Sepsis-associated acute kidney injury in patients with chronic kidney disease: Patient characteristics, prevalence, timing, trajectory, treatment and associated outcomes.

AIM: The features and outcomes of sepsis-associated acute kidney injury (SA-AKI) may be affected by chronic kidney disease (CKD). Accordingly, we aimed to compare SA-AKI in patients with or without CKD. METHODS: Retrospective cohort study in 12 intensive care units (ICU). We studied the prevalence, patient characteristics, timing, trajectory, treatment and outcomes of SA-AKI with and without CKD. RESULTS: Of 84 240 admissions, 7255 (8.6%) involved patients with CKD. SA-AKI was more common in patients with CKD (21% vs 14%; p < .001). CKD patients were older (70 vs. 60 years; p < .001), had a higher median Charlson co-morbidity index (5 vs. 3; p < .001) and acute physiology and chronic health evaluation (APACHE) III score (78 vs. 60; p < .001) and were more likely to receive renal replacement therapy (RRT) (25% vs. 17%; p < .001). They had less complete return to baseline function at ICU discharge (48% vs. 60%; p < .001), higher major adverse kidney events at day 30 (MAKE-30) (38% vs. 27%; p < .001), and higher hospital and 90-day mortality (21% vs. 13%; p < .001, and 27% vs. 16%; p < .001, respectively). After adjustment for patient characteristics and severity of illness, however, CKD was not an independent risk factor for increased 90-day mortality (OR 0.88; 95% CI 0.76-1.02; p = .08) or MAKE-30 (OR 0.98; 95% CI 0.80-1.09; p = .4). CONCLUSION: SA-AKI is more common in patients with CKD. Such patients are older, more co-morbid, have higher disease severity, receive different ICU therapies and have different trajectories of renal recovery and greater unadjusted mortality. However, after adjustment day-90 mortality and MAKE-30 risk were not increased by CKD.

Epidemiology of Hypophosphatemia in Critical Illness: A Multicentre, Retrospective Cohort Study.

INTRODUCTION: Hypophosphatemia is common in critically ill patients. We have described the epidemiology of hypophosphatemia in patients admitted to the Intensive Care Units. METHODS: A multicentre, retrospective cohort study of 12 ICUs in Queensland, Australia from January 1st, 2015, to December 31st, 2021. Exclusions included readmissions, renal replacement therapy, end-stage renal disease, and palliative intent admissions and transfers from other ICUs. Patients were classified into four groups based on the severity of the first episode of low serum phosphate (PO4): "None" (PO4: ≥ 0.81 mmol/L, ``Mild" (PO4: ≥ 0.50 & < 0.81 mmol/L) "Moderate" (PO4: ≥ 0.30 & < 0.50 mmol/L) and "Severe" (PO4: < 0.30 mmol/L). A mixed-effect logistic regression model, including hospital as a random effect, was developed to examine factors associated with 90-day case fatality. RESULTS: Of the 89,776 patients admitted, 68,699 patients were included in this study, with 23,485 (34.2%) having hypophosphatemia with onset mostly on Day 2 of ICU admission and correcting to normal 3 days after hypophosphatemia was identified. There was substantial variation among participating ICUs in phosphate replacement; the threshold, and the route by which it was replaced. Day-90 case fatality increased with severity of hypophosphatemia (None: 3,974 (8.8%), Mild: 2,306 (11%), Moderate: 377 (14%); Severe: 108 (21%) (p < 0.001)). Multivariable regression analysis showed that compared to those without hypophosphatemia, patients with moderate (odds ratio (OR) 1.24; 95% confidence intervals (CI) 1.07-1.44; p = 0.004) or severe (OR 1.49; 95% CI 1.13-1.97; p = 0.005) hypophosphatemia had increased risk of 90-day case fatality. CONCLUSION: Hypophosphatemia was common, and mostly occurred on day 2 with early correction of serum phosphate. Phosphate replacement practices were variable among ICUs. Moderate and severe hypophosphatemia was associated with increased 90-day case fatality.

Arterial catheter outcomes in intensive care: An analysis of 1117 patients.

