Interleukin-6 Receptor Antagonists in Critically Ill Patients with Covid-19.

BACKGROUND: The efficacy of interleukin-6 receptor antagonists in critically ill patients with coronavirus disease 2019 (Covid-19) is unclear. METHODS: We evaluated tocilizumab and sarilumab in an ongoing international, multifactorial, adaptive platform trial. Adult patients with Covid-19, within 24 hours after starting organ support in the intensive care unit (ICU), were randomly assigned to receive tocilizumab (8 mg per kilogram of body weight), sarilumab (400 mg), or standard care (control). The primary outcome was respiratory and cardiovascular organ support-free days, on an ordinal scale combining in-hospital death (assigned a value of -1) and days free of organ support to day 21. The trial uses a Bayesian statistical model with predefined criteria for superiority, efficacy, equivalence, or futility. An odds ratio greater than 1 represented improved survival, more organ support-free days, or both. RESULTS: Both tocilizumab and sarilumab met the predefined criteria for efficacy. At that time, 353 patients had been assigned to tocilizumab, 48 to sarilumab, and 402 to control. The median number of organ support-free days was 10 (interquartile range, -1 to 16) in the tocilizumab group, 11 (interquartile range, 0 to 16) in the sarilumab group, and 0 (interquartile range, -1 to 15) in the control group. The median adjusted cumulative odds ratios were 1.64 (95% credible interval, 1.25 to 2.14) for tocilizumab and 1.76 (95% credible interval, 1.17 to 2.91) for sarilumab as compared with control, yielding posterior probabilities of superiority to control of more than 99.9% and of 99.5%, respectively. An analysis of 90-day survival showed improved survival in the pooled interleukin-6 receptor antagonist groups, yielding a hazard ratio for the comparison with the control group of 1.61 (95% credible interval, 1.25 to 2.08) and a posterior probability of superiority of more than 99.9%. All secondary analyses supported efficacy of these interleukin-6 receptor antagonists. CONCLUSIONS: In critically ill patients with Covid-19 receiving organ support in ICUs, treatment with the interleukin-6 receptor antagonists tocilizumab and sarilumab improved outcomes, including survival. (REMAP-CAP ClinicalTrials.gov number, NCT02735707.).

Antibiotic De-Escalation Practices in the Intensive Care Unit: A Multicenter Observational Study.

BACKGROUND: There is little known about antibiotic de-escalation (ADE) practices in the intensive care unit (ICU). OBJECTIVE: The objective was to determine the proportion of patients who received ADE within 24 hours of actionable cultures and identify predictors of timely ADE. METHODS: Multicenter cohort study in ICUs of 15 hospitals in Australia and New Zealand. Adult patients were included if they were started on broad-spectrum antibiotics within 24 hours of ICU admission. The ADE was defined as switching from a broad-spectrum agent to a narrower-spectrum agent or antibiotic cessation. The primary outcome was ADE within 24 hours of an actionable culture, where ADE was possible. RESULTS: The 446 patients included in the study had a mean age of 63 ± 16 years, 60% were male, 32% were mechanically ventilated, and 19% were immunocompromised. Of these, 161 (36.1%) were not eligible for ADE and 37 (8.3%) for whom ADE within 24 hours of actionable culture could not be determined. In the remaining 248 patients, ADE occurred ≤24 hours in 60.5% (n = 150/248) after actionable cultures. In the multivariable logistic regression analysis, ADE was less likely to occur within 24 hours for patients with negative cultures (odds ratio [OR] = 0.48, 95% confidence interval [CI] = 0.25-0.92, P = 0.03). CONCLUSION AND RELEVANCE: Timely ADE may not occur in 40% of patients in the ICU and is less likely to occur in patients with negative cultures. Timely ADE can be improved, and patients with negative cultures should be targeted as part of antimicrobial stewardship efforts.

Long-Term Impact of a Smartphone App on Prescriber Adherence to Antibiotic Guidelines for Adult Patients With Community-Acquired Pneumonia: Interrupted Time-Series Study.

