Summary
What is known and objective
Several authors have demonstrated the relationship between voriconazole concentrations and the risk of therapeutic failure and adverse events However, the ...information about voriconazole concentrations in the critically ill patient is scarce. The aim of this study was to analyse the plasma concentrations and pharmacokinetic behaviour of voriconazole in critically ill patients and their association with the treatment response and development of toxicity.
Methods
A prospective, observational study was conducted. Patients admitted to an intensive care unit and on treatment with intravenous voriconazole were included. Plasma concentrations were measured between days 4 and 7 from the start of the treatment. The pharmacokinetic analysis was performed using the NONMEM® software. A regression model was used to evaluate the variables associated with the values outside the therapeutic range, as well as the relationship between the plasma concentrations and the treatment response and the development of hepatotoxicity.
Results and discussion
A total of 33 patients were included. Plasma concentrations outside the therapeutic range (1‐5.5 mg/L) were observed in 15 patients, being above the established range in 9 (27.3%) cases, and below it in 6 (18.2%) cases. The presence of a bilirubin value of >1.5 mg/dL and a C‐reactive protein >100 mg/dL was associated with supra‐therapeutic concentrations. Voriconazole concentrations greater than 5.5 mg/dL were associated with the development of hepatotoxicity.
What is new and conclusions
There is a wide variation in voriconazole concentrations in critically ill patients, being associated with a high frequency of adverse events. Close monitoring of these values is required in order to decrease the risk of therapeutic failure and toxicity.
The administration of intravenous voriconazole in critically ill patients is associated with a wide variability of concentrations. Bilirubin and C‐Reactive protein are associated with high concentrations of voriconazole, and, therefore, at the risk of toxicity.
OBJECTIVES:To describe the effectiveness of the Surviving Sepsis Campaign bundles with regard to both implementation and outcome in patients with septic shock and to determine the contribution of the ...various elements of the bundles to the outcome.
DESIGN:Quasi-experimental study with a historical comparison group.
SETTING:The three medical–surgical intensive care units of an academic tertiary care center.
PATIENTS:A total of 384 adult patients in septic shock were enrolled after the educational intervention (September 2005–August 2008) and 96 patients in the historical group (June 2004–May 2005).
INTERVENTION:A hospital-wide quality improvement program based on the implementation of the Surviving Sepsis Campaign guidelines performed between June 2005 and August 2005.
MEASUREMENTS AND RESULTS:In-hospital mortality was reduced from 57.3% in the historical group to 37.5% in the intervention group (p = .001). This difference remained significant after controlling for confounding factors (odds ratio, 0.50; 95% confidence interval, 0.28–0.89). The intervention group had also lower length of stay for survivors in the hospital (36.2 ± 34.8 days vs. 41.0 ± 26.3 days; p = .043) and in the intensive care units (8.4 ± 9.8 days vs. 11.0 ± 9.5 days; p = .004). Improvements in survival were related to the number of bundle interventions completed (p for trend <.001). Compliance with six or more interventions of the 6-hr resuscitation bundle was an independent predictor of survival (adjusted odds ratio, 0.30; 95% confidence interval, 0.17–0.53; p <.001). The only single intervention with impact on mortality was the achievement of ScvO2 ≥70% (adjusted odds ratio, 0.62; 95% confidence interval, 0.38–0.99; p = .048).
CONCLUSIONS:The implementation of the Surviving Sepsis Campaign guidelines was associated with a significant decrease in mortality. The benefits depend on the number of interventions accomplished within the time limits. The 6-hr resuscitation bundle showed greater compliance and effectiveness than the 24-hr management bundle. (Crit Care Med 2010; 38:1036–1043)
Anticipating and avoiding preventable intrahospital cardiac arrest and clinical deterioration are important priorities for international healthcare systems and institutions. One of the ...internationally followed strategies to improve this matter is the introduction of the Rapid Response Systems (RRS). Although there is vast evidence from the international community, the evidence reported in a Spanish context is scarce.
