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1.  Improvement in process of care and outcome in patients requiring intensive care unit admission for community acquired pneumonia 
BMC Infectious Diseases  2013;13:196.
Background
The present study was performed to assess the prognosis of patients admitted to the intensive care unit (ICU) for community acquired pneumonia (CAP) after implementation of new processes of care.
Methods
Two groups of patients with CAP were admitted to a 16-bed multidisciplinary ICU in an urban teaching hospital during two different periods: the years 1995–2000, corresponding to the historical group; and 2005–2010, corresponding to the intervention group. New therapeutic procedures were implemented during the period 2005–2010. These procedures included a sepsis management bundle derived from the Surviving Sepsis Campaign, use of a third-generation cephalosporin and levofloxacin as the initial empirical antimicrobial regimen, and noninvasive mechanical ventilation following extubation.
Results
A total of 317 patients were studied: 142 (44.8%) during the historical period and 175 (55.2%) during the intervention period. Sequential Organ Failure Assessment scores were higher in patients in the intervention group (7.2 ± 3.7 vs 6.2 ± 2.8; p=0.008). Mortality changed significantly between the two studied periods, decreasing from 43.6% in the historical group to 30.9% in the intervention group (p < 0.02). A restrictive transfusion strategy, use of systematic postextubation noninvasive mechanical ventilation in patients with severe chronic respiratory or cardiac failure patients, less frequent use of dobutamine and/or epinephrine in patients with sepsis or septic shock, and delivery of a third-generation cephalosporin associated with levofloxacin as empirical antimicrobial therapy were independently associated with better outcomes.
Conclusion
Positive outcomes in ICU patients with CAP have significantly increased in our ICU in recent years. Many new interventions have contributed to this improvement.
doi:10.1186/1471-2334-13-196
PMCID: PMC3655065  PMID: 23631630
Severe community acquired pneumonia; Intensive care unit; Antimicrobial therapy; Combination therapy
2.  Should highly active antiretroviral therapy be prescribed in critically ill HIV-infected patients during the ICU stay? A retrospective cohort study 
Background
The impact of highly active antiretroviral therapy (HAART) in HIV-infected patients admitted to the intensive care unit (ICU) remains controversial. We evaluate impact of HAART prescription in HIV-infected patients admitted to the ICU of Tourcoing Hospital from January 2000 to December 2009.
Results
There were 91 admissions concerning 85 HIV-infected patients. Reasons for ICU admission were an AIDS-related diagnosis in 46 cases (51%). Fifty two patients (57%) were on HAART at the time of ICU admission, leading to 21 immunovirologic successes (23%). During the ICU stay, HAART was continued in 29 patients (32%), and started in 3 patients (3%). Only one patient experienced an adverse event related to HAART. Mortality rate in ICU and 6 months after ICU admission were respectively 19% and 27%. Kaplan-Meier estimates of the cumulative unajusted survival probability over 6 months were higher in patients treated with HAART during the ICU stay (Log rank: p = 0.04). No benefit of HAART in ICU was seen in the adjusted survival proportion at 6 months or during ICU stay. Prescription of HAART during ICU was associated with a trend to lower incidence of new AIDS-related events at 6 months (respectively 17% and 34% with and without HAART, p = 0.07), and with higher incidence of antiretroviral resistance after ICU stay (respectively 25% and 7% with and without HAART, p = 0.02).
Conclusions
Our results suggest a lower death rate over 6 months in critically ill HIV-infected patients taking HAART during ICU stay. The optimal time to prescribe HAART in critically ill patients needs to be better defined.
