Impact of rapid diagnostic tests on the management of patients presenting with Enterobacteriaceae bacteremia.

OBJECTIVE: Pathogens are usually identified from blood cultures using a two-step procedure: Gram staining on the day of bacterial growth (D0), followed by identification and susceptibility testing the following day (D1). We aimed to evaluate the use of rapid tests performed on D0 in patients presenting with Enterobacteriaceae bacteremia. PATIENTS AND METHODS: Patients with≥1 positive monomicrobial blood culture with Gram staining suggestive of an Enterobacteriaceae were prospectively included. Two successive strategies were evaluated: i) conventional strategy (CS), ii) combination of a rapid identification test and third-generation cephalosporin susceptibility testing (rapid strategy, e.g. RS). RESULTS: Eighty-three patients were included (CS=42; RS=41). Compared with CS, the median delay of identification was significantly shorter with RS (22 hours [20-27] vs. 47 hours [42-53]; P<0.001). Patients in the RS group more frequently received an effective (82.9% vs. 73.8%, P=0.43) and appropriate (70.7% vs. 54.7%, P=0.17) antibiotic therapy on D1. Moreover, all five RS patients infected with a non-susceptible strain received an effective therapy on D1 versus only three of eight CS patients. CONCLUSIONS: Use of rapid testing was associated with a reduced time to result availability. This strategy should be useful to initiate an early effective and appropriate therapy and to improve the care of patients.

Sequential evaluation of pulmonary function and bronchial hyperresponsiveness in patients with nasal polyposis: a prospective study.

Nasal polyposis (NP) is commonly associated with nonspecific bronchial hyperresponsiveness (BHR) and/or asthma. The aim of this prospective study was to investigate the changes of pulmonary function and BHR in patients with nasal polyposis. Forty-four consecutive patients with NP were included in the study and were followed for 12 mo. Nonspecific BHR was assessed by a carbachol challenge test to determine the provocating dose (PD20) necessary to decrease FEV1 by 20% from baseline values; 17 of 22 patients who demonstrated BHR also exhibited asthma. Spirometric measurements and carbachol challenge were performed before initiating any treatment and 12 mo later. All patients were treated first with beclomethasone (600 microg/d). Intranasal ethmoidectomy was performed in 23 patients who did not improve when treated with topical steroids alone (nonresponders); in contrast, 21 patients were successfully treated with beclomethasone alone (responders). PD20 significantly decreased in the group of nonresponders (p = 0.018), whereas it remained unchanged in responders (p = 0.95). FEV1 (% pred) and FEF25-75 (% pred) significantly decreased in nonresponders (p < 0.001), whether BHR existed or not, whereas no significant change was observed in responders. Our results demonstrate that nonresponders who required nasal surgery exhibited an enhancement of BHR and a slight but significant decrease of FEV1 and FEF25-75 values. However, no change in pulmonary symptoms and/or asthma severity occurred. Clinical and functional follow-up of these patients should assess the long-term evolution of these parameters and their clinical relevance.

Allergen-stimulated T lymphocytes from allergic patients induce vascular cell adhesion molecule-1 (VCAM-1) expression and IL-6 production by endothelial cells.

Adhesion of inflammatory cells to endothelium is a critical step for their transvascular migration to inflammatory sites. To evaluate the relationship between T lymphocytes (TL) and vascular endothelium, supernatants from allergen-stimulated TL obtained from patients sensitive to Dermatophagoides pteronyssinus (Dpt) versus healthy subjects were added to endothelial cell (EC) cultures. TL were stimulated by autologous-activated antigen-presenting cells (APC) previously fixed in paraformaldehyde to prevent monokine secretion. Two parameters were measured: the expression of adhesion molecule and the production of IL-6. Related allergen-stimulated TL supernatants from allergic patients induced an increase of VCAM-1 and intercellular adhesion molecule-1 (ICAM-1) expression when supernatants of the control groups (TL exposed to an unrelated allergen or not stimulated or TL obtained from healthy subjects) did not. E-selectin expression was not modulated whatever the supernatant added to EC culture. IL-6 production by EC was significantly enhanced after activation with related allergen-stimulated TL supernatants from allergics compared with control supernatants. Induction of VCAM-1 expression was inhibited by adding neutralizing antibodies against IL-4, whereas IL-6 production and ICAM-1 expression were inhibited by anti-interferon-gamma (IFN-gamma) antibodies. Enhanced production of IL-4 and IFN-gamma was detected in related allergen-stimulated TL supernatants from allergic subjects compared with the different supernatants. These data suggest that allergen-specific TL present in the peripheral blood of allergic patients are of Th1 and Th2 subtypes. Their stimulation in allergic patients may lead to the activation of endothelial cells and thereby participate in leucocyte recruitment towards the inflammatory site.

High-dose and low-dose systemic corticosteroids are equally efficient in acute severe asthma.

The optimal amount of systemic corticosteroids to be used in acute severe asthma remains an unresolved issue. In this double-blind, randomized study we compared two doses of methylprednisolone (1 vs 6 mg.kg-1 q.d.) in asthmatics presenting with an acute severe asthma attack, unresponsive to an intensive beta 2-agonist regimen administered during a run-in period. Concurrent therapy, including oxygen, inhaled and intravenous salbutamol, and aminophylline was strictly standardized. The response was assessed by serial bedside spirometry. The primary outcome measurement was forced expiratory volume in one second (FEV1) (expressed as percentage of predicted values) at 24 and 44 h. The trial was designed in order to achieve a statistical power of 90%. Twenty three patients were included in the low-dose group and 24 in the high-dose group. Both groups were comparable in terms of demographic profiles, history of asthma, and severity of the current attack. Improvement in pulmonary function was similar in both groups. At 44 h, the mean (+/- SD) FEV1 values were 53 +/- 22 and 45 +/- 14% in the low and in the high-dose group respectively (NS). We conclude that high dose systemic corticosteroids offer no further benefit over low-doses in the treatment of severe acute asthma.