A nationwide cross-sectional research consisting of a voluntary 31-question online survey was performed. The Spanish Society of Intensive, Critical and Coronary Care Medicine (SEMICYUC) supported the research.
We received 62 fully completed surveys distributed within 13 of the 17 regions and two autonomous cities of Spain. Thirty-two of the participants had an established Rapid Response Team (RRT). Common frequency on measuring vital signs was at least once per shift but other frequencies were contemplated (48.4%), usually based on professional criteria (69.4%), as only 12 (19.4%) centers used Early Warning Scores (EWS) or automated alarms on abnormal parameters. In the sample, doctors, nurses (55%), and other healthcare professionals (39%) could activate the RRT via telephone, but only 11.3% of the sample enacted this at early signs of deterioration. The responders on the RRT are the Intensive Care Unit (ICU), doctors, and nurses, who are available 24/7 most of the time. Concerning the education and training of general ward staff and RRT members, this varies from basic to advanced and specific-specialized level, simulating a growing educational methodology among participants. A great number of participants have emergency resuscitation equipment (drugs, airway adjuncts, and defibrillators) in their general wards. In terms of quality improvement, only half of the sample registered RRT activity indicators. In terms of the use of communication and teamwork techniques, the most used is clinical debriefing in 29 centers.
In terms of the concept of RRS, we found in our context that we are in the early stages of the establishment process, as it is not yet a generalized concept in most of our hospitals. The centers that have it are in still in the process of maturing the system and adapting themselves to our context.
•Chlorhexidine bathing has been associated with a reduction in nosocomial infections.•Chlorhexidine-impregnated wipes lead to a reduction of multidrug-resistant bacteria colonization.•This effect is ...maintained in an endemic situation of multidrug-resistant bacteria.
Health–care associated infections are a major cause of morbidity and mortality in critical care units. The aim of this study is to evaluate the effectiveness of chlorhexidine gluconate (CHG)–impregnated wipes in the daily bathing of patients in an intensive care unit (ICU) to prevent cross-transmission and colonization by multidrug-resistant organisms (MDROs)
Prospective cohort study with an intervention of 11 months. The intervention consisted of using CHG-impregnated wipes for the daily bathing of patients on mechanical ventilation or colonized by MDROs. Monthly trends in the number of patients colonized by MDROs and the incidence of nosocomial infections were evaluated.
A total of 1,675 patients were admitted to the unit during the intervention period, and 430 (25.7%) were bathed with chlorhexidine wipes. A significant decrease was observed in the incidence of colonization by MDROs over the months (β = −0.209; r2 = 0.549; P = .027), and in the number of patients colonized compared with the equivalent period of the previous year (22.0% vs 18.4%; P = .01). No significant decrease was observed in the incidence of nosocomial infection between the two periods (4.11% vs 4.57%; P = .355). No dermatologic problems were observed in the treated patients.
The use of CHG-impregnated wipes reduces cross-transmission and colonization by MDROs in the ICUs in an endemic situation because of multidrug-resistant Enterobacteriaceae.
Effective treatment approaches for biofilms in endotracheal tubes (ETTs) are lacking. In this study, we evaluated the in vitro effects of five antimicrobials against biofilms formed by Klebsiella ...pneumoniae in ETTs. K. pneumoniae was added to minimal mucin medium prior to inoculation in microtiter plates containing ETT fragments. Biofilm susceptibility was assessed by crystal violet staining. At 24 h, the antimicrobials significantly reduced biofilm formation. At 48 h, all of the antimicrobial agents exhibited significant reductions in biofilm formation, even at concentrations above the minimum inhibitory concentration (MIC). Tigecycline and fosfomycin showed the greatest inhibition capacity, with good activity at concentrations twofold greater than the MIC. K. pneumoniae exhibited excellent biofilm formation ability, with formation in the first 24 h and significantly reduced antimicrobial activity. These results contribute to the establishment of new antibiotic breakpoints for the adequate management of infections associated with biofilm formation.
