[Detection of nasal colonization methicillin-resistant Staphylococcus aureus: a prospective study comparing real-time genic amplification assay vs selective chromogenic media]. / Détection de la colonisation nasale de Staphylococcus aureus résistant à la méthicilline : étude prospective comparant l'amplification génique temps réel vs les milieux chromogènes sélectifs.

UNLABELLED: In contrast to "classical" genic amplification, real-time genic amplification can be performed in every laboratory without the need of sophisticated isolation procedures. Moreover, real-time genic amplification allows an early detection of meticillin resistant Staphylococcus aureus colonization, 2 hours compared to 1 or 2 days for culture. OBJECTIVE: In order to assess the feasibility on Smartcycler of the IDI-MRSA real-time genic amplification assay in comparison with chromogenic media. METHODS: A prospective study has been initiated in July 2004: nasal swabs were taken from patients entering the ICU, vascular surgery, diabetology and geriatry wards. During a 4 months period, 682 specimens have been obtained from 508 patients. RESULTS: Sixty-four (9.3%) patients were positive by genic amplification and selective agar culture (CHROMagar MRSA, MRSASelect and/or ORSAB), 19 (2.9%) were positive by genic amplification only (3 of these patients were under antibiotic treatment); 572 specimens remained negative by both methods. The sensitivity and specificity of this assay were 100% and 96% respectively with a positive predictive value of 70% and negative predictive value of 100%. Initially 82 nasal specimens were unresolved (12%). 38 were resolved following a freeze-thaw cycle. Thus, 44 (6.4%) were unresolved specimens. Comparison between CHROMagar MRSA and MRSASelect showed a good correlation for the detection at 24 hours (5.5% and 5.6% respectively). These two chromogenic media allowed a much better detection of MRSA than ORSAB medium within 24H. CONCLUSION: The results obtained by the early real-time genic amplification for the detection of meticillin resistant Staphylococcus aureus are promising. Despite 6.4% amplification failure, we consider that IDI-MRSA real-time genic amplification assay represents a significant breakthrough in the detection of colonization.

Usefulness of a strategy based on bronchoscopy with direct examination of bronchoalveolar lavage fluid in the initial antibiotic therapy of suspected ventilator-associated pneumonia.

OBJECTIVES: To evaluate (a) the routine accuracy of bronchoalveolar lavage by direct examination (BAL-D) in diagnosing ventilator-associated pneumonia (VAP), and (b) the impact of a diagnostic strategy including clinical judgment, bronchoscopy, and BAL-D on the initial diagnosis and appropriateness of treatment when VAP is suspected. DESIGN AND SETTING: Prospective cohort study in two academic ICUs in Paris, France. PATIENTS AND PARTICIPANTS: Mechanically ventilated patients with suspected VAP underwent bronchoscopy with BAL and protected specimen brush (PSB). BAL-D results were available within 2 h, BAL on culture and PSB results after 24 h, and antibiotic susceptibility after 48 h. At each step in the strategy the senior and the resident in charge of the patient were asked their diagnosis and their therapeutic plan on the basis of presently available data. Definite diagnosis of suspected VAP was based on histology, appearance of cavitation, positive pleural fluid culture, results of PSB and BAL culture, and follow-up. MEASUREMENT AND RESULTS: A total of 110 episodes of suspected VAP were studied; 94 definite diagnoses were made (47 VAP, 47 no VAP). Using a threshold 1% of infected cells, BAL-D discriminated well between patients with and those without VAP (sensitivity 93.6%, specificity 91.5%, area under the receiver-operating characteristic curve 0.953). The senior clinical judgment was correct in 71% cases. It was correct in 78% and 94% of cases after airway visualization and BAL-D findings, respectively. After BAL-D the positive and negative predictive values in diagnosing VAP were 90% and 98%, respectively. However, the therapeutic plan was correct in only 65% using clinical judgment (15 untreated patients, 3 ineffective treatment, 15 useless treatment), 66% using airway visualization (14 untreated VAP, 4 ineffective treatment, 14 useless treatment), and 88% using BAL-D results (1 untreated patients, 6 ineffective, 4 useless), according to definite diagnosis and final antibiotic susceptibility testings. CONCLUSIONS: A strategy based on bronchoscopy and BAL-D generally leads to a rapid and appropriate treatment of nosocomial pneumonia in ventilated patients.