doi:10.1186/1742-6405-9-27
PMCID: PMC3544704  PMID: 23020962
HIV; Intensive care; HAART
3.  First Initial community-acquired meningitis due to extended-spectrum beta-lactamase producing Escherichia coli complicated with multiple aortic mycotic aneurysms 
We report the first case of extended-spectrum beta-lactamase producing E. coli community-acquired meningitis complicated with multiple aortic mycotic aneurysms. Because of the acute aneurysm expansion with possible impending rupture on 2 abdominal CT scan, the patient underwent prompt vascular surgery and broad spectrum antibiotic therapy but he died of a hemorrhagic shock. Extended-spectrum beta-lactamase producing E. coli was identified from both blood and cerebrospinal fluid culture before vascular treatment. The present case report does not however change the guidelines of Gram negative bacteria meningitis in adults.
doi:10.1186/1476-0711-11-4
PMCID: PMC3297508  PMID: 22321435
aortic mycotic aneurysm; ESBL producing Escherichia coli; meningitis
4.  Evaluation of "Candida score" in critically ill patients: a prospective, multicenter, observational, cohort study 
Introduction
Although prompt initiation of appropriate antifungal therapy is essential for the control of invasive Candida infections and an improvement of prognosis, early diagnosis of invasive candidiasis remains a challenge and criteria for starting empirical antifungal therapy in ICU patients are poorly defined. Some scoring systems, such as the "Candida score" could help physicians to differentiate patients who could benefit from early antifungal treatment from those for whom invasive candidiasis is highly improbable. This study evaluated the performance of this score in a cohort of critically ill patients.
Methods
A prospective, observational, multicenter, cohort study was conducted from January 2010 to March 2011 in five intensive care units in Nord-Pas de Calais, an area from North of France. All patients exhibiting, on ICU admission or during their ICU stay, a hospital-acquired severe sepsis or septic shock could be included in this study. The data collected included patient characteristics on ICU admission and at the onset of severe sepsis or septic shock. The "Candida score" was calculated at the onset of sepsis or shock. The incidence of invasive candidiasis was determined and its relationship with the value of the "Candida score" was studied.
Results
Ninety-four patients were studied. When severe sepsis or shock occurred, 44 patients had a score = 2, 29 patients had a score = 3, 17 patients had a score = 4, and 4 patients had a score = 5. Invasive candidiasis was observed in five (5.3%) patients. One patient had candidemia, three patients had peritonitis, and one patient had pleural infection. The rates of invasive candidiasis was 0% in patients with score = 2 or 3, 17.6% in patients with score = 4, and 50% in patients with score = 5 (p < 0.0001).
Conclusions
Our results confirm that the "Candida score" is an interesting tool to differentiate among ICU patients who exhibit hospital-acquired severe sepsis or septic shock those would benefit from early antifungal treatment (score > 3) from those for whom invasive candidiasis is highly improbable (score ≤ 3).
doi:10.1186/2110-5820-1-50
PMCID: PMC3247094  PMID: 22128895
5.  Severe pneumococcal pneumonia: impact of new quinolones on prognosis 
Background
Most guidelines have been proposing, for more than 15 years, a β-lactam combined with either a quinolone or a macrolide as empirical, first-line therapy of severe community acquired pneumonia (CAP) requiring ICU admission. Our goal was to evaluate the outcome of patients with severe CAP, focusing on the impact of new rather than old fluoroquinolones combined with β-lactam in the empirical antimicrobial treatments.
Methods
Retrospective study of consecutive patients admitted in a 16-bed general intensive care unit (ICU), between January 1996 and January 2009, for severe (Pneumonia Severity Index > or = 4) community-acquired pneumonia due to non penicillin-resistant Streptococcus pneumoniae and treated with a β-lactam combined with a fluoroquinolone.
Results
We included 70 patients of whom 38 received a β-lactam combined with ofloxacin or ciprofloxacin and 32 combined with levofloxacin. Twenty six patients (37.1%) died in the ICU. Three independent factors associated with decreased survival in ICU were identified: septic shock on ICU admission (AOR = 10.6; 95% CI 2.87-39.3; p = 0.0004), age > 70 yrs. (AOR = 4.88; 95% CI 1.41-16.9; p = 0.01) and initial treatment with a β-lactam combined with ofloxacin or ciprofloxacin (AOR = 4.1; 95% CI 1.13-15.13; p = 0.03).