Abbreviations
ETT
Endotracheal tube
MIC
Minimum inhibitory concentration
MBIC
Minimum biofilm inhibitory concentration
OD
Optical density
PBS
Phosphate-buffered saline
VAP
Ventilator-associated pneumonia
Objectives:
To assess the probability of reaching adequate pharmacokinetic/pharmacodynamics values for ceftolozane/tazobactam at different doses and degrees of renal functions in patients with ...Pseudomonas aeruginosa bacteremia.
Methods:
Six dosing regimens were evaluated: 0.5/0.25 g, 1/0.5 g, and 2/1 g every 8 hours given as 1 hour or 3 hours infusions. Pharmacokinetic data were obtained from the literature. Susceptibility data to ceftolozane were collected from patients with P aeruginosa infection treated with ceftolozane-tazobactam. Probability of reaching a fraction of time (fT) >40% minimum inhibitory concentration (MIC) and fT >100%MIC value for ceftolozane at 3 different renal clearance values was evaluated. For tazobactam, the probability of reaching an fT >40% and >70% for 3 limit values was calculated.
Results:
Thirty-seven strains were included. For ceftolozane, the probability of reaching a fT >40%MIC was greater than 90% for any degree of renal function. The probability of reaching a fT >100%MIC for 1 g dose infused over 1 hour and 3 hours was 82.2% and 86.4% for a creatinine clearance (ClCr) >90 mL/min. Using a 2 g dose, the probability was greater than 90% for both infusions rates. For tazobactam, the probability of reaching a value of fT >50% of the limit concentrations was greater than 90% for a ClCr of 70 mL/min. In the case of a ClCr >90 mL/min and limit concentration values ≥ 0.25 mg/mL, only extended infusions showed a probability >90%.
Conclusions and Relevance:
The standard doses of ceftolozane/tazobactam achieve an adequate fT >40%MIC value. However, doses of 2 g in extended infusion is necessary to reach a value of fT >100%MIC, especially in patients with an increased renal clearance and high levels of beta-lactamases expression.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Midregional proadrenomedullin (proADM) is a novel biomarker with potential prognostic utility in patients with community-acquired pneumonia. The aim of this study was to investigate the value of ...proADM levels for severity assessment and outcome prediction in severe sepsis and septic shock due to CAP.
Prospective observational study including 49 patients admitted to ICU with both a clinical and radiologic diagnosis of pneumonia and fulfilling criteria for severe sepsis or septic shock. The prognostic accuracy of proADM levels was compared with those of pneumonia severity index and of procalcitonin (PCT) and C-reactive protein (CRP).
49 patients with severe sepsis or septic shock due to CAP were included in the study. Mortality was 24.5% for ICU and 34.7% for hospital mortality. In all cases proADM values at ICU admission were pathological (considering normal proADM levels <4 nmol/L). ProADM consistently rose as PSI class advanced from II to V (p = 0.02). Median proADM levels were higher (p <0.01) in hospital non-survivors 5.0 (1.9-10.1) nmol/L vs. survivors 1.7 (1.3-3.1) nmol/L. These differences were also significant with respect to ICU mortality. The receiver-operating characteristic curve for proADM yielded an AUC of 0.72; better than the AUC for PCT and CRP (0.40 and 0.44 respectively) and similar to PSI (0.74).
In our study MR-proADM levels correlate with increasing severity of illness and death. High MR-proADM levels offer additional risk stratification in high-risk CAP patients.