A one-year prospective study of nosocomial bacteraemia in ICU and non-ICU patients and its impact on patient outcome.

A one-year, prospective, two-observational cohort study was performed to evaluate the incidence and outcome in hospitalized patients (ICU and non-ICU) of nosocomial bacteraemia, and to assess its prognostic value in the ICU group. A group of 18 098 hospitalized patients and a group of 291 consecutive ICU patients were followed. Prognostic factors were determined using single and multivariable analyses. 109 (90 non-ICU and 19 ICU) patients developed 118 nosocomial bacteraemic episodes. The incidence of nosocomial bacteraemia was 6.0 per 1000 admissions (95% confidence interval (CI): 5-7%) and 65 per 1000 admissions in ICU patients (95% CI: 4.5-8.5%). Gram-positive and Gram-negative bacteria were 63/133 (47%) and 70/133 (53%) of the isolated micro-organisms respectively. Crude mortality rates were 41/109 (38%) with adverse outcome associated with mechanical ventilation (OR: 3.6; 95% CI: 1.4-9.2, P =0.01), neutropenia (OR: 7.7; 95% CI: 0.8-73.1;P =0.07) while gastro-intestinal surgery was associated with an improved outcome (OR: 0.4; 95% CI: 0.16-0.96;P =0.04). Of the 291 ICU patients, 19 acquired 22 episodes of nosocomial bacteraemia, and 18 were referred from the wards with documented nosocomial bacteraemia. Of these 37 bacteraemic patients, 17 (46%) died. When adjusting for predictors of death (SAPS II>/=40, cardiac and neurological failure), nosocomial bacteraemia markedly influence the outcome in ICU patients (OR: 3.4; 95% CI: 1.3-8.7;P =0.010). This study suggests that the outcome of nosocomial bacteraemia in hospitalized patients is poor in ventilated and neutropenic patients and that nosocomial bacteraemia per se influenced outcome in ICU patients.

Procalcitonin (PCT) is useful in predicting the bacterial origin of an acute circulatory failure in critically ill patients.

OBJECTIVE: To evaluate the accuracy of procalcitonin (PCT) in predicting bacterial infection in ICU medical and surgical patients. SETTING: A 10-bed medical surgical unit. DESIGN: PCT, C-reactive protein (CRP), interleukin 6 (IL-6) dosages were sampled in four groups of patients: septic shock patients (SS group), shock without infection (NSS group), patients with systemic inflammatory response syndrome related to a proven bacterial infection (infect. group) and ICU patients without shock and without bacterial infection (control group). RESULTS: Sixty patients were studied (SS group:n=16, NSS group,n=18, infect. group,n=16, control group,n=10). The PCT level was higher in patients with proven bacterial infection (72+/-153 ng/ml vs 2.9+/-10 ng/ml,p=0.0003). In patients with shock, PCT was higher when bacterial infection was diagnosed (89 ng/ml+/-154 vs 4.6 ng/ml+/-12,p=0.0004). Moreover, PCT was correlated with severity (SAPS:p=0.00005, appearance of shock:p=0.0006) and outcome (dead: 71.3 g/ml, alive: 24.0 g/ml,p=0.006). CRP was correlated with bacterial infection (p<10(-5)) but neither with SAPS nor with day 28 mortality. IL-6 was correlated with neither infection nor day 28 mortality but was correlated with SAPS. Temperature and white blood cell count were unable to distinguish shocked patients with or without infection. Finally, when CRP and PCT levels were introduced simultaneously in a stepwise logistic regression model, PCT remained the unique marker of infection in patients with shock (PCT> or =5 ng/ml, OR: 6.2, 95% CI: 1.1-37,p=0.04). CONCLUSION: The increase of PCT is related to the appearance and severity of bacterial infection in ICU patients. Thus, PCT might be an interesting parameter for the diagnosis of bacterial infections in ICU patients.

Hemodynamic profile in severe ARDS: results of the European Collaborative ARDS Study.