Conclusion
Our results suggest that, when combined to a β-lactam, levofloxacin is associated with lower mortality than ofloxacin or ciprofloxacin in severe pneumococcal community-acquired pneumonia.
doi:10.1186/1471-2334-11-66
PMCID: PMC3065411  PMID: 21406091
6.  Epidemiology, Prognosis, and Evolution of Management of Septic Shock in a French Intensive Care Unit: A Five Years Survey 
Purpose. To evaluate the epidemiology, prognosis, and management of septic shock patients hospitalized in our intensive care unit (ICU). Materiel and Methods. Five-year monocenter observational study including 320 patients. Results. ICU mortality was 54.4%. Independent mortality risk factors were mechanical ventilation (OR = 4.97), Simplify Acute Physiology Score (SAPS) II > 60 (OR = 4.28), chronic alcoholism (OR = 3.38), age >65 years (OR = 2.65), prothrombin ratio <40% (OR = 2.37), and PaO2/FiO2 ratio <150 (OR = 1.91). These six mortality risk factors recovered allow screening immediately septic shock patients with a high mortality risk. Morbidity improved with time (diminution of septic shock complications, increase of the number of days alive free from mechanical ventilation and vasopressors on day 28), concomitant to an evolution of the management (earlier institution of all replacement and medical therapies and more initial volume expansion). There was no difference in mortality. Conclusion. Our study confirms a high mortality rate in septic shock patients despite a new approach of treatment.
doi:10.1155/2010/436427
PMCID: PMC2958629  PMID: 20981326
7.  Comparison of albicans vs. non-albicans candidemia in French intensive care units 
Critical Care  2010;14(3):R98.
Introduction
Candidemia raises numerous therapeutic issues for intensive care physicians. Epidemiological data that could guide the choice of initial therapy are still required. This analysis sought to compare the characteristics of intensive care unit (ICU) patients with candidemia due to non-albicans Candida species with those of ICU patients with candidemia due to Candida albicans.
Methods
A prospective, observational, multicenter, French study was conducted from October 2005 to May 2006. Patients exhibiting candidemia developed during ICU stay and exclusively due either to one or more non-albicans Candida species or to C. albicans were selected. The data collected included patient characteristics on ICU admission and at the onset of candidemia.
Results
Among the 136 patients analyzed, 78 (57.4%) had candidemia caused by C. albicans. These patients had earlier onset of infection (11.1 ± 14.2 days after ICU admission vs. 17.4 ± 17.7, p = 0.02), higher severity scores on ICU admission (SOFA: 10.4 ± 4.7 vs. 8.6 ± 4.6, p = 0.03; SAPS II: 57.4 ± 22.8 vs. 48.7 ± 15.5, P = 0.015), and were less often neutropenic (2.6% vs. 12%, p = 0.04) than patients with candidemia due to non-albicans Candida species.
Conclusions
Although patients infected with Candida albicans differed from patients infected with non-albicans Candida species for a few characteristics, no clinical factor appeared pertinent enough to guide the choice of empirical antifungal therapy in ICU.
doi:10.1186/cc9033
PMCID: PMC2911735  PMID: 20507569
8.  Resuscitation with low volume hydroxyethylstarch 130 kDa/0.4 is not associated with acute kidney injury 
Critical Care  2010;14(2):R40.
Introduction
Acute kidney injury (AKI) in the ICU is associated with poorer prognosis. Hydroxyethylstarch (HES) solutions are fluid resuscitation colloids frequently used in the ICU with controversial nephrotoxic adverse effects. Our study objective was to evaluate HES impact on renal function and organ failures.
Methods
This observational retrospective study included 363 patients hospitalized for more than 72 hours in our ICU. A hundred and sixty eight patients received HES during their stay and 195 did not. We recorded patients' baseline characteristics on admission and type and volume of fluid resuscitation during the first 3 weeks of ICU stay. We also noted the evolution of urine output, the risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function and end-stage kidney disease (RIFLE) classification and sepsis related organ failure assessment (SOFA) score over 3 weeks.
