Continuous vs Intermittent ß-Lactam Antibiotic Infusions in Critically Ill Patients With Sepsis: The BLING III Randomized Clinical Trial.

Importance: Whether ß-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients with sepsis is uncertain. Objective: To evaluate whether continuous vs intermittent infusion of a ß-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all-cause mortality at 90 days in critically ill patients with sepsis. Design, Setting, and Participants: An international, open-label, randomized clinical trial conducted in 104 intensive care units (ICUs) in Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom. Recruitment occurred from March 26, 2018, to January 11, 2023, with follow-up completed on April 12, 2023. Participants were critically ill adults (≥18 years) treated with piperacillin-tazobactam or meropenem for sepsis. Intervention: Eligible patients were randomized to receive an equivalent 24-hour dose of a ß-lactam antibiotic by either continuous (n = 3498) or intermittent (n = 3533) infusion for a clinician-determined duration of treatment or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was all-cause mortality within 90 days after randomization. Secondary outcomes were clinical cure up to 14 days after randomization; new acquisition, colonization, or infection with a multiresistant organism or Clostridioides difficile infection up to 14 days after randomization; ICU mortality; and in-hospital mortality. Results: Among 7202 randomized participants, 7031 (mean [SD] age, 59 [16] years; 2423 women [35%]) met consent requirements for inclusion in the primary analysis (97.6%). Within 90 days, 864 of 3474 patients (24.9%) assigned to receive continuous infusion had died compared with 939 of 3507 (26.8%) assigned intermittent infusion (absolute difference, -1.9% [95% CI, -4.9% to 1.1%]; odds ratio, 0.91 [95% CI, 0.81 to 1.01]; P = .08). Clinical cure was higher in the continuous vs intermittent infusion group (1930/3467 [55.7%] and 1744/3491 [50.0%], respectively; absolute difference, 5.7% [95% CI, 2.4% to 9.1%]). Other secondary outcomes were not statistically different. Conclusions and Relevance: The observed difference in 90-day mortality between continuous vs intermittent infusions of ß-lactam antibiotics did not meet statistical significance in the primary analysis. However, the confidence interval around the effect estimate includes the possibility of both no important effect and a clinically important benefit in the use of continuous infusions in this group of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03213990.

Prolonged vs Intermittent Infusions of ß-Lactam Antibiotics in Adults With Sepsis or Septic Shock: A Systematic Review and Meta-Analysis.

Importance: There is uncertainty about whether prolonged infusions of ß-lactam antibiotics improve clinically important outcomes in critically ill adults with sepsis or septic shock. Objective: To determine whether prolonged ß-lactam antibiotic infusions are associated with a reduced risk of death in critically ill adults with sepsis or septic shock compared with intermittent infusions. Data Sources: The primary search was conducted with MEDLINE (via PubMed), CINAHL, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov from inception to May 2, 2024. Study Selection: Randomized clinical trials comparing prolonged (continuous or extended) and intermittent infusions of ß-lactam antibiotics in critically ill adults with sepsis or septic shock. Data Extraction and Synthesis: Data extraction and risk of bias were assessed independently by 2 reviewers. Certainty of evidence was evaluated with the Grading of Recommendations Assessment, Development and Evaluation approach. A bayesian framework was used as the primary analysis approach and a frequentist framework as the secondary approach. Main Outcomes and Measures: The primary outcome was all-cause 90-day mortality. Secondary outcomes included intensive care unit (ICU) mortality and clinical cure. Results: From 18 eligible randomized clinical trials that included 9108 critically ill adults with sepsis or septic shock (median age, 54 years; IQR, 48-57; 5961 men [65%]), 17 trials (9014 participants) contributed data to the primary outcome. The pooled estimated risk ratio for all-cause 90-day mortality for prolonged infusions of ß-lactam antibiotics compared with intermittent infusions was 0.86 (95% credible interval, 0.72-0.98; I2 = 21.5%; high certainty), with a 99.1% posterior probability that prolonged infusions were associated with lower 90-day mortality. Prolonged infusion of ß-lactam antibiotics was associated with a reduced risk of intensive care unit mortality (risk ratio, 0.84; 95% credible interval, 0.70-0.97; high certainty) and an increase in clinical cure (risk ratio, 1.16; 95% credible interval, 1.07-1.31; moderate certainty). Conclusions and Relevance: Among adults in the intensive care unit who had sepsis or septic shock, the use of prolonged ß-lactam antibiotic infusions was associated with a reduced risk of 90-day mortality compared with intermittent infusions. The current evidence presents a high degree of certainty for clinicians to consider prolonged infusions as a standard of care in the management of sepsis and septic shock. Trial Registration: PROSPERO Identifier: CRD42023399434.