BACKGROUND: Access to arterial circulation through arterial catheters (ACs) is crucial for monitoring and decision-making in intensive care units (ICU) but carries the risk of complications including bloodstream infection (BSI). METHODS: We conducted a secondary analysis of data from four randomised controlled trials in Australian ICUs, investigating the efficacy of different AC interventions. De-identified data were combined into a single dataset, and per-patient outcomes analysed. The primary outcome was AC-BSI, defined as laboratory confirmed bloodstream infection (LCBI) type 1 or 2, with a concurrent local infection. All-cause AC failure was defined as any unplanned removal. AC infection and failure were reported as rates per 1000 catheter days and hours. RESULTS: Data from 1117 adult patients were analysed. Mean age was 58.8 years (±16.6); and 41% (n = 462) were male. Median AC dwell time was 110 h (IQR 28.3-168.0). There was one case (<0.1%; 0.18/1000 catheter days [95% CI 0.03-1.29]) of AC-BSI, and 14 cases of LCBI (1%; 13 LCBI-1 and 1 LCBI-2; 2.54/1000 catheter days [95% CI 1.51-4.30]). LCBI were most commonly Enterococcus faecalis; Escherichia coli and Klebsiella pneumoniae. There were four cases of local infection (<1%; 0.73/1000 catheter days [95% CI 0.27-1.94]). Overall AC failure rate was 13% (n = 146) or 26.53/1000 catheter days (95% CI 22.56-31.20). CONCLUSION: This study identified a relatively low incidence of complications. This is likely reflective of poor monitoring of ACs in intensive care. Better surveillance and a rigorous prospective evaluation of AC outcomes is required to understand the true risk ACs pose to critically ill patients.

Epidemiology of biliary tract-associated bloodstream infections and adequacy of empiric therapy: an Australian population-based study.

PURPOSE: Although the biliary tract is a common source of invasive infections, the epidemiology of cholangitis- and cholecystitis-associated bloodstream infection (BSI) is not well defined. The objective of this study was to determine the incidence, clinical determinants, microbiology of biliary tract-associated BSI, and predicted adequacy of common empiric therapy regimens. METHODS: All biliary tract-associated BSI in Queensland during 2000-2019 were identified using state-wide data sources. Predicted adequacy of empiric antimicrobial therapy was determined according to microbiological susceptibility data. RESULTS: There were 3,698 episodes of biliary tract-associated BSI occurred in 3,433 patients of which 2,147 (58.1%) episodes were due to cholangitis and 1,551 (41.9%) cholecystitis, for age- and sex-standardized incidence rates of 2.7, and 2.0 per 100,000 population, respectively. An increasing incidence of biliary tract-associated BSI was observed over the study that was attributable to an increase in cholangitis cases. There was a significant increased risk for biliary tract-associated BSI observed with advancing age and male sex. Patients with cholangitis were older, more likely to have healthcare associated infection, and have more comorbidities most notably liver disease and malignancies as compared to patients with cholecystitis. The distribution of infecting pathogens was significantly different with polymicrobial aetiologies more commonly observed with cholangitis (18.4% vs. 10.5%; p < 0.001). The combination of ampicillin/gentamicin/metronidazole was predicted to have the overall highest adequacy (96.1%), whereas amoxicillin/clavulanate had the lowest (77.0%). Amoxicillin/clavulanate (75.2% vs. 79.4%, p:0.03) and ceftriaxone/metronidazole (83.4% vs. 89.6%; p < 0.001) showed significantly inferior predicted adequacy for cholangitis as compared to cholecystitis. CONCLUSIONS: Bloodstream infections related to cholecystitis and cholangitis exhibit different epidemiology, microbiology, and requirements for empiric therapy.

The interaction of net ultrafiltration rate with urine output and fluid balance after continuous renal replacement therapy initiation: A multi-Centre study.