Results
Patients in the HES group were more severely ill on admission but AKI incidence was similar, as well as ICU mortality. The evolution of urine output (P = 0.74), RIFLE classification (P = 0.44) and SOFA score (P = 0.23) was not different. However, HES volumes administered were low (763+/-593 ml during the first 48 hours).
Conclusions
Volume expansion with low volume HES 130 kDa/0.4 was not associated with AKI.
doi:10.1186/cc8920
PMCID: PMC2887149  PMID: 20298543
9.  Inhibition of Bacterial Rna Polymerase by Streptolydigin: Stabilization of A Straight-Bridge-Helix Active-Center Conformation 
Cell  2005;122(4):541-552.
We define the target, mechanism, and structural basis of inhibition of bacterial RNA polymerase (RNAP) by the tetramic-acid antibiotic streptolydigin (Stl). Stl binds to a site adjacent to, but not overlapping, the RNAP active center and stabilizes an RNAP-active-center conformational state with a straight bridge helix. The results provide direct support for the proposals that alternative straight-bridge-helix and bent-bridge-helix RNAP-active-center conformations exist, and that cycling between straight-bridge-helix and bent-bridge-helix RNAP-active-center conformations is required for RNAP function. The results set bounds on models for RNAP function and suggest strategies for design of novel antibacterial agents.
doi:10.1016/j.cell.2005.07.017
PMCID: PMC2754413  PMID: 16122422
10.  Validation of a Prediction Rule for Prognosis of Severe Community-Acquired Pneumonia 
In a previous study, we developed a prognostic prediction rule, based on nine prognostic variables, capable to estimate and to adjust the mortality rate of patients admitted in intensive care unit for severe community-acquired pneumonia. A prospective multicenter study was undertaken to evaluate the performance of this rule. Five hundred eleven patients, over a 7-year period, were studied. The ICU mortality rate was 29.0%. In the 3 initial risk classes, we observed significantly increasing mortality rates (8.2% in class I, 22.8% in class II and 65.0% in class III) (p<0.001). Within each initial risk class, the adjustment risk score identified subclasses exhibiting significantly different mortality rates: 3.9% and 33.3% in class I; 3.1%, 12.9% and 63.3% in class II; and 55.8% and 82.5% in class III. Compared with mortality rates predicted by our previous study, only a few significant differences were observed. Our results demonstrate the performance and reproductibility of this prognostic prediction rule.
doi:10.2174/1874306400802010067
PMCID: PMC2606649  PMID: 19365534
Intensive care; community-acquired pneumonia; prognostic score.
11.  Interactions between the 2.4 and 4.2 regions of σS, the stress-specific σ factor of Escherichia coli, and the –10 and –35 promoter elements 
Nucleic Acids Research  2004;32(1):45-53.
The σs subunit of Escherichia coli RNA polymerase holoenzyme (EσS) is a key factor of gene expression upon entry into stationary phase and in stressful conditions. The selectivity of promoter recognition by EσS and the housekeeping Eσ70 is as yet not clearly understood. We used a genetic approach to investigate the interaction of σS with its target promoters. Starting with down-promoter variants of a σS promoter target, osmEp, altered in the –10 or –35 elements, we isolated mutant forms of σS suppressing the promoter defects. The activity of these suppressors on variants of osmEp and ficp, another target of σS, indicated that σS is able to interact with the same key features within a promoter sequence as σ70. Indeed, (i) σS can recognize the –35 element of some but not all its target promoters, through interactions with its 4.2 region; and (ii) amino acids within the 2.4 region participate in the recognition of the –10 element. More specifically, residues Q152 and E155 contribute to the strong preference of σS for a C in position –13 and residue R299 can interact with the –31 nucleotide in the –35 element of the target promoters.
doi:10.1093/nar/gkh155
PMCID: PMC373267  PMID: 14704342

Results 1-11 (11)