Use of therapeutic caffeine in acute care postoperative and critical care settings: a scoping review.

BACKGROUND: Caffeine is the most utilised psychoactive drug worldwide. However, caffeine withdrawal and the therapeutic use of caffeine in intensive care and in the perioperative period have not been well summarised. Our objective was to conduct a scoping review of caffeine withdrawal and use in the intensive care unit (ICU) and postoperative patients. METHODS: PubMed, Embase, CINAHL Complete, Scopus and Web of Science were systematically searched for studies investigating the effects of caffeine withdrawal or administration in ICU patients and in the perioperative period. Areas of recent systematic review such as pain or post-dural puncture headache were not included in this review. Studies were limited to adults. RESULTS: Of 2268 articles screened, 26 were included and grouped into two themes of caffeine use in in the perioperative period and in the ICU. Caffeine withdrawal in the postoperative period increases the incidence of headache, which can be effectively treated prophylactically with perioperative caffeine. There were no studies investigating caffeine withdrawal or effect on sleep wake cycles, daytime somnolence, or delirium in the intensive care setting. Administration of caffeine results in faster emergence from sedation and anaesthesia, particularly in individuals who are at high risk of post-extubation complications. There has only been one study investigating caffeine administration to facilitate post-anaesthetic emergence in ICU. Caffeine administration appears to be safe in moderate doses in the perioperative period and in the intensive care setting. CONCLUSIONS: Although caffeine is widely used, there is a paucity of studies investigating withdrawal or therapeutic effects in patients admitted to ICU and further novel studies are a priority.

Burden of community-onset bloodstream infections, Western Interior, British Columbia, Canada.

Although community-onset bloodstream infection (BSI) is recognized as a major cause of morbidity and mortality, its epidemiology has not been well defined in non-selected populations. We conducted population-based surveillance in the Interior Health West region of British Columbia, Canada in order to determine the burden associated with community-onset BSI. A total of 1088 episodes were identified for an overall annual incidence of 117·8/100 000 of which 639 (58·7%) were healthcare-associated (HA) and 449 (41·3%) were community-associated (CA) BSIs for incidences of 69·2 and 48·6/100 000, respectively. The incidence of community-onset BSI varied by age and gender and elderly males were at the highest risk. Overall 964 (88·6%) episodes resulted in hospital admission for a median length of stay of 8 days; the total days of acute hospitalization associated with community-onset BSI was 13 530 days or 1465 days/100 000 population per year. The in-hospital mortality rate was 10·6% (102/964) and this was higher for HA-BSI (72/569, 12·7%) compared to CA-BSI (30/395, 7·6%, P = 0·014) episodes. Community-onset BSI, especially HA-BSI, is associated with a major burden of illness.

Population-based assessment of the incidence, risk factors, and outcomes of anaerobic bloodstream infections.

BACKGROUND: Anaerobes are a relatively uncommon but important cause of bloodstream infection. However, their epidemiology has not been well defined in non-selected populations. We sought to describe the incidence of, risk factors for, and outcomes associated with anaerobic bacteremia. METHODS: Population-based surveillance for bacteremia with anaerobic microorganisms was conducted in the Calgary area (population 1.2 million) during the period from 2000 to 2008. RESULTS: A total of 904 incident cases were identified, for an overall population incidence of 8.7 per 100,000 per year; 231 (26 %) were nosocomial, 300 (33 %) were healthcare-associated community-onset, and 373 (41 %) were community-acquired. Elderly males were at the greatest risk. The most common pathogens identified were: Bacteroides fragilis group (3.6 per 100,000), Clostridium (non-perfringens) spp. (1.1 per 100,000), Peptostreptococcus spp. (0.9 per 100,000), and Clostridium perfringens (0.7 per 100,000). Non-susceptibility to metronidazole was 2 %, to clindamycin 17 %, and to penicillin 42 %. Relative to the general population, risk factors for anaerobic bloodstream infection included: male sex, increasing age, a prior diagnosis of cancer, chronic liver disease, heart disease, diabetes mellitus, stroke, inflammatory bowel disease, human immunodeficiency virus (HIV) infection, chronic obstructive pulmonary disease (COPD), and/or hemodialysis-dependent chronic renal failure (HDCRF). The 30-day mortality was 20 %. Increasing age, nosocomial acquisition, presence of malignancy, and several other co-morbid illnesses were independently associated with an increased risk of death. CONCLUSION: Anaerobic bloodstream infection is responsible for a significant burden of disease in general populations. The data herein establish the extent to which anaerobes contribute to morbidity and subsequent mortality. This information is key in developing preventative, empiric treatment and research priorities.

