Antibiotic prescribing for respiratory tract infection in patients with suspected and proven COVID-19: results from an antibiotic point prevalence survey in Scottish hospitals.

BACKGROUND: Bacterial co-infection is infrequently observed with SARS-CoV-2/COVID-19 infection outside of critical care, however, antibiotics are commonly prescribed. OBJECTIVES: To examine factors associated with antibiotic prescribing for suspected respiratory tract infection (RTI) and evaluate the nature and dynamics of prescribing in hospitalized patients with suspected and proven COVID-19 infection. METHODS: An antibiotic point prevalence survey in hospitalized adult patients was conducted in designated COVID-19 clinical areas (including critical care) in 15 Scottish hospitals. Antibiotics prescribed for RTI and factors associated with prescribing were investigated. RESULTS: Of 820 surveyed patients, 272 (prevalence 33.3%) received antibiotics for suspected RTI on the survey day and 58.8% were SARS-CoV-2 positive. Antibiotics were empirical in 91.9% and amoxicillin (24.6%), doxycycline (20.5%) and co-amoxiclav (15%) were most frequently prescribed. Oral antibiotics were prescribed in 54.5% and duration was recorded in 76.7% on wards for a median of 5 days. IV to oral switch occurred after a median of 2 days. Prescribing for RTI was independently and positively associated with COPD/chronic lung disease, purulent/bloody sputum, abnormal chest X-ray, and CRP ≥ 100 mg/L. Probable and definite hospital-acquired COVID-19 and diabetes were associated with a lower odds of receiving an antibiotic for RTI. CONCLUSIONS: Antibiotic prescribing for suspected RTI was commonly observed and predominantly empirical in suspected or proven COVID-19. Initiatives to reinforce stewardship principles including clinical review, effective use of microbiological diagnostics and better understanding of the role of biomarkers are central to further limit unnecessary antibiotic therapy in COVID-19.

Survey of antibiotic and antifungal prescribing in patients with suspected and confirmed COVID-19 in Scottish hospitals.

BACKGROUND: Concern regarding bacterial co-infection complicating SARS-CoV-2 has created a challenge for antimicrobial stewardship. Following introduction of national antibiotic recommendations for suspected bacterial respiratory tract infection complicating COVID-19, a point prevalence survey of prescribing was conducted across acute hospitals in Scotland. METHODS: Patients in designated COVID-19 units were included and demographic, clinical and antimicrobial data were collected from 15 hospitals on a single day between 20th and 30th April 2020. Comparisons were made between SARS-CoV-2 positive and negative patients and patients on non-critical care and critical care units. Factors associated with antibiotic prescribing in SARS-CoV-2 positive patients were examined using Univariable and multivariable regression analyses. FINDINGS: There were 820 patients were included, 64.8% were SARS-CoV-2 positive and 14.9% were managed in critical care, and 22.1% of SARS-CoV-2 infections were considered probable or definite nosocomial infections. On the survey day, antibiotic prevalence was 45.0% and 73.9% were prescribed for suspected respiratory tract infection. Amoxicillin, doxycycline and co-amoxiclav accounted for over half of all antibiotics in non-critical care wards and meropenem, piperacillin-tazobactam and co-amoxiclav accounted for approximately half prescribed in critical care. Of all SARS-CoV-2 patients, 38.3% were prescribed antibiotics. In a multivariable logistic regression analysis, COPD/chronic lung disease and CRP ≥ 100 mg/l were associated with higher odds and probable or confirmed nosocomial COVID-19, diabetes and management on an elderly care ward had lower odds of an antibiotic prescription. Systemic antifungals were prescribed in 9.8% of critical care patients and commenced a median of 18 days after critical care admission. INTERPRETATION: A relatively low prevalence of antibiotic prescribing in SARS-CoV-2 hospitalised patients and low proportion of broad spectrum antibiotics in non-critical care settings was observed potentially reflecting national antimicrobial stewardship initiatives. Broad spectrum antibiotic and antifungal prescribing in critical care units was observed indicating the importance of infection prevention and control and stewardship initiatives in this setting. FUNDING: The Scottish Antibiotic Prescribing Group is funded by Scottish Government.

Endothelium-derived contraction in a model of rheumatoid arthritis is mediated via angiotensin II type 1 receptors.

A role for endothelium-derived constricting factors (EDCF), and the angiotensin II type 1 receptor (AT1R) pathway, in the vascular impairment found in the rat Freund's complete adjuvant (FCA)-model of rheumatoid arthritis (RA) was examined. FCA arthritis was induced in rats±losartan. Vehicle-treated rats served as controls. Knee-joint swelling and red blood cell (RBC) aggregation were measured as indicators of inflammation and endothelium reactivity assessed by response to acetylcholine (ACh) on aortic rings. Results show that knee-joint swelling and RBC aggregation were elevated in the FCA+vehicle group and restored to control levels in the FCA+losartan-treated animals. ACh-induced relaxation of aortic rings taken from FCA+vehicle animals was significantly impaired compared to vehicle-controls and this vasoreactivity was restored to control levels in the FCA+losartan-treated group. Further examination of aorta from the FCA+vehicle animals revealed an EDCF that was reliant on cyclooxygenase-2 (but not cyclooxygenase-1), generation of superoxide anion generation (but not hydrogen peroxide) and activation of thromboxane-prostanoid receptor. Losartan administration in vivo or ex vivo (to aortic rings) prevented the generation of the EDCF. In summary, this is the first evidence of an EDCF in a model of RA and identifies this mechanism as potentially significant in the cardiovascular disorder associated with the disease.

Gender specific generation of nitroxyl (HNO) from rat endothelium.

Nitric oxide (NO) has long been accepted as the majority biological mediator underlying the critically important vasodilator function of the vascular endothelium yet there is growing evidence that the protonated one-electron reduction species of NO, nitroxyl (HNO), may also have biological activity. In this study we examined if there was a gender variation in the production of HNO from the endothelium of isolated segments of rat aorta. By use of recognized pharmacological inhibitors, we found that when the endothelium was stimulated by acetylcholine vascular relaxation was mediated entirely via NO in tissue from both males and females. The vasorelaxation induced by basal (non-stimulated) endothelium from females was also mediated entirely by NO. However, in contrast, the influence of basally active endothelium in males was mediated by both NO and HNO. The generation of HNO in males was dependent on endothelial nitric oxide synthase and relaxation was mediated via activation of soluble guanylate cyclase. We believe that this is the first evidence of a gender variation in the production of HNO and this may have important implications for our understanding of disparity in the development of cardiovascular disease between the sexes.