Disinfection and decontamination in the context of SARS-CoV-2-specific data.

Given the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as witnessed early in the coronavirus disease 2019 (COVID-19) pandemic, concerns arose with the existing methods for virus disinfection and decontamination. The need for SARS-CoV-2-specific data stimulated considerable research in this regard. Overall, SARS-CoV-2 is practically and equally susceptible to approaches for disinfection and decontamination that have been previously found for other human or animal coronaviruses. The latter have included techniques utilizing temperature modulation, pH extremes, irradiation, and chemical treatments. These physicochemical methods are a necessary adjunct to other prevention strategies, given the environmental and patient surface ubiquity of the virus. Classic studies of disinfection have also allowed for extrapolation to the eradication of the virus on human mucosal surfaces by some chemical means. Despite considerable laboratory study, practical field assessments are generally lacking and need to be encouraged to confirm the correlation of interventions with viral eradication and infection prevention. Transparency in the constitution and use of any method or chemical is also essential to furthering practical applications.

Non-primate animal models for pertussis: back to the drawing board?

Despite considerable progress in the understanding of clinical pertussis, the contemporary emergence of antimicrobial resistance for Bordetella pertussis and an evolution of concerns with acellular component vaccination have both sparked a renewed interest. Although simian models of infection best correlate with the observed attributes of human infection, several animal models have been used for decades and have positively contributed in many ways to the related science. Nevertheless, there is yet the lack of a reliable small animal model system that mimics the combination of infection genesis, variable upper and lower respiratory infection, systemic effects, infection resolution, and vaccine responses. This narrative review examines the history and attributes of non-primate animal models for pertussis and places context with the current use and needs. Emerging from the latter is the necessity for further such study to better create the optimal model of infection and vaccination with use of current molecular tools and a broader range of animal systems. KEY POINTS: • Currently used and past non-primate animal models of B. pertussis infection often have unique and focused applications. • A non-primate animal model that consistently mimics human pertussis for the majority of key infection characteristics is lacking. • There remains ample opportunity for an improved non-primate animal model of pertussis with the use of current molecular biology tools and with further exploration of species not previously considered.

In pursuit of the right tail for the COVID-19 incubation period.

Definition of the incubation period for COVID-19 is critical for implementing quarantine and thus infection control. Whereas the classical definition relies on the time from exposure to time of first symptoms, a more practical working definition is the time from exposure to time of first live virus excretion. For COVID-19, average incubation period times commonly span 5-7 days which are generally longer than for most typical other respiratory viruses. There is considerable variability reported however for the late right-hand statistical distribution. A small but yet epidemiologically important subset of patients may have the late end of the incubation period extend beyond the 14 days that is frequently assumed. Conservative assumptions of the right tail end distribution favor safety, but pragmatic working modifications may be required to accommodate high rates of infection and/or healthcare worker exposures. Despite the advent of effective vaccines, further attention and study in these regards are warranted. It is predictable that vaccine application will be associated with continued confusion over protection and its longevity. Measures for the application of infectivity will continue to be extremely relevant.

Environmental and decontamination issues for human coronaviruses and their potential surrogates.

Pandemic coronavirus disease-2019 (COVID-19) gives ample reason to generally review coronavirus (CoV) containment. For establishing some preliminary views on decontamination and disinfection, surrogate CoVs have commonly been assessed. This review serves to examine the existing science in regard to CoV containment generically and then to translate these findings into timely applications for COVID-19. There is widespread dissemination of CoVs in the immediate patient environment, and CoVs can potentially be spread via respiratory secretions, urine, and stool. Interpretations of the spread however must consider whether studies examine for viral RNA, virus viability by culture, or both. Presymptomatic, asymptomatic, and post-14 day virus excretion from patients may complicate the epidemiology. Whereas droplet spread is accepted, there continues to be controversy over the extent of possible airborne spread and especially now for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). CoVs are stable in body secretions and sewage at reduced temperatures. In addition to temperature, dryness or relative humidity, initial viral burden, concomitant presence of bioburden, and the type of surface can all affect stability. Generalizing, CoVs can be susceptible to radiation, temperature extremes, pH extremes, peroxides, halogens, aldehydes, many solvents, and several alcohols. Whereas detergent surfactants can have some direct activity, these agents are better used as complements to a complex disinfectant solution. Disinfectants with multiple agents and adverse pH are more likely to be best active at higher water temperatures. Real-life assessments should be encouraged with working dilutions. The use of decontamination and disinfection should be balanced with considerations of patient and caregiver safety. Processes should also be balanced with considerations for other potential pathogens that must be targeted. Given some CoV differences and given that surrogate testing provides experimental correlates at best, direct assessments with SARS-CoV, Middle East respiratory syndrome-related coronavirus (MERS-CoV), and SARS-CoV-2 are required.