Defining the epidemiology of bloodstream infections: the 'gold standard' of population-based assessment.

Bloodstream infections (BSIs) are a major cause of morbidity and mortality. Although population-based studies have been proposed as an optimal means to define their epidemiology, the merit of these designs has not been well documented. This report investigated the potential value of using population-based designs in defining the epidemiology of BSIs. Population-based BSI surveillance was conducted in Calgary, Canada (population 1.24 million) and illustrative comparisons were made between the overall and selected subgroup cohorts within five main themes. The value of population denominator data, and age and gender standardization for calculation and comparison of incidence rates were demonstrated. In addition, a number of biases including those related to differential admission rates, selected hospital admission, and referral bias were highlighted in non-population-based cohorts. Due to their comprehensive nature and intrinsic minimization of bias, population-based designs should be considered the gold standard means of defining the epidemiology of an infectious disease.

Population-based laboratory assessment of the burden of community-onset bloodstream infection in Victoria, Canada.

Although community-onset bloodstream infection (BSI) is recognized as a major cause of morbidity and mortality, its epidemiology has not been well defined in non-selected populations. We conducted population-based laboratory surveillance in the Victoria area, Canada during 1998-2005 in order to determine the burden associated with community-onset BSI. A total of 2785 episodes were identified for an overall annual incidence of 101·2/100,000. Males and the very young and the elderly were at highest risk. Overall 1980 (71%) episodes resulted in hospital admission for a median length of stay of 8 days; the total days of acute hospitalization associated with community-onset BSI was 28 442 days or 1034 days/100,000 population per year. The in-hospital case-fatality rate was 13%. Community-onset BSI is associated with a major burden of illness. These data support ongoing and future preventative and research efforts aimed at reducing the major impact of these infections.

Long-term mortality associated with community-onset bloodstream infection.

PURPOSE: Although bloodstream infection is widely recognized as an important cause of acute morbidity and mortality, long-term mortality outcomes are less well defined. The objective of this study was to define the early (≤28 days) and late (>28 days) mortality and assess determinants of late death following community-onset bloodstream infection. METHODS: All adult residents of the Calgary Zone who had community-onset bloodstream infections during the period 1 January 2003 and 31 December 2007 were included. The mortality outcome was assessed through to 31 December 2008. RESULTS: A total of 4,553 cases were identified, of which 2,105 (46%) were healthcare-associated and 2,448 (54%) were community-acquired. The 28-day, 90-day, and 365-day all-cause case-fatality rates were 561/4,553 (12%), 780/4,553 (17%), and 1,131 (25%), respectively. Within the first 28 days, the median time to death was 4 (interquartile range [IQR] 1-12) days, with 158 (28%) and 212 (38%) of early (≤28-day) deaths occurring by days 1 and 2, respectively. Among survivors to 28 days (n = 3,992), 570 (14%) suffered late 1-year mortality (i.e., death occurred between 29 and 365 days postinception). The most common causes of death in this cohort as listed by the vital statistics data were malignancy in 220 (39%), cardiovascular in 135 (24%), and infection-related in 37 (7%). Older age, higher Charlson score, prolonged initial admission duration, and healthcare-associated and polymicrobial infections were independently associated with late 1-year mortality. CONCLUSIONS: Community-onset bloodstream infection is associated with major early and late mortality.

Population-based study of the epidemiology and the risk factors for Pseudomonas aeruginosa bloodstream infection.

BACKGROUND: Detailed population-based data on the epidemiology of Pseudomonas aeruginosa bloodstream infections are sparse. We sought to describe the incidence rate, risk factors, and outcomes associated with P. aeruginosa bacteremia in a large Canadian health region. PATIENTS AND METHODS: A retrospective population-based surveillance for P. aeruginosa bacteremia was conducted in the Calgary Health Region (CHR, population:approx. 1.2 million) during the period from 2000 to 2006. RESULTS: A total of 284 incident cases of P. aeruginosa bacteremia were identified in CHR residents, corresponding to an annual incidence rate of 3.6/100,000.Nosocomial acquisition accounted for 45% of cases,healthcare-associated community onset for 34% of cases,and community-acquired (CA) cases for 21%. Relative to the general population, risk factors for blood stream infection included male sex, increasing age, hemodialysis,solid organ transplant, diagnosis of cancer, heart disease, HIV infection, diabetes mellitus, and/or chronic obstructive airway disease (COPD). Overall mortality was 29%. Factors associated with mortality in univariate analysis included pulmonary focus of infection and co-morbidities, including chronic liver disease, substance abuse, heart disease, COPD, and cancer, and increased with the burden of co-morbidities. Despite those patients with CA disease having fewer co-morbidities,they had a significantly higher mortality rate than either healthcare-associated cases or nosocomial cases(RR 1.88, p = 0.05). CONCLUSIONS: This study documents that P. aeruginosa bacteremic disease is responsible for a significant burden of illness in general populations and identifies those groups at increased risk of infection and subsequent mortality. This information can be used to identify those individuals likely to benefit from empiric anti-pseudomonal therapies.

