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Background: The optimal treatment duration for patients with bloodstream infection is understudied. The Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness (BALANCE) pilot randomized clinical trial (RCT) determined that it was feasible to enroll and randomize intensive care unit (ICU) patients with bloodstream infection to 7 versus 14 days of treatment, and served as the vanguard for the ongoing BALANCE main RCT. We performed this BALANCE-Ward pilot RCT to examine the feasibility and impact of potentially extending the BALANCE main RCT to include patients hospitalized on non-ICU wards.Methods: We conducted an open pilot RCT among a subset of six sites participating in the ongoing BALANCE RCT, randomizing patients with positive non-Staphylococcus aureus blood cultures on non-ICU wards to 7 versus 14 days of antibiotic treatment. The co-primary feasibility outcomes were recruitment rate and adherence to treatment duration protocol. We compared feasibility outcomes, patient/pathogen characteristics, and overall outcomes among those enrolled in this BALANCE-Ward and prior BALANCE-ICU pilot RCTs. We estimated the sample size and non-inferiority margin impacts of expanding the BALANCE main RCT to include non-ICU patients.Results: A total of 134 patients were recruited over 47 site-months (mean 2.9 patients/site-month, median 1.0, range 0.1-4.4 patients/site-month). The overall recruitment rate exceeded the BALANCE-ICU pilot RCT (mean 1.10 patients/site-month, p < 0.0001). Overall protocol adherence also exceeded the adherence in the BALANCE-ICU pilot RCT (125/134, 93% vs 89/115, 77%, p = 0.0003). BALANCE-Ward patients were older, with lower Sequential Organ Failure Assessment scores, and higher proportions of infections caused by Escherichia coli and genito-urinary sources of bloodstream infection. The BALANCE-Ward pilot RCT patients had an overall 90-day mortality rate of 17/133 (12.8%), which was comparable to the 90-day mortality rate in the ICU pilot RCT (17/115, 14.8%) (p = 0.65). Simulation models indicated there would be minimal sample size and non-inferiority margin implications of expanding enrolment to increasing proportions of non-ICU versus ICU patients.Conclusion: It is feasible to enroll non-ICU patients in a trial of 7 versus 14 days of antibiotics for bloodstream infection, and expanding the BALANCE RCT hospital-wide has the potential to improve the timeliness and generalizability of trial results.Trial Registration: Clinicaltrials.gov, NCT02917551. Registered on September 28, 2016. [ABSTRACT FROM AUTHOR]

