Exploring the use and impact of the Australian living guidelines for the clinical care of people with COVID-19: where to from here?

OBJECTIVES: The Australian National COVID-19 Clinical Evidence Taskforce has been developing, maintaining, and disseminating living guidelines and decision support tools (clinical flowcharts) for the care of people with suspected or confirmed COVID-19 since 2020. Living guidelines, a form of living evidence, are a relatively new approach; hence, more work is required to determine how to optimize their use to inform practice, policy, and decision-making and to explore implementation, uptake, and impact implications. An update of an earlier impact evaluation was conducted to understand sustained awareness and use of the guidelines; the factors that facilitate the widespread adoption of the guidelines and to explore the perceived strengths and opportunities for improvement of the guidelines. STUDY DESIGN AND SETTING: A mixed-methods impact evaluation was conducted. Surveys collected both quantitative and qualitative data and were supplemented with qualitative interviews. Participants included Australian healthcare practitioners providing care to individuals with suspected or confirmed COVID-19 and people involved in policy-making. Data were collected on awareness, use, impact, strengths, and opportunities for improvement of the guidelines and flow charts. RESULTS: A total of 148 participants completed the survey and 21 people were interviewed between January and March 2022. Awareness of the work of the Taskforce was high and more than 75% of participants reported that the guidelines were used within their workplace. Participants described the Taskforce website and guidelines as trustworthy, valuable, and reliable sources of up-to-date evidence-based information. The evaluation highlighted the varied ways the guidelines were being used across a range of settings and the diverse impacts they have from those at a clinical level to impacts at a policy level. Barriers to and enablers of impact and uptake of the guideline were explored. CONCLUSION: This evaluation highlights the value of living guidelines during a pandemic when the evidence base is rapidly changing and expanding. It presents useful understanding of the ways clinicians and others use living evidence to inform their clinical practice and decision-making and the diverse impacts the guidelines are having around Australia.

Awake proning in patients with COVID-19-related hypoxemic acute respiratory failure: A rapid practice guideline.

This rapid practice guideline provides evidence-based recommendations for the use of awake proning in adult patients with acute hypoxemic respiratory failure due to COVID-19. The panel included 20 experts from 12 countries, including one patient representative, and used a strict conflict of interest policy for potential financial and intellectual conflicts of interest. Methodological support was provided by the guidelines in intensive care, development, and evaluation (GUIDE) group. Based on an updated systematic review, and the grading of recommendations, assessment, development, and evaluation (GRADE) method we evaluated the certainty of evidence and developed recommendations using the Evidence-to-Decision framework. We conducted an electronic vote, requiring >80% agreement amongst the panel for a recommendation to be adopted. The panel made a strong recommendation for a trial of awake proning in adult patients with COVID-19 related hypoxemic acute respiratory failure who are not invasively ventilated. Awake proning appears to reduce the risk of tracheal intubation, although it may not reduce mortality. The panel judged that most patients would want a trial of awake proning, although this may not be feasible in some patients and some patients may not tolerate it. However, given the high risk of clinical deterioration amongst these patients, awake proning should be conducted in an area where patients can be monitored by staff experienced in rapidly detecting and managing clinical deterioration. This RPG panel recommends a trial of awake prone positioning in patients with acute hypoxemic respiratory failure due to COVID-19.

Extracorporeal Membrane Oxygenation as a Bridge to Surgical Repair of Postinfarct Ventricular Septal Defect.

Postinfarct ventricular septal defect (PIVSD) is associated with high mortality and the management of these patients has been a challenge with little improvement in outcomes. We commenced a protocol of veno-arterial extracorporeal membrane oxygenation (VA ECMO) for those patients who present in cardiogenic shock with the aim to improve end-organ function before definitive surgical repair to reduce postoperative mortality. This study reviewed the results of this strategy. This was a single-center, retrospective review of all patients who were admitted to our institution with PIVSD in cardiogenic shock from September 2015 to November 2019. Clinical and investigative data were evaluated. Eight patients were referred with PIVSD during this period in cardiogenic shock. One patient had an anterior PIVSD and the other seven had inferior PIVSD. Six patients underwent surgical repair at a median (interquartile range, IQR) of 7 (5-8) days after initiation of VA ECMO. Two patients did not undergo surgical repair. Five patients survived after surgery and one patient died postoperatively due to multiorgan failure. Preoperative use of VA ECMO is a feasible strategy for PIVSD and may improve the results of repair.

Genomic dissection of Klebsiella pneumoniae infections in hospital patients reveals insights into an opportunistic pathogen.