Defining microbial invasion of the bloodstream: a structured review.

Background: Microbial invasion of the bloodstream is associated with a major burden of illness. Despite its importance, there is inconsistency in utilization of terms used to define it.Objective: To characterize the contemporary use of terms to define microbial invasion of the bloodstream for surveillance and research purposes.Methods: Structured review of publications reported from 2000 to 2019.Results: The search strategy retrieved 10,095 citations of which bloodstream infection, bacteraemia and fungaemia were included in 2813, 6900 and 1054 articles, respectively. There was a tripling of the number of annual citations during the study and although bacteraemia was most frequent, there was a progressive increase in the use of the term bloodstream infection. Among the 100 reports randomly selected for detailed review, the terms bacteraemia, bloodstream infection and fungaemia were used in 57, 51 and 19 publications, respectively. Explicit definitions for bloodstream infection (26/51; 51%), bacteraemia (13/57; 23%) and fungaemia (7/19; 37%) were included in reports where these terms were used. Although nearly all (95%) of the studies indicated a positive blood culture as an inclusion criteria and/or definition, only a minority indicated means to exclude contaminants (33%) or specific attributes to support clinical significance (38%). Use of explicit definitions was more common among reports that exclusively used the term bloodstream infection as compared to bacteraemia.Conclusions: Terms have been inconsistently defined and imprecisely used to refer to microbial invasion of the bloodstream. Clinically relevant and objective definitions that are widely acceptable are needed for surveillance and research purposes.

Occurrence and determinants of enterococcal bloodstream infections: a population-based study.

Background: Although enterococci are common causes of bloodstream infections (BSIs), few studies have examined their epidemiology in non-selected populations.Objective: To examine the incidence and risk factors for development of enterococcal BSI.Methods: Surveillance for incident enterococcal BSI was conducted among all residents of the western interior of British Columbia, Canada during 2011-2018.Results: The overall annual incidence was 10.0 per 100,000 and was 6.6 and 2.7 per 100,000 for E. faecalis and E. faecium, respectively. Among the overall cohort of 145 incident cases of enterococcal BSI, 22 (15.2%) were community-associated, 63 (43.5%) were healthcare associated and 60 (41.4%) were hospital-onset. Enterococcal BSI was predominantly a disease of older adults with rare cases occurring among those aged less than 40 years. Males showed significantly increased risk compared to females (14.3 vs. 5.6 per 100,000; incidence rate ratio; IRR; 2.6; 95% confidence interval; CI; 1.8-3.8; p < .0001) and this was most pronounced with advanced age. Several co-morbid illnesses were associated with increased risk (IRR; 95% CI) for development of enterococcal BSI most importantly cancer (8.8; 6.0-12.9; p < .0001), congestive heart failure (5.7; 3.1-9.7; p < .0001), diabetes mellitus (4.4; 3.0-6.3; p < .0001) and stroke (3.7; 1.9-6.5; .0001). As compared to patients with E. faecalis, patients with E. faecium BSI were more likely to be of hospital-onset, more likely to have an intra-abdominal/pelvic focus, and trended towards higher 30-day case-fatality rate.Conclusions: Enterococci are relatively common causes of BSI. Although E faecalis and E faecium share commonalities they are epidemiologically distinguishable on several criteria.

Development and testing of a low cost simulation manikin for extracorporeal cardiopulmonary resuscitation (ECPR) using 3-dimensional printing.