OBJECTIVE: Although the acute respiratory distress syndrome (ARDS) was identified as long as 30 years ago, potential therapeutic objectives have been defined from small series rather than large trials. Moreover, relationships between ARDS and hemodynamics are unclear. The European Collaborative ARDS Study was designed to identify factors influencing the pathogenesis, severity, and prognosis of ARDS. Analysis of the hemodynamic profiles collected during this study and of their contribution to the above-mentioned facets of ARDS is the focus of the present report. DESIGN: Prospective clinical study. SETTING: 38 European intensive care units (ICUs). PATIENTS AND METHODS: We collected 2758 sets of data from 586 patients, including baseline data, data on proven or suspected causes of ARDS differentiating direct and nondirect lung injury, and data on baseline status including multiple organ dysfunction (MOD) with differentiation of primary ARDS from ARDS secondary to severe systemic disorders. Events during follow-up were also recorded, including whether the acute respiratory failure did or did not improve after 24 h (groups A and B, respectively). When available, hemodynamic data were recorded at enrollment (day 0), on days 1-3, 7, 14, and 21, and at discharge or at the time of death in the ICU. RESULTS: Although the rate of pre-existing disease and the nature and rate of complications varied widely among etiologic categories, differences in the hemodynamic profile occurred only between primary and secondary ARDS. Both at inclusion and during the course of the illness, variables that were used to investigate Va/Q mismatch [arterial oxygen tension (PaO2, arterial oxygen saturation, right-to-left shunt, and the PaO2/fractional inspired oxygen (FIO2) ratio] predicted survival. High pulmonary artery pressure (PAP) and low systemic artery pressure (SAP) were also related to the prognosis. In the logistic regression model including hemodynamic and oxygen-related variables, however, the only independent predictors of survival were the ratio of right over left ventricular stroke work (RVSW/LVSW) and the PaO2/FIO2 ratio at admission. On day 2, the best prognostic model included: age [odds ratio (OR) = 1.04, p = 0.0004], opportunistic pneumonia as the cause of ARDS (OR = 3.2, p = 0.03), existence of MOD (OR = 1.9, p = 0.03), PaO2/FIO2 (OR = 0.96, p = 0.005), and RVSW/LVSW (OR = 25, p = 0.02). A high RVSW/LVSW ratio, high systolic PAP, low diastolic SAP, and low PaO2/FIO2, and increased right atrial pressure were negative prognostic indicators during follow-up. CONCLUSION: In addition to the cause of ARDS and the early time-course of lung function, a high systolic PAP and a low diastolic SAP were strong independent indicators of survival.

Effect of subcutaneous tunneling on internal jugular catheter-related sepsis in critically ill patients: a prospective randomized multicenter study.

OBJECTIVE: To evaluate the effect of catheter tunneling on internal jugular catheter-related sepsis in critically ill patients. DESIGN: A prospective randomized controlled study involving 3 intensive care units (ICUs), stratified by number of catheter lumina (1 or 2) and center. SETTING: The 10-bed medical-surgical and 10-bed surgical ICUs at Saint Joseph Hospital and 8-bed surgical ICU at Clinique de la Défense, Paris, France. PATIENTS: Every patient older than 18 years admitted to the ICUs between March 1, 1993, and July 17,1996, who required a jugular venous catheter for more than 48 hours. INTERVENTION: Random allocation to tunneled or nontunneled catheters. MEASUREMENTS: Times to occurrence of systemic catheter-related sepsis, catheter-related septicemia, or a quantitative catheter-tip culture with a cutoff of 103 colony-forming units per milliliter. RESULTS: A total of 241 patients were randomized. Ten patients in whom jugular puncture was not achieved were subsequently excluded. The proportion of patients receiving mechanical ventilation (87%) and mean+/-SD age (65+/-4 years), Simplified Acute Physiologic Score (13.3+/-4.9), Organ System Failure score (1.5+/-1.0), and duration of catheterization (8.7+/-5.0 days) were similar in both groups. Taking into account the first 231 catheters (114 nontunneled [control], 117 tunneled), we found that tunnelization decreased catheter-related sepsis (odds ratio [OR], 0.33; 95% confidence interval [CI], 0.13-0.83; P=.02), catheter-related septicemia (OR, 0.23; 95% CI, 0.07-0.81; P=.02), and, though not statistically significant, positive quantitative tip-culture rate (OR, 0.62; 95% CI, 0.35-1.10; P=.10). These results were slightly modified after adjustment on parameters either imbalanced between both groups (duration of catheter placement and cancer at admission) or prognostic (insertion by a resident, use of antibiotics at catheter insertion, cancer, and sex). CONCLUSION: The incidence of internal jugular catheter-related infections in critically ill patients can be reduced by using subcutaneous tunnelization.

