mercredi 5 février 2020 

14h10 - 15h10


 
S03

Infectiologie I

MODÉRATEUR(S) :  François BARBIER (Orléans), Saad NSEIR (Lille)  
  

Risk Factors for Candidemia: A Prospective Matched Case-Control Study

Orateur(s) :   Julien POISSY (Lille) 

Auteur(s) :  Lauro DAMONTI (Bern)   Anne BIGNON (Lille)   Nina KHANNA (Bsael)   Matthias VON KIETZELL (Saint Gallen)   Katia BOGGIAN (Saint Gallen)   Dionysios NEOFYTOS (Geneva, SUISSE)   Fanny VUOTTO (Lille)   Valerie COITEUX (Lille)   Florent ARTRU (Lille)   Stefan ZIMMERLI (Bern)   Jean-luc PAGANI (Lausanne)   Thierry CALANDRA (Lausanne)   Boualem SENDID (Lille)   Daniel POULAIN (Lille)   Christian VAN DELDEN (Geneva)   Frédéric LAMOTH (Lausanne)   Oscar MARCHETTI (Lausanne)   Pierre-yves BOCHUD (Lausanne)  

14h10 - 14h25
Durée de la présentation : 10 min
Durée de la discussion : 5 min


Abstract : 
Risk Factors for Candidemia: A Prospective Matched Case-Control Study

Introduction / Rationale :
Candidemia is an opportunistic infection associated with high morbidity and mortality in hospitalized patients, both inside and outside intensive care units (ICUs). Identification of patients at risk for preemptive approach and early detection is crucial. Prospective control-matched studies and comparison between ICU and non-ICU patients are lacking in this field. We aim to identify and compare specific risk factors in ICU and non ICU patients.

Méthodes / Patients and Methods :
This was a prospective multicenter matched case-control study assessing risk factors for candidemia and death in candidemic patients, both outside and inside ICUs, from 6 teaching hospitals. Controls were matched to cases based on age, hospitalization ward, hospitalization duration and, when applicable, type of surgery. Risk factors were analyzed by univariate and multivariate conditional regression models, as a basis for a new scoring system to predict candidemia.

Résultats / Results :
The study included 192 cases and 411 matched controls. 44% were hospitalized inside ICU and 56% outside. Independent risk factors for candidemia within the ICU population included total parenteral nutrition (TPN) (OR=6.75, p<0.001), acute kidney injury (OR=4.77, p<0.001), heart disease (OR=3.78, p=0.006), previous septic shock (OR=2.39, p=0.02) and exposure to aminoglycosides (OR=2.28, p=0.05). Independent risk factors for candidemia within the non-ICU population included central venous catheter (CVC) (OR=9.77, p<0.001), TPN (OR=3.29, p=0.003), exposure to glycopeptides (OR=3.31, p=0.04), and to nitroimidazoles (OR=3.12, p=0.04).
The weighted scores and their ROC curves are presented in figure 1. The weighted ICU-score was as follows: TPN, +2.5; AKI, +1.5; heart disease, +1.5; previous septic shock, +1.0; aminoglycosides, +1.0. AUC of the ROC curve was 0.768. The optimal cut-off was ≥4 (sensitivity=69%, specificity=70%). The best cut-off to optimize specificity was ≥5 (sensitivity=43%, specificity=88%). The weighted non-ICU score was as follows: CVC, +2.5; nitroimidazole : +1.0; TPN, +1.0; Glycopeptide : +1.0. AUC of the ROC curve was 0.717. The optimal cut-off was ≥2 (sensitivity=83%, specificity=50%). The best cut-off to optimize specificity was ≥4 (sensitivity=51%, specificity=81%).
Independent factors for death in candidemic patients in ICU patients were septic shock (OR=4.09, p=0.003), acute kidney injury (OR=3.45, p=0.02), the number of antibiotics to which patients were exposed before candidemia (OR=1.37 per unit, p=0.02). For non-ICU patients, acute kidney injury (OR=11.9, p=0.002) and septic shock (OR=8.70, p=0.002) were the only variables significantly associated with death

Discussion / Discussion :


Conclusion / Conclusion :
Risk factors for candidemia differ between ICU and non-ICU settings, including different patterns of antibiotic exposure, leading to different weighted scores predictive of candidemia, with better performances for ICU-patients.
 

A Stronger Signal of ART-123 Efficacy in Patients with Sepsis Associated Coagulopathy Enrolled into the SCARLET Trial in France.

