequences of a delayed injury. In conclusion, preventive iNO reduces the consequences of lung I/R injuries by a mechanism based on tissue or endothelium triggering.

Administration, Inhalation↗