PURPOSE: During continuous renal replacement therapy (CRRT), a high net ultrafiltration rate (NUF) may worsen the decrease in urine output (UO) associated with starting CRRT. However, fluid balance (FB) may modulate this association. We aimed to examine the relationship between NUF, UO and FB at the start of CRRT. METHODS: A retrospective cohort study of 1030 CRRT-treated patients admitted to two tertiary ICUs. RESULTS: Median age was 60 years (IQR, 48-70), median APACHE III was 94 (IQR, 76-114) and median NUF rate was 0.7 mL/kg/h. In the 24 h after CRRT started, the mean hourly UO decreased from 25.5 mL to 11.9 mL (P < 0.001). Moreover, after adjusting for multiple confounders on multivariable analysis, a higher NUF was not significantly associated with a lower UO (-1.5 mL/kg for every 1 mL/kg/h increase in NUF; 95% CI -3.1 to 0.04; p = 0.064). In addition, pre-CRRT FB did not modulate the above relationship between higher NUF and lower UO. CONCLUSION: A higher NUF rate was not significantly associated with a greater immediate and sustained reduction in UO after CRRT commencement. FB before CRRT was also not associated with a greater reduction in UO. These findings do not provide evidence for an effect of NUF on renal function.

How a positive fluid balance develops in acute kidney injury: A binational, observational study.

PURPOSE: A positive fluid balance (FB) is associated with harm in intensive care unit (ICU) patients with acute kidney injury (AKI). We aimed to understand how a positive balance develops in such patients. METHODS: Multinational, retrospective cohort study of critically ill patients with AKI not requiring renal replacement therapy. RESULTS: AKI occurred at a median of two days after admission in 7894 (17.3%) patients. Cumulative FB became progressively positive, peaking on day three despite only 848 (10.7%) patients receiving fluid resuscitation in the ICU. In those three days, persistent crystalloid use (median:60.0 mL/h; IQR 28.9-89.2), nutritional intake (median:18.2 mL/h; IQR 0.0-45.9) and limited urine output (UO) (median:70.8 mL/h; IQR 49.0-96.7) contributed to a positive FB. Although UO increased each day, it failed to match input, with only 797 (10.1%) patients receiving diuretics in ICU. After adjustment, a positive FB four days after AKI diagnosis was associated with an increased risk of hospital mortality (OR 1.12;95% confidence intervals 1.05-1.19;p-value <0.001). CONCLUSION: Among ICU patients with AKI, cumulative FB increased after diagnosis and was associated with an increased risk of mortality. Continued crystalloid administration, increased nutritional intake, limited UO, and minimal use of diuretics all contributed to positive FB. KEY POINTS: Question How does a positive fluid balance develop in critically ill patients with acute kidney injury? Findings Cumulative FB increased after AKI diagnosis and was secondary to persistent crystalloid fluid administration, increasing nutritional fluid intake, and insufficient urine output. Despite the absence of resuscitation fluid and an increasing cumulative FB, there was persistently low diuretics use, ongoing crystalloid use, and a progressive escalation of nutritional fluid therapy. Meaning Current management results in fluid accumulation after diagnosis of AKI, as a result of ongoing crystalloid administration, increasing nutritional fluid, limited urine output and minimal diuretic use.

Proteus species bloodstream infections: Comparative epidemiology of three species.

BACKGROUND: Although Proteus species are occasional causes of serious infections, their epidemiology has not been well defined. The objective was to describe the overall and species-specific occurrence and determinants of Proteus species bloodstream infection (BSI) in a large Australian population. METHODS: All Queensland residents with Proteus species BSI identified within the publicly funded healthcare system between 2000 and 2019 were included. RESULTS: A total of 2,143 incident episodes of Proteus species BSI were identified among 2,079 Queensland residents. The prevalence of comorbid illness differed with higher Charlson comorbidity scores observed with P. penneri and P. vulgaris, and higher prevalence of liver disease with P. penneri, higher comorbid cancer with P. vulgaris, and lower diabetes and renal disease prevalence with P. mirabilis BSIs. CONCLUSION: This study provides novel information on the epidemiology of Proteus species BSI.

Current Fluid Management Practice in Critically Ill Adults on Continuous Renal Replacement Therapy: A Binational, Observational Study.

