Modification of a virulence-associated phenotype after growth of Listeria monocytogenes on food.

AIM: To assess the effect of different foods, which have been implicated or not in cases of listeriosis, on the in vitro virulence-associated phenotype level of different Listeria monocytogenes strains. METHODS AND RESULTS: The virulence-associated phenotype level of L. monocytogenes was studied with the in vitro cell test based on a plaque-forming assay with a human adenocarcinoma cell line (HT-29) monolayer. Three strains of L. monocytogenes were grown in preparations (homogenate, 1-mum filtrate or 0.2-mum filtrate) of different food extracts ['rillettes' (potted minced pork), milk, raw salmon and cold-smoked salmon] or in a control medium, brain heart infusion (BHI). The bacterial suspensions grown in food extracts or in BHI at 37 degrees C were diluted with their growth medium (food extract or BHI) or with minimum essential medium before seeding on confluent HT-29 cell monolayers. Filtration of food extracts had no significant effect on the plaque numbers formed by the bacteria. A significant decrease in the plaque numbers was noted for the three strains when they grew in the rillettes extracts, compared with the other food extracts and BHI. The levels of in vitro virulence-associated phenotype of the strains after growth in the rillettes extract were similar to or lower than that of the hypovirulent internal reference strain L. monocytogenes 442. After growth in milk and cold-smoked salmon, the impact on virulence-associated phenotype depended on the strain. In contrast, plaque-forming assay indicated increased virulence-associated phenotype when the strains were switched from a nutrient-rich medium (food extract or BHI) to a minimum essential medium. CONCLUSIONS: In vitro virulence-associated phenotype level of the studied strains grown in BHI or cold-smoked salmon was the same as the control virulent strain EGD. In contrast, the nutrients present in rillettes may therefore substantially reduce the number of plaques but not the growth of L. monocytogenes. The utilization of minimum essential medium as diluent attenuates changes the effect of the food extract on virulence-associated phenotype in vitro. SIGNIFICANCE AND IMPACT OF THE STUDY: In the experimental design of this study, we showed that the nature of the food could affect the in vitro virulence-associated phenotype level of L. monocytogenes.

Resistant herpes simplex virus type 1 infection: an emerging concern after allogeneic stem cell transplantation.

Fourteen cases of severe acyclovir-resistant herpes simplex virus type 1 (HSV-1) infection, 7 of which showed resistance to foscarnet, were diagnosed among 196 allogeneic stem cell transplant recipients within a 29-month period. Recipients of unrelated stem cell transplants were at higher risk. All patients received foscarnet; 8 subsequently received cidofovir. Strains were initially foscarnet-resistant in 3 patients and secondarily so in 4 patients. In vitro resistance to acyclovir or foscarnet was associated with clinical failure of these drugs; however, in vitro susceptibility to foscarnet was associated with complete response in only 5 of 7 patients. No strain from any of the 7 patients was resistant in vitro to cidofovir; however, only 3 of 7 patients achieved complete response. Therefore, acyclovir- and/or foscarnet-resistant HSV-1 infections after allogeneic stem cell transplantation have become a concern; current strategies need to be reassessed and new strategies must be evaluated in this setting.

Half the families of intensive care unit patients experience inadequate communication with physicians.

OBJECTIVE: Effective communication of simple, clear information to families of intensive care unit (ICU) patients is a vital component of quality care. The purpose of this study was to identify factors associated with poor comprehension by family members of the status of ICU patients. DESIGN: Prospective study. SETTING: University-affiliated medical intensive care unit. PATIENTS AND METHODS: A total of 102 patients admitted to an ICU for >2 days. INTERVENTION: The representatives of 76 patients who were visited by at least one person during their ICU stay were interviewed. RESULTS: Mean patient age was 54+/-17 yrs and mean Simplified Acute Physiology Score II at admission was 40+/-20. The representative was the spouse in 47 cases (62%). Among representatives, 25 (33%) were of foreign descent and 12 (16%) did not speak French. Mean duration of the first meeting with a physician was 10+/-6 mins. In 34 cases (54%), the representative failed to comprehend the diagnosis, prognosis, or treatment of the patient. Factors associated with poor comprehension by representatives included patient-related, family-related, and physician-related factors. Patient-related factors included age <50 yrs (p = .03), unemployment (p = .01), referral from a hematology or oncology ward (p = .006), admission for acute respiratory failure (p = .005) or coma (p = .01), and a relatively favorable prognosis (p = .04). Family-related factors were foreign descent (p = .007), no knowledge of French (p = .03), representative not the spouse (p = .03), and no healthcare professional in the family (p = .01). Physician-related factors were first meeting with representative <10 mins (p = .03) and failure to give the representative an information brochure (p = .02). Moreover, after the first meeting, caregivers accurately predicted poor comprehension by representatives (p = .03). CONCLUSIONS: Patient information is frequently not communicated effectively to family members by ICU physicians. Physicians should strive to identify patients and families who require special attention and to determine how their personal style of interrelating with family members may impair communication.

