Publications by authors named "Nathalie Layios"

18 Publications

  • Page 1 of 1

Duration of antibiotic treatment using procalcitonin-guided treatment algorithms in older patients: a patient-level meta-analysis from randomized controlled trials.

Age Ageing 2021 May 17. Epub 2021 May 17.

Critical Care and Peri-operative Medicine, Monash Health, Melbourne, Australia.

Background: Older patients have a less pronounced immune response to infection, which may also influence infection biomarkers. There is currently insufficient data regarding clinical effects of procalcitonin (PCT) to guide antibiotic treatment in older patients.

Objective And Design: We performed an individual patient data meta-analysis to investigate the association of age on effects of PCT-guided antibiotic stewardship regarding antibiotic use and outcome.

Subjects And Methods: We had access to 9,421 individual infection patients from 28 randomized controlled trials comparing PCT-guided antibiotic therapy (intervention group) or standard care. We stratified patients according to age in four groups (<75 years [n = 7,079], 75-80 years [n = 1,034], 81-85 years [n = 803] and >85 years [n = 505]). The primary endpoint was the duration of antibiotic treatment and the secondary endpoints were 30-day mortality and length of stay.

Results: Compared to control patients, mean duration of antibiotic therapy in PCT-guided patients was significantly reduced by 24, 22, 26 and 24% in the four age groups corresponding to adjusted differences in antibiotic days of -1.99 (95% confidence interval [CI] -2.36 to -1.62), -1.98 (95% CI -2.94 to -1.02), -2.20 (95% CI -3.15 to -1.25) and - 2.10 (95% CI -3.29 to -0.91) with no differences among age groups. There was no increase in the risk for mortality in any of the age groups. Effects were similar in subgroups by infection type, blood culture result and clinical setting (P interaction >0.05).

Conclusions: This large individual patient data meta-analysis confirms that, similar to younger patients, PCT-guided antibiotic treatment in older patients is associated with significantly reduced antibiotic exposures and no increase in mortality.
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http://dx.doi.org/10.1093/ageing/afab078DOI Listing
May 2021

Continuous infusion, therapeutic drug monitoring and outpatient parenteral antimicrobial therapy with ceftazidime/avibactam: a retrospective cohort study.

J Glob Antimicrob Resist 2021 May 12;26:15-19. Epub 2021 May 12.

Department of Infectious Diseases and General Internal Medicine, University Hospital of Liège, Liège, Belgium.

Objectives: Based on recent pharmacokinetic/pharmacodynamic (PK/PD) evidence, continuous-infusion (CI) β-lactam administration is increasingly recommended for serious infections. Since 2016, the combination ceftazidime/avibactam (CAZ/AVI) is administered as per the manufacturer's instructions as an intermittent infusion of 2.5 g every 8 h. Thus, CI has not yet been evaluated in clinical trials.

Methods: We aimed to evaluate the use of CI of CAZ/AVI in a retrospective case series from December 2016 to October 2019. All isolates displayed in vitro susceptibility to CAZ/AVI according to EUCAST definitions. Patients were initially given CAZ/AVI as CI of 5 g every 12 h, and dosages were adjusted according to therapeutic drug monitoring of ceftazidime with a therapeutic goal of ≥4-5 × MIC in plasma and/or at the site of infection.

Results: CAZ/AVI was administered by CI in 10 patients with infections mainly caused by multidrug-resistant Pseudomonas aeruginosa (54.5%) and Klebsiella pneumoniae (36.4%). Bacteraemia occurred in 30% of cases. Sepsis or septic shock was present in 20% of cases. CAZ/AVI was used as monotherapy in 60% of cases. Clinical cure and microbiological eradication were achieved in 80% and 90% of cases, respectively. The 30-day mortality after CAZ/AVI treatment onset was 10%. The therapeutic goals of ≥4-5 × MIC in plasma and/or at the site of infection were achieved in 100% and 87.5% of cases, respectively, without adverse events.

Conclusion: Despite a limited number of patients, CI of CAZ/AVI provided promising results after optimisation of PK/PD parameters both in plasma and at the site of infection.
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http://dx.doi.org/10.1016/j.jgar.2021.04.015DOI Listing
May 2021

Meropenem: continuous or extended infusion?