INTERSEPT: an international, multicenter, placebo-controlled trial of monoclonal antibody to human tumor necrosis factor-alpha in patients with sepsis. International Sepsis Trial Study Group.

OBJECTIVE: To determine the safety and efficacy of BAY x 1351, a murine monoclonal antibody to recombinant human tumor necrosis factor (TNF)-alpha, in patients with sepsis. DESIGN: An international, multicenter, prospective, placebo-controlled trial in patients with sepsis, stratified into shock/nonshock groups. SETTING: Forty acute clinical care facilities in 14 countries. PATIENTS: Of the 564 patients enrolled in the study, 553 patients received study drug or placebo. INTERVENTIONS: Patients received 15 mg/kg or 3 mg/kg of BAY x 1351, or placebo, as a single intravenous infusion. MEASUREMENTS AND MAIN RESULTS: The patients were well matched for severity of illness and for risk factors known to influence the outcome of sepsis. There was no difference in 28-day mortality rates between groups (placebo group 66 [39.5%] of 167;3 mg/kg group 57 [31.5%] of 181; 15 mg/kg group 87 [42.4%] of 205). Approximately 9 months after this study had begun, an interim safety examination of NORASEPT, a North American Sepsis Trial using the same monoclonal antibody, indicated that there was no benefit to patients in the nonshock group and further enrollment of these nonshock septic patients into INTERSEPT was stopped. The analysis therefore focused on the 420 patients in shock. The primary efficacy variable was the 28-day, all-cause mortality rate: placebo group 57 (42.9%) of 133; 3-mg/kg group 51 (36.7%) of 139; and 15-mg/kg group 66 (44.6%) of 148 (not significant). Two secondary efficacy variables were identified prospectively: shock reversal and frequency of organ failures. Life-table analysis showed that in patients who survived 28 days, there was a more rapid reversal of shock in both treatment groups compared with placebo (15-mg/kg group vs. placebo group log-rank statistic p = .007, 3-mg/kg group vs. placebo group p = .01). Similarly, in patients surviving 28 days, there was a significant delay in the time to the onset of first organ failure (log rank 15 mg/kg vs. placebo p = .03, 3 mg/kg vs. placebo p = .07), and more patients in the placebo group developed at least one organ failure: 15-mg/kg group 33 (40.2%) of 82; 3-mg/kg group 39 (44.3%) of 88; and placebo group 45 (59.2%) of 76 (15 mg/kg vs. placebo p = .03, 3 mg/kg vs. placebo p = .06). No significant adverse events were associated with the monoclonal antibody treatment. CONCLUSIONS: INTERSEPT provides additional clinical data implicating TNF-alpha as an integral mediator of septic shock. The study suggested a possible role for anti-TNF antibody as adjunctive therapy, but this possibility requires confirmation by another clinical trial.

Mortality of nosocomial pneumonia in ventilated patients: influence of diagnostic tools.

The overmortality induced by nosocomial infections, especially pneumonia in ventilated patients (VNP), is still a matter of controversy because it is difficult to know precisely the respective effects of VNP per se and both the underlying illness and the severity of the disease that indicates ICU stay. During a 3-yr period, for each patient mechanically ventilated for more than 48 h we recorded underlying illness, reason for mechanical ventilation, clinical and therapeutic data collected during the first 48 h of ventilation, and death in the ICU. Patients with suspicion of VNP (S-VNP) according to clinical, radiologic, and biologic criteria underwent bronchoscopy with protected specimen brush (PSB) and bronchoalveolar lavage culture (BAL-C). VNP was confirmed (C-VNP) if PSB > or = 10(3) cfu/ml and/or BAL-C > or = 10(4) cfu/ml. Prognostic multivariate analysis was performed introducing S-VNP and C-VNP as time-dependent covariates. Of the 387 studied patients, 112 S-VNP and 56 C-VNP were observed with overall mortality of 43% (168 patients). MacCabe, APACHE II score, shock, use of sedatives and absence of enteral nutrition were additively associated with an increased mortality as well as C-VNP (relative risk [RR]: 1.8, p = 0.007). Nevertheless, when S-VNP and C-VNP were simultaneously introduced in the Cox model, only S-VNP remained associated with increased mortality. In patients suspected of VNP, confirmation of VNP using PSB and/or BAL-C adds no prognostic information. Whether this could be explained by the lack of sensitivity of protected distal samples or the severity of underlying conditions of S-VNP patients is still an open issue. A multivariate analysis based on follow-up data during the ICU course of ventilated patients will be initiated in the near future.