Background: Surveillance of antimicrobial resistance is vital to guiding empirical treatment of infections. Collating and reporting routine data on clinical isolate testing may offer more timely information about resistance patterns than traditional surveillance network methods. Methods: Using routine microbiology testing data collected from the Bacteremia Antibiotic Length Actually Needed for Clinical Effectiveness retrospective cohort study, we conducted a descriptive secondary analysis among critically ill patients in whom bloodstream infections had been diagnosed in 14 intensive care units (ICUs) in Canada. The participating sites were located within tertiary care teaching hospitals and represented 6 provinces and 10 cities. More than 80% of the study population was accrued from 2011-2013. We assessed the epidemiologic features of the infections and corresponding antimicrobial susceptibility profiles. Susceptibility testing was done according to Clinical Laboratory Standards Institute guidelines at accredited laboratories. Results: A total of 1416 pathogens were isolated from 1202 patients. The most common organisms were Escherichia coli (217 isolates [15.3%]), Staphylococcus aureus (175 [12.4%]), coagulase-negative staphylococci (117 [8.3%]), Klebsiella pneumoniae (86 [6.1%]) and Streptococcus pneumoniae (85 [6.0%]). The contribution of individual pathogens varied by site. For 13 ICUs, gram-negative susceptibility rates were high for carbapenems (95.4%), tobramycin (91.2%) and piperacillin--tazobactam (90.0%); however, the proportion of specimens susceptible to these agents ranged from 75.0%-100%, 66.7%-100% and 75.0%-100%, respectively, across sites. Fewer gram-negative bacteria were susceptible to fluoroquinolones (84.5% [range 64.1%-97.2%]). A total of 145 patients (12.1%) had infections caused by highly resistant microorganisms, with significant intersite variation (range 2.6%-24.0%, א² = 57.50, p < 0.001). Interpretation: We assessed the epidemiologic features of bloodstream infections in a geographically diverse cohort of critically ill Canadian patients using routine pathogen and susceptibility data extracted from readily available microbiology testing databases. Expanding data sharing across more ICUs, with serial measurement and prompt reporting, could provide much-needed guidance for empiric treatment for patients as well as system-wide prevention methods to limit antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Background: Bacteremia is a leading cause of mortality and morbidity in critically ill adults. No previous randomized controlled trials have directly compared shorter versus longer durations of antimicrobial treatment in these patients. Methods/Design: This is a multicenter pilot randomized controlled trial in critically ill patients with bacteremia. Eligible patients will be adults with a positive blood culture with pathogenic bacteria identified while in the intensive care unit. Eligible, consented patients will be randomized to either 7 days or 14 days of adequate antimicrobial treatment for the causative pathogen(s) detected on blood cultures. The diversity of pathogens and treatment regimens precludes blinding of patient and clinicians, but allocation concealment will be extended to day 7 and outcome adjudicators will be blinded. The primary outcome for the main trial will be 90-day mortality. The primary outcome for the pilot trial is feasibility defined by (i) rate of recruitment exceeding 1 patient per site per month and (ii) adherence to treatment duration protocol = 90%. Secondary outcomes include intensive care unit, hospital and 90-day mortality rates, relapse rates of bacteremia, antibiotic-related side effects and adverse events, rates of Clostridium difficile infection, rates of secondary infection or colonization with antimicrobial resistant organisms, ICU and hospital lengths of stay, mechanical ventilation and vasopressor duration in intensive care unit, and procalcitonin levels on the day of randomization, and day 7, 10 and 14 after the index blood culture. Discussion: The BALANCE pilot trial will inform the design and execution of the subsequent BALANCE main trial, which will evaluate shorter versus longer duration treatment for bacteremia in critically ill patients, and thereby provide an evidence basis for treatment duration decisions for these infections. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is a wide geographic and temporal variability of bacterial resistance among microbial causes of ventilator-associated pneumonia (VAP). The contribution of multi-drug resistant (MDR) pathogens to the VAP etiology in Saudi Arabia was never studied. We sought to examine the extent of multiple-drug resistance among common microbial causes of VAP. MATERIALS AND METHODS: We conducted a retrospective susceptibility study in the adult intensive care unit (ICU) of King Abdulaziz Medical City, Riyadh, Saudi Arabia. Susceptibility results of isolates from patients diagnosed with VAP between October 2004 and June 2009 were examined. The US National Healthcare Safety Network definition of MDR was adopted. RESULTS: A total of 248 isolates including 9 different pathogens were included. Acinetobacter spp. was highly (60-89%) resistant to all tested antimicrobials, including carbapenems (three- and four-class MDR prevalence were 86% and 69%, respectively). Pseudomonas aeruginosa was moderately (13-31%) resistant to all tested antimicrobials, including antipseudomonal penicillins (three- and four-class MDR prevalence were 13% and 10%, respectively). With an exception of ampicillin (fully resistant), Klebsiella spp. had low (0-13%) resistance to other tested antimicrobials with no detected MDR. Staphylococcus aureus was fully susceptible to vancomycin with 42% resistance to oxacillin. There were significant increasing trends of MDR Acinetobacter spp. however not P. aeruginosa during the study. Resistant pathogens were associated with worse profile of ICU patients but not patients' outcomes. CONCLUSION: Acinetobacter in the current study was an increasingly resistant VAP-associated pathogen more than seen in many parts of the world. The current finding may impact local choice of initial empiric antibiotics. [ABSTRACT FROM AUTHOR]