The impact of a cognitive impairment support program on patients in an acute care setting: a pre-test post-test intervention study.

BACKGROUND: Patients with cognitive impairment are at greater risk of hospital acquired complications, longer hospital stays, and poor health outcomes compared to patients without cognitive impairment. The Cognitive Impairment Support Program is a multi-disciplinary approach to improve screening rates and awareness of patients with cognitive impairment and guide clinician response and communication during their hospitalisation to improve health outcomes. OBJECTIVE: This study evaluated the impact of implementing the Cognitive Impairment Support Program on patient hospital acquired complications, patient reported quality of life and staff satisfaction in an outer metropolitan hospital. DESIGN: A pre-test post-test design was used to collect data in two 6-month time periods between March 2020 and November 2021. PARTICIPANTS: Patients aged ≥ 65 years, admitted to a participating ward for > 24 h. INTERVENTION: The Cognitive Impairment Support Program consisted of four components: cognitive impairment screening, initiation of a Cognitive Impairment Care Plan, use of a Cognitive Impairment Identifier and associated staff education. MEASURES: The primary outcome was hospital acquired complications experienced by patients with cognitive impairment identified using clinical coding data. Secondary outcomes were patient quality of life and a staff confidence and perceived organisational support to care for patients with cognitive impairment. RESULTS: Hospital acquired complication rates did not vary significantly between the two data collection periods for patients experiencing cognitive impairment with a 0.2% (95% confidence interval: -5.7-6.1%) reduction in admissions with at least one hospital acquired complication. Patients in the post intervention period demonstrated statistically significant improvements in many items in two of the Dementia Quality of Life Measure domains: memory and everyday life. The staff survey indicated statistically significant improvement in clinical staff confidence to care for patients with cognitive impairment (p = 0.003), satisfaction with organisational support for patients (p = 0.004) and job satisfaction (p ≤ 0.001). CONCLUSION: This study provides evidence that a multicomponent Cognitive Impairment Support Program had a positive impact on staff confidence and satisfaction and patient quality of life. Broader implementation with further evaluation of the multicomponent cognitive impairment intervention across a range of settings using varied patient outcomes is recommended.

Fathers attending the birth of their baby: Views, intentions and needs.

BACKGROUND: There is limited information about fathers' views, intentions and needs leading up to childbirth. AIMS: This study explores the factors influencing fathers' intention to attend the birth, and the needs and supports required leading up to childbirth. METHODS: Cross-sectional survey of 203 prospective fathers attending antenatal appointments at an outer metropolitan public teaching hospital in Brisbane, Australia. RESULTS: A total of 201/203 (99.0%) participants intended to attend the birth. The reported reasons included: responsibility (99.5%), protectiveness (99.0%), love for their partner (99.0%), the right thing to do (98.0%), desire to see the birth (98.0%), the perception that partners should attend (97.4%), duty (96.4%) and partner preference (91.4%). Some felt pressured by their partner (12.8%), society (10.8%), cultural expectations (9.6%) and family (9.1%), and 10.6% perceived adverse consequences for not attending. Most participants (94.6%) felt well supported, experienced good communication (72.4%), had the opportunity to ask questions (69.8%) and received an explanation of events (66.3%). They were less often supported by antenatal visits (46.7%) and by a plan for future visits (32.2%). Ten per cent of all fathers and 13.8% of experienced fathers requested better mental health support, and 9.0% prefer better clinician communication. CONCLUSIONS: Most fathers intend to attend childbirth for personal and moral reasons; however, a small proportion feel pressured. Most fathers feel well supported, although potential improvements include planning for future visits, provision of information, mental health support, clinician communication, increased involvement in their partner's care, the opportunity to ask questions and more frequent clinic visits.