BACKGROUND: There has been an explosive growth of ECPR within new and established ECMO programs worldwide with the concomitant need for simulation trainers. However, current commercially available ECMO simulation models are expensive and lack many standard cardiorespiratory resuscitative (CPR) features. OBJECTIVE: To use 3-dimensional (3D) printing to develop a training manikin for comprehensive ECPR simulation. METHODS: A standard commercially available CPR manikin with airway model was used as the base model for modification. An inexpensive 3D printer was used to print a modular plastic pelvis. A medical silicone gel incorporated silicone femoral vasculature component was manufactured with connection to a gravity fed vascular system. RESULTS: The resulting modified manikin included the modular in-house designed ECMO cannulation and vascular structures wedded to the commercially available airway and CPR components. In simulation exercise involving first responders, paramedics, and emergency and critical care physicians, the model was reported as realistic with ultrasound views, cannulation, and resuscitative components functional. The entire cost for development of the ECMO component was estimated at $2000 Australian dollars AUD, including the printer purchase and supplies. Future reuse of components is estimated to cost less than $5 AUD per simulation run. CONCLUSIONS: A novel in-house modified manikin for ECPR was developed that was cost-efficient and realistic to use from first response through to establishment of ECMO circulation.

When not to start antibiotics: avoiding antibiotic overuse in the intensive care unit.

BACKGROUND: Most intensive care unit (ICU) patients receive broad-spectrum antibiotics. While lifesaving in some, in others these treatments may be unnecessary and place patients at risk of antibiotic-associated harms. OBJECTIVES: To review the literature exploring how we diagnose infection in patients in the ICU and address the safety and utility of a 'watchful waiting' approach to antibiotic initiation with selected patients in the ICU. SOURCES: A semi-structured search of PubMed and Cochrane Library databases for articles published in English during the past 15 years was conducted. CONTENT: Distinguishing infection from non-infectious mimics in ICU patients is uniquely challenging. At present, we do not have access to a rapid point-of-care test that reliably differentiates between individuals who need antibiotics and those who do not. A small number of studies have attempted to compare early aggressive versus conservative antimicrobial strategies in the ICU. However, this body of literature is small and not robust enough to guide practice. IMPLICATIONS: This issue will not likely be resolved until there are diagnostic tests that rapidly and reliably identify the presence or absence of infection in the ICU population. In the meantime, prospective trials that identify clinical situations wherein it is safe to delay or withhold antibiotic initiation in the ICU until the presence of an infection is proven are warranted.

Clinical applications of intravenous immunoglobulins (IVIg)--beyond immunodeficiencies and neurology.

The clinical use of intravenous immunoglobulin (IVIg) has expanded beyond its traditional place in the treatment of patients with primary immunodeficiencies. Due to its multiple anti-inflammatory and immunomodulatory properties, IVIg is used successfully in a wide range of autoimmune and inflammatory conditions. Recognized autoimmune indications include idiopathic thrombocytopenic purpura (ITP), Kawasaki disease, Guillain-Barré syndrome and other autoimmune neuropathies, myasthenia gravis, dermatomyositis and several rare diseases. Several other indications are currently under investigation and require additional studies to establish firmly the benefit of IVIg treatment. Increasing attention is being turned to the use of IVIg in combination with other agents, such as immunosuppressive agents or monoclonal antibodies. For example, recent studies suggest that combination therapy with IVIg and rituximab (an anti-CD20 monoclonal antibody) may be effective for treatment of autoimmune mucocutaneous blistering diseases (AMBDs), with sustained clinical remission. The combination of IVIg and rituximab has also been used in the setting of organ transplantation. Firstly, IVIg +/- rituximab has been administered to highly human leucocyte antigen (HLA)-sensitized patients to reduce anti-HLA antibody levels, thereby allowing transplantation in these patients. Secondly, IVIg in combination with rituximab is effective in the treatment of antibody-mediated rejection following transplantation. Treatment with polyclonal IVIg is a promising adjunctive therapy for severe sepsis and septic shock, but its use remains controversial and further study is needed before it can be recommended routinely. This review covers new developments in these fields and highlights the broad range of potential therapeutic areas in which IVIg may have a clinical impact.

Surveillance for antimicrobial resistant organisms: potential sources and magnitude of bias.

Surveillance has been recognized as a fundamental component in the control of antimicrobial- resistant infections. Although surveillance data have been widely published and utilized by researchers and decision makers, little attention has been paid to assessment of their validity. We conducted this review in order to identify and explore potential types and magnitude of bias that may influence the validity or interpretation of surveillance data. Six main potential areas were assessed. These included bias related to use of inadequate or inappropriate (1) denominator data, (2) case definitions, and (3) case ascertainment; (4) sampling bias; (5) failure to deal with multiple occurrences, and (6) those related to laboratory practice and procedures. The magnitude of these biases varied considerably for the above areas within different study populations. There are a number of potential biases that should be considered in the methodological design and interpretation of antimicrobial-resistant organism surveillance.

