Hospital Specialist Palliative Care Team Influence on End-of-Life Care in Coronavirus Disease 2019? A Retrospective Observational Cohort Study.

Objectives: The coronavirus 19 disease (COVID-19) pandemic has led to a renewed focus on end-of-life care. The majority of COVID-19 deaths occur in hospital, with patients cared for by generalists and hospital specialist palliative care teams (HSPCTs). This project aims at exploring the potential influences of HSPCTs on end-of-life care in COVID-19. Methods: A retrospective observational study was carried out by exploring four end-of-life care themes in a Scottish hospital population who died from COVID-19. Comparison was made between cohorts seen by HSPCTs versus generalist clinicians. Results: Analysis of 119 patients across NHS Greater Glasgow and Clyde (NHSGGC) health board demonstrated that COVID-19 patients seen by HSPCTs were more likely to be younger (median 77 vs. 81 years; p = 0.02), have a cancer diagnosis (21.7% vs. 5.4%; p = 0.01), die sooner after admission (median four vs. six days; p < 0.01), and be commenced on a syringe driver (89.1% vs. 42.5%; p < 0.01). Differences detected across four end-of-life care themes comparing HSPCTs with generalist teams were minimal with documentation and prescribing in keeping with available guidance. Conclusion: Consistencies in end-of-life care observed across NHSGGC cohorts draw attention to the potential wider impact of HSPCT roles, including education, guideline development, and mentoring. Understanding such diverse effects is important to support funding and development of HSPCTs. Further research is required to better quantify the impact and heterogenous influences of HSPCTs in general.

Oral versus intravenous antibiotics for bone and joint infections: the OVIVA non-inferiority RCT.

BACKGROUND: Management of bone and joint infection commonly includes 4-6 weeks of intravenous (IV) antibiotics, but there is little evidence to suggest that oral (PO) therapy results in worse outcomes. OBJECTIVE: To determine whether or not PO antibiotics are non-inferior to IV antibiotics in treating bone and joint infection. DESIGN: Parallel-group, randomised (1 : 1), open-label, non-inferiority trial. The non-inferiority margin was 7.5%. SETTING: Twenty-six NHS hospitals. PARTICIPANTS: Adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least 6 weeks of antibiotics, and who had received ≤ 7 days of IV therapy from definitive surgery (or start of planned curative treatment in patients managed non-operatively). INTERVENTIONS: Participants were centrally computer-randomised to PO or IV antibiotics to complete the first 6 weeks of therapy. Follow-on PO therapy was permitted in either arm. MAIN OUTCOME MEASURE: The primary outcome was the proportion of participants experiencing treatment failure within 1 year. An associated cost-effectiveness evaluation assessed health resource use and quality-of-life data. RESULTS: Out of 1054 participants (527 in each arm), end-point data were available for 1015 (96.30%) participants. Treatment failure was identified in 141 out of 1015 (13.89%) participants: 74 out of 506 (14.62%) and 67 out of 509 (13.16%) of those participants randomised to IV and PO therapy, respectively. In the intention-to-treat analysis, using multiple imputation to include all participants, the imputed risk difference between PO and IV therapy for definitive treatment failure was -1.38% (90% confidence interval -4.94% to 2.19%), thus meeting the non-inferiority criterion. A complete-case analysis, a per-protocol analysis and sensitivity analyses for missing data each confirmed this result. With the exception of IV catheter complications [49/523 (9.37%) in the IV arm vs. 5/523 (0.96%) in the PO arm)], there was no significant difference between the two arms in the incidence of serious adverse events. PO therapy was highly cost-effective, yielding a saving of £2740 per patient without any significant difference in quality-adjusted life-years between the two arms of the trial. LIMITATIONS: The OVIVA (Oral Versus IntraVenous Antibiotics) trial was an open-label trial, but bias was limited by assessing all potential end points by a blinded adjudication committee. The population was heterogenous, which facilitated generalisability but limited the statistical power of subgroup analyses. Participants were only followed up for 1 year so differences in late recurrence cannot be excluded. CONCLUSIONS: PO antibiotic therapy is non-inferior to IV therapy when used during the first 6 weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within 1 year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy. FUTURE WORK: Further work is required to define the optimal total duration of therapy for bone and joint infection in the context of specific surgical interventions. Currently, wide variation in clinical practice suggests significant redundancy that likely contributes to the excess and unnecessary use of antibiotics. TRIAL REGISTRATION: Current Controlled Trials ISRCTN91566927. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 38. See the NIHR Journals Library website for further project information.