Crit Care 2020 05 5;24(1):192. Epub 2020 May 5.

Department of Intensive Care Unit, University Hospital of Liège, Liège, Belgium.

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http://dx.doi.org/10.1186/s13054-020-02883-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201795PMC
May 2020

Soluble GPVI is elevated in injured patients: shedding is mediated by fibrin activation of GPVI.

Blood Adv 2018 02;2(3):240-251

Australian Cancer Research Foundation Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, and.

Soluble glycoprotein VI (sGPVI) is shed from the platelet surface and is a marker of platelet activation in thrombotic conditions. We assessed sGPVI levels together with patient and clinical parameters in acute and chronic inflammatory conditions, including patients with thermal injury and inflammatory bowel disease and patients admitted to the intensive care unit (ICU) for elective cardiac surgery, trauma, acute brain injury, or prolonged ventilation. Plasma sGPVI was measured by enzyme-linked immunosorbent assay and was elevated on day 14 after thermal injury, and was higher in patients who developed sepsis. sGPVI levels were associated with sepsis, and the value for predicting sepsis was increased in combination with platelet count and Abbreviated Burn Severity Index. sGPVI levels positively correlated with levels of D-dimer (a fibrin degradation product) in ICU patients and patients with thermal injury. sGPVI levels in ICU patients at admission were significantly associated with 28- and 90-day mortality independent of platelet count. sGPVI levels in patients with thermal injury were associated with 28-day mortality at days 1, 14, and 21 when adjusting for platelet count. In both cohorts, sGPVI associations with mortality were stronger than D-dimer levels. Mechanistically, release of GPVI was triggered by exposure of platelets to polymerized fibrin, but not by engagement of G protein-coupled receptors by thrombin, adenosine 5'-diphosphate, or thromboxane mimetics. Enhanced fibrin production in these patients may therefore contribute to the observed elevated sGPVI levels. sGPVI is an important platelet-specific marker for platelet activation that predicts sepsis progression and mortality in injured patients.
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http://dx.doi.org/10.1182/bloodadvances.2017011171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5812322PMC
February 2018

Sepsis prediction in critically ill patients by platelet activation markers on ICU admission: a prospective pilot study.

Intensive Care Med Exp 2017 Dec 12;5(1):32. Epub 2017 Jul 12.

Laboratory of Thrombosis and Hemostasis, GIGA-Cardiovascular Sciences, University of Liège, Department of Cardiology, University Hospital of Liège, Liège, Belgium.

Background: Platelets have been involved in both immune surveillance and host defense against severe infection. To date, whether platelet phenotype or other hemostasis components could be associated with predisposition to sepsis in critical illness remains unknown. The aim of this work was to identify platelet markers that could predict sepsis occurrence in critically ill injured patients.

Methods: This single-center, prospective, observational, 7-month study was based on a cohort of 99 non-infected adult patients admitted to ICUs for elective cardiac surgery, trauma, acute brain injury, and post-operative prolonged ventilation and followed up during ICU stay. Clinical characteristics and severity score (SOFA) were recorded on admission. Platelet activation markers, including fibrinogen binding to platelets, platelet membrane P-selectin expression, plasma soluble CD40L, and platelet-leukocytes aggregates were assayed by flow cytometry at admission and 48 h later, and then at the time of sepsis diagnosis (Sepsis-3 criteria) and 7 days later for sepsis patients. Hospitalization data and outcomes were also recorded.

Methods: Of the 99 patients, 19 developed sepsis after a median time of 5 days. These patients had a higher SOFA score at admission; levels of fibrinogen binding to platelets (platelet-Fg) and of D-dimers were also significantly increased compared to the other patients. Levels 48 h after ICU admission no longer differed between the two patient groups. Platelet-Fg % was an independent predictor of sepsis (P = 0.0031). By ROC curve analysis, cutoff point for Platelet-Fg (AUC = 0.75) was 50%. In patients with a SOFA cutoff of 8, the risk of sepsis reached 87% when Platelet-Fg levels were above 50%. Patients with sepsis had longer ICU and hospital stays and higher death rate.

