17 research outputs found
Efficacy of short and long acting bronchodilators in mechanically ventilated patients with chronic obstructive pulmonary disease
No full textThe delivery of bronchodilators -particularly beta2-agonists- by metered dose inhaler (MDI) in mechanically ventilated. COPD patients have received considerable interest in recent years. This is because the use of an MDI has several advantages over the nebulizer in terms of ease of administration reduced cost and safety. Provided that the technique of administration is proper MDIs seem to be as effective as nebulizers despite a significantly lower dose of bronchodilator delivered by the MDI. While several studies have examined the effect of various ventilatory parameters (like tidal volume increase application of an end-inspiratory pause different flow/time profile different flow rate) on bronchodilator efficacy the effect of spontaneous respiratory efforts on beta2-agomst induced bronchodilation has never been studied in humans. Furthermore, while the duration of the bronchodilator response to short as well as long-acting beta2-agonists has been established in spontaneously breathing COPD patients it has not been studied in mechanically ventilated patients with COPD exacerbation. Hence, the following questions were studied: - duration of the bronchodilator effect induced by the short-acting beta2-agonist salbutamol, - influence of respiratory efforts on beta2-agonist induced bronchodilation in mechanically ventilated COPD patients. - duration of the bronchodilator effect induced by the long-acting beta2-agonist salmeterol in mechanically ventilated COPD patients. The resulting main conclusions were the following: In mechanically ventilated patients with COPD exacerbation administration of the short-acting beta2-agonist salbutamol as well as the long-acting beta2-agonist salmeterol by MDI and a spacer device causes significant reduction of respiratory resistance indices (Rmin and Rmax), In mechanically ventilated patients with COPD exacerbation administration of 600 μg of the short-acting, beta2-agonist salbutamol caused a significant bronchodilator response which was evident at 15 minutes after administration and remained relatively constant for approximately 3 hours although significant inter-patient variability was noticed. - The magnitude of bronchodilation induced by salbutamol delivered by an MDI and a spacer device in mechanically ventilated COPD patients is not affected by the presence or absence of active respiratory efforts. - In mechanically ventilated patients with COPD exacerbation administration of 100 μg of the long-acting beta2-agonist salmeterol caused a significant bronchodilator response which was evident at 30 minutes after administration and remained relatively constant for approximately 8 hours. Duration of bronchodilator effect varied significantly among patients precluding definite conclusions regarding an optimum dosing schedule which should be titrated according to objective indices of bronchodilation.Η χορήγηση βρογχοδιασταλτικών φαρμάκων με κύριο εκπρόσωπο τους β2-αγωνιστές σε μηχανικά αεριζόμενους ασθενείς με χρόνια αποφρακτική πνευμονοπάθεια (ΧΑΠ) μέσω δοσιμετρικής συσκευής (ΔΣ) έχει αποκτήσει ιδιαίτερο ενδιαφέρον τα τελευταία χρόνια. Οι ΔΣ εμφανίζουν σημαντικά πλεονεκτήματα σε σύγκριση με τους νεφελοποιητές όσον αφορά την ευκολία χρήσης το κόστος και την ασφάλεια. Υπό την προϋπόθεση δε της τήρησης ορθής τεχνικής χορήγησης ο συνδυασμός ΔΣ-αεροθαλάμου φαίνεται να είναι εξίσου αποτελεσματικός με τους νεφελοποιητές παρά τη χορήγηση σημαντικά χαμηλότερης δόσης φαρμάκου. Ενώ λοιπόν έχει διερευνηθεί η επίδραση των διαφόρων παραμέτρων του αναπνευστήρα (όπως π.χ. η αύξηση του αναπνεόμενου όγκου η προσθήκη τελοεισπνευστικής παύσης το σχήμα και το μέγεθος της εισπνευστικής ροής) στην αποτελεσματικότητα των χορηγουμένων β2-αγωνιστών, η επίδραση της ύπαρξης αναπνευστικών προσπαθειών του ασθενούς στο βρογχοδιασταλτικό αποτέλεσμα δεν έχει μελετηθεί. Πέραν τούτου, σε αντίθεση με μη διασωληνωμένους ασθενείς όπου η διάρκεια δράσης τόσο των βραχείας όσο και των μακράς διάρκειας δράσης β2-αγωνιστών είναι γνωστή η διάρκεια του βρογχοδιασταλτικού αποτελέσματος των φαρμάκων αυτών δεν έχει μελετηθεί σε διασωληνωμένους ασθενείς. Η παρούσα διατριβή μελέτησε τα έξης ερωτήματα: - τη διάρκεια του βρογχοδιασταλτικού αποτελέσματος του βραχείας διάρκειας δράσης β2-αγωνιστή σαλβουταμόλη, - τη διάρκεια του βρογχοδιασταλτικού αποτελέσματος του μακράς διάρκειας δράσης β2-αγωνιστή σαλμετερόλη, - την επίδραση των αναπνευστικών προσπαθειών του ασθενούς επί του μεγέθους της προκαλούμενης βρογχοδιαστολής. Τα συμπεράσματα που προέκυψαν από τις μελέτες αυτές είναι τα ακολούθα: - Σε μηχανικά αεριζόμενους ασθενείς με έξαρση ΧΑΠ η χορήγηση τόσο του βραχείας διάρκειας δράσης β2-αγωνιστή σαλβουταμόλη όσο και του μακράς διάρκειας δράσης β2-αγωνιστή σαλμετερόλη με ΔΣ και αεροθάλαμο οδηγεί σε σημαντική ελάττωση των εισπνευστικών αντιστάσεων (Rmin και Rmax). - Σε διασωληνωμένους ασθενείς με έξαρση ΧΑΠ η χορήγηση 600 μg σαλβουταμόλης μέσω ΔΣ και αεροθαλάμου