Introduction: Data are sparse as to whether obesity influences the risk of death in critically ill patients with septic shock. We sought to examine the possible impact of obesity, as assessed by body mass index (BMI), on hospital mortality in septic shock patients. Methods: We performed a nested cohort study within a retrospective database of patients with septic shock conducted in 28 medical centers in Canada, United States and Saudi Arabia between 1996 and 2008. Patients were classified according to the World Health Organization criteria for BMI. Multivariate logistic regression analysis was performed to evaluate the association between obesity and hospital mortality. Results: Of the 8,670 patients with septic shock, 2,882 (33.2%) had height and weight data recorded at ICU admission and constituted the study group. Obese patients were more likely to have skin and soft tissue infections and less likely to have pneumonia with predominantly Gram-positive microorganisms. Crystalloid and colloid resuscitation fluids in the first six hours were given at significantly lower volumes per kg in the obese and very obese patients compared to underweight and normal weight patients (for crystalloids: 55.0±40.1 ml/kg for underweight, 43.2±33.4 for normal BMI, 37.1±30.8 for obese and 27.7±22.0 for very obese). Antimicrobial doses per kg were also different among BMI groups. Crude analysis showed that obese and very obese patients had lower hospital mortality compared to normal weight patients (odds ratio (OR) 0.80, 95% confidence interval (CI) 0.66 to 0.97 for obese and OR 0.61, 95% CI 0.44 to 0.85 for very obese patients). After adjusting for baseline characteristics and sepsis interventions, the association became non-significant (OR 0.80, 95% CI 0.62 to 1.02 for obese and OR 0.69, 95% CI 0.45 to 1.04 for very obese). Conclusions: The obesity paradox (lower mortality in the obese) documented in other populations is also observed in septic shock. This may be related in part to differences in patient characteristics. However, the true paradox may lie in the variations in the sepsis interventions, such as the administration of resuscitation fluids and antimicrobial therapy. Considering the obesity epidemic and its impact on critical care, further studies are warranted to examine whether a weight-based approach to common therapeutic interventions in septic shock influences outcome. [ABSTRACT FROM AUTHOR]

AIMS: There is an uncertainty about what constitutes an optimal level of blood glucose (BG) in critically ill patients. The objective of this study is to identify the optimal BG target for glycemic control in critically ill patients that is associated with survival benefit with the least hypoglycemia risk. SETTING AND DESIGN: This is a nested cohort study within a randomized control trial conducted in a tertiary care center in King Abdulaziz Medical City, Riyadh, Kingdom of Saudi Arabia. METHODS: The study was carried out in a single center to assess the effect of intensive insulin therapy [IIT; target BG 4.4-6.1 mmol/L (80-110 mg/dL)] versus conventional insulin therapy [CIT; target BG 10-11.1 mmol/L (180-200 mg/dL)] in a medical/surgical ICU. All patients were divided into six groups based on the mean daily BG levels. A logistic regression model was used to determine the association of BG and ICU mortality. We compared different outcomes below and above different BG thresholds of 0.1 mmol/L (2 mg/dL) increments using multivariate analyses. STATISTICAL ANALYSIS: Data are presented as mean ± SD or median with interquartile ranges, unless otherwise indicated. Differences between the six groups were assessed using the c² test. A P-value equal or less than 0.05 was considered to indicate statistical significance. The results were expressed as adjusted odds ratio (aOR) and 95% confidence intervals (CI). Statistical analyses were carried out using the Statistical Analysis Software (SAS, release 8, SAS Institute Inc., Cary, NC, USA). RESULTS: Among six groups, the ICU mortality was least in patients with BG <8.7 mmol/L (<157 mg/dL) compared with patients with BG ?8.7 mmol/L (?157 mg/dL) [11.5% vs. 21.5%, P = 0.002]. When analyzed using 0.1 mmol increments in average BG, we found that mortality remained unchanged by increasing thresholds of BG up to 8.0 mmol/L (144 mg/dL) and started to rise with thresholds of BG of 8.1 mmol/L (146 mg/dL) and above. The risk of hypoglycemia was the highest with a BG threshold of 6.1 mmol/L (110 mg/ dL) and gradually decreased with increasing BG levels to plateau with a BG level of 7.2 mmol/L (130 mg/ dL) and higher. CONCLUSION: Our study suggests that a BG level of 8.1 mmol/L (146 mg/dL) and below represents an optimal level in critically ill patients. [ABSTRACT FROM AUTHOR]