INTRODUCTION: In critically ill patients undergoing continuous renal replacement therapy (CRRT), a positive fluid balance (FB) is associated with adverse outcomes. However, current FB management practices in CRRT patients are poorly understood. We aimed to study FB and its components in British and Australian CRRT patients to inform future trials. METHODS: We obtained detailed electronic health record data on all fluid-related variables during CRRT and hourly FB for the first 7 days of treatment. RESULTS: We studied 1,616 patients from three tertiary intensive care units (ICUs) in two countries. After the start of CRRT, the mean cumulative FB became negative at 31 h and remained negative over 7 days to a mean nadir of -4.1 L (95% confidence interval (CI) of -4.6 to -3.5). The net ultrafiltration (NUF) rate was the dominant fluid variable (-67.7 mL/h; standard deviation (SD): 75.7); however, residual urine output (-34.7 mL/h; SD: 54.5), crystalloid administration (48.1 mL/h; SD: 44.6), and nutritional input (36.4 mL/h; SD: 29.7) significantly contributed to FB. Patients with a positive FB after 72 h of CRRT were more severely ill, required high-dose vasopressors, and had high lactate concentrations (5.0 mmol/L; interquartile range: 2.3-10.5). A positive FB was independently associated with increased hospital mortality (odds ratio: 1.70; 95% CI; p = 0.004). CONCLUSION: In the study ICUs, most CRRT patients achieved a predominantly NUF-dependent negative FB. Patients with a positive FB at 72 h had greater illness severity and haemodynamic instability. Achieving equipoise for conducting trials that target a negative early FB in such patients may be difficult.

Nimodipine prophylaxis in aneurysmal subarachnoid hemorrhage, a question of tradition or evidence: A scoping review.

BACKGROUND: The prophylactic use of nimodipine following subarachnoid hemorrhage is a practice established four decades ago when clinical management differed from current and the concept of Delayed Cerebral Ischemia (DCI) was not established. The applicability of the original studies is limited by the fact of not reflecting current practice; by utilising a dichotomised outcome measure such as good neurological outcome versus death and vegetative state; by applying variable dosing regimens and including all causes of poor neurological outcome different than DCI. This study aims to review the available evidence to discuss the ongoing role of nimodipine in contemporaneous clinical practice. METHODS: PRISMA guidelines based review, evaluated the evidence on the prophylactic use of nimodipine. The following search engines: Medline, Embase, Cochrane, Web of Science and PubMed, identified Randomized Control Trials (RCTs) with neurological benefit as outcome measure and the impact of fixed versus weight-based nimodipine dosing regimens. RESULTS: Eight RCT were selected. Three of those trials with a total of 349 patients, showed a reduction on death and vegetative state (pooled RR: 0.62; 95 % confidence interval-CI: 0.45, 0.86) related to DCI. Amongst all studies, all cause death (pooled RR = 0.73, [95 % CI: 0.56, 0.97]) favoured a fixed-dose regimen (pooled RR: 0.60; [95 % CI: 0.43, 0.85]). CONCLUSION: Available evidence demonstrates that nimodipine only reduces the risk for DCI-related death or vegetative state and that fixed-dose regimens favour all cause infarct and death independent of DCI. Contemporaneous studies assessing the benefit of nimodipine beyond death or vegetative states and applying individualized dosing are warranted.

Time to positivity is a risk factor for death among patients with bloodstream infections: a population-based cohort.

OBJECTIVES: Studies examining time to positivity (TTP) of blood cultures as a risk factor for death have shown conflicting results. The study objective was to examine the effect of TTP on all-cause-30-day case-fatality among a population-based cohort of patients with bloodstream infections (BSI). METHODS: A retrospective cohort study including all residents of Queensland, Australia with incident monomicrobial BSI managed in the publicly funded healthcare system from 2000 to 2019 was performed. Clinical, TTP and all-cause 30-day case-fatality information was obtained from state-wide sources. RESULTS: A cohort of 88 314 patients was assembled. The median TTP was 14 hours, with 5th, 25th, 75th, and 95th percentiles of 4, 10, 20, and 53 hours, respectively. The TTP varied significantly by BSI aetiology. The 30-day all-cause case-fatality rate was 2606/17 879 (14.6%), 2834/24 272 (11.7%), 2378/20 359 (11.7%), and 2752/22 431 (12.3%) within the first, second, third, and fourth TTP quartiles, respectively (p < 0.0001). After adjustment for age, sex, onset, comorbidity, and focus of infection, TTP within 10 hours (first quartile) was associated with a significantly increased risk for death (odds ratio 1.43; 95% CI, 1.35-1.50; p < 0.001). After adjustment for confounding variables (odds ratio; 95% CI), TTP within the first quartile for Staphylococcus aureus (1.56; 1.41-1.73), Streptococcus pneumoniae (1.91; 1.49-2.46), ß-hemolytic streptococci (1.23; 1.00-1.50), Pseudomonas species (2.23; 1.85-2.69), Escherichia coli (1.37; 1.23-1.53), Enterobacterales (1.38; 1.16-1.63), other Gram-negatives (1.68; 1.36-2.06), and anaerobes (1.58; 1.28-1.94) increased the risk for case-fatality. DISCUSSION: This population-based analysis provides evidence that TTP is an important determinant of mortality among patients with BSI.