οδηγεί σε σημαντική βρογχοδιασταλτική απάντηση η οποία είναι εμφανής στα 15 λεπτά μετά τη χορήγησή της και διαρκεί περίπου 3 ώρες. Όσον αφορά δε τη διάρκεια της βρογχοδιασταλτικής απάντησης παρατηρήθηκε μη προβλέψιμη υψηλού βαθμού διακύμανση μεταξύ των ασθενών γεγονός το οποίο δεν επιτρέπει την έκδοση συγκεκριμένων οδηγιών αναφορικά με το βέλτιστο δοσολογικό σχήμα. - Η ύπαρξη αναπνευστικών προσπαθειών του ασθενούς κατά τη διάρκεια μοντέλου υποστηριζόμενου μηχανικού αερισμού τύπου pressure support δεν επηρεάζει την αποτελεσματικότητα της χορηγούμενης σαλβουταμόλης. - Σε διασωληνωμένους ασθενείς με έξαρση ΧΑΠ η χορήγηση 100 μg σαλμετερόλης μέσω ΔΣ και αεροθαλάμου οδηγεί σε σημαντική βρογχοδιασταλτική απάντηση η οποία είναι εμφανής στα 30 λεπτά μετά τη χορήγηση της και διαρκεί περίπου 6 ώρες. Όσον αφορά δε τη διάρκεια της βρογχοδιασταλτικής απάντησης παρατηρήθηκε μη προβλέψιμη υψηλού βαθμού διακύμανση μεταξύ των ασθενών, γεγονός το οποίο δεν επιτρέπει την έκδοση συγκεκριμένων οδηγιών αναφορικά με το βέλτιστο δασολογικό σχήμα. Αντ’ αυτού το μεσοδιάστημα μεταξύ των δόσεων θα πρέπει να εξατομικεύεται βάσει συγκεκριμένων δεικτών βρογχοδιασταλτικής απάντησης
Impact of prolonged treatment with linezolid on the human gut flora
No full textSummaryA 79-year-old male was treated for 6 months with linezolid for prosthetic knee joint osteomyelitis. At the end of this 6-month period, quantitative stool cultures revealed partial loss of the normal gut flora and concomitant colonization by opportunistic pathogens such as Pseudomonas aeruginosa and other Gram-negatives. Follow-up cultures at 6 weeks after antibiotic discontinuation revealed restoration of the normal flora. Prolonged linezolid administration may lead to replacement of normal gut flora by pathogenic microorganisms, which under certain conditions might cause systemic infections
Pharmacokinetic evaluation of linezolid administered intravenously in obese patients with pneumonia
No full textAltered linezolid pharmacokinetics (PK) in obese individuals has been hypothesized in previous studies. However, specific dosing recommendations for this population are still lacking. The main goal of this study was to evaluate PK/pharmacodynamic (PKPD) target attainment when using a 600 mg intravenous q12h linezolid dose against MRSA in obese patients with pneumonia.Fifteen obese pneumonia patients with a confirmed or suspected MRSA involvement treated with 600 mg of intravenous linezolid q12h were studied for 3 days. Population PK modelling was used to characterize the PK variability and to screen for influential patient characteristics. Monte Carlo simulations were carried out to investigate the PTA and time to target attainment for linezolid dosing against MRSA.A two-compartment model with linear elimination adequately described the data. Body weight and age both have a significant effect on linezolid clearance. Simulations demonstrate that the probability of attaining PKPD targets is low. Moreover, the PTA decreases with weight, and increases with age. Standard linezolid dosing in obese pneumonia patients with MRSA (MICs of 1-4 mg/L) leads to unacceptably low (near zero to 60%) PTA for patient
Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort
No full textObjectives: We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged- infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies. Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries. Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT≥MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving β-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of ≥ 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025]. Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved
Epidemiology of intra-abdominal infection and sepsis in critically ill patients: “AbSeS”, a multinational observational cohort study and ESICM Trials Group Project
No full textPurpose: To describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock). Methods: We performed a multicenter (n = 309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis. Results: The cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation. Conclusion: This multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection. © 2019, The Author(s)
Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort
No full textObjectives: We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged- infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies. Methods: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries. Results: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT≥MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving β-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P=0.012]. Additionally, in patients with a SOFA score of ≥ 9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P=0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P=0.025]. Conclusions: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infection
DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current β-Lactam Antibiotic Doses Sufficient for Critically Ill Patients?