Conclusions: Platelet-bound fibrinogen levels assayed by flow cytometry within 24 h of ICU admission help identifying critically ill patients at risk of developing sepsis.
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http://dx.doi.org/10.1186/s40635-017-0145-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5505890PMC
December 2017

Decreased Antibiotic Consumption in the Belgian Community: Is It Credible?

Clin Infect Dis 2016 Feb 3;62(3):403-4. Epub 2015 Oct 3.

Department of Intensive Care Unit, University Hospital of Liège, Belgium.

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http://dx.doi.org/10.1093/cid/civ868DOI Listing
February 2016

Serum markers of sepsis in burn patients: it takes more to convince!

Crit Care Med 2015 Mar;43(3):e100-1

Burn Centre and General Intensive Care Department, University of Liège, University Hospital, Sart-Tilman, Liège, Belgium.

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http://dx.doi.org/10.1097/CCM.0000000000000815DOI Listing
March 2015

Prevention of ventilator-associated pneumonia and ventilator-associated conditions: a randomized controlled trial with subglottic secretion suctioning.

Crit Care Med 2015 Jan;43(1):22-30

1Department of General Intensive Care, University Hospital of Liege, Liège, Belgium. 2Department of Medicine, University Hospital of Liege, Liège, Belgium. 3Department of Emergency Medicine, University Hospital of Liege, Liège, Belgium.

Objectives: Ventilator-associated pneumonia diagnosis remains a debatable topic. New definitions of ventilator-associated conditions involving worsening oxygenation have been recently proposed to make surveillance of events possibly linked to ventilator-associated pneumonia as objective as possible. The objective of the study was to confirm the effect of subglottic secretion suctioning on ventilator-associated pneumonia prevalence and to assess its concomitant impact on ventilator-associated conditions and antibiotic use.

Design: Randomized controlled clinical trial conducted in five ICUs of the same hospital.

Patients: Three hundred fifty-two adult patients intubated with a tracheal tube allowing subglottic secretion suctioning were randomly assigned to undergo suctioning (n = 170, group 1) or not (n = 182, group 2).

Main Results: During ventilation, microbiologically confirmed ventilator-associated pneumonia occurred in 15 patients (8.8%) of group 1 and 32 patients (17.6%) of group 2 (p = 0.018). In terms of ventilatory days, ventilator-associated pneumonia rates were 9.6 of 1,000 ventilatory days and 19.8 of 1,000 ventilatory days, respectively (p = 0.0076). Ventilator-associated condition prevalence was 21.8% in group 1 and 22.5% in group 2 (p = 0.84). Among the 47 patients with ventilator-associated pneumonia, 25 (58.2%) experienced a ventilator-associated condition. Neither length of ICU stay nor mortality differed between groups; only ventilator-associated condition was associated with increased mortality. The total number of antibiotic days was 1,696 in group 1, representing 61.6% of the 2,754 ICU days, and 1,965 in group 2, representing 68.5% of the 2,868 ICU days (p < 0.0001).

Conclusions: Subglottic secretion suctioning resulted in a significant reduction of ventilator-associated pneumonia prevalence associated with a significant decrease in antibiotic use. By contrast, ventilator-associated condition occurrence did not differ between groups and appeared more related to other medical features than ventilator-associated pneumonia.
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http://dx.doi.org/10.1097/CCM.0000000000000674DOI Listing
January 2015

Modelled target attainment after meropenem infusion in patients with severe nosocomial pneumonia: the PROMESSE study.

J Antimicrob Chemother 2015 Jan 12;70(1):207-16. Epub 2014 Sep 12.

Department of Infectious Diseases and General Internal Medicine, University Hospital of Liège, Liège, Belgium.

Objectives: The objective of this study was to propose an optimal treatment regimen of meropenem in critically ill patients with severe nosocomial pneumonia.