BACKGROUND: Mobile health platforms like smartphone apps that provide clinical guidelines are ubiquitous, yet their long-term impact on guideline adherence remains unclear. In 2016, an antibiotic guidelines app, called SCRIPT, was introduced in Auckland City Hospital, New Zealand, to provide local antibiotic guidelines to clinicians on their smartphones. OBJECTIVE: We aimed to assess whether the provision of antibiotic guidelines in a smartphone app resulted in sustained changes in antibiotic guideline adherence by prescribers. METHODS: We analyzed antibiotic guideline adherence rates during the first 24 hours of hospital admission in adults diagnosed with community-acquired pneumonia using an interrupted time-series study with 3 distinct periods post app implementation (ie, 3, 12, and 24 months). RESULTS: Adherence increased from 23% (46/200) at baseline to 31% (73/237) at 3 months and 34% (69/200) at 12 months, reducing to 31% (62/200) at 24 months post app implementation (P=.07 vs baseline). However, increased adherence was sustained in patients with pulmonary consolidation on x-ray (9/63, 14% at baseline; 23/77, 30% after 3 months; 32/92, 35% after 12 month; and 32/102, 31% after 24 months; P=.04 vs baseline). CONCLUSIONS: An antibiotic guidelines app increased overall adherence, but this was not sustained. In patients with pulmonary consolidation, the increased adherence was sustained.

Lopinavir-ritonavir and hydroxychloroquine for critically ill patients with COVID-19: REMAP-CAP randomized controlled trial.

PURPOSE: To study the efficacy of lopinavir-ritonavir and hydroxychloroquine in critically ill patients with coronavirus disease 2019 (COVID-19). METHODS: Critically ill adults with COVID-19 were randomized to receive lopinavir-ritonavir, hydroxychloroquine, combination therapy of lopinavir-ritonavir and hydroxychloroquine or no antiviral therapy (control). The primary endpoint was an ordinal scale of organ support-free days. Analyses used a Bayesian cumulative logistic model and expressed treatment effects as an adjusted odds ratio (OR) where an OR > 1 is favorable. RESULTS: We randomized 694 patients to receive lopinavir-ritonavir (n = 255), hydroxychloroquine (n = 50), combination therapy (n = 27) or control (n = 362). The median organ support-free days among patients in lopinavir-ritonavir, hydroxychloroquine, and combination therapy groups was 4 (- 1 to 15), 0 (- 1 to 9) and-1 (- 1 to 7), respectively, compared to 6 (- 1 to 16) in the control group with in-hospital mortality of 88/249 (35%), 17/49 (35%), 13/26 (50%), respectively, compared to 106/353 (30%) in the control group. The three interventions decreased organ support-free days compared to control (OR [95% credible interval]: 0.73 [0.55, 0.99], 0.57 [0.35, 0.83] 0.41 [0.24, 0.72]), yielding posterior probabilities that reached the threshold futility (≥ 99.0%), and high probabilities of harm (98.0%, 99.9% and > 99.9%, respectively). The three interventions reduced hospital survival compared with control (OR [95% CrI]: 0.65 [0.45, 0.95], 0.56 [0.30, 0.89], and 0.36 [0.17, 0.73]), yielding high probabilities of harm (98.5% and 99.4% and 99.8%, respectively). CONCLUSION: Among critically ill patients with COVID-19, lopinavir-ritonavir, hydroxychloroquine, or combination therapy worsened outcomes compared to no antiviral therapy.

Quality of antimicrobial prescribing improved by the introduction of ePrescribing at Auckland City Hospital.

Improving antimicrobial prescribing is a difficult process often requiring labour-intensive, multi-modal interventions. Many hospitals have introduced ePrescribing systems but the effect on antimicrobial prescribing, without treatment choice decision support systems, has not been well described. We sought to determine whether the introduction of ePrescribing improved prescribing quality. Patient records for inpatients on four rehabilitation wards, two using ePrescribing and two using the National Medication Chart, during February 2017, were retrospectively reviewed to identify all antimicrobial prescriptions, which were then reviewed for quality. Documentation of indication was significantly better on ePrescribing wards (45/46, 98%) compared to National Medication Chart wards (47/59, 80%). Adherence to guidelines (32/46, 70% vs 33/59, 56%), appropriateness of therapy (42/46, 91% vs 50/59, 85%) and documentation of duration, stop or review dates (35/46, 76% vs 38/59, 64%) did not significantly differ. ePrescribing can improve the quality of antimicrobial prescribing when Antimicrobial Stewardship principles are used in system customisation but cannot address all factors impacting on prescribing quality.