Treatment of bone and joint infection usually requires a long course of antibiotics. Doctors usually give these by injection through a vein (intravenously) for the first 4­6 weeks, rather than by mouth (orally). Although intravenous (IV) administration is more expensive and less convenient for patients, most doctors believe that it is more effective. However, there is little evidence to support this. The OVIVA (Oral Versus IntraVenous Antibiotics) trial set out to challenge this assumption. A total of 1054 patients from 26 UK hospitals were randomly allocated to receive the first 6 weeks of antibiotic therapy either intravenously or orally. Irrespective of the route of administration, the choice of antibiotic was left to an infection specialist so as to ensure that the most appropriate antibiotics were given. Patients were followed up for 1 year. Thirty-nine participants were lost to follow-up. Among the remaining 1015 participants, treatment failure occurred in 14.6% of those treated intravenously and 13.2% of those treated with PO antibiotics. This difference could easily have occurred by chance. Even if it was not by chance, the difference does not suggest that PO therapy is associated with worse outcomes than IV therapy and is too small to conclude that PO therapy is better than IV therapy. Participants in the IV group stayed in hospital longer and 10% of them had complications related to the IV line used for administering the antibiotics. In addition, their treatment was, overall, more expensive. We conclude that PO antibiotic therapy has no disadvantages for the early management of bone and joint infection. It is also cheaper and associated with fewer complications.

Oral versus Intravenous Antibiotics for Bone and Joint Infection.

BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).

Late Ebola virus relapse causing meningoencephalitis: a case report.

BACKGROUND: There are thousands of survivors of the 2014 Ebola outbreak in west Africa. Ebola virus can persist in survivors for months in immune-privileged sites; however, viral relapse causing life-threatening and potentially transmissible disease has not been described. We report a case of late relapse in a patient who had been treated for severe Ebola virus disease with high viral load (peak cycle threshold value 13.2). METHODS: A 39-year-old female nurse from Scotland, who had assisted the humanitarian effort in Sierra Leone, had received intensive supportive treatment and experimental antiviral therapies, and had been discharged with undetectable Ebola virus RNA in peripheral blood. The patient was readmitted to hospital 9 months after discharge with symptoms of acute meningitis, and was found to have Ebola virus in cerebrospinal fluid (CSF). She was treated with supportive therapy and experimental antiviral drug GS-5734 (Gilead Sciences, San Francisco, Foster City, CA, USA). We monitored Ebola virus RNA in CSF and plasma, and sequenced the viral genome using an unbiased metagenomic approach. FINDINGS: On admission, reverse transcriptase PCR identified Ebola virus RNA at a higher level in CSF (cycle threshold value 23.7) than plasma (31.3); infectious virus was only recovered from CSF. The patient developed progressive meningoencephalitis with cranial neuropathies and radiculopathy. Clinical recovery was associated with addition of high-dose corticosteroids during GS-5734 treatment. CSF Ebola virus RNA slowly declined and was undetectable following 14 days of treatment with GS-5734. Sequencing of plasma and CSF viral genome revealed only two non-coding changes compared with the original infecting virus. INTERPRETATION: Our report shows that previously unanticipated, late, severe relapses of Ebola virus can occur, in this case in the CNS. This finding fundamentally redefines what is known about the natural history of Ebola virus infection. Vigilance should be maintained in the thousands of Ebola survivors for cases of relapsed infection. The potential for these cases to initiate new transmission chains is a serious public health concern. FUNDING: Royal Free London NHS Foundation Trust.

Daptomycin use in patients with osteomyelitis: a preliminary report from the EU-CORE(SM) database.

