Building-level wastewater surveillance of SARS-CoV-2 is associated with transmission and variant trends in a university setting.

The University of South Carolina (UofSC) was among the first universities to include building-level wastewater surveillance of SARS-CoV-2 to complement clinical testing during its reopening in the Fall 2020 semester. In the Spring 2021 semester, 24h composite wastewater samples were collected twice per week from 10 residence halls and the on-campus student isolation and quarantine building. The isolation and quarantine building served as a positive control site. The wastewater was analyzed using RT-ddPCR for the quantification of nucleocapsid genes (N1 and N2) to identify viral transmission trends within residence halls. Log10 SARS-CoV-2 RNA concentrations were compared to both new clinical cases identified in the days following wastewater collection and recovered cases returning to sites during the days preceding sample collection to test temporal and spatial associations. There was a statistically significant positive relationship between the number of cases reported from the sites during the seven-day period following wastewater sampling and the log10 viral RNA copies/L (overall IRR 1.08 (1.02, 1.16) p-value 0.0126). Additionally, a statistically significant positive relationship was identified between the number of cases returning to the residence halls after completing isolation during the seven-day period preceding wastewater sampling and the log10 viral RNA copies/L (overall 1.09 (1.01, 1.17) p-value 0.0222). The statistical significance of both identified cases and recovered return cases on log10 viral RNA copies/L in wastewater indicates the importance of including both types of clinical data in wastewater-based epidemiology (WBE) research. Genetic mutations associated with variants of concern (VOCs) were also monitored. The emergence of the Alpha variant on campus was identified, which contributed to the second wave of COVID-19 cases at UofSC. The study was able to identify sub-community transmission hotspots for targeted intervention in real-time, making WBE cost-effective and creating less of a burden on the general public compared to repeated individual testing methods.

Safety analysis of fidaxomicin in comparison with oral vancomycin for Clostridium difficile infections.

Fidaxomicin is a novel macrocyclic antibiotic recently approved by the US Food and Drug Administration for the treatment of Clostridium difficile-associated diarrhea in adults. We reviewed safety data from nonclinical studies and clinical trials (phases 1, 2A, and 3) with fidaxomicin. In nonclinical studies, fidaxomicin was administered orally at approximately 1 g/kg/d to dogs for up to 3 months with no significant target-organ toxicities observed. A total of 728 adults have received oral fidaxomicin in clinical trials to date: 116 healthy volunteers and 612 patients with C. difficile infection. In phase 3 clinical trials, fidaxomicin was well tolerated, with a safety profile comparable with oral vancomycin. There were no differences in the incidence of death or serious adverse events between the 2 drugs. Fidaxomicin appears to be well tolerated. Continued monitoring of adverse events in the postmarketing setting will provide additional information about the full safety profile of fidaxomicin.

Wastewater surveillance of SARS-CoV-2 mutational profiles at a university and its surrounding community reveals a 20G outbreak on campus.

Wastewater surveillance of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been leveraged during the Coronavirus Disease 2019 (COVID-19) pandemic as a public health tool at the community and building level. In this study, we compare the sequence diversity of SARS-CoV-2 amplified from wastewater influent to the Columbia, South Carolina, metropolitan wastewater treatment plant (WWTP) and the University of South Carolina campus during September 2020, which represents the peak of COVID-19 cases at the university during 2020. A total of 92 unique mutations were detected across all WWTP influent and campus samples, with the highest frequency mutations corresponding to the SARS-CoV-2 20C and 20G clades. Signature mutations for the 20G clade dominated SARS-CoV-2 sequences amplified from localized wastewater samples collected at the University of South Carolina, suggesting that the peak in COVID-19 cases during early September 2020 was caused by an outbreak of the 20G lineage. Thirteen mutations were shared between the university building-level wastewater samples and the WWTP influent collected in September 2020, 62% of which were nonsynonymous substitutions. Co-occurrence of mutations was used as a similarity metric to compare wastewater samples. Three pairs of mutations co-occurred in university wastewater and WWTP influent during September 2020. Thirty percent of the detected mutations, including 12 pairs of concurrent mutations, were only detected in university samples. This report affirms the close relationship between the prevalent SARS-CoV-2 genotypes of the student population at a university campus and those of the surrounding community. However, this study also suggests that wastewater surveillance at the building-level at a university offers important insight by capturing sequence diversity that was not apparent in the WWTP influent, thus offering a balance between the community-level wastewater and clinical sequencing.

Template protocol for clinical trials investigating vaccines--focus on safety elements.

This document is intended as a guide to the protocol development for trials of prophylactic vaccines. The template may serve phases I-IV clinical trials protocol development to include safety relevant information as required by the regulatory authorities and as deemed useful by the investigators. This document may also be helpful for future site strengthening efforts.

Pharmacy compounding primer for physicians: prescriber beware.

Since the development of federal standards for drug approval, the practice of medicine has historically involved the compounding of medications based on a physician's determination that a US FDA-approved product either did not exist, or could not be used for medical reasons. Today, prescriptions for non-FDA-approved compounded drugs may be driven by fanciful and largely unregulated pharmacy advertisements to physicians and patients and/or payer reimbursement policies, thus placing prescribers in the backseat for clinical decision making. This article outlines essential differences between FDA-approved drugs and compounded drugs and reasserts the primary medical role of physicians for determining what medical circumstances may necessitate treatment with non-FDA-approved products. In addition, liability concerns when prescribing non-FDA-approved drugs are discussed. While representing a US perspective, underlying principles apply globally in the setting of magistral and extemporaneous formulations produced outside national regulatory frameworks.