Antimicrobial prescribing practices at a tertiary-care center in patients diagnosed with COVID-19 across the continuum of care.

In a single-center review of antibiotic prescribing in COVID-19 patients, 10% of patients received antimicrobials, and inpatients encounters had the highest rate and spectrum of prescribing. Prescribing rate, spectrum, and duration appeared to increase with disease severity in inpatients. Antimicrobial prescribing in patients managed in ambulatory encounters was less common.

Impact of ketamine as an adjunct sedative in acute respiratory distress syndrome due to COVID-19 Pneumonia.

PURPOSE: Deep sedation is sometimes needed in acute respiratory distress syndrome. Ketamine is a sedative that has been shown to have analgesic and sedating properties without having a detrimental impact on hemodynamics. This pharmacological profile makes ketamine an attractive sedative, potentially reducing the necessity for other sedatives and vasopressors, but there are no studies evaluating its effect on these medications in patients requiring deep sedation for acute respiratory distress syndrome. MATERIALS AND METHODS: This is a retrospective, observational study in a single center, quaternary care hospital in southeast Texas. We looked at adults with COVID-19 requiring mechanical ventilation from March 2020 to September 2020. RESULTS: We found that patients had less propofol requirements at 72 h after ketamine initiation when compared to 24 h (median 34.2 vs 54.7 mg/kg, p = 0.003). Norepinephrine equivalents were also significantly lower at 48 h than 24 h after ketamine initiation (median 38 vs 62.8 mcg/kg, p = 0.028). There was an increase in hydromorphone infusion rates at all three time points after ketamine was introduced. CONCLUSIONS: In this cohort of patients with COVID-19 ARDS who required mechanical ventilation receiving ketamine we found propofol sparing effects and vasopressor requirements were reduced, while opioid infusions were not.

Patterns of prescription dispensation and over-the-counter medication sales in Sweden during the COVID-19 pandemic.

INTRODUCTION: On February 26th 2020, a high alert was issued in Sweden in response to the diagnosis of the first few coronavirus disease 2019 (COVID-19) cases in the country. Subsequently, a decreased supply of essential goods, including medical products, was anticipated. We aimed to explore the weekly patterns of prescription dispensing and over-the-counter (OTC) medication sales in Sweden in 2020 compared with previous years, to assess the influence of the government restrictions on medication sales, and to assess whether there is evidence of medication stockpiling in the population. METHODS: Aggregated data on the weekly volume of defined daily doses (DDDs) of prescription medication dispensed and OTC sales from 2015 to 2020 were examined. From 2015-2019 data, the predicted weekly volume of DDDs for 2020 was estimated and compared to the observed volume for each ATC anatomical main group and therapeutic subgroup. RESULTS: From mid-February to mid-March 2020, there were increases in the weekly volumes of dispensed medication, peaking in the second week of March with a 46% increase in the observed versus predicted number of DDDs dispensed (16,440 vs 11,260 DDDs per 1000 inhabitants). A similar pattern was found in all age groups, in both sexes, and across metropolitan and non-metropolitan regions. In the same week in March, there was a 96% increase in the volume of OTC sold (2,504 vs 1,277 DDDs per 1000 inhabitants), specifically in ATC therapeutic subgroups including vitamins, antipyretics, painkillers, and nasal, throat, cough and cold preparations. CONCLUSION: Beginning in mid-February 2020, there were significant changes in the volume of prescription medication dispensed and OTC drugs sold. The weekly volume of DDDs quickly decreased following recommendations from public authorities. Overall, our findings suggest stockpiling behavior over a surge in new users of medication.

Sales of antibiotics and hydroxychloroquine in India during the COVID-19 epidemic: An interrupted time series analysis.