Impact of a smartphone app on prescriber adherence to antibiotic guidelines in adult patients with community acquired pneumonia or urinary tract infections.

BACKGROUND: Mobile phone apps have been shown to enhance guideline adherence by prescribers, but have not been widely evaluated for their impact on guideline adherence by prescribers caring for inpatients with infections. OBJECTIVES: To determine whether providing the Auckland City Hospital (ACH) antibiotic guidelines in a mobile phone app increased guideline adherence by prescribers caring for inpatients with community acquired pneumonia (CAP) or urinary tract infections (UTIs). METHODS: We audited antibiotic prescribing during the first 24 hours after hospital admission in adults admitted during a baseline and an intervention period to determine whether provision of the app increased the level of guideline adherence. To control for changes in prescriber adherence arising from other factors, we performed similar audits of adherence to antibiotic guidelines in two adjacent hospitals. RESULTS: The app was downloaded by 145 healthcare workers and accessed a total of 3985 times during the three month intervention period. There was an increase in adherence to the ACH antibiotic guidelines by prescribers caring for patients with CAP from 19% (37/199) to 27% (64/237) in the intervention period (p = 0.04); but no change in guideline adherence at an adjacent hospital. There was no change in adherence to the antibiotic guidelines by prescribers caring for patients with UTI at ACH or at the two adjacent hospitals. CONCLUSIONS: Provision of antibiotic guidelines in a mobile phone app can significantly increase guideline adherence by prescribers. However, providing an app which allows easy access to antibiotic guidelines is not sufficient to achieve high levels of prescriber adherence.

Survey of antimicrobial stewardship practices in public hospitals in New Zealand district health boards.

AIMS: To determine what antimicrobial stewardship (AMS) practices exist in New Zealand public hospitals. METHODS: A quantitative survey based on recommended components of hospital AMS programmes was sent to the 20 DHBs in June 2016. RESULTS: Ten of the 20 DHBs had an AMS committee, nine had dedicated AMS pharmacist full-time equivalents (FTEs) and eight had lead clinician FTEs. Only one DHB met FTE recommendations for AMS pharmacists and two for clinicians (0.3 and 0.1 FTEs per 100 acute beds, respectively). All DHBs had conducted at least one antimicrobial audit in the preceding 12 months, most had their own antimicrobial guidelines (19/20) and prescribing policies (18/20), and 12 reported on antimicrobial usage by at least one metric (eg, defined daily doses). Staff education on AMS had been given at most DHBs in the previous year, but only three reported having AMS ward rounds. All DHBs had surveillance programmes for resistant organisms and most produced antibiograms (16/20). All reported barriers to implementation of an AMS programme. CONCLUSIONS: Hospital AMS programmes are in their infancy in New Zealand, with wide variation in practices seen. National co-ordination is required to assist DHBs in developing effective programmes to improve antimicrobial use.

Previous antibiotic-related adverse drug reactions do not reduce expectations for antibiotic treatment of upper respiratory tract infections.

BACKGROUND: Patients' expectations may influence prescribers' decisions about antibiotic prescribing for upper respiratory tract infection (URTI). We examined whether a history of an antibiotic related adverse drug reaction (aADR) influenced a person's perception about the safety of antibiotics or their expectation of receiving an antibiotic prescription for an URTI. METHODS: We developed a questionnaire and surveyed 103 hospital inpatients, 38 of whom (37%) reported past experience of aADR. RESULTS: Of the 88 participants who reported recent antibiotic use, participants with a history of aADR reported increased perception of harm from their last antibiotic treatment (P<0.05). Overall, 41/103 (40%) participants expected their doctors to prescribe antibiotics to treat an URTI. Participants' perceptions of antibiotic safety or expectation of antibiotic treatment for an URTI did not differ between those who had personal experience of an aADR compared with those with no history of aADR. CONCLUSIONS: The almost universal belief that antibiotics are safe, beneficial medications, even among people with prior aADR, helps to explain the strong patient expectations for antibiotic treatment in a range of conditions. Educational campaigns about the prescription of antibiotics for viral URTI should include information that the risk of harm far outweighs any potential benefits.