Background: Serum procalcitonin is commonly used to differentiate systemic inflammation due to infection from non-infectious causes. Limited data exist on the value of procalcitonin in predicting relative adrenal insufficiency (RAI). This study evaluated the value of procalcitonin in predicting RAI and mortality in cirrhotic patients with septic shock., Methods: This was a post-hoc analysis of a randomized placebo-controlled trial that evaluated low-dose hydrocortisone in cirrhotic patients with septic shock. Extracted first study-day data included serum procalcitonin, baseline serum cortisol, cortisol level after 250 microg - adrenocorticotropic hormone stimulation test and 28 - day mortality. RAI was defined as a baseline serum cortisol < 10 microg/dL or cortisol not rising by > 9 microg/dL after stimulation. Procalcitonin > 0.5 ng/mL was considered high., Results: Forty-five patients had serum procalcitonin measured (mean = 2.7 +/- 3.2 ng/mL, first and third quartiles were 0.3 and 3.3 ng/mL, respectively). Most (78%) patients had high procalcitonin levels. RAI was present in 34 (76%) patients. Patients with high procalcitonin were more likely to have RAI (odds ratio, 4.8; 95% confidence interval, 1.1 - 22.1). Receiver operator characteristic curve analysis showed that the best cut-off for detecting RAI was 1.0 ng/mL (sensitivity = 79% and specificity = 55%). High serum procalcitonin was not associated with 28 -day mortality (80% for normal procalcitonin and 77% for high procalcitonin, p = 0.61)., Conclusions: High serum procalcitonin was highly associated with RAI in cirrhotic patients with septic shock. Procalcitonin was not associated with 28 - day mortality in this patient population.

Background: Ventilator-associated pneumonia (VAP) prevention is an important patient safety initiative. We describe the impact of a multidisciplinary surveillance program on VAP rates in a tertiary medical-surgical-trauma intensive care unit (ICU)., Methods: An epidemiologic surveillance program was established in 2003 as a joint project between ICU and Infection Prevention and Control Department to regularly report VAP rates to guide evidence-based VAP preventive strategies. VAP cases were diagnosed according to predefined criteria and prospectively recorded by a research physician. VAP microbiology, risk factors, and outcomes were noted., Results: Of 2,812 ventilated patients, 433 (15.4%) developed VAP corresponding to 15.9 episodes per 1,000 ventilator-days. The rate decreased from 19.1 in 2003 to 6.3 per 1,000 ventilator-days in 2009. On multivariate analysis, VAP was associated with accidental extubation (hazard ratio [HR], 4.11; 95% confidence interval [CI]: 1.93-8.73), trauma versus medical diagnosis (HR, 2.59; 95% CI: 2.07-3.23), chronic obstructive pulmonary disease (HR, 1.55; 95% CI: 1.08-2.22), and neuromuscular blockade (HR, 1.39; 95% CI: 1.07-1.81). The most common isolated pathogens were Gram-negative organisms. VAP patients had longer mechanical ventilation duration, ICU and hospital length of stay, but similar ICU and hospital mortality compared with non-VAP patients., Conclusion: The study showed a reduction in VAP rates with active surveillance, reporting and evidence-based preventive strategies and identified several modifiable risk factors, which should be the focus of additional interventions., (Copyright © 2012 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

Our aim was to evaluate end-of-life practices in a tertiary intensive care unit in Saudi Arabia. A prospective observational study was conducted in the medical-surgical intensive care unit of a teaching hospital in Riyadh, Saudi Arabia. Over the course of the one-year study period, 176 patients died and 77% of these deaths were preceded by end-of-life decisions. Of these, 66% made do-not-resuscitate decisions, 30% decided to withhold life support and 4% withdrew life support. These decisions were made after a median time of four days (Q1 to Q3: 1 to 9) and at least one day before death (Q1 to Q3: 1 to 4). The patients' families or surrogates were informed for 88% of the decisions and all decisions were documented in the patients' medical records. Despite religious and cultural values, more than three-quarters of the patients whose deaths were preceded by end-of-life decisions gave do-not-resuscitate decisions before death. These decisions should be made early in the patients' stay in the intensive care unit.