Validity of electronic surveillance systems: a systematic review.

Electronic surveillance that utilises information held in databases is more efficient than conventional infection surveillance methods. Validity is not well-defined, however. We systematically reviewed studies comparing the utility of electronic and conventional surveillance methods. Publications were identified using Medline (1980-2007) and bibliographic review. The sensitivity and specificity of electronic compared with conventional surveillance was reported. Twenty-four studies were included. Six studies reported that nosocomial infections could be detected utilising microbiology data alone with good overall sensitivity (range: 63-91%) and excellent specificity (range: 87 to >99%). Two studies used three laboratory-based algorithms for the detection of infection outbreaks yielding variable utility measures (sensitivity, range: 43-91%; specificity, range: 67-86%). Seven studies using only administrative data including discharge coding (International Classification of Diseases, 9th edn, Clinical Modification) and pharmacy data claimed databases had good sensitivity (range: 59-96%) and excellent specificity (range: 95 to >99%) in detecting nosocomial infections. Six studies combined both laboratory and administrative data for a range of infections, and overall had higher sensitivity (range: 71-94%) but lower specificity (range: 47 to >99%) than with use of either alone. Three studies evaluated community-acquired infections with variable results. Electronic surveillance has moderate to excellent utility compared with conventional methods for nosocomial infections. Future studies are needed to refine electronic algorithms further, especially with community-onset infections.

Culturing rate and the surveillance of bloodstream infections: a population-based assessment.

OBJECTIVES: Diagnosis of a bloodstream infection (BSI) requires a positive blood culture. However, low culturing rates will underestimate the true incidence of BSI and high rates may increase the risk of false-positive results. We sought to investigate the relationship between culturing rates and the incidence of BSI at the population level. METHODS: Population-based surveillance was conducted in the western interior of British Columbia, Canada, between 1 April 2010 and 31 March 2017. RESULTS: Among 60 243 blood culture sets drawn, 5591 isolates were obtained, of which 2303 were incident, 1929 were repeat positive and 1359 were contaminants. Overall annual rates of culturing, incident, repeat positive and contaminant isolates were 4832, 185, 155 and 109 per 100 000 population, respectively. During the 84-month study, there was an increase in the culturing rate that reached a plateau at 48 months (5403 cultures per 100 000 per year). The rate of both repeat isolates and contaminants increased linearly with an increasing culturing rate. However, the incident isolate rate reached an inflection point at a rate of approximately 5550 per 100 000 annually, at which point the increase in incident isolates per culture sample was diminished. At a culturing rate above 6123 per 100 000 per year, the number of repeat isolates exceeded that of incident isolates. CONCLUSIONS: The determined incidence of BSI will increase with increased culturing in a population. Further studies are needed to explore optimal BSI culturing rates in other populations.

Neonatal activation of CD28 signaling overcomes T cell anergy and prevents autoimmune diabetes by an IL-4-dependent mechanism.

Optimal T cell responsiveness requires signaling through the T cell receptor (TCR) and CD28 costimulatory receptors. Previously, we showed that T cells from autoimmune nonobese diabetic (NOD) mice display proliferative hyporesponsiveness to TCR stimulation, which may be causal to the development of insulin-dependent diabetes mellitus (IDDM). Here, we demonstrate that anti-CD28 mAb stimulation restores complete NOD T cell proliferative responsiveness by augmentation of IL-4 production. Whereas neonatal treatment of NOD mice with anti-CD28 beginning at 2 wk of age inhibits destructive insulitis and protects against IDDM by enhancement of IL-4 production by islet-infiltrating T cells, administration of anti-CD28 beginning at 5-6 wk of age does not prevent IDDM. Simultaneous anti-IL-4 treatment abrogates the preventative effect of anti-CD28 treatment. Thus, neonatal CD28 costimulation during 2-4 wk of age is required to prevent IDDM, and is mediated by the generation of a Th2 cell-enriched nondestructive environment in the pancreatic islets of treated NOD mice. Our data support the hypothesis that a CD28 signal is requisite for activation of IL-4-producing cells and protection from IDDM.

Population-based laboratory surveillance for tribe Proteeae isolates in a large Canadian health region.