Klebsiella pneumoniae is a major cause of opportunistic healthcare-associated infections, which are increasingly complicated by the presence of extended-spectrum beta-lactamases (ESBLs) and carbapenem resistance. We conducted a year-long prospective surveillance study of K. pneumoniae clinical isolates in hospital patients. Whole-genome sequence (WGS) data reveals a diverse pathogen population, including other species within the K. pneumoniae species complex (18%). Several infections were caused by K. variicola/K. pneumoniae hybrids, one of which shows evidence of nosocomial transmission. A wide range of antimicrobial resistance (AMR) phenotypes are observed, and diverse genetic mechanisms identified (mainly plasmid-borne genes). ESBLs are correlated with presence of other acquired AMR genes (median n = 10). Bacterial genomic features associated with nosocomial onset are ESBLs (OR 2.34, p = 0.015) and rhamnose-positive capsules (OR 3.12, p < 0.001). Virulence plasmid-encoded features (aerobactin, hypermucoidy) are observed at low-prevalence (<3%), mostly in community-onset cases. WGS-confirmed nosocomial transmission is implicated in just 10% of cases, but strongly associated with ESBLs (OR 21, p < 1 × 10-11). We estimate 28% risk of onward nosocomial transmission for ESBL-positive strains vs 1.7% for ESBL-negative strains. These data indicate that K. pneumoniae infections in hospitalised patients are due largely to opportunistic infections with diverse strains, with an additional burden from nosocomially-transmitted AMR strains and community-acquired hypervirulent strains.

Genomic surveillance of antimicrobial resistant bacterial colonisation and infection in intensive care patients.

BACKGROUND: Third-generation cephalosporin-resistant Gram-negatives (3GCR-GN) and vancomycin-resistant enterococci (VRE) are common causes of multi-drug resistant healthcare-associated infections, for which gut colonisation is considered a prerequisite. However, there remains a key knowledge gap about colonisation and infection dynamics in high-risk settings such as the intensive care unit (ICU), thus hampering infection prevention efforts. METHODS: We performed a three-month prospective genomic survey of infecting and gut-colonising 3GCR-GN and VRE among patients admitted to an Australian ICU. Bacteria were isolated from rectal swabs (n = 287 and n = 103 patients ≤2 and > 2 days from admission, respectively) and diagnostic clinical specimens between Dec 2013 and March 2014. Isolates were subjected to Illumina whole-genome sequencing (n = 127 3GCR-GN, n = 41 VRE). Multi-locus sequence types (STs) and antimicrobial resistance determinants were identified from de novo assemblies. Twenty-three isolates were selected for sequencing on the Oxford Nanopore MinION device to generate completed reference genomes (one for each ST isolated from ≥2 patients). Single nucleotide variants (SNVs) were identified by read mapping and variant calling against these references. RESULTS: Among 287 patients screened on admission, 17.4 and 8.4% were colonised by 3GCR-GN and VRE, respectively. Escherichia coli was the most common species (n = 36 episodes, 58.1%) and the most common cause of 3GCR-GN infection. Only two VRE infections were identified. The rate of infection among patients colonised with E. coli was low, but higher than those who were not colonised on admission (n = 2/33, 6% vs n = 4/254, 2%, respectively, p = 0.3). While few patients were colonised with 3GCR- Klebsiella pneumoniae or Pseudomonas aeruginosa on admission (n = 4), all such patients developed infections with the colonising strain. Genomic analyses revealed 10 putative nosocomial transmission clusters (≤20 SNVs for 3GCR-GN, ≤3 SNVs for VRE): four VRE, six 3GCR-GN, with epidemiologically linked clusters accounting for 21 and 6% of episodes, respectively (OR 4.3, p = 0.02). CONCLUSIONS: 3GCR-E. coli and VRE were the most common gut colonisers. E. coli was the most common cause of 3GCR-GN infection, but other 3GCR-GN species showed greater risk for infection in colonised patients. Larger studies are warranted to elucidate the relative risks of different colonisers and guide the use of screening in ICU infection control.

Preparation for airway management in Australia and New Zealand ICUs during the COVID -19 pandemic.

BACKGROUND: This paper aimed to describe the airway practices of intensive care units (ICUs) in Australia and New Zealand specific to patients presenting with COVID-19 and to inform whether consistent clinical practice was achieved. Specific clinical airway guidelines were endorsed in March 2020 by the Australian and New Zealand Intensive Care Society (ANZICS) and College of Intensive Care Medicine (CICM). METHODS AND FINDINGS: Prospective, structured questionnaire for all ICU directors in Australia and New Zealand was completed by 69 ICU directors after email invitation from ANZICS. The online questionnaire was accessible for three weeks during September 2020 and analysed by cloud-based software. Basic ICU demographics (private or public, metropolitan or rural) and location, purchasing, airway management practices, guideline uptake, checklist and cognitive aid use and staff training relevant to airway management during the COVID-19 pandemic were the main outcome measures. The 69 ICU directors reported significant simulation-based inter-professional airway training of staff (97%), and use of video laryngoscopy (94%), intubation checklists (94%), cognitive aids (83%) and PPE "spotters" (89%) during the airway management of patients with COVID-19. Tracheal intubation was almost always performed by a Specialist (97% of ICUs), who was more likely to be an intensivist than an anaesthetist (61% vs 36%). There was a more frequent adoption of specific airway guidelines for the management of COVID-19 patients in public ICUs (94% vs 71%) and reliance on specialist intensivists to perform intubations in private ICUs (92% vs 53%). CONCLUSION: There was a high uptake of a standardised approach to airway management in COVID-19 patients in ICUs in Australia and New Zealand, likely due to endorsement of national guidelines.