BACKGROUND: We assessed the impact of the coronavirus disease 2019 (COVID-19) epidemic in India on the consumption of antibiotics and hydroxychloroquine (HCQ) in the private sector in 2020 compared to the expected level of use had the epidemic not occurred. METHODS AND FINDINGS: We performed interrupted time series (ITS) analyses of sales volumes reported in standard units (i.e., doses), collected at regular monthly intervals from January 2018 to December 2020 and obtained from IQVIA, India. As children are less prone to develop symptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we hypothesized a predominant increase in non-child-appropriate formulation (non-CAF) sales. COVID-19-attributable changes in the level and trend of monthly sales of total antibiotics, azithromycin, and HCQ were estimated, accounting for seasonality and lockdown period where appropriate. A total of 16,290 million doses of antibiotics were sold in India in 2020, which is slightly less than the amount in 2018 and 2019. However, the proportion of non-CAF antibiotics increased from 72.5% (95% CI: 71.8% to 73.1%) in 2019 to 76.8% (95% CI: 76.2% to 77.5%) in 2020. Our ITS analyses estimated that COVID-19 likely contributed to 216.4 million (95% CI: 68.0 to 364.8 million; P = 0.008) excess doses of non-CAF antibiotics and 38.0 million (95% CI: 26.4 to 49.2 million; P < 0.001) excess doses of non-CAF azithromycin (equivalent to a minimum of 6.2 million azithromycin treatment courses) between June and September 2020, i.e., until the peak of the first epidemic wave, after which a negative change in trend was identified. In March 2020, we estimated a COVID-19-attributable change in level of +11.1 million doses (95% CI: 9.2 to 13.0 million; P < 0.001) for HCQ sales, whereas a weak negative change in monthly trend was found for this drug. Study limitations include the lack of coverage of the public healthcare sector, the inability to distinguish antibiotic and HCQ sales in inpatient versus outpatient care, and the suboptimal number of pre- and post-epidemic data points, which could have prevented an accurate adjustment for seasonal trends despite the robustness of our statistical approaches. CONCLUSIONS: A significant increase in non-CAF antibiotic sales, and particularly azithromycin, occurred during the peak phase of the first COVID-19 epidemic wave in India, indicating the need for urgent antibiotic stewardship measures.

Relation of prior statin and anti-hypertensive use to severity of disease among patients hospitalized with COVID-19: Findings from the American Heart Association's COVID-19 Cardiovascular Disease Registry.

BACKGROUND: Statins have anti-inflammatory and immunomodulatory effects that may reduce the severity of coronavirus disease 2019 (COVID-19), in which organ dysfunction is mediated by severe inflammation. Large studies with diverse populations evaluating statin use and outcomes in COVID-19 are lacking. METHODS AND RESULTS: We used data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 US hospitals enrolled in the American Heart Association's COVID-19 Cardiovascular Disease (CVD) Registry to evaluate the associations between statin use and outcomes. Prior to admission, 42% of subjects (n = 4,449) used statins (7% on statins alone, 35% on statins plus anti-hypertensives). Death (or discharge to hospice) occurred in 2,212 subjects (21%). Outpatient use of statins, either alone or with anti-hypertensives, was associated with a reduced risk of death (adjusted odds ratio [aOR] 0.59, 95% CI 0.50-0.69), adjusting for demographic characteristics, insurance status, hospital site, and concurrent medications by logistic regression. In propensity-matched analyses, use of statins and/or anti-hypertensives was associated with a reduced risk of death among those with a history of CVD and/or hypertension (aOR 0.68, 95% CI 0.58-0.81). An observed 16% reduction in odds of death among those without CVD and/or hypertension was not statistically significant. CONCLUSIONS: Patients taking statins prior to hospitalization for COVID-19 had substantially lower odds of death, primarily among individuals with a history of CVD and/or hypertension. These observations support the continuation and aggressive initiation of statin and anti-hypertensive therapies among patients at risk for COVID-19, if these treatments are indicated based upon underlying medical conditions.

Utilization of drugs with reports on potential efficacy or harm on COVID-19 before, during, and after the first pandemic wave.

PURPOSE: Conflicting information on potential benefits of drugs as well as reports on hypothetical harm of commonly used drugs in COVID-19 treatment have challenged clinicians and healthcare systems. We analyzed the change in ambulatory drug utilization before, during, and after the first wave of the pandemic in 2020. METHODS: We explored dispensing data of nearly 19 000 pharmacies at the expense of the statutory health insurance funds covering 88% of Germany's population. We analyzed utilization of publicly discussed drugs with conflicting information. Drug utilization as number of packages dispensed per week from January to June 2020, reflecting 314 million claims, was compared with 2019. RESULTS: Utilization of hydroxychloroquine increased +110% during March 2020 and then slightly decreased until week April 13-19. Renin-angiotensin-aldosterone system inhibitors and simvastatin/atorvastatin increased, +78% and +74%, respectively, and subsequently decreased below 2019 levels. Utilization of azithromycin and all systemic antibiotics decreased continuously from March 2-8 until June to levels considerably lower compared to 2019 (June 22-28: azithromycin: -55%, all systemic antibiotics: -27%). Pneumococcal vaccines utilization initially increased +373%, followed by supply shortages. Paracetamol utilization showed an initial increase of +111%, mainly caused by an increase of over-the-counter dispensings. CONCLUSIONS: Apart from the pandemic itself, the data suggest that dissemination of misinformation and unsound speculations as well as supply shortages influenced drug prescribing, utilization, and purchasing behavior. The findings can inform post-pandemic policy to prevent unfounded over- and underprescribing and off-label use as well as drug shortages during a public health crisis.