Pseudomonas stutzeri bloodstream infection is a prevailing community-onset disease with important mortality rates: results from a retrospective observational study in Australia.

BACKGROUND: The recognition of Pseudomonas stutzeri as a cause of infections in humans has been increasing. However, only case reports and small series of P. stutzeri bloodstream infections have been published. Epidemiological data on these infections are extremely scarce. Our objective was to describe the incidence, epidemiology, antimicrobial resistance rates, and outcomes of P. stutzeri bloodstream infections in a large population-based cohort in Australia. METHODS: Retrospective, laboratory-based surveillance study conducted in Queensland, Australia (population ≈ 5 million) during 2000-2019. Clinical information was obtained from public hospital admissions and vital statistics databases. RESULTS: In total, 228 episodes of P. stutzeri bloodstream infections were identified. Increased incidence was observed in the later years, especially in older men, and was higher during the rainy months of the year and in the warmest and more humid regions of the state. The majority of bloodstream infections were community-onset with 120 (52.6%) community-associated and 59 (25.9%) ambulatory healthcare-associated episodes. Only 49 cases (21.5%) were nosocomial. The most common foci of infection were skin and soft tissue, lower respiratory tract, and intra-abdominal. No isolate showed antimicrobial resistance. Thirty-one patients (13.6%) died. The mortality rate in patients with a respiratory infectious source was higher (21%). CONCLUSIONS: P. stutzeri bloodstream infection was predominantly a community-onset condition including ambulatory healthcare related cases, with increasing incidence, especially in older males. No antimicrobial resistance was observed. Mortality was high in patients with respiratory infectious source. This new observational data have implications when considering the epidemiology of these infections and for patient management.

Determinants of 90-day case fatality among older patients admitted to intensive care units: A retrospective cohort study.

BACKGROUND: A recent systematic review identified highly variable case-fatality rates among studies of older patients admitted to intensive care units (ICUs). However, structural and process determinants including patient resident status, tertiary ICU status, and treatment limitations were unavailable. OBJECTIVE: The objective of this study was to evaluate the role of determinants such as resident status, tertiary ICU, and treatment limitations on 90-day case fatality among older ICU patients. METHODS: A retrospective cohort of all Queensland residents aged 75 years and older admitted to four ICUs within the Metro North Hospital and Health Service was included. The impact of Metro North Hospital and Health Service resident status, tertiary ICU, treatment limitations, and other known determinants on 90-day all-cause case fatality (case-fatality) was assessed. RESULTS: Of the 2144 eligible first admissions included, 1365 were residents, and 893 were nonelective admissions. The case-fatality rates were higher in residents (21% vs 12%, p < 0.001), nonelective admissions (32% vs 7%, p < 0.001), and non-tertiary ICU admissions (27% vs 16%, p < 0.001). The case fatality increased progressively with age, being highest (29.6%) in the >90 years age-group. Multivariable mixedeffects logistic regression modelling demonstrated that presence of treatment limitations was strongly associated with case fatality, but neither resident status nor the tertiary ICU was associated. CONCLUSION: The presence of treatment limitations should be considered when evaluating variations in case fatality among cohorts of older ICU patients, in addition to variables with well-established association with case fatality such as comorbidities and illness severity.

Vibrio species bloodstream infections in Queensland, Australia.