What the forks? A longitudinal quality improvement study tracking cutlery numbers in a public teaching and research hospital staff tearoom.

OBJECTIVES: To evaluate the circulation lifespan of forks and teaspoons in an institutional tearoom. DESIGN: Longitudinal quality improvement study, based on prospective tracking of marked teaspoons and forks. SETTING: Staff tearoom in a public teaching and research hospital, Brisbane. PARTICIPANTS: Tearoom patrons blinded to the purposes of the study. INTERVENTION: Stainless steel forks and teaspoons (18 each) were marked with red spots and introduced alongside existing cutlery (81 items) in the tearoom. MAIN OUTCOME MEASURES: Twice weekly count of marked forks and teaspoons for seven weeks; baseline and end of study count of all utensils on day 45. RESULTS: The loss of marked teaspoons (six of 18) was greater than that of forks (one of 18) by the conclusion of the study period (P = 0.038). The overall rate of utensil loss was 2.2 per 100 days for teaspoons and spoons, and -2.2 per 100 days for forks and knives. CONCLUSIONS: Teaspoon disappearance is a more substantial problem than fork migration in a multidisciplinary staff tearoom, and may reflect different kleptomaniacal or individual appropriation tendencies. If giving cutlery this Christmas, give teaspoons, not forks. The symbolism of fork rebirth or resurrection is appropriate for both Christmas and Easter, and forks are also mighty useful implements for eating cake!

Perceptions of pregnant women regarding antidepressant and anxiolytic medication use during pregnancy.

OBJECTIVE: The objective of this study was to explore attitudes and decision-making by pregnant women regarding antidepressant and anxiolytic use during pregnancy. METHOD: An observational study at an outer metropolitan hospital in Brisbane, Queensland. Pregnant women presenting for their first antenatal clinic visit were invited to complete a questionnaire. Participants were asked about current or previous antidepressant/anxiolytic use, influences on drug decision-making and the adequacy of information received. Perceptions were measured on a 7-point Likert scale. RESULTS: A total of 503 pregnant women were surveyed. The background prevalence of anxiety and depression was 30.0% (151), with 9.3% (47) respondents using antidepressant or anxiolytic medications during the current pregnancy. Of these 47 women, 68% ceased these medications during or while trying to become pregnant, most commonly due to potential side effects to the baby (16), health professional advice (8) and symptomatology that was under control (7). While the effect was modest, decision-making was most strongly influenced by general practitioners, family and the internet. CONCLUSIONS: Most women cease antidepressant/anxiolytic medication before and during pregnancy for reasons other than stability of condition. This study reveals an unmet need for accessible reliable information to guide pregnant women and their care providers.

Prolonged Infusion Piperacillin-Tazobactam Decreases Mortality and Improves Outcomes in Severely Ill Patients: Results of a Systematic Review and Meta-Analysis.

OBJECTIVE: Piperacillin-tazobactam is a commonly used antibiotic in critically ill patients; however, controversy exists as to whether mortality in serious infections can be decreased through administration by prolonged infusion compared with intermittent infusion. The purpose of this systematic review and meta-analysis was to describe the impact of prolonged infusion piperacillin-tazobactam schemes on clinical endpoints in severely ill patients. DESIGN: We conducted a systematic literature review and meta-analysis searching MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library from inception to April 1, 2017, for studies. INTERVENTIONS: Mortality rates were compared between severely ill patients receiving piperacillin-tazobactam via prolonged infusion or intermittent infusion. Included studies must have reported severity of illness scores, which were transformed into average study-level mortality probabilities. MEASUREMENTS AND MAIN RESULTS: Two investigators independently screened titles, abstracts, and full texts of studies meeting inclusion criteria for this systematic review and meta-analysis. Variables included author name, publication year, study design, demographics, total daily dose(s), average estimated creatinine clearance, type of prolonged infusion, prevalence of combination therapy, severity of illness scores, infectious sources, all-cause mortality, clinical cure, microbiological cure, and hospital and ICU length of stay. The review identified 18 studies including 3,401 patients who received piperacillin-tazobactam, 56.7% via prolonged infusion. Across all studies, the majority of patients had an identified primary infectious source. Receipt of prolonged infusion was associated with a 1.46-fold lower odds of mortality (95% CI, 1.20-1.77) in the pooled analysis. Patients receiving prolonged infusion had a 1.77-fold higher odds of clinical cure (95% CI, 1.24-2.54) and a 1.22-fold higher odds of microbiological cure (95% CI, 0.84-1.77). Subanalyses were conducted according to high (≥ 20%) and low (< 20%) average study-level mortality probabilities. In studies reporting higher mortality probabilities, effect sizes were variable but similar to the pooled results. CONCLUSIONS: Receipt of prolonged infusion of piperacillin-tazobactam was associated with reduced mortality and improved clinical cure rates across diverse cohorts of severely ill patients.

