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1.  Tolerability of High Doses of Daptomycin in the Treatment of Prosthetic Vascular Graft Infection: A Retrospective Study 
Infectious Diseases and Therapy  2014;3(2):215-223.
In treatment of prosthetic vascular graft infection (PVGI), appropriate antimicrobial treatment is crucial for controlling the septic process and preventing re-infection of the new graft. Glycopeptides are the mainstay of treatment for device-related infections by methicillin-resistant Staphylococcus aureus strains, but with some limitations, especially concerning vancomycin-intermediate and glycopeptide-intermediate S. aureus. We report our experience using a high dose of daptomycin (DAP) for treatment of PVGI.
We reviewed medical reports of 26 patients treated with high doses of DAP (>8 mg/kg) and beta-lactams/aminosides for PVGI, defined as positive bacterial culture of intraoperative specimens or blood samples and/or clinical, biological, and radiological signs of infection. Clinical success was defined by resolution of all clinical signs at the end of follow-up, without the need for additional antibiotic therapy, and/or negative culture in case of new surgery.
Cultures of intraoperative samples were positive in 21 patients (80.8%). Blood and intraoperative cultures were concomitantly positive in 10 patients. The main microorganism identified in microbiological samples was S. aureus (n = 18). Surgery was performed in 23 patients (88.4%). The mean duration of the DAP regimen was 12.3 ± 11.9 days. DAP was discontinued in 26 patients [need to switch to microbiological results (n = 19), bacterial pneumonia (n = 2), and increased creatine phosphokinase levels (n = 4)]. One patient had myalgia, while 9 received concomitant statins.
High-dose DAP therapy shows a satisfactory toxicity profile even in severely ill patients with multiple comorbidities, and may favorably compete with vancomycin, especially concerning the risk of induced nephrotoxicity.
Electronic supplementary material
The online version of this article (doi:10.1007/s40121-014-0035-9) contains supplementary material, which is available to authorized users.
PMCID: PMC4269615  PMID: 25186318
Biofilm; Daptomycin; Prosthetic vascular graft infection; Staphylococcus aureus; Staphylococcal infection
2.  One-year mortality in patients requiring prolonged mechanical ventilation: multicenter evaluation of the ProVent score 
Critical Care  2014;18(4):R155.
Current severity-of-illness indexes are unable to assess the long-term prognosis of patients requiring prolonged mechanical ventilation. A prognostic scoring system (Prognosis for Prolonged Ventilation score - ProVent - score) seems able to evaluate one-year mortality of such patients. However, testing of the model outside the developers' centers has not been reported. So, it is unclear how the ProVent score performs in non-US and non-tertiary ICUs. The goal of our study was to evaluate its performances in a French multicenter, community hospital-based setting.
In three primary ICUs, 201 patients requiring mechanical ventilation for at least 21 days were enrolled in a retrospective cohort study. ICU mortality was abstracted from medical records and, for patients discharged alive from the ICU, one-year mortality was determined by telephone calls to patients’ general practitioners.
One-year mortality was 60% (n = 120). On day 21 of ventilation, ProVent score value was 0 in 19 patients (9%), 1 in 63 patients (31%), 2 in 64 patients (32%), 3 in 37 patients (18%), and ≥4 in 18 patients (9%), respectively. For ProVent score values ranging from 0 to ≥4, one-year mortality rates were 21%, 43%, 67%, 78%, and 94%, respectively. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve for the ProVent score was 0.74 (95% confidence interval 0.671 to 0.809). Stepwise logistic regression analysis showed that only three variables (age ≥65 years, vasopressors, and hemodialysis) were independently associated with one-year mortality in our population. In assigning one point to each variable, we created a French ProVent score. The Hosmer-Lemeshow goodness-of-fit statistic was 1.36 (DF = 6, P = 0.857) and the AUC of the ROC curve was 0.742 (95% confidence interval 0.673 to 0.810). One-year mortality rates for French ProVent score ranging from 0 to 3 were 34.6%, 70.9%, 83.3% and 100%, respectively (P <0.0001).
The ProVent score is able, even in non-US ICUs and in community hospitals, to accurately identify among patients requiring prolonged mechanical ventilation those who are at high risk of one-year mortality. Its simplification appears possible. However, further validation of this French ProVent score in a larger external sample is indicated.
PMCID: PMC4223371  PMID: 25037939
3.  Factors predictive of treatment failure in staphylococcal prosthetic vascular graft infections: a prospective observational cohort study: impact of rifampin 
BMC Infectious Diseases  2014;14:228.
There exists considerable debate concerning management of prosthetic vascular graft infection (PVGI), especially in terms of antimicrobial treatment. This report studies factors associated with treatment failure in a cohort of patients with staphylococcal PVGI, along with the impact of rifampin (RIF).
All data on patients with PVGI between 2006 and 2010 were reviewed. Cure was defined as the absence of evidence of infection during the entire post-treatment follow-up for a minimum of one year. Failure was defined as any other outcome.