The tribe Proteeae comprises the genera Proteus, Morganella and Providencia. Few studies have specifically investigated the epidemiology of infections caused by the Proteeae, and none has been conducted in a large non-selected population. The present study was a population-based laboratory surveillance in the Calgary Health Region (population 1.2 million), Canada during 2000-2005 that aimed to define the incidence, demographical risk-factors for acquisition and antimicrobial susceptibilities of Proteeae isolates. In total, 5047 patients were identified from whom Proteeae isolates were obtained (an annual incidence of 75.9/100 000), with females and the elderly being at highest risk. Incidence rates were 64.8, 7.7 and 3.4/100,000/year for the genera Proteus, Morganella and Providencia, respectively. Overall, 85% of infections were community-onset, and the overall rate of bacteraemic disease was 2.0/100,000. Compared with other species, Proteus mirabilis occurred at a much higher frequency, especially among females, and was less likely to be isolated from hospital-onset infections or to be part of a polymicrobial infection. Among isolates from community-onset infections, Providencia spp. were less likely to be from outpatients and more likely to be from nursing home residents. There were low overall rates of resistance to ciprofloxacin (4%) and gentamicin (5%), with Prot. mirabilis generally being the most susceptible. Members of the Proteeae were isolated frequently in both the community and hospital settings, but were infrequent causes of invasive disease. The occurrence, demographical risk-factors and microbiology of Proteeae isolates varied according to the individual species.

Treatment of infections caused by metallo-beta-lactamase-producing Pseudomonas aeruginosa in the Calgary Health Region.

This study reviewed 56 patients with significant metallo-beta-lactamase (MBL)-producing Pseudomonas aeruginosa infections between May 2002 and March 2004 to identify features associated with mortality. Immunosuppression (p 0.002), bacteraemia (p 0.08) and inadequate antimicrobial therapy (p <0.001) were associated with death. Among those patients treated with adequate therapy, the use of multiple drug treatment regimens (two or three active agents) was associated with a non-significant two-fold increase in survival (p 0.45). Further prospective studies are warranted to determine the optimal treatment of MBL-producing P. aeruginosa infections.

Population-based surveillance of invasive pyogenic streptococcal infection in a large Canadian region.

Pyogenic streptococci are a major cause of invasive infection. This study presents the results of a population-based laboratory surveillance for invasive pyogenic streptococcal infections among residents of the Calgary Health Region (population 1 million) between 1 July 1999 and 30 June 2004. The overall annual incidence rate was 18.65/100,000 population, with isolates belonging to the Streptococcus milleri group forming the most important aetiology (incidence of 8.65/100,000 population). Invasive infection with groups A, B, G and C streptococci occurred at annual rates of 4.27, 3.13, 1.83 and 0.41/100,000 population, respectively. There was a close relationship between increasing age and development of an invasive pyogenic streptococcal infection, and the incidence of infection was higher among males than among females. Differences in the seasonal occurrence and focus of infection occurred between the different groups.

Cost of intensive care unit-acquired bloodstream infections.

Intensive care unit-acquired (ICU-acquired) bloodstream infections (BSI) are an important complication of critical illness. The objective of this study was to quantify the excess length of stay, mortality and cost attributable to ICU-acquired BSI. A matched cohort study was conducted in all adult ICUs in the Calgary Health Region between 1 May 2000 and 30 April 2003. One hundred and forty-four patients with ICU-acquired BSI were matched (1:1) to patients without ICU-acquired BSI. Patients with ICU-acquired BSI had a significantly increased median length of ICU stay {15.5 [interquartile range (IQR) 8-26] days vs 12 [IQR 7-18.5] days, P=0.003} and median costs of hospital care [85,137 dollars (IQR 45,740-131,412 dollars) vs 67,879 dollars (IQR 35,043-115,915 dollars, P=0.02) compared with patients without ICU-acquired BSI. The median excess length of ICU stay was two days and the median cost attributable to ICU-acquired BSI was 12,321 dollars per case. Sixty (42%) of the cases died compared with 37 (26%) of the controls [P=0.002, attributable mortality 16%, 95% confidence interval (CI) 5.9-26.0%]. Patients with ICU-acquired BSI were at increased risk for in-hospital death (odds ratio=2.64, 95%CI 1.40-5.29). Among survivor-matched pairs, the median excess lengths of ICU and hospital stay attributable to development of ICU-acquired BSI were two and 13.5 days, respectively, and the attributable cost due to ICU-acquired BSI was 25,155 dollars per case survivor. Critically ill patients who develop ICU-acquired BSI suffer excess morbidity and mortality, and incur significantly increased healthcare costs. These data support expenditures on infection prevention and control programmes and further research into reducing the impact of these infections.