Monique Nys

An enzyme-linked immunosorbent assay was developed to study the subclass distribution of immunoglobulin G (IgG) specific to the core glycolipid (CGL) of the Re mutant of Salmonella minnesota R595 in serum samples from individuals with an IgG response toward these antigens. In a group of healthy blood donors, we detected predominantly the IgG2 and IgG1 subclasses. In a group of patients in an intensive care unit who developed infectious complications due to gram-negative bacteria, the anti-CGL IgG activity was due mainly to the IgG2 and IgG3 subclasses. In all serum samples found to be IgG positive, the assay for anti-CGL IgG2 was positive. This subclass was revealed to play a predominant role in patients displaying a seroconversion or a significant rise in their antibody response toward CGL. IgG4 was found or appeared only in patients with confirmed bacteremia. In addition, we observed a drop in anti-CGL IgG2 before the death of patients undergoing a septic shock or an irreversible ...

In bronchoalveolar lavage (BAL) fluid from ventilated patients, cytotoxic oxidant activity is correlated with neutrophil activation. The aim of the present study was to investigate the hypothesis that BAL fluid induces activation of the transcription nuclear factor-kappaB (NF-kappaB) in human alveolar cells, in correlation with inflammatory mediators. We measured endotoxin, inflammatory cytokines [interleukin-1beta (IL-1beta), IL-8], nitrated proteins and the activity of myeloperoxidase (MPO) in BAL fluid from ventilated patients developing bronchopneumonia ( n =19 samples) or with acute respiratory distress syndrome (ARDS) ( n =14), and from ARDS/infection-free patients ( n =11). We also exposed alveolar cells to the BAL fluid or to human MPO, H(2)O(2) or HOCl, and tested nuclear extracts for the activation of NF-kappaB. IL-1beta, IL-8, nitrated protein, MPO and endotoxin levels were significantly higher in BAL fluid from patients with bronchopneumonia than in that from the ARDS an...

1. To address the question of whether endotoxaemia could be involved in the inflammatory response induced by long-term strenuous exercise, 18 male marathon runners [mean age 41 +/- 2 (SEM) years] were studied. Their performance in the marathon ranged from 2 h 46 min to 4 h 42 min. 2. Four venous blood samples were drawn: at rest, just before the race (baseline); within 15 min following the completion of the marathon; after 1 h of recovery; and the morning after the race. 3. The following humoral markers of the inflammatory response to exercise were measured: polymorphonuclear myeloperoxidase (MPO), anaphylatoxin C5a (C5a), tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Plasma endotoxin was measured by a sensitive and rapid chromogenic Limulus assay. All inflammatory markers were significantly increased (P < 0.001) after the race, reaching in most cases peak values in the first blood sample drawn following the completion of the marathon [MPO, 298 +/- 19 ng/ml (...

Combination antibiotic therapy for ventilator associated pneumonia (VAP) is often used to broaden the spectrum of activity of empirical treatment. The relevance of such synergy is commonly supposed but poorly supported. The aim of the present study was to compare the clinical outcome and the course of biological variables in patients treated for a VAP, using a monotherapy with a beta-lactam versus a combination therapy. Patients with VAP were prospectively randomised to receive either cefepime alone or cefepime in association with amikacin or levofloxacin. Clinical and inflammatory parameters were measured on the day of inclusion and thereafter. Seventy-four mechanically ventilated patients meeting clinical criteria for VAP were enrolled in the study. VAP was microbiologically confirmed in 59 patients (84%). Patients were randomised to receive cefepime (C group, 20 patients), cefepime with amikacin (C-A group, 19 patients) or cefepime with levofloxacin (C-L group, 20 patients). No s...

Ventilator-associated pneumonia diagnosis remains a debatable topic. New definitions of ventilator-associated conditions involving worsening oxygenation have been recently proposed to make surveillance of events possibly linked to ventilator-associated pneumonia as objective as possible. The objective of the study was to confirm the effect of subglottic secretion suctioning on ventilator-associated pneumonia prevalence and to assess its concomitant impact on ventilator-associated conditions and antibiotic use. Randomized controlled clinical trial conducted in five ICUs of the same hospital. Three hundred fifty-two adult patients intubated with a tracheal tube allowing subglottic secretion suctioning were randomly assigned to undergo suctioning (n = 170, group 1) or not (n = 182, group 2). During ventilation, microbiologically confirmed ventilator-associated pneumonia occurred in 15 patients (8.8%) of group 1 and 32 patients (17.6%) of group 2 (p = 0.018). In terms of ventilatory day...

We have developed an ELISA for IgM and IgG antibodies to the core glycolipid (CGL) of the Re mutant Salmonella minnesota R 595, and to lipid A. Anti-CGL antibodies have been detected in sera from 37% of healthy blood donors, whereas anti-lipid A activities were found in 13% of individuals only. The anti-CGL and anti-lipid A activities were examined in patients in a surgical intensive care unit, selected on the basis of a definite risk of infectious complications due to Gram-negative bacteria. Of the patients who developed such infections, the rate of favourable outcome was significantly higher in patients with either stable positive or increasing anti-CGL activities than in patients found to be negative. Our results provide clear evidence that anti-CGL antibodies contribute to host defence against various Gram-negative bacteria.