Usefulness of airway visualization in the diagnosis of nosocomial pneumonia in ventilated patients.

UNLABELLED: Clinical diagnosis of nosocomial pneumonia in ventilated patients remains a challenge in the ICU as none of the clinical biological and radiologic parameters can predict its diagnosis. To our knowledge, however, the accuracy of direct visualization of the bronchial tree has never been investigated. PURPOSE: To evaluate the interest of airway visualization and to select independent parameters that predict nosocomial pneumonia in ventilated patients. SETTING: A ten-bed medical-surgical ICU. METHODS: All consecutive patients suspected of having nosocomial pneumonia who underwent bronchoscopy with protected specimen brush, culture examination of BAL, and direct examination of BAL were studied. Clinical and biological data and airways findings were recorded prospectively. Patients were classified as having pneumonia or not according to the results of distal bacteriologic samples, follow-up, and histologic study. Respective accuracies of each variable were calculated using univariate analysis and stepwise logistic regression. RESULTS: Ninety-one patients with suspected nosocomial pneumonia were studied. Patients were randomly assigned to a construction group (n = 46) and a validation group (n = 45). Using multivariate analysis, 3 factors were associated with pneumonia (a decrease in PaO2/fraction of inspired oxygen ratio > or = 50 mm Hg, odds ratio [OR] = 9.97, p = 0.026; the presence of distal purulent secretions, OR = 7.46, p = 0.044; the persistence of distal secretions surging from distal bronchi during exhalation, OR = 12.25, p = 0.013). These three factors remained associated with pneumonia in the validation group. Interobserver repeatability of the bronchoscopic parameters was good. Having 2 or more of these 3 independent factors was able to predict pneumonia with a 94% sensitivity and a 89% specificity in the construction group and with a 78% sensitivity and a 89% specificity in the validation group. CONCLUSION: We conclude that direct visualization of the bronchial tree can immediately and accurately predict nosocomial pneumonia in ventilated patients before obtaining definite results of protected samples.

Reappraisal of distal diagnostic testing in the diagnosis of ICU-acquired pneumonia.

BACKGROUND: The thresholds of the diagnostic procedures performed to diagnose ICU-acquired pneumonia (IAP) are either speculated or incompletely tested. PURPOSE: To evaluate the best threshold of protected specimen brush (PSB), plugged telescoping catheter (PTC), BAL culture (BAL C), and direct examination of cytocentrifugated lavage fluid (BAL D) to diagnose IAP. Each mechanically ventilated patient with suspected IAP underwent bronchoscopy successively with PSB, PTC, and BAL in the lung segment identified radiographically. POPULATION: One hundred twenty-two episodes of suspected IAP (occurring in 26% of all mechanically ventilated patients) were studied. Forty-five patients had definite IAP, and 58 had no IAP. Diagnosis was uncertain in 19 cases. RESULTS: Using the classic thresholds, sensitivity was 67% for PSB, 54% for PTC, 59% for BAL D, and 77% for BAL C. Specificity was 88% for PSB, 77% for PTC, 98% for BAL D, and 77% for BAL C. We used receiver operating characteristics methods to reappraise thresholds. Decreasing the thresholds to 500 cfu/mL for PSB, 10(2) cfu/mL for PTC, 2% cells containing bacteria for BAL D, 4 x 10(3) cfu/mL for BAL C increased the sensitivities (plus 14%, 23%, 25%, 10%, respectively) and moderately decreased the specificities (minus 4%, 9%, 2%, 4%, respectively) of the four examinations. The association of PSB with a 500 cfu/mL threshold and BAL D with a 2% threshold recovered all but one episode of pneumonia (SE 96 +/- 4%) with a 84 +/- 10% specificity. For a similar ICU population, these "best" thresholds increased negative predictive value with a minimal decrease of positive predictive value. They need to be confirmed in multiple ICU settings in prospective fashion.