Time to wait: a systematic review of strategies that affect out-patient waiting times.

Objective Out-patient waiting times pose a significant challenge for public patients in need of specialist evaluation and intervention. The aim of the present study was to identify and categorise effective strategies to reduce waiting times for specialist out-patient services with a focus on the Australian healthcare system. Methods A systematic review of major health databases was conducted using the key terms 'outpatient*' AND 'waiting time', 'process*' AND 'improvement in outpatient clinics'. Identified articles were assessed for their relevance by sequential review of the title, abstract and full text. References of the selected manuscripts were scanned for additional relevant articles. Selected articles were evaluated for consistent and emerging themes. Results In all, 152 articles were screened, of which 38 were included in the present review. Numerous strategies identified in the articles were consolidated into 26 consistent approaches. Three overarching themes were identified as significantly affecting waiting times: resource realignment, operational efficiency and process improvement. Conclusions Strategies to align resources, increase operational efficiency and improve processes provide a comprehensive approach that may reduce out-patient waiting times. What is known about the topic? Out-patient waiting times are a challenge in most countries that seek to provide universal access to health care for all citizens. Although there has been extensive research in this area, many patients still experience extensive delays accessing specialist care, particularly in the public health sector. The multiple factors that contribute to bottlenecks and inefficiencies in the referral process and affect patient waiting times are often poorly understood. What does this paper add? This paper reviews the published healthcare literature to identify strategies that affect specialist out-patient waiting times for patients. The findings suggest that there are numerous operational strategies that affect waiting times. These strategies may be categorised into three overarching themes (resource alignment, operational efficiencies and out-patient processes) that, when actioned in a coordinated approach, have the potential to significantly reduce out-patient waiting times. What are the implications for practitioners? This paper identifies evidence-based strategies for aligning resources, improving operational efficiency and streamlining processes, which may provide improvements to specialist out-patient waiting times for patients. Addressing the identified organisational, person-related, cultural and attitudinal factors will assist health system managers and health practitioners target the most appropriate improvement activities to reduce waiting times.

Continuous versus Intermittent ß-Lactam Infusion in Severe Sepsis. A Meta-analysis of Individual Patient Data from Randomized Trials.

RATIONALE: Optimization of ß-lactam antibiotic dosing for critically ill patients is an intervention that may improve outcomes in severe sepsis. OBJECTIVES: In this individual patient data meta-analysis of critically ill patients with severe sepsis, we aimed to compare clinical outcomes of those treated with continuous versus intermittent infusion of ß-lactam antibiotics. METHODS: We identified relevant randomized controlled trials comparing continuous versus intermittent infusion of ß-lactam antibiotics in critically ill patients with severe sepsis. We assessed the quality of the studies according to four criteria. We combined individual patient data from studies and assessed data integrity for common baseline demographics and study endpoints, including hospital mortality censored at 30 days and clinical cure. We then determined the pooled estimates of effect and investigated factors associated with hospital mortality in multivariable analysis. MEASUREMENTS AND MAIN RESULTS: We identified three randomized controlled trials in which researchers recruited a total of 632 patients with severe sepsis. The two groups were well balanced in terms of age, sex, and illness severity. The rates of hospital mortality and clinical cure for the continuous versus intermittent infusion groups were 19.6% versus 26.3% (relative risk, 0.74; 95% confidence interval, 0.56-1.00; P = 0.045) and 55.4% versus 46.3% (relative risk, 1.20; 95% confidence interval, 1.03-1.40; P = 0.021), respectively. In a multivariable model, intermittent ß-lactam administration, higher Acute Physiology and Chronic Health Evaluation II score, use of renal replacement therapy, and infection by nonfermenting gram-negative bacilli were significantly associated with hospital mortality. Continuous ß-lactam administration was not independently associated with clinical cure. CONCLUSIONS: Compared with intermittent dosing, administration of ß-lactam antibiotics by continuous infusion in critically ill patients with severe sepsis is associated with decreased hospital mortality.