Infection management processes in intensive care and their association with mortality.

BACKGROUND: ICU-specific tables of antimicrobial susceptibility for key microbial species ('antibiograms'), antimicrobial stewardship (AMS) programmes and routine rounds by infectious diseases (ID) physicians are processes aimed at improving patient care. Their impact on patient-centred outcomes in Australian and New Zealand ICUs is uncertain. OBJECTIVES: To measure the association of these processes in ICU with in-hospital mortality. METHODS: The Australian and New Zealand Intensive Care Society (ANZICS) Adult Patient Database and Critical Care Resources registry were used to extract patient-level factors, ICU-level factors and the year in which each process took place. Descriptive statistics and hierarchical logistic regression were used to determine the relationship between each process and in-hospital mortality. RESULTS: The study included 799 901 adults admitted to 173 ICUs from July 2009 to June 2016. The proportion of patients exposed to each process of care was 38.7% (antibiograms), 77.5% (AMS programmes) and 74.0% (ID rounds). After adjusting for confounders, patients admitted to ICUs that used ICU-specific antibiograms had a lower risk of in-hospital mortality [OR 0.95 (99% CI 0.92-0.99), P = 0.001]. There was no association between the use of AMS programmes [OR 0.98 (99% CI 0.94-1.02), P = 0.16] or routine rounds with ID physicians [OR 0.96 (99% CI 0.09-1.02), P = 0.09] and in-hospital mortality. CONCLUSIONS: Use of ICU-specific antibiograms was associated with lower in-hospital mortality for patients admitted to ICU. For hospitals that do not perform ICU-specific antibiograms, their implementation presents a low-risk infection management process that might improve patient outcomes.

Nosocomial infections amongst critically ill COVID-19 patients in Australia.

Purpose: To determine the frequency of nosocomial infections including hospital-acquired pneumonia (HAP) and bloodstream infection (BSI), amongst critically ill patients with COVID-19 infection in Australian ICUs and to evaluate associations with mortality and length of stay (LOS). Methods: The effect of nosocomial infections on hospital mortality was evaluated using hierarchical logistic regression models to adjust for illness severity and mechanical ventilation. Results: There were 490 patients admitted to 55 ICUs during the study period. Adjusted odds ratio (OR) for hospital mortality was 1.61 (95% confidence interval (CI) 0.61-4.27, p = 0.3) when considering BSI, and 1.76 (95% CI 0.73-4.21, p = 0.2) for HAP. The average adjusted ICU LOS was significantly longer for patients with BSI (geometric mean 9.0 days vs 6.3 days, p = 0.04) and HAP (geometric mean 13.9 days vs 6.0 days p<0.001). Conclusion: Nosocomial infection rates amongst patients with COVID-19 were low and their development was associated with a significantly longer ICU LOS.

Improving sepsis care for hospital inpatients using existing medical emergency response systems.

BACKGROUND: Sepsis is a medical emergency; timely management has been shown to reduce mortality. We aimed to improve the care of inpatients who developed sepsis after hospital admission by integrating a sepsis bundle with an existing medical emergency team (MET). METHODS: We performed a before-and-after study at an Australian institution. A multimodal intervention was implemented including formation of a working group, development of a guideline, standard documentation, education, audit and feedback. The primary outcome was the proportion of MET calls where there was compliance with the sepsis resuscitation bundle within one hour of MET call. RESULTS: There was an improvement in completion of the entire resuscitation bundle (OR 2.33, 95%, CI: 1.23 - 4.41) and lactate measurement (OR 2.72, CI: 1.53, 4.84) within one hour of MET call. There was a non-significant reduction in the median time to antibiotic administration in patients where antibiotics were initiated or changed at the MET call (60 mins vs. 44 mins, p = 0.8). In hospital mortality was observed to fall from 22.1% to 11.4%, but after adjusting for age and baseline illness severity this differences was not statistically significant (OR 0.52, CI: 0.23, 1.19, p = 0.12). CONCLUSION: The implementation of a multimodal sepsis bundle and the utilisation of an existing MET call system demonstrated an increase in the overall uptake of a sepsis bundle. This was associated with an observed reduction in all-cause in-hospital mortality, although this difference was not statistically significant after adjustment for confounders. Further interventions with a focus on nursing education and engagement may improve timely antibiotic administration.