Predictors of short-term mortality in critically ill patients with solid malignancies.

UNLABELLED: Admission of cancer patients with serious medical complications to the ICU remains controversial primarily because of the high short-term mortality rates in these patients. However, the cancer patient population is heterogeneous regarding age, underlying conditions, and curability of their disease, suggesting that large variations may occur in the effectiveness of intensive care within this subgroup of critically ill patients. OBJECTIVES: To identify factors predicting 30-day mortality in patients with solid tumors admitted to a medical ICU. PATIENTS AND METHODS: We conducted a retrospective study in 120 consecutive cancer patients (excluding patients with hematological malignancies) admitted to the medical ICU of a 650-bed university hospital between January 1990 and July 1997. Medical history, physical and laboratory test findings at admission, and therapeutic interventions within the first 24 h in the ICU were recorded. The study endpoint was vital status 30 days after ICU admission. Stepwise logistic regression was used to identify independent prognostic factors. RESULTS: The observed 30-day mortality rate was 58.7 % (n = 68), with most deaths (92 %) occurring in the ICU. Univariate predictors of 30-day mortality were either protective [prior surgery for the cancer (p = 0.01) and complete remission (p = 0.01)] or associated with higher mortality [Knaus scale C or D (p = 0.02), shock (p = 0.04), need for vasopressors (p = 0.0006) or for mechanical ventilation (p = 0.0001), SAPS II score greater than 36 (p = 0.0001), LOD score greater than 6 (p = 0.0001), and ODIN score > 2 (p = 0.0001)]. Three variables were independent predictors: previous surgery for the cancer (OR 0.20, 95 % CI 0.07-0.58), LOD score > 6 (OR 1.26, 95 % CI 1.09-1.44), and need for mechanical ventilation (OR 3.55, 95 % CI; 1.26-6.7). Variables previously thought to be indicative of a poor prognosis (i. e., advanced age, metastatic or progressive disease, neutropenia or bone marrow transplantation) were not predictive of outcome. CONCLUSION: When transfer to an ICU is considered an option by patients and physicians, 30-day mortality is better estimated by an evaluation of acute organ dysfunction than by the characteristics of the underlying malignancy.

Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in non-human immunodeficiency virus-infected patients: retrospective study of 31 patients.

The aim of this retrospective study was to assess whether corticosteroid adjunctive therapy (CAT) could prevent death in immunocompromised patients with severe Pneumocystis carinii pneumonia (PCP) who do not have human immunodeficiency virus (HIV) infection, similarly to what has been demonstrated for HIV-infected patients. The charts of all non-HIV-infected patients who were admitted to two medical intensive care units between 1988 and 1996 because of severe PCP, defined by an arterial oxygen pressure (determined while the patient was breathing room air) of <70 mm Hg, and who were treated with trimethoprim-sulfamethoxazole were analyzed retrospectively. Thirty-one patients met the study criteria, of whom 23 received CAT (within 72 hours of antibiotic therapy) and eight did not receive CAT. The need for mechanical ventilation (10 [43%] of 23 vs. 4 [50%] of 8) and the mortality rate (9 [39%] of 23 vs. 4 [50%] of 8) were similar for the two groups. Although this small study does not have a statistical power high enough to rule out the possibility of a difference, the results suggest that CAT does not improve the survival of non-HIV-infected patients as has been described for HIV-infected patients with severe PCP.

Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study.