Changes in B-type Natriuretic Peptide and Related Hemodynamic Parameters Following a Fluid Challenge in Critically Ill Patients with Severe Sepsis or Septic Shock.

CONTEXT: Severe sepsis or septic shock. AIMS: The aim of this study is to examine the effect of a fluid challenge on the B-type natriuretic peptide (BNP) and the hemodynamic state. SETTINGS AND DESIGN: This observational study was conducted in an intensivist-led academic, mixed medical-surgical Intensive Care Unit. SUBJECTS AND METHODS: Focused transthoracic echocardiogram, plasma BNP, and hemodynamic measurements were recorded at baseline and following a 500 ml fluid challenge in thirty patients. Independent predictors of the percentage (%) change in stroke volume (SV) were sought. Next, these independent predictors were assessed for a relationship with the percentage change in BNP. STATISTICAL ANALYSIS USED: Multiple linear regressions, Wilcoxon rank-sum test, t-test, and Pearson's correlation were used. Data analysis was carried out using SAS. The 5% significance level was used. RESULTS: Using a multiple regression models, the percentage increase in SV was independently predicted by the percentage increase in mean arterial pressure, left ventricular end-diastolic volume/dimension (LVEDV/LVEDd), ejection fraction, and a decrease in Acute Physiology and Chronic Health Evaluation II score (P < 0.0001). Preload, measured using LVEDV1 (before the fluid challenge) was significantly larger in the fluid nonresponders (%SV increase <15%) vs. the responders (%SV increase ≥15%). Finally, the percentage change in BNP was positively correlated with left ventricular size at end diastole LVEDd, r = 0.4, P < 0.035). CONCLUSIONS: An increase in BNP soon after a fluid challenge may have some predictive utility of a large LVEDd, which in turn can be used to independently predict the SV response to a fluid challenge.

Is prolonged infusion of piperacillin/tazobactam and meropenem in critically ill patients associated with improved pharmacokinetic/pharmacodynamic and patient outcomes? An observation from the Defining Antibiotic Levels in Intensive care unit patients (DALI) cohort.

OBJECTIVES: We utilized the database of the Defining Antibiotic Levels in Intensive care unit patients (DALI) study to statistically compare the pharmacokinetic/pharmacodynamic and clinical outcomes between prolonged-infusion and intermittent-bolus dosing of piperacillin/tazobactam and meropenem in critically ill patients using inclusion criteria similar to those used in previous prospective studies. METHODS: This was a post hoc analysis of a prospective, multicentre pharmacokinetic point-prevalence study (DALI), which recruited a large cohort of critically ill patients from 68 ICUs across 10 countries. RESULTS: Of the 211 patients receiving piperacillin/tazobactam and meropenem in the DALI study, 182 met inclusion criteria. Overall, 89.0% (162/182) of patients achieved the most conservative target of 50% fT>MIC (time over which unbound or free drug concentration remains above the MIC). Decreasing creatinine clearance and the use of prolonged infusion significantly increased the PTA for most pharmacokinetic/pharmacodynamic targets. In the subgroup of patients who had respiratory infection, patients receiving ß-lactams via prolonged infusion demonstrated significantly better 30 day survival when compared with intermittent-bolus patients [86.2% (25/29) versus 56.7% (17/30); P = 0.012]. Additionally, in patients with a SOFA score of ≥9, administration by prolonged infusion compared with intermittent-bolus dosing demonstrated significantly better clinical cure [73.3% (11/15) versus 35.0% (7/20); P = 0.035] and survival rates [73.3% (11/15) versus 25.0% (5/20); P = 0.025]. CONCLUSIONS: Analysis of this large dataset has provided additional data on the niche benefits of administration of piperacillin/tazobactam and meropenem by prolonged infusion in critically ill patients, particularly for patients with respiratory infections.