Background: Recent studies have reported a high prevalence of relative adrenal insufficiency in patients with liver cirrhosis. However, the effect of corticosteroid replacement on mortality in this high-risk group remains unclear. We examined the effect of low-dose hydrocortisone in patients with cirrhosis who presented with septic shock., Methods: We enrolled patients with cirrhosis and septic shock aged 18 years or older in a randomized double-blind placebo-controlled trial. Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 μg/dL from baseline after stimulation with 250 μg of intravenous corticotropin. Patients were assigned to receive 50 mg of intravenous hydrocortisone or placebo every six hours until hemodynamic stability was achieved, followed by steroid tapering over eight days. The primary outcome was 28-day all-cause mortality., Results: The trial was stopped for futility at interim analysis after 75 patients were enrolled. Relative adrenal insufficiency was diagnosed in 76% of patients. Compared with the placebo group (n = 36), patients in the hydrocortisone group (n = 39) had a significant reduction in vasopressor doses and higher rates of shock reversal (relative risk [RR] 1.58, 95% confidence interval [CI] 0.98-2.55, p = 0.05). Hydrocortisone use was not associated with a reduction in 28-day mortality (RR 1.17, 95% CI 0.92-1.49, p = 0.19) but was associated with an increase in shock relapse (RR 2.58, 95% CI 1.04-6.45, p = 0.03) and gastrointestinal bleeding (RR 3.00, 95% CI 1.08-8.36, p = 0.02)., Interpretation: Relative adrenal insufficiency was very common in patients with cirrhosis presenting with septic shock. Despite initial favourable effects on hemodynamic parameters, hydrocortisone therapy did not reduce mortality and was associated with an increase in adverse effects. (Current Controlled Trials registry no. ISRCTN99675218.).

Purpose: The objective of our study was to evaluate the beneficial effect of IIT in reducing mortality and morbidity in critically ill trauma patients admitted to ICU., Method and Material: Nested cohort study within a Randomized Controlled Trial. All trauma patients with GCS < or = 9 included in the original trial were included in this study. Primary outcome was ICU mortality., Result: There was no difference in ICU mortality between IIT and CIT groups (6.5% vs. 5.5%, p = 0.67). After adjustment for baseline characteristics, IIT therapy was also not associated with mortality (Adjusted Hazard Ratio 1.33, 95% CI 0.35-5.05). IIT therapy was associated with a significant increase in the incidence of hypoglycemia as compared to CIT, at least one hypoglycemia episode occurred in 18.5% of patients in IIT and 1.3% in the CIT group (P < 0.0001)., Conclusion: IIT was not associated with survival improvement in trauma patients admitted to ICU and was associated with increased incidence of hypoglycemia.

Background: The objective of this study was to determine whether caloric intake independently influences mortality and morbidity of critically ill patients., Methods: The study was conducted as a nested cohort study within a randomized controlled trial in a tertiary care intensive care unit (ICU). The main exposure in the study was average caloric intake/target for the first 7 ICU days. The primary outcomes were ICU and hospital mortality. Secondary outcomes included ICU-acquired infections, ventilator-associated pneumonia (VAP), duration of mechanical ventilation days, and ICU and hospital length of stay (LOS). The authors divided patients (n = 523) into 3 tertiles according to the percentage of caloric intake/target: tertile I <33.4%, tertile II 33.4%-64.6%, and tertile III >64.6%. To adjust for potentially confounding variables, the authors assessed the association between caloric intake/target and the different outcomes using multivariate logistic regression for categorical outcomes (tertile I was used as reference) and multiple linear regression for continuous outcomes., Results: Tertile III was associated with higher adjusted hospital mortality, higher risk of ICU-acquired infections, and a trend toward higher VAP rate. Increasing caloric intake was independently associated with a significant increase in duration of mechanical ventilation, ICU LOS, and hospital LOS., Conclusions: The data demonstrate that near-target caloric intake is associated with significantly increased hospital mortality, ICU-acquired infections, mechanical ventilation duration, and ICU and hospital LOS. Further studies are needed to explore whether reducing caloric intake would improve the outcomes in critically ill patients.