To assess the severity of intensive care unit (ICU)-acquired pneumonia (ICUAP) according to the bacteria involved, classified into seven groups: third-generation cephalosporin-resistant non-fermenting Gram-negative bacilli (resistant C3NF); sensitive C3NF; methicillin-resistant Staphylococcus aureus; methicillin-sensitive Staphylococcus aureus; extended-spectrum beta-lactamase-producing Enterobacteriaceae; Enterobacteriaceae not producing extended-spectrum beta-lactamase; Haemophilus influenzae and Streptococcus pneumoniae. Over a 4-year period, sequential organ failure assessment (SOFA) score was prospectively measured daily in 453 adult patients with ICUAP. ICUAP severity was evaluated by the severity of sepsis and by the occurrence of new organ dysfunctions or failures (OD/F) during ICUAP. Septic shock occurred in 21% of all cases of ICUAP. The occurrence of new OD/F during ICUAP was similar regardless of the identified microorganism. These new OD/F represented less than 11% of SOFAmax, defined as the sum of all OD/F occurring at any time during the ICU stay. There was a significant association between SOFApreICUAP, defined as the sum of all the OD/F occurring before ICUAP, and ICUAP severity. In the multivariate analysis, the type of bacteria was not a risk factor (RF) for occurrence of septic shock and mortality. Age and SOFApreICUAP were RF for the sepsis severity. The ICUAP severity was an RF for ICU mortality. ICUAP was responsible for a minor proportion of OD/F occurring during the ICU stay. Severity of ICUAP was related to clinical status prior to ICUAP, but not to the type of bacteria. ICU mortality depended on the severity of ICUAP.

To determine the effect of antibiotic class pressure on the susceptibility of bacteria during sequential periods of antibiotic homogeneity. Prospective study in a mixed ICU with three separated subunits of eight, eight, and ten beds. The study examined the 1,721 patients with a length of stay longer than 2 days. Three different antibiotic regimens were used sequentially over 2 years as first-choice empirical treatment: cephalosporins, fluoroquinolone, or a penicillin-beta-lactamase inhibitor combination. Each regimen was applied for 8 months in each subunits of the ICU, using "latin square" design. We treated 731 infections in 546 patients (32% of patients staying more than 48 h). There were 25.5 ICU-acquired infections per 1,000 patient-days. Infecting pathogens and colonizing bacteria were found in 2,739 samples from 1,666 patients (96.8%). No significant change in global antibiotic susceptibility was observed over time. However, a decrease in the susceptibility of several species was observed for antibiotics used as the first-line therapy in the unit. Selection pressure of antibiotics and occurrence of resistance during treatment was documented within an 8-month rotation period. Antibiotic use for periods of several months induces bacterial resistance in common pathogens.

To test the usefulness of procalcitonin serum level for the reduction of antibiotic consumption in intensive care unit patients. Single-center, prospective, randomized controlled study. Five intensive care units from a tertiary teaching hospital. All consecutive adult patients hospitalized for >48 hrs in the intensive care unit during a 9-month period. Procalcitonin serum level was obtained for all consecutive patients suspected of developing infection either on admission or during intensive care unit stay. The use of antibiotics was more or less strongly discouraged or recommended according to the Muller classification. Patients were randomized into two groups: one using the procalcitonin results (procalcitonin group) and one being blinded to the procalcitonin results (control group). The primary end point was the reduction of antibiotic use expressed as a proportion of treatment days and of daily defined dose per 100 intensive care unit days using a procalcitonin-guided approach. Secondary end points included: a posteriori assessment of the accuracy of the infectious diagnosis when using procalcitonin in the intensive care unit and of the diagnostic concordance between the intensive care unit physician and the infectious-disease specialist. There were 258 patients in the procalcitonin group and 251 patients in the control group. A significantly higher amount of withheld treatment was observed in the procalcitonin group of patients classified by the intensive care unit clinicians as having possible infection. This, however, did not result in a reduction of antibiotic consumption. The treatment days represented 62.6±34.4% and 57.7±34.4% of the intensive care unit stays in the procalcitonin and control groups, respectively (p=.11). According to the infectious-disease specialist, 33.8% of the cases in which no infection was confirmed, had a procalcitonin value>1µg/L and 14.9% of the cases with confirmed infection had procalcitonin levels<0.25 µg/L. The ability of procalcitonin to differentiate between certain or probable infection and possible or no infection, upon initiation of antibiotic treatment was low, as confirmed by the receiving operating curve analysis (area under the curve=0.69). Finally, procalcitonin did not help improve concordance between the diagnostic confidence of the infectious-disease specialist and the ICU physician. Procalcitonin measuring for the initiation of antimicrobials did not appear to be helpful in a strategy aiming at decreasing the antibiotic consumption in intensive care unit patients.