A Multicenter Randomized Trial of Continuous versus Intermittent ß-Lactam Infusion in Severe Sepsis.

RATIONALE: Continuous infusion of ß-lactam antibiotics may improve outcomes because of time-dependent antibacterial activity compared with intermittent dosing. OBJECTIVES: To evaluate the efficacy of continuous versus intermittent infusion in patients with severe sepsis. METHODS: We conducted a randomized controlled trial in 25 intensive care units (ICUs). Participants commenced on piperacillin-tazobactam, ticarcillin-clavulanate, or meropenem were randomized to receive the prescribed antibiotic via continuous or 30-minute intermittent infusion for the remainder of the treatment course or until ICU discharge. The primary outcome was the number of alive ICU-free days at Day 28. Secondary outcomes were 90-day survival, clinical cure 14 days post antibiotic cessation, alive organ failure-free days at Day 14, and duration of bacteremia. MEASUREMENTS AND MAIN RESULTS: We enrolled 432 eligible participants with a median age of 64 years and an Acute Physiology and Chronic Health Evaluation II score of 20. There was no difference in ICU-free days: 18 days (interquartile range, 2-24) and 20 days (interquartile range, 3-24) in the continuous and intermittent groups (P = 0.38). There was no difference in 90-day survival: 74.3% (156 of 210) and 72.5% (158 of 218); hazard ratio, 0.91 (95% confidence interval, 0.63-1.31; P = 0.61). Clinical cure was 52.4% (111 of 212) and 49.5% (109 of 220); odds ratio, 1.12 (95% confidence interval, 0.77-1.63; P = 0.56). There was no difference in organ failure-free days (6 d; P = 0.27) and duration of bacteremia (0 d; P = 0.24). CONCLUSIONS: In critically ill patients with severe sepsis, there was no difference in outcomes between ß-lactam antibiotic administration by continuous and intermittent infusion. Australian New Zealand Clinical Trials Registry number (ACT RN12612000138886).

Antenatal and postnatal radiologic diagnosis of holocarboxylase synthetase deficiency: a systematic review.

BACKGROUND: Holocarboxylase synthetase deficiency results in impaired activation of enzymes implicated in glucose, fatty acid and amino acid metabolism. Antenatal imaging and postnatal imaging are useful in making the diagnosis. Untreated holocarboxylase synthetase deficiency is fatal, while antenatal and postnatal biotin supplementation is associated with good clinical outcomes. Although biochemical assays are required for definitive diagnosis, certain radiologic features assist in the diagnosis of holocarboxylase synthetase deficiency. OBJECTIVE: To review evidence regarding radiologic diagnostic features of holocarboxylase synthetase deficiency in the antenatal and postnatal period. MATERIALS AND METHODS: A systematic review of all published cases of holocarboxylase synthetase deficiency identified by a search of Pubmed, Scopus and Web of Science. RESULTS: A total of 75 patients with holocarboxylase synthetase deficiency were identified from the systematic review, which screened 687 manuscripts. Most patients with imaging (19/22, 86%) had abnormal findings, the most common being subependymal cysts, ventriculomegaly and intraventricular hemorrhage. CONCLUSION: Although the radiologic features of subependymal cysts, ventriculomegaly, intraventricular hemorrhage and intrauterine growth restriction may be found in the setting of other pathologies, these findings should prompt consideration of holocarboxylase synthetase deficiency in at-risk children.

Vancomycin-associated nephrotoxicity in the critically ill: a retrospective multivariate regression analysis*.