Use of volatile agents for sedation in the intensive care unit: A national survey in France.

BACKGROUND: Current intensive care unit (ICU) sedation guidelines recommend strategies using non-benzodiazepine sedatives. This survey was undertaken to explore inhaled ICU sedation practice in France. METHODS: In this national survey, medical directors of French adult ICUs were contacted by phone or email between July and August 2019. ICU medical directors were questioned about the characteristics of their department, their knowledge on inhaled sedation, and practical aspects of inhaled sedation use in their department. RESULTS: Among the 374 ICUs contacted, 187 provided responses (50%). Most ICU directors (73%) knew about the use of inhaled ICU sedation and 21% used inhaled sedation in their unit, mostly with the Anaesthetic Conserving Device (AnaConDa, Sedana Medical). Most respondents had used volatile agents for sedation for <5 years (63%) and in <20 patients per year (75%), with their main indications being: failure of intravenous sedation, severe asthma or bronchial obstruction, and acute respiratory distress syndrome. Sevoflurane and isoflurane were mainly used (88% and 20%, respectively). The main reasons for not using inhaled ICU sedation were: "device not available" (40%), "lack of medical interest" (37%), "lack of familiarity or knowledge about the technique" (35%) and "elevated cost" (21%). Most respondents (80%) were overall satisfied with the use of inhaled sedation. Almost 75% stated that inhaled sedation was a seducing alternative to intravenous sedation. CONCLUSION: This survey highlights the widespread knowledge about inhaled ICU sedation in France but shows its limited use to date. Differences in education and knowledge, as well as the recent and relatively scarce literature on the use of volatile agents in the ICU, might explain the diverse practices that were observed. The low rate of mild adverse effects, as perceived by respondents, and the users' satisfaction, are promising for this potentially important tool for ICU sedation.

Medication utilization in patients in New York hospitals during the COVID-19 pandemic.

PURPOSE: Utilization of hydroxychloroquine, chloroquine, and supportive therapy drugs in hospitals in New York during the early weeks of the coronavirus disease 2019 (COVID-19) pandemic was analyzed. SUMMARY: Drug utilization trends for 7 medications used to treat patients with suspected or confirmed COVID-19 at 47 New York hospitals were identified. The data demonstrated sharp increases in aggregate utilization of hydroxychloroquine and chloroquine and the number of patients receiving either drug beginning on March 15, with a notable 20% median increase per day through March 31. The net quantity of drug charge units per day for midazolam, propofol, ketamine, cisatracurium, and fentanyl also increased during the study period. Following peak utilization, use of all study drugs decreased at different times throughout April 2020. The data were used to provide information to various stakeholders in the drug supply chain during the initial surge of the pandemic. CONCLUSION: This analysis describes the increased use, beginning in mid-March 2020, of hydroxychloroquine, chloroquine, midazolam, propofol, ketamine, cisatracurium, and fentanyl in 47 hospitals in New York State. The increased utilization of supportive therapy drugs was consistent with the surge in patients with presumed or confirmed COVID-19 during the study period. These data and observations can help clinicians, health-system leaders, manufacturers, wholesalers, and policymakers understand the impact of current and future pandemics on the drug supply chain.

The emerging spectrum of COVID-19 neurology: clinical, radiological and laboratory findings.

Preliminary clinical data indicate that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with neurological and neuropsychiatric illness. Responding to this, a weekly virtual coronavirus disease 19 (COVID-19) neurology multi-disciplinary meeting was established at the National Hospital, Queen Square, in early March 2020 in order to discuss and begin to understand neurological presentations in patients with suspected COVID-19-related neurological disorders. Detailed clinical and paraclinical data were collected from cases where the diagnosis of COVID-19 was confirmed through RNA PCR, or where the diagnosis was probable/possible according to World Health Organization criteria. Of 43 patients, 29 were SARS-CoV-2 PCR positive and definite, eight probable and six possible. Five major categories emerged: (i) encephalopathies (n = 10) with delirium/psychosis and no distinct MRI or CSF abnormalities, and with 9/10 making a full or partial recovery with supportive care only; (ii) inflammatory CNS syndromes (n = 12) including encephalitis (n = 2, para- or post-infectious), acute disseminated encephalomyelitis (n = 9), with haemorrhage in five, necrosis in one, and myelitis in two, and isolated myelitis (n = 1). Of these, 10 were treated with corticosteroids, and three of these patients also received intravenous immunoglobulin; one made a full recovery, 10 of 12 made a partial recovery, and one patient died; (iii) ischaemic strokes (n = 8) associated with a pro-thrombotic state (four with pulmonary thromboembolism), one of whom died; (iv) peripheral neurological disorders (n = 8), seven with Guillain-Barré syndrome, one with brachial plexopathy, six of eight making a partial and ongoing recovery; and (v) five patients with miscellaneous central disorders who did not fit these categories. SARS-CoV-2 infection is associated with a wide spectrum of neurological syndromes affecting the whole neuraxis, including the cerebral vasculature and, in some cases, responding to immunotherapies. The high incidence of acute disseminated encephalomyelitis, particularly with haemorrhagic change, is striking. This complication was not related to the severity of the respiratory COVID-19 disease. Early recognition, investigation and management of COVID-19-related neurological disease is challenging. Further clinical, neuroradiological, biomarker and neuropathological studies are essential to determine the underlying pathobiological mechanisms that will guide treatment. Longitudinal follow-up studies will be necessary to ascertain the long-term neurological and neuropsychological consequences of this pandemic.