Effect of previous antimicrobial therapy on the accuracy of the main procedures used to diagnose nosocomial pneumonia in patients who are using ventilation.

We evaluated the effect of antibiotic treatment received before the suspicion of pneumonia on the diagnostic yield of protected specimen brush (PSB), direct examination (BAL D) and culture (BAL C) of lavage fluid on consecutive mechanically ventilated patients with suspected nosocomial pneumonia. Bronchoscopy was always performed before any treatment for suspected pneumonia. One hundred and sixty-one patients with suspected pneumonia underwent PSB and BAL before any institution or change in antibiotic therapy (AB). Sixty-five patients received AB for an earlier septic episode (ON AB group) and 96 patients did not (OFF AB group). All but two strains recovered were highly resistant to previous AB. Sensitivity and specificity of each test were not different between the ON AB and OFF AB groups as well as the percentage of complete agreement between the 3 procedures, 74 and 67% respectively. We conclude that previous AB received to treat an earlier septic episode unrelated to suspected pneumonia do not affect the diagnostic yield of PSB and BAL.

Circulating interleukin-8 concentrations in patients with multiple organ failure of septic and nonseptic origin.

OBJECTIVES: Interleukin (IL)-8, a pro-inflammatory cytokine, is a potent chemoattractant factor and an activator of neutrophils produced by many cell types after stimulation by IL-1, tumor necrosis factor (TNF), or microbial products such as endotoxins. We investigated whether the presence of measurable IL-8 in plasma was associated with the clinical status of severely ill septic or nonseptic patients susceptible to the development of multiple organ failure. DESIGN: Cohort study. SETTING: A collaborative study between an intensive care unit and a research laboratory. SUBJECTS: Circulating IL-8 concentrations were measured in the plasma of 27 patients with sepsis syndrome and in 16 patients with noninfectious shock because these two conditions put patients at risk for the development of multiple organ failure. Sixteen of 27 patients with severe infection and 13 of 16 patients with noninfectious pathologies developed multiple organ failure. MEASUREMENTS AND MAIN RESULTS: A specific enzyme-linked immunosorbent assay (ELISA) for IL-8 was set up with a monoclonal and a rabbit polyclonal antihuman IL-8 using a sandwich technique. High concentrations of circulating IL-8 were found in the plasma of patients with sepsis syndrome. Among septic patients, a significant difference was observed between concentrations of IL-8 in survivors (n = 16) and nonsurvivors (n = 11) (81 +/- 13 pg/mL vs. 3326 +/- 1219 pg/mL, respectively; p = .001). A correlation was noticed between plasma IL-8 and IL-6 concentrations (r2 = .42; p = .001), while no correlation was observed between IL-8 and TNF-alpha values, or between IL-8 and IL-1 beta. Although the mortality rate of nonseptic, multiple organ failure patients was 92%, low plasma concentrations of IL-8 were found (78 +/- 34 pg/mL), while high plasma concentrations were measured in septic, multiple organ failure patients (mortality rate 69%) who were sampled at a similar stage. By contrast, increased IL-6 values were observed in both septic and nonseptic, multiple organ failure patients. CONCLUSIONS: In septic patients, high amounts of circulating IL-8 concentrations correlate with fatal outcome, whereas only low plasma concentrations of IL-8 are present in patients with nonseptic, multiple organ failure. This finding suggests that the signals involved in the exacerbation of IL-8 production are different, depending on infectious or noninfectious etiology.

[General principles of choice of antibiotics for antibiotic prophylaxis in surgery]. / Principes généraux du choix d'un antibiotique pour l'antibioprophylaxie en chirurgie.

A large amount of knowledge has been obtained in the field of prophylactic antibiotics over the past few years. Only procedures with a reasonable risk (incidence or severity) ought to be covered. Antibiotics must be present not only in plasma but also in the tissues during the surgical procedure. In most cases a very short prophylaxis, usually using a single bolus, is convenient. The best cost/benefit ratio has to be obtained. Several points remain unclear and require further investigations: what is the best dosage? What is the adequate timing for reinjections according to the duration of surgical procedure, and to the risk of postoperative infection using a "risk index"? Must we modulate the type of prophylaxis according to the duration of hospital stay before surgery? What is the value of selective decontamination of the digestive tract?