Features of enteric disease from human coronaviruses: Implications for COVID-19.

Coronaviruses have long been studied in both human and veterinary fields. Whereas the initial detection of endemic human respiratory coronaviruses was problematic, detection of these and newly discovered human coronaviruses has been greatly facilitated with major advances in the laboratory. Nevertheless, technological factors can affect the accuracy and timeliness of virus detection. Many human coronaviruses can be variably found in stool samples. All human coronaviruses have been variably associated with symptoms of gastroenteritis. Coronaviruses can occasionally be cultured from enteric specimens, but most detection is accomplished with genetic amplification technologies. Excretion of viral RNA in stool can extend for a prolonged period. Culture-positive stool samples have been found to exceed a fourteen day period after onset of infection for some coronaviruses. Virus can also sometimes be cultured from patients' respiratory samples during the late incubation period. Relatively asymptomatic patients may excrete virus. Both viable and nonviable virus can be found in the immediate environment of the patient, the health care worker, and less often the public. These lessons from the past study of animal and human coronaviruses can be extended to presumptions for severe acute respiratory syndrome coronavirus 2. Already, the early reports from the coronavirus disease-2019 pandemic are confirming some concerns. These data have the cumulative potential to cause us to rethink some current and common public health and infection control strategies.

Does oral vancomycin use necessitate therapeutic drug monitoring?

PURPOSE: Oral vancomycin use has generally increased as a consequence of the need to treat and/or prevent Clostridium (Clostridiodes) difficile-associated disease (CDAD). This review examines the cumulative scientific evidence that guides therapeutic monitoring of oral vancomycin therapy. METHODS: The existing publications were reviewed from the time of the drug's inception to July 2019. This review utilized access as available in PubMed, EMBASE, CINAHL Plus, and the Cochrane Library. RESULTS: Case reports and small patient series have documented anecdotal-associated elevations in serum levels. Correlation of absorbed vancomycin with subsequent toxicity is difficult to determine, but serum levels approaching those obtained after parenteral administration have raised concern. Prolonged usage and total dosing over 500 mg/day among adult age ranges have been associated with accumulation. In addition, risk factors for vancomycin accumulation systemically after oral dosing include renal compromise, combined oral and other enteral therapy, severe CDAD, other intercurrent bowel inflammation, polypharmacy, and increased patient complexity/morbidity. CONCLUSION: Until systemic toxicity from oral vancomycin absorption is better understood, individual considerations should be made for therapeutic serum monitoring during oral vancomycin treatment. Therapeutic drug monitoring is suggested for several high-risk situations in which high blood levels may be anticipated.

Neuropsychiatric Adverse Events from Topical Ophthalmic Timolol.

Timolol is a commonly-used topical antiglaucoma medication and has proven to be highly efficacious for most recipients. Among the reported adverse events, the neuropsychiatric spectrum has been cited, albeit for a small proportion of those treated. This review summarizes the cumulative published experience of such side effects and assesses the quality of evidence. As for other beta-blockers, whether orally or topically administered, various central nervous systems dysfunctions have been detailed in either case reports or larger patient series. The adverse event commonly resolves following drug termination. Rigorous and more definitive studies of causation are lacking, and to some, such paucity has reduced the belief of a cause and effect relationship. Until otherwise proven, deference should be afforded to the potential for topical timolol to cause neuropsychiatric side effects, and at-risk patients should be closely monitored when they are prescribed this pharmacological agent.