Comparing actual and forecasted numbers of unique patients dispensed select medications for opioid use disorder, opioid overdose reversal, and mental health, during the COVID-19 pandemic, United States, January 2019 to May 2020.

BACKGROUND: COVID-19 community mitigation measures (e.g., stay-at-home orders) may worsen mental health and substance use-related harms such as opioid use disorder and overdose and limit access to medications for these conditions. We used nationally-representative data to assess dispensing of select substance use and mental health medications during the pandemic in the U.S. METHODS: IQVIA Total Patient Tracker data were used to calculate U.S. monthly numbers of unique patients dispensed buprenorphine, extended-release (ER) intramuscular naltrexone, naloxone, selective serotonin or serotonin-norepinephrine reuptake inhibitors, benzodiazepines, and for comparison, HMG-CoA reductase inhibitors (statins) and angiotensin receptor blockers (ARBs) between January 2019-May 2020. Forecasted estimates of number of unique patients dispensed medications, generated by exponential smoothing statistical forecasting, were compared to actual numbers of patients by month to examine access during mitigation measures (March 2020-May 2020). RESULTS: Between March 2020-May 2020, numbers of unique patients dispensed buprenorphine and numbers dispensed naloxone were within forecasted estimates. Numbers dispensed ER intramuscular naltrexone were significantly below forecasted estimates in March 2020 (-1039; 95 %CI:-1528 to -550), April 2020 (-2139; 95 %CI:-2629 to -1650), and May 2020 (-2498; 95 %CI:-2987 to -2009). Numbers dispensed antidepressants and benzodiazepines were significantly above forecasted estimates in March 2020 (977,063; 95 %CI:351,384 to 1,602,743 and 450,074; 95 % CI:189,999 to 710,149 additional patients, respectively), but were within forecasted estimates in April 2020-May 2020. Dispensing patterns for statins and ARBs were similar to those for antidepressants and benzodiazepines. CONCLUSIONS: Ongoing concerns about the impact of the COVID-19 pandemic on substance use and mental health underscore the need for innovative strategies to facilitate continued access to treatment.

Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) Cohort Study.

Among 2,186 U.S. adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. Although observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through inclusive prospective controlled trials. SIGNIFICANCE: Evaluating the potential role of COVID-19 treatments in patients with cancer in a large observational study, there was no statistically significant 30-day all-cause mortality benefit with hydroxychloroquine or high-dose corticosteroids alone or in combination; remdesivir showed potential benefit. Treatment receipt reflects clinical decision-making and suggests disparities in medication access.This article is highlighted in the In This Issue feature, p. 1426.

Clinical presentations, laboratory and radiological findings, and treatments for 11,028 COVID-19 patients: a systematic review and meta-analysis.

This systematic review and meta-analysis investigated the comorbidities, symptoms, clinical characteristics and treatment of COVID-19 patients. Epidemiological studies published in 2020 (from January-March) on the clinical presentation, laboratory findings and treatments of COVID-19 patients were identified from PubMed/MEDLINE and Embase databases. Studies published in English by 27th March, 2020 with original data were included. Primary outcomes included comorbidities of COVID-19 patients, their symptoms presented on hospital admission, laboratory results, radiological outcomes, and pharmacological and in-patient treatments. 76 studies were included in this meta-analysis, accounting for a total of 11,028 COVID-19 patients in multiple countries. A random-effects model was used to aggregate estimates across eligible studies and produce meta-analytic estimates. The most common comorbidities were hypertension (18.1%, 95% CI 15.4-20.8%). The most frequently identified symptoms were fever (72.4%, 95% CI 67.2-77.7%) and cough (55.5%, 95% CI 50.7-60.3%). For pharmacological treatment, 63.9% (95% CI 52.5-75.3%), 62.4% (95% CI 47.9-76.8%) and 29.7% (95% CI 21.8-37.6%) of patients were given antibiotics, antiviral, and corticosteroid, respectively. Notably, 62.6% (95% CI 39.9-85.4%) and 20.2% (95% CI 14.6-25.9%) of in-patients received oxygen therapy and non-invasive mechanical ventilation, respectively. This meta-analysis informed healthcare providers about the timely status of characteristics and treatments of COVID-19 patients across different countries.PROSPERO Registration Number: CRD42020176589.