CONTEXT: Tumor necrosis factor alpha (TNF-alpha) is believed to be a cytokine central to pathogenesis of septic shock. TNF2, a polymorphism within the TNF-alpha gene promoter, has been associated with enhanced TNF-alpha production and negative outcome in some severe infections. OBJECTIVES: To investigate the frequency of the TNF2 allele in patients with septic shock and to determine whether the allele is associated with the occurrence and outcome of septic shock. DESIGN: Multicenter case-control study conducted from March 1996 to June 1997. SETTING: Seven medical intensive care units in university hospitals. SUBJECTS: Eighty-nine patients with septic shock and 87 healthy unrelated blood donors. MAIN OUTCOME MEASURES: Frequency of the TNF2 allele among patients with septic shock and among those who died and the level of corresponding TNF-alpha concentrations. RESULTS: Mortality among patients with septic shock was 54%, consistent with the predicted mortality from the Simplified Acute Physiologic Score (SAPS II) value. The polymorphism frequencies of the controls and the patients with septic shock differed only at the TNF2 allele (39% vs 18% in the septic shock and control groups, respectively, P =.002). Among the septic shock patients, TNF2 polymorphism frequency was significantly greater among those who had died (52% vs 24% in the survival group, P =.008). Concentrations of TNF-alpha were higher in 68% and 52% with the TNF2 and TNF1 polymorphisms, respectively, but their median values (48 pg/mL vs 29 pg/mL) were not statistically different (P = .31). After controlling for age and the probability of death, derived by the SAPS II score, multiple logistic regression analysis showed that, for the same rank of SAPS II value, patients with the TNF2 allele had a 3.7-fold risk of death (95% confidence interval, 1.37-10.24). CONCLUSION: The TNF2 allele is strongly associated with susceptibility to septic shock and death due to septic shock.

Changing use of intensive care for hematological patients: the example of multiple myeloma.

OBJECTIVE: Intensivists generally view patients with hematological malignancies as poor candidates for intensive care. Nevertheless, hematologists have recently developed more aggressive treatment protocols capable of achieving prolonged complete remissions in many of these patients. This change mandates a reappraisal of indications for ICU admission in each type of hematological disease. Improved knowledge of the prognosis is of assistance in making treatment decisions. PATIENTS AND METHODS: The records of 75 myeloma patients consecutively admitted to our ICU between 1992 and 1998 were reviewed retrospectively and predictors of 30-day mortality were identified using stepwise logistic regression. RESULTS: The median age was 56 years (37-84). Chronic health status (Knaus scale) was C or D in 39 cases. Fifty-five patients (73%) had stage III disease and 17 had a complete or partial remission. Autologous bone marrow transplantation had been performed in 28 patients (37%). ICU admission occurred between 1992 and 1995 in 41 patients (54.7%), and between 1996 and 1998 in 34 patients (45.3%). The median SAPS II and LOD scores were 60 (23-107) and 7 (0-21), respectively. Reasons for ICU admission were acute respiratory failure in 39 patients (52%) and shock in 31 (41%). Forty-six patients (61%) required mechanical ventilation. Fifty patients (66%) received vasopressors and 24 dialysis. Thirty-day mortality was 57%. Only five parameters were independently associated with 30-day mortality in the multivariate model: female gender (OR = 5.12), mechanical ventilation (OR = 16.7) and use of vasopressor agents (OR = 5.67) were associated with a higher mortality rate, whereas disease remission (OR = 0.16) and ICU admission between 1996 and 1998 (OR = 0.09) were associated with a lower one. CONCLUSION: The prognosis for myeloma patients in the ICU is improving over time. This may reflect either recent therapeutic changes in hematological departments and ICUs or changes in patient selection for ICU admission. Hematologists and intensivists should work closely together to select hematological patients likely to benefit from ICU admission.

Estimation of direct cost and resource allocation in intensive care: correlation with Omega system.

OBJECTIVE: An instrument able to estimate the direct costs of stays in Intensive Care Units (ICUs) simply would be very useful for resource allocation inside a hospital, through a global budget system. The aim of this study was to propose such a tool. DESIGN: Since 1991, a region-wide common data base has collected standard data of intensive care such as the Omega Score, Simplified Acute Physiologic Score, length of stay, length of ventilation, main diagnosis and procedures. The Omega Score, developed in France in 1986 and proved to be related to the workload, was recorded on each patient of the study. SETTING: Eighteen ICUs of Assistance Publique-Hôpitaux de Paris (AP-HP) and suburbs. PATIENTS: 1) Hundred twenty-one randomly selected ICU patients; 2) 12,000 consecutive ICU stays collected in the common data base in 1993. MEASUREMENTS: 1) On the sample of 121 patients, medical expenditure and nursing time associated with interventions were measured through a prospective study. The correlation between Omega points and direct costs was calculated, and regression equations were applied to the 12,000 stays of the data base, leading to estimated costs. 2) From the analytic accounting of AP-HP, the mean direct cost per stay and per unit was calculated, and compared with the mean associated Omega score from the data base. In both methods a comparison of actual and estimated costs was made. RESULTS: The Omega Score is strongly correlated to total direct costs, medical direct costs and nursing requirements. This correlation is observed both in the random sample of 121 stays and on the data base' stays. The discrepancy of estimated costs through Omega Score and actual costs may result from drugs, blood product underestimation and therapeutic procedures not involved in the Omega Score. CONCLUSIONS: The Omega system appears to be a simple and relevant indicator with which to estimate the direct costs of each stay, and then to organise nursing requirements and resource allocation.