BACKGROUND: Osteomyelitis is a complex and heterogeneous group of infections that require surgical and antimicrobial interventions. Because treatment failure or intolerance is common, new treatment options are needed. Daptomycin has broad Gram-positive activity, penetrates bone effectively and has bactericidal activity within biofilms. This is the first report on clinical outcomes in patients with osteomyelitis from the multicentre, retrospective, non-interventional European Cubicin(®) Outcomes Registry and Experience (EU-CORE(SM)), a large database on real-world daptomycin use. PATIENTS AND METHODS: In total, 220 patients were treated for osteomyelitis; the population was predominantly elderly, with predisposing baseline conditions such as diabetes and chronic renal/cardiac diseases. RESULTS: Most patients (76%) received prior antibiotic treatment, and first-line treatment failure was the most frequent reason to start daptomycin. Common sites of infection were the knee (22%) or hip (21%), and the most frequently isolated pathogens were Staphylococcus aureus (33%) and coagulase-negative staphylococci (32%). Overall, 52% of patients had surgery, 55% received concomitant antibiotics and 29% received a proportion of daptomycin therapy as outpatients. Clinical success was achieved in 75% of patients. Among patients with prosthetic device-related osteomyelitis, there was a trend towards higher success rates if the device was removed. Daptomycin was generally well tolerated. CONCLUSIONS: This analysis suggests that daptomycin is an effective and well-tolerated treatment option for osteomyelitis and highlights the importance of optimal surgical intervention and appropriate microbiological diagnosis for clinical outcomes.

Daptomycin for the treatment of infective endocarditis: results from a European registry.

OBJECTIVES: Infective endocarditis (IE) is a complex infection associated with high mortality. Daptomycin, a cyclic lipopeptide antibiotic highly active against Gram-positive bacteria, has recently been incorporated into IE treatment guidelines. This retrospective analysis provides insights into the use of daptomycin in IE in the European Cubicin(®) Outcomes Registry Experience (EU-CORE(SM)) between 2006 and 2010. PATIENTS AND METHODS: Three hundred and seventy-eight (10%) of 3621 enrolled patients received daptomycin for treatment of IE. Two hundred and fifty-nine (69%) had left-sided IE (LIE) and 182 patients (48%) underwent concomitant surgery. RESULTS: Staphylococcus aureus was the most frequently identified pathogen (n=92; methicillin susceptible, n=50) and daptomycin was used empirically in 134 patients. Among cases of second-line therapy (n=312), the most common reason for switching to daptomycin was failure of the previous regimen (including glycopeptides and penicillins). Daptomycin was administered at 6 mg/kg in 224 patients and at ≥ 8 mg/kg in 72 patients. Clinical success rates were 80% overall, 91% for right-sided IE (RIE) and 76% for LIE, with similar rates seen for infections caused by methicillin-susceptible S. aureus (84%) and methicillin-resistant S. aureus (81%). The clinical success rate in patients treated with ≥ 8 mg/kg daptomycin was 90% [n=72 (RIE, 91%; LIE, 89%)]. No new safety signals were observed. CONCLUSIONS: In patients with IE registered in EU-CORE, daptomycin was most frequently used as second-line treatment after treatment failure. The majority of patients had LIE and most commonly received daptomycin for the treatment of staphylococcal infections. Clinical success was high in this difficult-to-treat population. The role of doses ≥ 8 mg/kg per day in the empirical treatment of IE deserves further investigation.

Scottish Antimicrobial Prescribing Group (SAPG): development and impact of the Scottish National Antimicrobial Stewardship Programme.

In 2008, the Scottish Management of Antimicrobial Resistance Action Plan (ScotMARAP) was published by the Scottish Government. One of the key actions was initiation of the Scottish Antimicrobial Prescribing Group (SAPG), hosted within the Scottish Medicines Consortium, to take forward national implementation of the key recommendations of this action plan. The primary objective of SAPG is to co-ordinate and deliver a national framework or programme of work for antimicrobial stewardship. This programme, led by SAPG, is delivered by NHS National Services Scotland (Health Protection Scotland and Information Services Division), NHS Quality Improvement Scotland, and NHS National Education Scotland as well as NHS board Antimicrobial Management Teams. Between 2008 and 2010, SAPG has achieved a number of early successes, which are the subject of this review: (i) through measures to optimise prescribing in hospital and primary care, combined with infection prevention measures, SAPG has contributed significantly to reducing Clostridium difficile infection rates in Scotland; (ii) there has been engagement of all key stakeholders at local and national levels to ensure an integrated approach to antimicrobial stewardship within the wider healthcare-associated infection agenda; (iii) development and implementation of data management systems to support quality improvement; (iv) development of training materials on antimicrobial stewardship for healthcare professionals; and (v) improving clinical management of infections (e.g. community-acquired pneumonia) through quality improvement methodology. The early successes achieved by SAPG demonstrate that this delivery model is effective and provides the leadership and focus required to implement antimicrobial stewardship to improve antimicrobial prescribing and infection management across NHS Scotland.