OBJECTIVES: To evaluate the influence of vancomycin dose, serum trough concentration, and dosing strategy on the evolution of acute kidney injury in critically ill patients. DESIGN: Retrospective, single-center, observational study. SETTING: University Hospital ICU, Birmingham, UK. PATIENTS: All critically ill patients receiving vancomycin from December 1, 2004, to August 31, 2009. INTERVENTION: None. MEASUREMENTS AND MAIN RESULTS: The prevalence of new onset nephrotoxicity was reported using Risk, Injury, Failure, Loss, End-stage renal disease criteria, and independent factors predictive of nephrotoxicity were identified using logistic regression analysis. Complete data were available for 1,430 patients. Concomitant vasoactive therapy (odds ratio = 1.633; p < 0.001), median serum vancomycin (odds ratio = 1.112; p < 0.001), and duration of therapy (odds ratio = 1.041; p ≤ 0.001) were significant positive predictors of nephrotoxicity. Intermittent infusion was associated with a significantly greater risk of nephrotoxicity than continuous infusion (odds ratio = 8.204; p ≤ 0.001). CONCLUSIONS: In a large dataset, higher serum vancomycin concentrations and greater duration of therapy are independently associated with increased odds of nephrotoxicity. Furthermore, continuous infusion is associated with a decreased likelihood of nephrotoxicity compared with intermittent infusion. This large dataset supports the use of continuous infusion of vancomycin in critically ill patients.

Continuous infusion of beta-lactam antibiotics in severe sepsis: a multicenter double-blind, randomized controlled trial.

BACKGROUND: Beta-lactam antibiotics are a commonly used treatment for severe sepsis, with intermittent bolus dosing standard therapy, despite a strong theoretical rationale for continuous administration. The aim of this trial was to determine the clinical and pharmacokinetic differences between continuous and intermittent dosing in patients with severe sepsis. METHODS: This was a prospective, double-blind, randomized controlled trial of continuous infusion versus intermittent bolus dosing of piperacillin-tazobactam, meropenem, and ticarcillin-clavulanate conducted in 5 intensive care units across Australia and Hong Kong. The primary pharmacokinetic outcome on treatment analysis was plasma antibiotic concentration above the minimum inhibitory concentration (MIC) on days 3 and 4. The assessed clinical outcomes were clinical response 7-14 days after study drug cessation, ICU-free days at day 28 and hospital survival. RESULTS: Sixty patients were enrolled with 30 patients each allocated to the intervention and control groups. Plasma antibiotic concentrations exceeded the MIC in 82% of patients (18 of 22) in the continuous arm versus 29% (6 of 21) in the intermittent arm (P = .001). Clinical cure was higher in the continuous group (70% vs 43%; P = .037), but ICU-free days (19.5 vs 17 days; P = .14) did not significantly differ between groups. Survival to hospital discharge was 90% in the continuous group versus 80% in the intermittent group (P = .47). CONCLUSIONS: Continuous administration of beta-lactam antibiotics achieved higher plasma antibiotic concentrations than intermittent administration with improvement in clinical cure. This study provides a strong rationale for further multicenter trials with sufficient power to identify differences in patient-centered endpoints.

A snapshot of guideline compliance reveals room for improvement: a survey of peripheral arterial catheter practices in Australian operating theatres.

AIM: To report a study in Australian operating theatres of compliance by the anaesthetic team with best peripheral arterial catheter practice for blood gas sampling and infection prevention. Comparisons are made with research recommendations and Centres for Disease Control Guidelines. BACKGROUND: There is wide global usage of peripheral arterial catheters in the operating theatre for haemodynamic monitoring and blood gas analysis. Frequent blood sampling from arterial catheters can lead to statistically significant blood loss and provide an infective potential. Evidence-based research and clinical guidelines prescribe best practice. DESIGN: Cross-sectional descriptive survey METHODS: Data were collected in 2009 from 64 major Australian hospitals using a self-designed internet survey. RESULTS/FINDINGS: Hand hygiene prior to catheter insertion was the only infection prevention practice entirely adherent with guidelines. The recommended ratio of discard to dead space volume of 2:1 to decrease unnecessary blood loss during blood gas sampling was reported by only 11 (17%) respondents. Less than 32 (50%) respondents used the preferred solution, chlorhexidine to disinfect the insertion site. Access ports were reported as 'never disinfected' before use by 30 (47%) respondents. CONCLUSION: The complex operating theatre environment presents barriers, which contribute to non-adherence with guidelines. These barriers need to be identified to plan strategies for improvement. A quality audit tool is proposed for development by nurses in collaboration with the anaesthetic team, providing a needed method to assess ongoing compliance with best peripheral arterial catheter care. Further international research would test the generalizability of our Australian findings.

