The impact of immunosuppressive therapy on secondary infections and antimicrobial use in COVID-19 inpatients: a retrospective cohort study.

BACKGROUND: Immunosuppressive therapies have become a cornerstone of the management of severe COVID-19. The impact of these therapies on secondary infections and antimicrobial prescribing remains unclear. We sought to assess antimicrobial use and the incidence of bacterial and fungal infections in patients with severe COVID-19, and to explore their associations with receipt of immunosuppressive therapies. METHODS: Our retrospective cohort study included 715 hospitalised, adult patients with severe COVID-19 admitted to St George's Hospital, London, UK, during the first UK pandemic wave (1st March-10th June 2020). Co-infections (occurring within 48 h of admission) and secondary infections (≥ 48 h) were defined as a positive microbiological culture with supporting clinical, radiological or laboratory data to suggest true infection. Cox regression models with time-dependent covariates were used to explore the association between immunosuppressant use and secondary infection. RESULTS: Microbiologically confirmed co-infection occurred in 4.2% (n = 30) and secondary infection in 9.3% (n = 66) of the cohort (n = 715) and were associated with in-hospital mortality (48% vs 35%, OR 1.8, 95%CI 1.1-2.7, p = 0.01). Respiratory (n = 41, 39%) and bloodstream infections (n = 38, 36%) predominated, with primarily Gram-negative pathogens. 606 (84.7%) patients received an antimicrobial, amounting to 742 days of therapy per 1000 patient-days (DOTs). In multivariable models, receipt of high-dose steroids (≥ 30 mg prednisolone or equivalent) or tocilizumab was significantly associated with increased antimicrobial consumption (+ 5.5 DOTs, 95%CI 3.4-7.7 days) but not secondary infection (HR 0.56, 95%CI 0.26-1.18). CONCLUSIONS: Bacterial and fungal infections in severe COVID-19 were uncommon. Receipt of steroids or tocilizumab was independently associated with antimicrobial consumption despite its lack of association with secondary infection. These findings should galvanise efforts to promote antimicrobial stewardship in patients with COVID-19.

Assessing the Impact of COVID-19 on Antimicrobial Stewardship Activities/Programs in the United Kingdom.

Since first identified in late 2019, the acute respiratory syndrome coronavirus (SARS-CoV2) and the resulting coronavirus disease (COVID-19) pandemic has overwhelmed healthcare systems worldwide, often diverting key resources in a bid to meet unprecedented challenges. To measure its impact on national antimicrobial stewardship (AMS) activities, a questionnaire was designed and disseminated to antimicrobialstewardship leads in the United Kingdom (UK). Most respondents reported a reduction in AMS activity with 64% (61/95) reporting that COVID-19 had a negative impact on routine AMS activities. Activities reported to have been negatively affected by the pandemic include audit, quality improvement initiatives, education, AMS meetings, and multidisciplinary working including ward rounds. However, positive outcomes were also identified, with technology being increasingly used as a tool to facilitate stewardship e.g., virtual meetings and ward rounds and increased the acceptance of using procalcitonin tests to distinguish between viral and bacterial infections. The COVID-19 pandemic has had a significant impact on the AMS activities undertaken across the UK. The long-term impact of the reduced AMS activities on incidence of AMR are not yet known. The legacy of innovation, use of technology, and increased collaboration from the pandemic could strengthen AMS in the post-pandemic era and presents opportunities for further development of AMS.

Scaled-up development of magnetically recyclable Fe3O4/La(OH)3 composite for river water phosphate removal: From bench-scale to pilot-scale study.