Customized probability models for early severe sepsis in adult intensive care patients. Intensive Care Unit Scoring Group.

OBJECTIVE: To develop customized versions of the Simplified Acute Physiology Score II (SAPS II) and the 24-hour Mortality Probability Model II (MPM II) to estimate the probability of mortality for intensive care unit patients with early severe sepsis. DESIGN AND SETTING: Logistic regression models developed for patients with severe sepsis in a database of adult medical and surgical intensive care units in 12 countries. PATIENTS: Of 11,458 patients in the intensive care unit for at least 24 hours, 1130 had severe sepsis based on criteria of the American College of Chest Physicians and the Society of Critical Care Medicine (systemic inflammatory response syndrome in response to infection, plus hypotension, hypoperfusion, or multiple organ dysfunction). RESULTS: In patients with severe sepsis, mortality was higher (48.0% vs 19.6% among other patients) and 28-day survival was lower. The customized SAPS II was well calibrated (P = .92 for the goodness-of-fit test) and discriminated well (area under the receiver operating characteristic [ROC] curve, 0.78). Performance in the validation sample was equally good (P = .85 for the goodness-of-fit test; area under the ROC curve, 0.79). The customized MPM II was well calibrated (P = .92 for the goodness-of-fit test) and discriminated well (area under the ROC curve, 0.79). Performance in the validation sample was equally good (P = .52 for the goodness-of-fit test; area under the ROC curve, 0.75). The models are independent of each other; either can be used alone to estimate the probability of mortality of patients with severe sepsis. CONCLUSIONS: Customization provides a simple technique to apply existing models to a subgroup of patients. Accurately assessing the probability of hospital mortality is a useful adjunct for clinical trials.

Different ratios of the piperacillin-tazobactam combination for treatment of experimental meningitis due to Klebsiella pneumoniae producing the TEM-3 extended-spectrum beta-lactamase.

We evaluated the pharmacokinetics and therapeutic efficacies of piperacillin and tazobactam, a beta-lactamase inhibitor, given either alone or in different combinations (80:10, 200:10, and 80:25 mg/kg/h), in experimental meningitis due to a strain of Klebsiella pneumoniae producing the TEM-3 extended-spectrum beta-lactamase. Treatment was administered intravenously as a 7-h constant infusion preceded by a bolus of 20% of the total dose. The mean (+/- standard deviation) rates of penetration into the cerebrospinal fluid (CSF) of infected animals were 6.7 +/- 3.9% for piperacillin given alone and 36.3 +/- 21.9% for tazobactam given alone. Combination treatment significantly magnified the concentration of either drug in CSF. Concentrations of bacteria in CSF increased throughout therapy in animals given either drug alone, even at high dosages. In animals given the combination at dosages of 80:10 and 200/10 mg/kg/h, only a suboptimal reduction of CSF bacterial titers was obtained in vivo, i.e. -0.49 +/- 0.34 and -0.73 +/- 0.49 log CFU/ml/h, respectively. An increase in the tazobactam dosage within the combination (80:25 mg/kg/h) was required in order to obtain a significantly faster elimination of viable organisms from the CSF (-0.97 +/- 0.35 log CFU/ml/h). The study shows that tazobactam is able to provide effective protection against piperacillin hydrolysis by the TEM-3 enzyme within the CSF. Appropriate dosage regimens of various beta-lactam-tazobactam combinations may deserve comparative studies in experimental meningitis caused by organisms producing extended-spectrum beta-lactamases.

[Acute respiratory insufficiency caused by hyperinfestation with strongyloides. BALF diagnosis and favourable outcome]. / Insuffisance respiratoire aiguë liée à une anguillulose d'hyperinfestation. Diagnostic par LBA et évolution favorable.

Hyperinfestation with Strongyloides is a severe complication in immunodepressed patients. It may present with various clinical signs, notably acute respiratory failure. Diagnosis may be difficult, particularly when the strongyloidiasis is associated with septicaemia caused by Gram-negative organisms. We report a new case of hyperinfestation with Strongyloides in a patient treated for periarteritis nodosa. This case was remarkable on two scores: the diagnosis problem raised by the presence of intrapulmonary haemorrhages, and the favourable outcome of an acute and initially severe respiratory failure which had required assisted ventilation. The role played in the patient's cure by the doses of thiabendazole given and the duration of their administration is discussed.