Antimicrobial-Resistant Klebsiella pneumoniae Carriage and Infection in Specialized Geriatric Care Wards Linked to Acquisition in the Referring Hospital.

Background: Klebsiella pneumoniae is a leading cause of extended-spectrum ß-lactamase (ESBL)-producing hospital-associated infections, for which elderly patients are at increased risk. Methods: We conducted a 1-year prospective cohort study, in which a third of patients admitted to 2 geriatric wards in a specialized hospital were recruited and screened for carriage of K. pneumoniae by microbiological culture. Clinical isolates were monitored via the hospital laboratory. Colonizing and clinical isolates were subjected to whole-genome sequencing and antimicrobial susceptibility testing. Results: K. pneumoniae throat carriage prevalence was 4.1%, rectal carriage 10.8%, and ESBL carriage 1.7%, and the incidence of K. pneumoniae infection was 1.2%. The isolates were diverse, and most patients were colonized or infected with a unique phylogenetic lineage, with no evidence of transmission in the wards. ESBL strains carried blaCTX-M-15 and belonged to clones associated with hospital-acquired ESBL infections in other countries (sequence type [ST] 29, ST323, and ST340). One also carried the carbapenemase blaIMP-26. Genomic and epidemiological data provided evidence that ESBL strains were acquired in the referring hospital. Nanopore sequencing also identified strain-to-strain transmission of a blaCTX-M-15 FIBK/FIIK plasmid in the referring hospital. Conclusions: The data suggest the major source of K. pneumoniae was the patient's own gut microbiome, but ESBL strains were acquired in the referring hospital. This highlights the importance of the wider hospital network to understanding K. pneumoniae risk and infection prevention. Rectal screening for ESBL organisms on admission to geriatric wards could help inform patient management and infection control in such facilities.

Critical care of tropical disease in low income countries: Report from the Task Force on Tropical Diseases by the World Federation of Societies of Intensive and Critical Care Medicine.

Tropical disease results in a great burden of critical illness. The same life-saving and supportive therapies to maintain vital organ functions that comprise critical care are required by these patients as for all other diseases. In low income countries, the little available data points towards high mortality rates and big challenges in the provision of critical care. Improving critical care in low income countries requires a focus on hospital design, training, triage, monitoring & treatment modifications, the basic principles of critical care, hygiene and the involvement of multi-disciplinary teams. As a large proportion of critical illness from tropical disease is in low income countries, the impact and reductions in mortality rates of improved critical care in such settings could be substantial.

Pneumonia in the tropics: Report from the Task Force on tropical diseases by the World Federation of Societies of Intensive and Critical Care Medicine.

The aetiology of community acquired pneumonia varies according to the region in which it is acquired. This review discusses those causes of CAP that occur in the tropics and might not be readily recognizable when transplanted to other sites. Various forms of pneumonia including the viral causes such as influenza (seasonal and avian varieties), the coronaviruses and the Hantavirus as well as bacterial causes, specifically the pneumonic form of Yersinia pestis and melioidosis are discussed.

Gastrointestinal Carriage Is a Major Reservoir of Klebsiella pneumoniae Infection in Intensive Care Patients.

BACKGROUND: Klebsiella pneumoniae is an opportunistic pathogen and leading cause of hospital-associated infections. Intensive care unit (ICU) patients are particularly at risk. Klebsiella pneumoniae is part of the healthy human microbiome, providing a potential reservoir for infection. However, the frequency of gut colonization and its contribution to infections are not well characterized. METHODS: We conducted a 1-year prospective cohort study in which 498 ICU patients were screened for rectal and throat carriage of K. pneumoniae shortly after admission. Klebsiella pneumoniae isolated from screening swabs and clinical diagnostic samples were characterized using whole genome sequencing and combined with epidemiological data to identify likely transmission events. RESULTS: Klebsiella pneumoniae carriage frequencies were estimated at 6% (95% confidence interval [CI], 3%-8%) among ICU patients admitted direct from the community, and 19% (95% CI, 14%-51%) among those with recent healthcare contact. Gut colonization on admission was significantly associated with subsequent infection (infection risk 16% vs 3%, odds ratio [OR] = 6.9, P < .001), and genome data indicated matching carriage and infection isolates in 80% of isolate pairs. Five likely transmission chains were identified, responsible for 12% of K. pneumoniae infections in ICU. In sum, 49% of K. pneumoniae infections were caused by the patients' own unique strain, and 48% of screened patients with infections were positive for prior colonization. CONCLUSIONS: These data confirm K. pneumoniae colonization is a significant risk factor for infection in ICU, and indicate ~50% of K. pneumoniae infections result from patients' own microbiota. Screening for colonization on admission could limit risk of infection in the colonized patient and others.