Patients And Methods: Among 55 patients in intensive care treated with 1 g of meropenem every 8 h for severe nosocomial pneumonia, 30 were assigned to intermittent infusion (II; over 0.5 h) and 25 to extended infusion (EI; over 3 h) groups. Based on plasma and epithelial lining fluid (ELF) concentrations determined at steady-state, pharmacokinetic modelling and Monte Carlo simulations were undertaken to assess the probability of attaining drug concentrations above the MIC for 40%-100% of the time between doses (%T > 1-fold and 4-fold MIC), for 1 or 2 g administered by either method.

Results: Penetration ratio, measured by the ELF/plasma ratio of AUCs, was statistically higher in the EI group than in the II group (mean ± SEM: 0.29 ± 0.030 versus 0.20 ± 0.033, P = 0.047). Considering a maximum susceptibility breakpoint of 2 mg/L, all dosages and modes of infusions achieved 40%-100% T > 1-fold MIC in plasma, but none did so in ELF, and only the 2 g dose over EI achieved 40%-100% T > 4-fold MIC in plasma.

Conclusions: The optimum regimen to treat severe nosocomial pneumonia was 2 g of meropenem infused over 3 h every 8 h. This regimen achieved the highest pharmacodynamic targets both in plasma and in ELF.
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http://dx.doi.org/10.1093/jac/dku354DOI Listing
January 2015

The Severity of ICU-Acquired Pneumonia.

Curr Infect Dis Rep 2013 Oct;15(5):380-4

Department of General Intensive Care, University Hospital of Liege, Domaine Universitaire du Sart-Tilman, 4000, Liège, Belgium,

Much controversy exists about pneumonia in intensive care-especially, ventilator-associated pneumonia (VAP)-about its diagnosis and its attributable mortality. A better consensus exists about its prevention and its treatment. VAP occurs in already critically ill patients, and the relationship between preexisting organ dysfunction or failures and the severity of VAP has been recently highlighted. The role of the underlying disease should be considered as dominant, and this fact explains the paradox that exists between the high mortality of VAP and the relative minor effect of prevention measures on mortality.
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http://dx.doi.org/10.1007/s11908-013-0359-8DOI Listing
October 2013

Procalcitonin for antibiotic treatment in intensive care unit patients.

Curr Infect Dis Rep 2013 Oct;15(5):394-9

Department of General Intensive Care, University Hospital Centre of Liege, Domaine universitaire du Sart-Tilman, 4000, Liege, Belgium,

Procalcitonin (PCT), a 116-aminoacids prohormone, has been substantially studied over the last 2 decades in the field of sepsis. Disappointingly low sensitivity values led to the abandonment of the concept of it as a diagnostic tool and then to its being considered more as a prognostic marker with a good correlation with severe infection. Later on, growing concerns about multidrug-resistant bacteria in the ICU environment and about the cost and side effects of antibiotics suggested that PCT might prove to be a valuable asset in stewardship programs. Numerous but hardly comparable randomized controlled trials assessing either initiation or deescalation in ICU patients have been published. Stewardship encompassing PCT should focus on the latter, because of the high negative predictive value of this biomarker. However, there still would be safety concerns if a systematic implementation of PCT were to be considered in daily stewardship programs in the ICU, especially in extra-thoracic sepsis.
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http://dx.doi.org/10.1007/s11908-013-0360-2DOI Listing
October 2013

The authors reply.

Crit Care Med 2013 Mar;41(3):e28

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http://dx.doi.org/10.1097/CCM.0b013e31827c04b6DOI Listing
March 2013

The authors reply.

Crit Care Med 2013 Feb;41(2):e19

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http://dx.doi.org/10.1097/CCM.0b013e318275cba9DOI Listing
February 2013

Procalcitonin usefulness for the initiation of antibiotic treatment in intensive care unit patients.

Crit Care Med 2012 Aug;40(8):2304-9

Department of General Intensive Care, University Hospital of Liege, Domaine universitaire de Liège, Liege, Belgium.

Objectives: To test the usefulness of procalcitonin serum level for the reduction of antibiotic consumption in intensive care unit patients.

Design: Single-center, prospective, randomized controlled study.

Setting: Five intensive care units from a tertiary teaching hospital.