In this study, we evaluate the effect of extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (Levitronix) on the pharmacokinetic of amikacin in critically ill patients. Twelve ...patients with ECMO and three with Levitronix devices who started treatment with amikacin were included. Amikacin pre (Cmax) and post (Cmin) dose serum concentrations were measured during the first 72–96 hours of treatment initiation. Pharmacokinetic parameters were performed by Bayesian adjustment. The median initial dose was 1,000 mg (range600–1,400 mg). Mean plasma concentrations were Cmax 58.6 mg/L (17.0 mg/L); Cmin 9.58 mg/L (7.8 mg/L). Patients with an ECMO device had a higher volume of distribution (0.346 0.033 vs. 0.288 0.110 L/kg) and a lower plasma clearance (1.58 0.21 vs. 3.73 1.03 L/h) than the control group. This phenomenon was also observed in those patients with simultaneous use of ECMO and hemodilafiltration. For patients with Levitronix system, no significant alterations in the volume of distribution were observed, although a lower plasma clearance was noticed. Placement of ECMO devices alters the pharmacokinetic parameters of amikacin in the critically ill patients and should be considered when selecting the initial dose.
•Cmax/MIC ratio of amikacin in critically ill patients is associated with clinical response to treatment.•Selection of amikacin-resistant strains may be associated with the initial Cmax/MIC ...ratio.•AUC/MIC ratio is not associated with treatment response but may be used as a predictor of amikacin-induced renal toxicity.•Amikacin dose should be individualised based on changes in pathophysiological status, infection focus and amikacin MICs.
This study evaluated the association between the pharmacokinetic/pharmacodynamic index and treatment response to amikacin in critically ill patients.
An observational prospective study was designed. Critically ill adult patients with infection due to amikacin-sensitive Gram-negative bacteria treated with amikacin were included. Amikacin maximum (Cmax) and minimum (Cmin) plasma concentration samples were taken during the first 48–96h after the beginning of treatment. The impact of Cmax/MIC ratio and area under the concentration–time curve (AUC)/MIC ratio on early and final clinical response, microbiological eradication, development of resistant strains and renal toxicity was analysed using a multivariate model.
A total of 85 patients received amikacin treatment, of whom 71 (83.5%) achieved a Cmax/MIC >6, 66 (77.6%) a Cmax/MIC >8, 64 (75.3%) a Cmax/MIC >10 and 72 (84.7%) an AUC/MIC >65. Clinical response at the end of treatment was significantly greater in patients with Cmax/MIC >6 OR=5.48 (95% CI 1.28–11.40), Cmax/MIC >8 OR=6.01 (2.41–12.2) and Cmax/MIC >10 OR=8.02 (2.21–14.2). Cmax/MIC >10 was associated with a non-significant increase in microbiological eradication OR=2.84 (0.76–10.61). Achieving Cmax/MIC >6 was associated with a lower proportion of patients with selection of resistant strains or with an increase in amikacin MIC (27.8% vs. 10.2%). Amikacin AUC was associated with development of nephrotoxicity ROC curve 0.77 (0.66–0.87).
The Cmax/MIC ratio of amikacin in critically ill patients is directly related to the response to treatment and the selection of resistant strains.
BackgroundContinuous renal replacement therapy (CRRT) is common practice in critical care patients with acute renal failure.ObjectivesTo evaluate the adequacy of antimicrobial doses calculated based ...on the total drug clearance and dose recommended by different guides in critically ill patients undergoing CRRT.MethodsRetrospective observational study. Patients admitted to a critical care unit during May 2014 to May 2016 and subjected to CRRT were included. The recommended dose was established as the product of the usual dose of the drug by total drug clearance.Results177 antimicrobial agents, used in 64 patients were analysed; 45 (25.4%) antimicrobials were given in an insufficient dose (<20%) according to the theoretical calculation. Following the recommendations in the revised guidelines, between 10% and 20% of antimicrobials were given in insufficient doses. A higher success rate of treatment in those patients not receiving a low drug dosage was seen (35.2% vs 24.0%).ConclusionsThere is a great disparity between the antimicrobial dose prescribed, recommended and calculated based on drug clearance in critically ill patients undergoing CRRT.
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