No full textBackground. Morbidity and mortality for critically ill patients with infections remains a global healthcare prob- lem. We aimed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations as- sociated with maximal activity and whether antibiotic concentrations affect patient outcome.
Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 β-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharma- cokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentra- tion (MIC) of the pathogen at both 50% (50% f T>MIC) and 100% (100% f T>MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome.
Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (inter- quartile range [IQR], 48–73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14–24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f T>MIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P = .009). Positive clinical outcome was associated with increasing 50% f T>MIC and 100% f T>MIC ratios (OR, 1.02 and 1.56, respectively; P < .03), with significant interaction with sickness severity status.
Conclusions. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic ex- posure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients
Epidemiology of intra-abdominal infection and sepsis in critically ill patients: "AbSeS", a multinational observational cohort study and ESICM Trials Group Project
No full textPurposeTo describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock).MethodsWe performed a multicenter (n=309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis.ResultsThe cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation.ConclusionThis multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection
Antimicrobial lessons from a large observational cohort on intra-abdominal infections in intensive care units
No full textSevere intra-abdominal infection commonly requires intensive care. Mortality is high and is mainly determined by disease-specific characteristics, i.e. setting of infection onset, anatomical barrier disruption, and severity of disease expression. Recent observations revealed that antimicrobial resistance appears equally common in community-acquired and late-onset hospital-acquired infection. This challenges basic principles in anti-infective therapy guidelines, including the paradigm that pathogens involved in community-acquired infection are covered by standard empiric antimicrobial regimens, and second, the concept of nosocomial acquisition as the main driver for resistance involvement. In this study, we report on resistance profiles of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterococcus faecalis and Enterococcus faecium in distinct European geographic regions based on an observational cohort study on intra-abdominal infections in intensive care unit (ICU) patients. Resistance against aminopenicillins, fluoroquinolones, and third-generation cephalosporins in E. coli, K. pneumoniae and P. aeruginosa is problematic, as is carbapenem-resistance in the latter pathogen. For E. coli and K. pneumoniae, resistance is mainly an issue in Central Europe, Eastern and South-East Europe, and Southern Europe, while resistance in P. aeruginosa is additionally problematic in Western Europe. Vancomycin-resistance in E. faecalis is of lesser concern but requires vigilance in E. faecium in Central and Eastern and South-East Europe. In the subcohort of patients with secondary peritonitis presenting with either sepsis or septic shock, the appropriateness of empiric antimicrobial therapy was not associated with mortality. In contrast, failure of source control was strongly associated with mortality. The relevance of these new insights for future recommendations regarding empiric antimicrobial therapy in intra-abdominal infections is discussed
Poor timing and failure of source control are risk factors for mortality in critically ill patients with secondary peritonitis
No full textPurpose: To describe data on epidemiology, microbiology, clinical characteristics and outcome of adult patients admitted in the intensive care unit (ICU) with secondary peritonitis, with special emphasis on antimicrobial therapy and source control.
Methods: Post hoc analysis of a multicenter observational study (Abdominal Sepsis Study, AbSeS) including 2621 adult ICU patients with intra-abdominal infection in 306 ICUs from 42 countries. Time-till-source control intervention was calculated as from time of diagnosis and classified into 'emergency' (< 2 h), 'urgent' (2-6 h), and 'delayed' (> 6 h). Relationships were assessed by logistic regression analysis and reported as odds ratios (OR) and 95% confidence interval (CI).
Results: The cohort included 1077 cases of microbiologically confirmed secondary peritonitis. Mortality was 29.7%. The rate of appropriate empiric therapy showed no difference between survivors and non-survivors (66.4% vs. 61.3%, p = 0.1). A stepwise increase in mortality was observed with increasing Sequential Organ Failure Assessment (SOFA) scores (19.6% for a value ≤ 4-55.4% for a value > 12, p < 0.001). The highest odds of death were associated with septic shock (OR 3.08 [1.42-7.00]), late-onset hospital-acquired peritonitis (OR 1.71 [1.16-2.52]) and failed source control evidenced by persistent inflammation at day 7 (OR 5.71 [3.99-8.18]). Compared with 'emergency' source control intervention (< 2 h of diagnosis), 'urgent' source control was the only modifiable covariate associated with lower odds of mortality (OR 0.50 [0.34-0.73]).
Conclusion: 'Urgent' and successful source control was associated with improved odds of survival. Appropriateness of empirical antimicrobial treatment did not significantly affect survival suggesting that source control is more determinative for outcome