Antibiotic Consumption and Stewardship at a Hospital outside of an Early Coronavirus Disease 2019 Epicenter.

There are scant data on the impact of coronavirus disease 2019 (COVID-19) on hospital antibiotic consumption, and no data from outside epicenters. At our nonepicenter hospital, antibiotic days of therapy (DOT) and bed days of care (BDOC) were reduced by 151.5/month and 285/month, respectively, for March to June 2020 compared to 2018-2019 (P = 0.001 and P < 0.001). DOT per 1,000 BDOC was increased (8.1/month; P = 0.001). COVID-19 will impact antibiotic consumption, stewardship, and resistance in ways that will likely differ temporally and by region.

The first wave of COVID-19 in Malta; a national cross-sectional study.

INTRODUCTION: The COVID-19 pandemic has posed major challenges to all aspects of healthcare. Malta's population density, large proportion of elderly and high prevalence of diabetes and obesity put the country at risk of uncontrolled viral transmission and high mortality. Despite this, Malta achieved low mortality rates compared to figures overseas. The aim of this paper is to identify key factors that contributed to these favorable outcomes. METHODS: This is a retrospective, observational, nationwide study which evaluates outcomes of patients during the first wave of the pandemic in Malta, from the 7th of March to the 24th of April 2020. Data was collected on demographics and mode of transmission. Hospitalization rates to Malta's main general hospital, Mater Dei Hospital, length of in-hospital stay, intensive care unit admissions and 30-day mortality were also analyzed. RESULTS: There were 447 confirmed cases in total; 19.5% imported, 74.2% related to community transmission and 6.3% nosocomially transmitted. Ninety-three patients (20.8%) were hospitalized, of which 4 were children. Patients with moderate-severe disease received hydroxychloroquine and azithromycin, in line with evidence available at the time. A total of 4 deaths were recorded, resulting in an all-cause mortality of 0.89%. Importantly, all admitted patients with moderate-severe disease survived to 30-day follow up. CONCLUSION: Effective public health interventions, widespread testing, remote surveillance of patients in the community and a low threshold for admission are likely to have contributed to these favorable outcomes. Hospital infection control measures were key in preventing significant nosocomial spread. These concepts can potentially be applied to stem future outbreaks of viral diseases. Patients with moderate-severe disease had excellent outcomes with no deaths reported at 30-day follow up.

Impact of multiplex respiratory virus testing on antimicrobial consumption in adults in acute care: a randomized clinical trial.

OBJECTIVES: Inappropriate use of antibiotics is associated with development of antimicrobial resistance. In respiratory infections it is often difficult to differentiate between viral and bacterial infections, and empirical treatment is common. Enhanced viral testing is expected to clarify clinical decision-making and reduce the prescription of antibacterial agents, but the impact of such information on patient care is unclear. METHODS: We conducted a (1:1) randomized controlled clinical trial involving 998 adults with respiratory symptoms, fever, chest pain or poor general condition in the emergency unit of a tertiary hospital. Multiplex PCR results for 496 patients were available in 24 hours (intervention group) and those for the remaining 502 patients were available in 7 days (control group). Our primary outcome measures were the duration of hospitalization and the consumption of antibiotics within 30 days of enrolment. RESULTS: In all, 841 of 998 (84%) patients had respiratory symptoms at study entry. A respiratory virus was detected in 175 (17.5%). The mean duration of hospitalization was 4.2 days (SD 5.4) in the intervention group and 4.1 days (SD 4.9) in the control group (difference 0.1, 95% CI -0.5 to 0.6, p 0.810). The mean days on antibiotics were 11.3 days (SD 12.6) in the intervention group and 10.4 days (SD 11.4) in the control group (difference 0.9, 95% CI -0.6 to 2.4, p 0.235). CONCLUSIONS: Multiplex PCR testing for respiratory viruses with results available within 24 hours did not reduce the consumption of bacterial antibiotics or the length of hospital stay in adults presenting with respiratory symptoms, fever, chest pain or reduced general condition in acute care.