Corrigendum to "Statistical analysis plan for the BLING III study: a phase 3 multicentre randomised controlled trial of continuous versus intermittent ß-lactam antibiotic infusion in critically ill patients with sepsis" [Crit Care Resusc 23(3) (2021) 273-284].

[This corrects the article DOI: 10.51893/2021.3.oa4.].

Guide-wire fragment embolisation in paediatric peripherally inserted central catheters.

OBJECTIVE: To report guide-wire fragment embolisation of paediatric peripherally inserted central catheter (PICC) devices and explore the safety profile of four commonly used devices. DESIGN, SETTING AND PARTICIPANTS: Clinical incidents involving paediatric PICC devices in Queensland public hospitals were reviewed. A PICC user-experience survey was conducted at five public hospitals with 32 clinicians. A device design evaluation was undertaken, and magnetic resonance imaging (MRI) safety was tested by a simulation study. MAIN OUTCOME MEASURES: Embolisation events; technical mistakes, multiple attempts and breakages during insertion; willingness to use the device; failure modes and risk priority rating; movement and/or temperature change on exposure to MRI. RESULTS: Six clinical incidents of silent guide-wire embolisation, and four near misses were identified; all were associated with one type of device. The survey found that this device had a reported broken-wire embolisation rate of 0.9/100 insertions with no events in other devices; two of the four devices had a higher all-cause embolisation rate (3.3/100 insertions v 0.4/100 insertions) and lower clinician acceptance (68%-71% v 91%-100%). All devices had 6-17 identified failure modes; the two devices that allowed removal of a guide wire through a septum had the highest overall risk rating. Guide-wire exposure to MRI was rated a potential safety risk due to movement. CONCLUSIONS: There is marked variation in the safety profile of 3 Fr PICC devices in clinical use, and safety performance can be linked to design factors. Pre-MRI screening of all children who have previously had a PICC device inserted is recommended. We advocate a decision-making model for evaluation of device safety.

A Multicenter Observational Study Evaluating Outcomes Associated With Antibiotic Combination Versus Monotherapy in Patients With Septic Shock.

OBJECTIVES: To explore the association between antibiotic combination therapy and in-hospital mortality in patients with septic shock in two tertiary ICUs in different countries. DESIGN: Retrospective observational study. SETTING: ICUs of two tertiary hospitals, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia, and Rigshospitalet, Copenhagen, Denmark. PATIENTS: Adult patients with antibiotic treatment greater than or equal to 72 hours and vasopressor therapy greater than or equal to 24 hours. INTERVENTION: Combination versus mono antibiotic therapy. MEASUREMENTS AND MAIN RESULTS: Combination antibiotic therapy was defined as receiving two or more antibiotics from different classes, started within 12 hours of each other and with an overlapping duration of greater than or equal to 12 hours. Bivariate and multiple logistic regression analysis were performed comparing combination antibiotic therapy versus antibiotic monotherapy on in-hospital mortality. The analysis was adjusted for age, gender, centre, Acute Physiology and Chronic Health Evaluation II score, and chronic health evaluation. In total, 1,667 patients were included with 953 (57%) receiving combination therapy. Patients given combination therapy were older (60 ± 16 vs 56 ± 18), more likely admitted to Rigshospitalet (58% vs 16%), and had a higher Acute Physiology and Chronic Health Evaluation II score (26 ± 8 vs 23 ± 8). Combination therapy was associated with an increased mortality in univariate analysis (odds ratio = 1.33; 95% CI, 1.07-1.66); however, there was no significant association in the adjusted analysis (odds ratio = 0.88; 95% CI, 0.68-1.15). CONCLUSIONS: In this retrospective study, no association was found between use of combination therapy and in-hospital mortality. The large differences between centers probably reflect local traditions and lack of definitive evidence.