Orateur(s) :   Bruno FRANÇOIS (Limoges) 

Auteur(s) :  Maud FIANCETTE (La Roche-Sur-Yon)   Julie HELMS (Strasbourg)   Emmanuelle MERCIER (Tours)   Jean-Baptiste LASCARROU (Nantes)   Xavier WITTEBOLE (Brussels)   Amanda RADFORD (Waltham)   Toshihiko KAYANOKI (Waltham)   Kosuke TANAKA (Waltham)   David FINEBERG (Waltham)   Jean-Louis VINCENT (Brussels, BELGIQUE)  

14h25 - 14h40
Durée de la présentation : 10 min
Durée de la discussion : 5 min


Abstract : 
A Stronger Signal of ART-123 Efficacy in Patients with Sepsis Associated Coagulopathy Enrolled into the SCARLET Trial in France.

Introduction / Rationale :
To assess the effect of recombinant human soluble thrombomodulin (ART-123) treatment on 28-day all-cause mortality in patients with sepsis associated coagulopathy (SAC) enrolled in France, the highest enrolling country, as compared to the global population of patients in the randomized, double-blinded, placebo-controlled, SCARLET phase 3 study (NCT01598831), and especially to evaluate factors that may have contributed to greater mortality reduction in the French patients.

Méthodes / Patients and Methods :
Among the global patient population with SAC defined as an international normalized ratio (INR) >1.40, platelet count >30-<150 x 109 or >30% decrease in 24 hours, and with concomitant cardiovascular and/or respiratory failure, patients in France were analyzed. All subjects were treated with 0.06 mg/kg/day of intravenous ART-123 (n=75/395) or placebo (n=74/405) for up to 6 days in addition to standard of care.

Résultats / Results :
In the SCARLET trial, ART-123 did not significantly reduce 28-day all-cause mortality (800 patients from 149 sites in 26 countries) with an absolute risk reduction (ARR) of 2.55% (P=0.32) in ART-123 treated patients with SAC, and 5.4% in those patients who maintained protocol specified coagulopathy (INR > 1.40, platelet count > 30 x 109) at baseline prior to study drug dosing. In France, there were 149/800 (18.6%) patients enrolled at 16/149 (10.7%) sites. Considering all randomized and dosed patients in France as compared to those patients that maintained protocol specified coagulopathy, the 28-day ARR for ART-123 was higher in France than for the global population. Patients enrolled in France were more likely to have the protocol specified coagulopathy criteria at baseline than in other countries. They also had overall more severe baseline disease as measured by the number of patients with at least 3 organ dysfunctions (cardiovascular, respiratory, renal, and hepatic) and a higher APACHE II score than the other patients. However, they were less likely to be treated by renal replacement therapy (RRT) or to receive heparin at baseline. In France there was a greater proportion of enrollment from individual sites enrolling 6 patients or more.

Discussion / Discussion :


Conclusion / Conclusion :
The trend towards a higher difference of mortality benefit in patients treated with ART-123 and enrolled in France may be attributed to better patient selection, and a higher rate of patients meeting the protocol specified coagulopathy criteria at baseline by primarily high enrolling research sites.
 

Use and impact of aminoglycoside empirical therapy in extended spectrum beta-lactamase enterobacteriaceae bloodstream infections in intensive care unit

Orateur(s) :   Lucie BENETAZZO (Tourcoing) 

Auteur(s) :  Pierre-Yves DELANNOY (Tourcoing)   Olivier LEROY (Tourcoing)   Olivier ROBINEAU (Tourcoing)   Agnes MEYBECK (Tourcoing)  

14h40 - 14h55
Durée de la présentation : 10 min
Durée de la discussion : 5 min


Abstract : 
Use and impact of aminoglycoside empirical therapy in extended spectrum beta-lactamase enterobacteriaceae bloodstream infections in intensive care unit

Introduction / Rationale :
Aminoglycosides are prescribed in severe infections for bactericidal activity and broadening of the spectrum. As the prevalence of extended-spectrum beta-lactamase producing enterobacteriaceae (ESBLE) increases, aminoglycosides may be interesting for their treatment. However, their use is limited by their toxicity, especially renal. Our study evaluated the impact of an aminoglycoside in empirical treatment of ESBLE bloodstream infection in intensive care unit (ICU).

Méthodes / Patients and Methods :
Between January 2011 and September 2017, patients treated for ESBLE bacteraemia in the ICU of 5 French hospitals from Hauts de France were included in a retrospective observational cohort study. In order to evaluate the impact of the empirical prescription of an aminoglycoside, a bivariate and multivariate analysis were performed. The primary endpoint was mortality on day 30. Secondary endpoints were empirical antibiotic therapy adequacy and renal failure rates.