BACKGROUND: Vibrio species bloodstream infections have been associated with significant mortality and morbidity. Limited information is available regarding the epidemiology of bloodstream infections because of Vibrio species in the Australian context. AIMS: The objective of this study was to define the incidence and risk factors for developing Vibrio species bloodstream infections and compare differences between different species. METHODS: All patients with Vibrio spp. isolated from positive blood cultures between 1 January 2000 and 31 December 2019 were identified by the state-wide Pathology Queensland laboratory. Demographics, clinical foci of infections and comorbid conditions were collected in addition to antimicrobial susceptibility results. RESULTS: About 100 cases were identified between 2000 and 2019 with an incidence of 1.2 cases/1 million person-years. Seasonal and geographical variation occurred with the highest incidence in the summer months and in the tropical north. Increasing age, male sex and multiple comorbidities were identified as risk factors. Vibrio vulnificus was isolated most frequently and associated with the most severe disease. Overall case fatality was 19%. CONCLUSIONS: There is potential for increasing cases of Vibrio species infections globally with ageing populations and climate change. Ongoing clinical awareness is required to ensure optimal patient outcomes.

Publication outcomes among intensive care trainees.

There is a paucity of literature describing the research productivity among trainees in intensive care medicine. We sought to examine the occurrence and determinants of successful publication outcomes associated with intensive care training. The study cohort consisted of all individuals admitted to fellowship of the College of Intensive Care Medicine of Australia and New Zealand (CICM) from 2012 to 2019. The primary outcome measure of this study was manuscripts indexed on PubMed within one year after and four years prior to admittance to CICM fellowship. Four hundred and eighty-five fellows were identified of whom 216 (45%) had at least one publication; 129 (27%) had one, 34 (7%) had two, 21 (4%) had three and 32 (7%) had four or more publications. Overall 138 (28%) fellows had at least one publication that was likely associated with their mandatory CICM training project for which they were first (n = 110; 80%) and/or corresponding (n = 72; 52%) author in the majority of cases. Overall 107 different senior/mentor authors were identified, with 13 individuals supporting more than one publication. Although gender and location at the time of fellowship award were not associated, location of receipt of medical degree, shorter time period between medical school graduation and fellowship award, more recent year of award, and completion of medical degree/fellowship in the same geographical region were associated with project publication. A minority of CICM fellows have PubMed-indexed publications related to their training. Further efforts are warranted to better define the determinants of successful project publication to optimise future opportunities.

Mortality, hospital length of stay, and recurrent bloodstream infections associated with extended-spectrum beta-lactamase-producing Escherichia coli in a low prevalence region: A 20-year population-based large cohort study.

OBJECTIVES: This population-based study aimed to investigate the risk factors and effect of extended-spectrum beta-lactamase (ESBL) production on clinical outcomes in Escherichia coli bloodstream infection (BSI) patients. METHODS: The study population was defined as patients aged ≥15 years with E. coli BSI in Queensland, Australia, from 2000 to 2019. Outcomes were defined as 30-day case fatality, hospital length of stay (LOS), and recurrent E. coli BSI. RESULTS: A total of 27,796 E. coli BSIs were identified, of which 1112 (4.0%) were ESBL-producers. Patients with ESBL-Ec BSI were more frequently older, male, with comorbidity, recurrent E. coli BSI, and less likely with community-associated community-onset infections as compared to non-ESBL-Ec BSI patients. The standardized mortality rate of ESBL-Ec BSI increased 8-fold from 2000 to 2019 (1 to 8 per million residents) and case fatality was 12.8% (n = 142) at 30 days from positive blood culture. Patients with ESBL-Ec BSI were not at higher risk of 30-day case fatality (adjusted hazard ratio [HR] = 0.98, 95% CI: 0.83-1.17), but had higher risk of recurring episodes (adjusted subdistribution HR = 1.58, 95% CI: 1.29-1.92) and observed 14% longer LOS (adjusted incidence rate ratio = 1.14, 95% CI: 1.10-1.18) than non-ESBL-Ec BSI patients. CONCLUSION: In this large patient cohort, ESBL-Ec BSI did not increase case fatality risk but observed higher hospital LOS and recurrent E. coli BSI than non-ESBL-Ec BSI. Clinical resources are warranted to account for the higher morbidity risk associated with ESBL production and incidence.