The use of magnetic lanthanum-based materials for phosphate removal from river water has gained increasing attention. However, challenges to produce and use lanthanum-based materials in large-scale or pilot-scale studies remain. In this work, a kilogram-scale Fe3O4/La(OH)3 magnetically recyclable composite for removing phosphate from river water was developed through a low-temperature precipitation route. The composite was used to remove phosphate from river water at both bench- and pilot-scales. Based on the bench-scale tests, the developed Fe3O4/La(OH)3 composite was found to have excellent magnetic particle separation efficiency (>98%) and a sorption capacity of 11.77 mg/g for phosphate. A 1.0 g/L dosage of the composite in the river water sample was able to selectively reduce the phosphate level from 0.089 to 0.005 mg/L in 60 min over five consecutive adsorption cycles. At the pilot-scale, the Fe3O4/La(OH)3 composite only achieved 36.0% phosphate removal efficiency, which is considerably different from the bench-scale results over an operational time of five months and a total treatment volume of 300 m3. This significantly reduced removal efficiency is mainly attributable to turbidity, suspended solids, and organic matter in the river water and the deteriorated magnetic separation efficiency. This study revealed potential challenges and shed new insights on moving magnetic nanocomposite-based technology from the bench-scale to the pilot-scale, which can inspire new designs for the application of similar technology.

Pentiptycene-derived light-driven molecular brakes: substituent effects of the brake component.

Five pentiptycene-derived stilbene systems (1 R; R = H, OM, NO, Pr, and Bu) have been prepared and investigated as light-driven molecular brakes that have different-sized brake components (1 H<1 OM<1 NO<1 Pr<1 Bu). At room temperature (298 K), rotation of the pentiptycene rotor is fast (k(rot)=10(8)-10(9)  s(-1)) with little interaction with the brake component in the trans form ((E)-1 R), which corresponds to the brake-off state. When the brake is turned on by photoisomerization to the cis form ((Z)-1 R), the pentiptycene rotation can be arrested on the NMR spectroscopic timescale at temperatures that depend on the brake component. In the cases of (Z)-1 NO, (Z)-1 Pr, and (Z)-1 Bu, the rotation is nearly blocked (k(rot)=2-6 s(-1)) at 298 K. It is also demonstrated that the rotation is slower in [D(6)]DMSO than in CD(2)Cl(2). A linear relationship between the free energies of the rotational barrier and the steric parameter A values is present only for (Z)-1 H, (Z)-1 OM, and (Z)-1 NO, and it levels off on going from (Z)-1 NO to (Z)-1 Pr and (Z)-1 Bu. DFT calculations provide insights into the substituent effects in the rotational ground and transition states. The molar reversibility of the E-Z photoswitching is up to 46%, and both the E and Z isomers are stable under the irradiation conditions.

Safety and Efficacy of Intermittent High-Dose Liposomal Amphotericin B Antifungal Prophylaxis in Haemato-Oncology: An Eight-Year Single-Centre Experience and Review of the Literature.

Triazoles remain first-line agents for antifungal prophylaxis in high-risk haemato-oncology patients, but their use is increasingly contraindicated due to drug-drug interactions and additive toxicities with novel treatments. In this retrospective, single-centre, observational study, we present our eight-year experience of antifungal prophylaxis using intermittent high-dose liposomal Amphotericin B (L-AmB). All adults identified through our Antifungal Stewardship Programme as receiving L-AmB prophylaxis at 7.5 mg/kg once-weekly between February 2012 and January 2020 were included. Adverse reactions, including infusion reactions, electrolyte loss, and nephrotoxicity, were recorded. 'Breakthrough' invasive fungal infection (IFI) occurring within four weeks of L-AmB was classified using European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) criteria. Moreover, 114 courses of intermittent high-dose L-AmB prophylaxis administered to 92 unique patients were analysed. Hypokalaemia was the most common grade 3-4 adverse event, with 26 (23%) courses. Grade 3 nephrotoxicity occurred in 8 (7%) and reversed in all six patients surviving to 90 days. There were two (1.8%) episodes of breakthrough IFI, one 'probable' and one 'possible'. In this study, the largest evaluation of intermittent high-dose L-AmB prophylaxis conducted to date, toxicity was manageable and reversible and breakthrough IFI was rare. L-AmB prophylaxis represents a viable alternative for patients with a contraindication to triazoles.