84 patients (72 M/12 F, median age 64.5 ± 11 y) with diabetes mellitus (n = 25), obesity (n = 48), coronary artery disease (n = 48), renal failure (n = 24) or COPD (n = 22) were treated for PVGI (median follow-up was 470 ± 469 d). PVGI was primarily intracavitary (n = 47). Staphylococcus aureus (n = 65; including 17 methicillin-resistant S. aureus) and coagulase-negative Staphylocococcus (n = 22) were identified. Surgical treatment was performed in 71 patients. In univariate analysis, significant risk factors associated with failure were renal failure (p = 0.04), aortic aneurysm (p = 0.03), fever (p = 0.009), aneurysm disruption (p = 0.02), septic shock in the peri-operative period (p = 0.005) and antibiotic treatment containing RIF (p = 0.03). In multivariate analysis, 2 variables were independently associated with failure:septic shock [OR 4.98: CI 95% 1.45-16.99; p=0.01] and antibiotic containing rifampin [OR: 0.32: CI95% 0.10-0.96; p=0.04].
Results of the present study suggest that fever, septic shock and non-use of antibiotic treatment containing RIF are associated with poor outcome.
PMCID: PMC4049509  PMID: 24775563
Vascular graft infection; Prosthesis infection; Staphylococci; Rifampin
4.  Intra-abdominal aortic graft infection: prognostic factors associated with in-hospital mortality 
BMC Infectious Diseases  2014;14:215.
Mortality associated with aortic graft infection is considerable. The gold standard for surgical treatment remains explantation of the graft. However, prognostic factors associated with early mortality due to this surgical procedure are not well-known.
Retrospective analysis of patients admitted in our center between January 2006 and October 2011 for aortic graft infection. The primary endpoint was in-hospital mortality. A bivariate analysis of characteristics of patients associated with in-hospital outcome was performed.
Twenty five evaluable patients were studied. All patients were male. Their mean age was 67 ± 8.4 years. Most of them (92%) had severe underlying diseases. An in situ prosthetic graft replacement, mainly using cryopreserved arterial allografts, was performed in all patients, excepted one who underwent extra-anatomic bypass. Causative organisms were identified in 23 patients (92%). The in-hospital mortality rate was 48%. Among pre-operative characteristics, age ≥ 70 years, creatinine ≥ 12 mg/L and C reactive protein ≥ 50 mg/L were significantly associated with in-hospital mortality. Hospital mortality rates increased with the number of risk factor present on ICU admission, and were 0%, 14.3%, 85.7% and 100% for 0, 1, 2 and 3 factors, respectively. The only intra-operative factor associated with prognosis was an associated intestinal procedure due to aorto-enteric fistula. SAPS II, SOFA score and occurrence of medical or surgical complications were postoperative characteristics associated with in-hospital mortality.
Morbidity and mortality associated with surgical approach of aortic graft infections are considerable. Age and values of creatinine and C Reactive protein on hospital admission appear as the most important determinant of in hospital mortality. They could be taken into account for guiding the surgical strategy.
PMCID: PMC4013799  PMID: 24754963
Aortic graft; Aortic surgery; Prosthetic infection; Prognosis
5.  Improvement in process of care and outcome in patients requiring intensive care unit admission for community acquired pneumonia 
BMC Infectious Diseases  2013;13:196.
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.
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.
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.
Positive outcomes in ICU patients with CAP have significantly increased in our ICU in recent years. Many new interventions have contributed to this improvement.
PMCID: PMC3655065  PMID: 23631630
Severe community acquired pneumonia; Intensive care unit; Antimicrobial therapy; Combination therapy
6.  Should highly active antiretroviral therapy be prescribed in critically ill HIV-infected patients during the ICU stay? A retrospective cohort study 
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.
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).
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.
PMCID: PMC3544704  PMID: 23020962
HIV; Intensive care; HAART
7.  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.
PMCID: PMC3297508  PMID: 22321435
aortic mycotic aneurysm; ESBL producing Escherichia coli; meningitis
8.  Evaluation of "Candida score" in critically ill patients: a prospective, multicenter, observational, cohort study 
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.
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.
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).
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).
PMCID: PMC3247094  PMID: 22128895
9.  Severe pneumococcal pneumonia: impact of new quinolones on prognosis 
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.
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.
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).
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.
PMCID: PMC3065411  PMID: 21406091
10.  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.
PMCID: PMC2958629  PMID: 20981326
11.  Comparison of albicans vs. non-albicans candidemia in French intensive care units 
Critical Care  2010;14(3):R98.
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.
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.
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.
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.
PMCID: PMC2911735  PMID: 20507569
12.  Resuscitation with low volume hydroxyethylstarch 130 kDa/0.4 is not associated with acute kidney injury 
Critical Care  2010;14(2):R40.
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.
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.
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).
Volume expansion with low volume HES 130 kDa/0.4 was not associated with AKI.
PMCID: PMC2887149  PMID: 20298543
13.  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.
PMCID: PMC2754413  PMID: 16122422
14.  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.
PMCID: PMC2606649  PMID: 19365534
Intensive care; community-acquired pneumonia; prognostic score.
15.  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.
PMCID: PMC373267  PMID: 14704342

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