Patients: All consecutive adult patients hospitalized for >48 hrs in the intensive care unit during a 9-month period.

Interventions: Procalcitonin serum level was obtained for all consecutive patients suspected of developing infection either on admission or during intensive care unit stay. The use of antibiotics was more or less strongly discouraged or recommended according to the Muller classification. Patients were randomized into two groups: one using the procalcitonin results (procalcitonin group) and one being blinded to the procalcitonin results (control group). The primary end point was the reduction of antibiotic use expressed as a proportion of treatment days and of daily defined dose per 100 intensive care unit days using a procalcitonin-guided approach. Secondary end points included: a posteriori assessment of the accuracy of the infectious diagnosis when using procalcitonin in the intensive care unit and of the diagnostic concordance between the intensive care unit physician and the infectious-disease specialist.

Measurements And Main Results: There were 258 patients in the procalcitonin group and 251 patients in the control group. A significantly higher amount of withheld treatment was observed in the procalcitonin group of patients classified by the intensive care unit clinicians as having possible infection. This, however, did not result in a reduction of antibiotic consumption. The treatment days represented 62.6±34.4% and 57.7±34.4% of the intensive care unit stays in the procalcitonin and control groups, respectively (p=.11). According to the infectious-disease specialist, 33.8% of the cases in which no infection was confirmed, had a procalcitonin value>1µg/L and 14.9% of the cases with confirmed infection had procalcitonin levels<0.25 µg/L. The ability of procalcitonin to differentiate between certain or probable infection and possible or no infection, upon initiation of antibiotic treatment was low, as confirmed by the receiving operating curve analysis (area under the curve=0.69). Finally, procalcitonin did not help improve concordance between the diagnostic confidence of the infectious-disease specialist and the ICU physician.

Conclusions: Procalcitonin measuring for the initiation of antimicrobials did not appear to be helpful in a strategy aiming at decreasing the antibiotic consumption in intensive care unit patients.
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http://dx.doi.org/10.1097/CCM.0b013e318251517aDOI Listing
August 2012

Severity of ICU-acquired pneumonia according to infectious microorganisms.

Intensive Care Med 2011 Jul 26;37(7):1128-35. Epub 2011 May 26.

Department of General Intensive Care, University Hospital of Liege, University of Liege, Domaine Universitaire de Liège, 4000, Liege, Belgium.

Purpose: To assess the severity of intensive care unit (ICU)-acquired pneumonia (ICUAP) according to the bacteria involved, classified into seven groups: third-generation cephalosporin-resistant non-fermenting Gram-negative bacilli (resistant C3NF); sensitive C3NF; methicillin-resistant Staphylococcus aureus; methicillin-sensitive Staphylococcus aureus; extended-spectrum beta-lactamase-producing Enterobacteriaceae; Enterobacteriaceae not producing extended-spectrum beta-lactamase; Haemophilus influenzae and Streptococcus pneumoniae.

Methods: Over a 4-year period, sequential organ failure assessment (SOFA) score was prospectively measured daily in 453 adult patients with ICUAP. ICUAP severity was evaluated by the severity of sepsis and by the occurrence of new organ dysfunctions or failures (OD/F) during ICUAP.

Results: Septic shock occurred in 21% of all cases of ICUAP. The occurrence of new OD/F during ICUAP was similar regardless of the identified microorganism. These new OD/F represented less than 11% of SOFAmax, defined as the sum of all OD/F occurring at any time during the ICU stay. There was a significant association between SOFApreICUAP, defined as the sum of all the OD/F occurring before ICUAP, and ICUAP severity. In the multivariate analysis, the type of bacteria was not a risk factor (RF) for occurrence of septic shock and mortality. Age and SOFApreICUAP were RF for the sepsis severity. The ICUAP severity was an RF for ICU mortality.

Conclusions: ICUAP was responsible for a minor proportion of OD/F occurring during the ICU stay. Severity of ICUAP was related to clinical status prior to ICUAP, but not to the type of bacteria. ICU mortality depended on the severity of ICUAP.
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http://dx.doi.org/10.1007/s00134-011-2255-8DOI Listing
July 2011