Nathalie Layios

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

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.

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

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.

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

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.

Severity of ICU-acquired pneumonia according to infectious microorganisms

PurposeTo 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.MethodsOver 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.ResultsSeptic 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.ConclusionsICUAP 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.

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

To the Editor: Diagnosis of septic complications during acute burn care remains a big challenge. Infectious biomarkers commonly used in a general population of critically ill patients are disappointing in burn patients. In this context, we read with interest the recent study published by Paratz et al (1). Authors emphasize the inefficiency of procalcitonin in sepsis diagnosis during burn care. However, procalcitonin should be better assessed during a de-escalation strategy of antibiotic treatment, as advocated in general intensive care (2). Authors also state that serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an early indicator of sepsis in burn patients. We have some remarks regarding this statement. First, NT-proBNP may fluctuate according to age, gender, anemia, obesity, and, more importantly, renal insufficiency (3). The latter is an important confounder for interpretation of NTproBNP. However, there was no adjustment for renal function. Second, the time frame before infection occurrence as well as the diagnostic workup leading to source determination were not explicitly described. This could have lead to misinterpretation between colonization and infection, thus explaining a surprisingly high rate of early infections. Furthermore, prevalence of inhalation injury was higher among patients with sepsis. Subsequent exacerbated inflammatory response or right ventricular dysfunction may therefore have induced bias. In conclusion, it seems difficult to establish whether NTproBNP is a reliable predictive marker of burn sepsis or just a systemic inflammatory response syndrome marker, apart from being a marker of ventricular stretching. NT-proBNP is increasingly reported in critically ill patients. Paratz et al (1) focused their analysis on a very specific population. It calls for further studies aiming to define pathophysiology, role, and interest of NT-proBNP in burn patients. Meanwhile, we make a plea against using the otherwise expensive NT-proBNP assay to justify a liberal antibiotic prescription without evidence of infection. 3. Hartling L, Hamm M, Milne A, et al: Validity and Inter-Rater Reliability Testing of Quality Assessment Instruments. Rockville, 2012. Available at: http://www.ncbi.nlm.nih.gov/books/NBK92293/. Accessed October 7, 2014 4. Sanderson S, Tatt ID, Higgins JP: Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: A systematic review and annotated bibliography. Int J Epidemiol 2007; 36:666–676 5. Olivo SA, Macedo LG, Gadotti IC, et al: Scales to assess the quality of randomized controlled trials: A systematic review. Phys Ther 2008; 88:156–175 6. Wells GA, Shea B, O’Connell D, et al: The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in metaanalyses. 2011. Available at: http://www.ohri.ca/programs/clinical_ epidemiology/oxford.asp. Accessed October 7, 2014 Assessment of Methodological Quality for Included Studies Is Necessary in a Systematic Review

The Severity of ICU-Acquired Pneumonia

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.

Procalcitonin for Antibiotic Treatment in Intensive Care Unit Patients

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.

Erratum: Elevated basal levels of circulating activated platelets predict ICU-acquired sepsis and mortality: a prospective study.

Platelets are now considered to be immune and inflammatory agents as well as key cells in coagulation, and as such have been implicated in the pathophysiology of sepsis [1]. Thrombocytopenia is associated with sepsis severity and poor prognosis, and hyperactivated platelets probably contribute to microvascular thrombosis and organ failure. In the present study, we evaluated platelet activation markers as potential predictive markers of sepsis and of mortality among four commonly encountered populations of patients admitted to ICUs.

Erratum: Prospective immune profiling in critically ill adults: before, during and after severe sepsis and septic shock.

Author details Department of General Intensive Care, University Hospital Centre of Liege, Domaine Sart-Tilman B35, Liege 4000, Belgium. GIGA-Cardiovascular Sciences, Laboratory of Thrombosis and Hemostasis, University of Liege, Domaine Sart-Tilman B35, 4000 Liege, Belgium. CHU de Liege, Domaine Sart-Tilman B35, 4000 Liege, Belgium. Laboratory Hematology, University Hospital Centre of Liege, Liege, Belgium. Systems and Modeling, Department of Electrical Engineering and Computer Science and GIGA-R, University of Liege, Domaine Sart-Tilman B35, 4000 Liege, Belgium. Reference 1. Layios N. Prospective immune profiling in critically ill adults: before, during and after severe sepsis and septic shock. Crit Care. 2015;19(Suppl 1):P43.