High levels of portal TNF-alpha during abdominal aortic surgery in man.

During shock or multiple organ dysfunction syndrome, translocation of bacteria and/or lipopolysaccharide (LPS) from the ischaemic gut might occur and could explain the excess of cytokine production detectable in plasma. To test this hypothesis, we studied a model of mild gut ischaemia due to bowel manipulation and aortic clamping in patients undergoing abdominal aortic surgery (n = 14). Per-operative levels of LPS and cytokines were measured before clamping and after reperfusion, and compared in systemic and portal blood. Systemic levels of LPS and cytokines were measured in a control group of patients undergoing internal carotid surgery (n = 7). Portal LPS was detectable (i.e., > 12 pg/ml) in 36% of the patients undergoing aortic surgery after bowel manipulation, and in 71% after clamp release. Similar levels of LPS were observed in portal and systemic blood after clamp release. Circulating tumour necrosis factor alpha (TNF-alpha) was observed in all patients undergoing aortic surgery. Levels of portal TNF-alpha were higher than those in systemic blood after bowel manipulation as well as after reperfusion (P = 0.02 and 0.007, respectively). LPS was never detected in control patients and TNF-alpha was detectable in only two out of seven patients. Mean levels of IL-6 were similar in the two groups, with a peak on the day following surgery, confirming that circulating IL-6 is associated with any surgical procedures. Our data indicate that bowel manipulation, aortic clamping and reperfusion lead to similar levels of portal and systemic circulating LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

Is protected specimen brush a reproducible method to diagnose ICU-acquired pneumonia?

UNLABELLED: Protected specimen brush (PSB) is considered to be one of the standard methods for the diagnosis of ventilator-associated pneumonia, but to our knowledge, intraindividual variability in results has not been reported previously. PURPOSE: To compare the results of two PSB performed in the same subsegment on patients with suspected ICU-acquired pneumonia (IAP). STUDY DESIGN: Between October 1991 and April 1992, each mechanically ventilated patient with suspected IAP underwent bronchoscopy with two successive PSB in the lung segment identified as abnormal on radiographs. Results of the two PSB cultures were compared using 10(3) cfu/ml cutoff for a positive result. Four definite diagnoses were established during the follow up: definite pneumonia, probable pneumonia, excluded pneumonia, and uncertain pneumonia. POPULATION: Forty-two episodes in 26 patients were studied; 60 percent of patients received prior antibiotic therapy. Thirty-two microorganisms were isolated from 24 pairs of PSB. Definite diagnosis was definite pneumonia in 7, probable pneumonia in 8, excluded pneumonia in 17, and uncertain pneumonia in 10 cases. RESULTS: The PSB recovered the same microorganisms and argued for a good qualitative reproducibility. The distinction of positive and negative results on the basis of the 10(3) cfu/ml classic threshold was less reproducible. For 24 percent of the microorganisms recovered and in 16.7 percent of episodes of suspected IAP, the two consecutive samples gave results spread out on each side of the 10(3) cfu/ml cutoff. Discordance was higher when definite diagnosis was certain or probable than when diagnosis was excluded (p = 0.015). There was no statistical effect of the order of samples between the two specimens for bacterial index and microorganism concentrations. CONCLUSION: These findings argue for the poor repeatability of PSB in suspected IAP and question the yield of the 10(3) cfu/ml threshold. In attempting to diagnose IAP, the results of PSB must be interpreted with caution considering the intraindividual variability.

Expression of tumor necrosis factor-alpha gene in alveolar macrophages from patients with the adult respiratory distress syndrome.