Anaphylactic reaction to local administration of rifamycin SV.

BACKGROUND AND OBJECTIVE: Systemic reactions during anesthesia are commonly attributed to muscle relaxants, hypnotics, macromolecular solutions, latex, or parenteral antibiotics. After exclusion of these different components as causes, we were interested in the potential implication of rifamycin in the systemic reaction, which occurred during anesthesia, and in the immunologic mechanism by which it can trigger this reaction. METHODS: We report four cases of systemic reactions occurring after local administration of rifamycin. Three patients needed orthopedic surgery, and the fourth needed a urethrotomy. Severe systemic reactions occurred in all four patients when the surgeon washed the incision area with a rifamycin solution. All patients correctly responded to appropriate treatment and recovered. Skin tests were performed 2 months after the incident with the drugs used during anesthesia, latex, and rifamycin. To assess the relationship with a possible IgE-mediated mechanism, two in vitro tests were concomitantly performed to evaluate the cell reactivity to rifamycin: (1) determination of histamine release from peripheral basophils and (2) platelet cytotoxicity test, which explored the presence on platelets of specific IgE antibodies bound to the low-affinity receptor for IgE. RESULTS: Skin tests were performed with different drugs used during surgery, and results were only positive for rifamycin in the four cases, accompanied in two cases by a systemic reaction. Histamine release from basophils was positive in three of four patients. The platelet cytotoxicity test results were positive in all four cases. CONCLUSION: It appears that rifamycin, used locally during surgery, is apt to trigger severe systemic anaphylactic reactions, which are linked to an IgE-related process. This situation is worth pointing out, especially in patients who undergo repeated orthopedic operations during which, at least in Europe, rifamycin is commonly used for the prevention of local sepsis.

[Extraosseous Ewing's sarcoma with thoracic localization]. / Sarcome d'Ewing extra-osseux à localisation thoracique.

We report two cases of extraosseous Ewing's sarcoma revealed by large volume thoracic tumour lesions, occurring in a clinical context of an alteration in general health. The tumour mass was occupying the upper half of the left hemithorax, and was invading the thoracic wall posteriorly in the first case; it occupied the whole of the right hemithorax with invasion of the first three ribs in the second case. The first patient received five treatments with chemotherapy, using cyclophosphamide in association with adriamycin, which led to a partial response and was completed with surgical excision and a further five doses of chemotherapy using cyclophosphamide in association with etoposide. Subsequently radiotherapy was given. There was an unfavorable outcome, with recurrence in the 13th month. The second patient received three courses of chemotherapy using cyclophosphamide in association with actinomycin D and vincristine, which allowed for an 80% reduction in the tumour volume. Surgical resection was then carried out, followed by five courses with the same chemotherapy protocol. Forty-two months after the diagnosis this patient remained in complete remission. These two cases enable us to stress the value of associating a chemotherapy protocol consisting of cyclophosphamide, actinomycin D and vincristine, with systemic surgical excision in tumours with a high potential for development.

Specific histamine release capacity of peptides selected from the modelized Der p I protein, a major allergen of Dermatophagoides pteronyssinus.

Dust mite allergens are considered as a major cause of allergic disease and as a risk factor for asthma. Der p I, a 222 amino-acid residue globular glycoprotein, is one of the major allergens from Dermatophagoides pteronyssinus (Dpt) mites. In this study, we have used predictive conventional algorithms (i.e. hydrophilicity, mobility, accessibility) and a three-dimensional model of Der p I derived from comparison to actinidin and papain to select continuous amino acid sequences as potential B cell epitopes. Four peptides, 52-71, 117-133, 176-187, 188-199 were synthesized. Their antigenic reactivity was investigated, mainly by measuring their capacity to induce in vitro histamine release. Results indicated that only Dpt-sensitive patients react specifically to Der p I-derived peptides and more frequently to 52-71 and 117-133. For each peptide, the intensity of response was dependent on the patient tested and on the peptide concn. The capacity of peptides to induce histamine release was demonstrated to be correlated with the serum level of anti-Der p I IgE (r = 0.86; p less than 10(-2)). Taken together these data emphasize, in Dpt-sensitive patients, the heterogeneity of the specific response to synthetic Der p I-derived peptides and underline the possible variety of epitopes belonging to the allergen Der p I.

Specific activation of platelets from patients allergic to Dermatophagoides pteronyssinus by synthetic peptides derived from the allergen Der p I.

Previous studies have shown that Fc epsilon RII-bearing platelets from patients with allergic disorders could be stimulated either by anti-human IgE antibodies or the relevant allergens to generate cytotoxic mediators. In this report, the reactivity of platelets from Dermatophagoides pteronyssinus (D. pt)-sensitive patients to three Der p I-derived synthetic peptides (52-71, 117-133 and 188-199) was investigated. The platelet stimulation observed in D. pt-sensitive patients was demonstrated to be allergen-specific and to be mediated by IgE. These Der p I-derived peptides failed to stimulate platelets from healthy donors or platelets from non-D. pt-allergic patients. D. pt-sensitive patients responded more frequently to the peptides 52-71 and 117-133 than to the peptide 188-199. Thus, in this model, synthetic peptides selected for their assumed accessibility on the native antigen could be associated to an IgE-dependent biological activity.