Résultats / Results :
Three hundred and seven patients were included, 169 received an aminoglycoside as initial treatment. The death rate at day 30 was 40%. We did not find any difference in mortality between aminoglycoside and non-aminoglycoside group (43.4% vs 39.3%, p = 0.545). Renal impairment occurred in aminoglycoside and non-aminoglycoside groups in 20.7% and 23.9%, respectively (p = 0.59). The adequacy rate of empirical antibiotic therapy was higher in the aminoglycoside group (91.7% vs 77%, p = 0.001). An age greater than 70 years, a history of transplantation, or the nosocomial origin of bacteremia were associated with mortality at day 30. Maintenance of amines more than 48 hours after bacteremia, occurrence of ARDS or acute renal failure also increased mortality on day 30.

Discussion / Discussion :


Conclusion / Conclusion :
Our study did not show any impact of aminoglycoside empirical prescription for the treatment of ESBLE bacteraemia even if it led to an increase in the adequacy rate of empirical therapy. We did not find any renal toxicity caused by aminoglycosides.
 

Impact of a restrictive antibiotic policy on the emergence of extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-E) in the ICU. A quasi-experimental observational study

Orateur(s) :   Christophe LE TERRIER (Pointe-À-Pitre) 

Auteur(s) :  Marco VINETTI (Pointe-À-Pitre)   Régine RICHARD (Pointe-À-Pitre)   Bruno JARRIGE (Pointe-À-Pitre)   Sébastien BREUREC (Pointe-À-Pitre)   Michel CARLES (Pointe-À-Pitre)   Guillaume THIERY (Pointe-À-Pitre)  

14h55 - 15h10
Durée de la présentation : 10 min
Durée de la discussion : 5 min


Abstract : 
Impact of a restrictive antibiotic policy on the emergence of extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-E) in the ICU. A quasi-experimental observational study

Introduction / Rationale :
Massive consumption of antibiotics in the intensive care unit (ICU) is a major determinant of extended-spectrum beta-lactamase–producing Enterobacteriaceae (ESBL-E) spreading. We evaluated whether a stewardship program including restrictive antibiotic policy in the ICU would reduce ESBL-E emergence without worsening patient’s outcomes.

Méthodes / Patients and Methods :
We conducted an observational quasi-experimental pre-post intervention study of all consecutive patients with length of stay (LOS) superior to 48h to the medical-surgical ICU of University Hospital of Guadeloupe. From Jan 1, 2014 to Dec 31, 2014, a liberal strategy was used including a broad-spectrum antibiotic as initial empirical treatment in case of sepsis or suspected infection, followed by de-escalation after 48-72h. From Jan 1, 2015 to Dec 31, 2015, a restrictive strategy was adopted which consisted of limitation of broad-spectrum antibiotics, avoidance of antibiotics targeting anaerobic microbiota and shortening of antibiotic duration. In addition, antibiotic therapy was initiated only after microbiological identification, except in cases of septic shock, acute respiratory distress syndrome and meningitis, where an empiric therapy was started immediately after the microbiological samples were taken. Our primary outcome was the incidence of ICU-acquired ESBL-E and the main secondary outcome were all-cause ICU mortality and the rate of ESBL-E infections.

Résultats / Results :
1009 and 1067 patients were admitted to ICU during the liberal and the restrictive strategy period of the study respectively. Among them, 767 and 826 patients were hospitalized > 48h and were enrolled in the study. During the restrictive strategy period, less patients were treated with antibiotic therapy (41 vs 52%; p<0.001), treatment duration was shorter (5 vs 6 days; p=0.01) and antibiotics targeting anaerobic pathogens were significantly less administrated (87.1% vs 37.5%; p0.0001). The rate of ICU-acquired ESBL-E carriage was significantly lower during the restrictive strategy period (18.9% vs 11.1%; p<0.0001). Similarly, ICU-acquired ESBL-E infection rate and ICU mortality were lower during the restrictive strategy period. In multivariate analysis, the length of stay in the ICU, the number of antibiotic administrated and the restrictive strategy period were independently associated with a lower rate of ESBL-E acquisition.

Discussion / Discussion :


Conclusion / Conclusion :
In a large cohort of consecutive ICU patients, a stewardship program including a restrictive antibiotic strategy has proven effective in terms of reduction of antibiotic consumption, especially broad spectrum antibiotics and those targeting anaerobic microbiota. This strategy was associated with a lower rate of ESBL-E acquisition without worsening patient’s outcomes.