The adult respiratory distress syndrome (ARDS) is a complex syndrome in which pathogenesis is multifactorial. TNF-alpha, known to be pivotal in tissue damage, has been shown to have high levels in blood and alveolar fluid in ARDS. The identification of the cells responsible for this production in the alveolar milieu has not yet been reported. In order to evaluate the TNF-alpha gene expression in ARDS we have analyzed by in situ hybridization, using RNA probes, alveolar macrophages (AM) obtained by BAL from seven patients with ARDS, eight patients with miscellaneous respiratory diseases, and three control patients. In freshly collected AM from patients with ARDS, 66 +/- 14.5% cells expressed the TNF-alpha gene without in vitro stimulation. This TNF-alpha expression does not result from the BAL procedure itself since only a few unstimulated control AM contained TNF-alpha mRNA transcripts. TNF-alpha expression in AM is not restricted to patients with ARDS since it has also been observed in miscellaneous respiratory diseases; however, this expression is a constant feature in ARDS. These results demonstrated the major role of AM in the intra-alveolar production of TNF-alpha, and they point out the necessity in ARDS for a specific intra-alveolar therapy.

Single-dose amoxycillin-clavulanic acid vs. cefotetan for prophylaxis in elective colorectal surgery: a multicentre, prospective, randomized study. The PRODIGE Group.

A prospective, multicentre, randomized trial was carried out in 19 hospitals in order to compare the efficacy of amoxycillin-clavulanic acid with cefotetan as antibiotic prophylaxis in patients undergoing elective colorectal surgery. Since the main purpose of the study was to demonstrate equivalence between the two regimens, the protocol planned the inclusion of 200 patients. Eligible patients were randomly assigned to receive either amoxycillin-clavulanic acid (2.2 g) or cefotetan (2 g) in a single infusion on the induction of anaesthesia. Failure of prophylaxis was defined as occurrence of infection of intestinal origin, either minor (wound cellulitis) or major (abscess, peritonitis, septicaemia) within the 30-day postoperative period. Among 221 randomized patients, 208 (105 amoxycillin-clavulanic acid, 103 cefotetan) aged 66 +/- 12 years (mean +/- SD) were evaluated while 13 were withdrawn. Colorectal cancer was the indication for surgery in 73% of cases. Eleven (10 +/- 6%, 95% confidence interval) and 13 (13 +/- 7%) failures were observed in the amoxycillin-clavulanic acid and cefotetan groups (P = 0.63 chi-square test) respectively. Most infections occurred before the 10th postoperative day (8% failures at this time, estimated by the Kaplan-Meier method). The results of the trial demonstrate that amoxycillin-clavulanic acid and cefotetan have similar efficacy when used for prophylaxis of infection after elective colorectal surgery.

Influence of surgery on in-vitro cytokine production by human monocytes.

Surgery leads to significant modulation of the immune system, in which cytokines play a major role. Circulating interleukin 6 (IL-6) and IL-1 have been reported following surgery whereas tumor necrosis factor alpha (TNF-alpha) is only found in gut ischemia-associated surgery. We have investigated the consequences of surgery on in-vitro cytokine production by human monocytes stimulated by lipopolysaccharide (LPS) and staphylococcal toxic shock syndrome toxin-1 (TSST-1). Comparisons were made between the responsiveness of cells obtained the day before (D-1), during (D0) and after (D1, D2, D3) surgery. Patients undergoing abdominal aortic surgery (N = 9), carotid surgery (N = 4) and spinal surgery (N = 4) have been studied. A significant decrease of TNF-alpha, IL-1 beta and IL-1 alpha production by monocytes prepared from blood samples taken during the surgery was noticed, whereas IL-6 production was not significantly modified. On D2 a significant increase of monocyte responsiveness was observed and levels of cytokine productions rose back to initial values by the end of the follow up. The diminished in-vitro cytokine production observed during surgery might be the consequence of the effects of anaesthetic drugs, whereas the enhancement observed on D2 might reflect the surgical stress, leading to in-vivo priming of circulating monocytes.

[Isolated dissecting aneurysm of the superior mesenteric artery. Dysplasia, a rare cause of mesenteric ischemia. Report of a case]. / Dissection isolée de l'artère mésentérique supérieure. La dysplasie, une cause rare d'ischémie mésentérique. Une observation.

We report a case of successful surgical revascularization of the superior mesenteric artery in a patient presenting with intestinal ischaemia due to fibrodysplasia. This is a rare pathology, with 5 cases operated in our institution and only 16 cases reported in the literature. Angiography may show other sites of arterial dysplasia. In such cases, success depends on early surgical revascularization.