Due to the rapid spread of coronavirus disease 2019 (COVID-19), there is an increasing shortage of protective gear necessary to keep health care providers safe from infection. As of 9 April 2020, the CDC reported 9,282 cumulative cases of COVID-19 among U.S. health care workers (CDC COVID-19 Response Team, MMWR Morb Mortal Wkly Rep 69:477–481, 2020, https://doi.org/10.15585/mmwr.mm6915e6). N95 respirators are recommended by the CDC as the ideal method of protection from COVID-19. Although N95 respirators are traditionally single use, the shortages have necessitated the need for reuse. Effective methods of N95 decontamination that do not affect the fit or filtration ability of N95 respirators are essential. Numerous methods of N95 decontamination exist; however, none are universally accessible. In this study, we describe an effective, standardized, and reproducible means of decontaminating N95 respirators using widely available materials. The N95 decontamination method described in this work will provide a valuable resource for hospitals, health care centers, and outpatient practices that are experiencing increasing shortages of N95 respirators due to the COVID-19 pandemic.
1The SARS-CoV-2 pandemic has caused a severe, international shortage of N95 2 respirators, which are essential to protect healthcare providers from infection. Given the 3 contemporary limitations of the supply chain, it is imperative to identify effective means 4 of decontaminating, reusing, and thereby conserving N95 respirator stockpiles. To be 5 effective, decontamination must result in sterilization of the N95 respirator without 6 impairment of respirator filtration or user fit. Although numerous methods of N95 7 decontamination exist, none are universally accessible. In this work we describe a 8 microwave-generated steam decontamination protocol for N95 respirators for use in 9 healthcare systems of all sizes, geographies, and means. Using widely available glass 10 containers, mesh from commercial produce bags, a rubber band, and a 1100W 11 commercially available microwave, we constructed an effective, standardized, and 12 reproducible means of decontaminating N95 respirators. Employing this methodology 13 against MS2 phage, a highly conservative surrogate for SARS-CoV-2 contamination, we 14 report an average 6-log 10 plaque forming unit (PFU) (99.9999%) and a minimum 5-log 10 15 PFU (99.999%) reduction after a single three-minute microwave treatment. Notably, 16 quantified respirator fit and function were preserved, even after 20 sequential cycles of 17 microwave steam decontamination. This method provides a valuable means of effective 18 decontamination and reuse of N95 respirators by frontline providers facing urgent need. 19
The streptothricin natural product mixture (also known as nourseothricin) was discovered in the early 1940s, generating intense initial interest because of excellent gram-negative activity. Here, we establish the activity spectrum of nourseothricin and its main components, streptothricin F (S-F, 1 lysine) and streptothricin D (S-D, 3 lysines), purified to homogeneity, against highly drug-resistant, carbapenem-resistant Enterobacterales (CRE) and Acinetobacter baumannii. For CRE, the MIC50 and MIC90 for S-F and S-D were 2 and 4 μM, and 0.25 and 0.5 μM, respectively. S-F and nourseothricin showed rapid, bactericidal activity. S-F and S-D both showed approximately 40-fold greater selectivity for prokaryotic than eukaryotic ribosomes in in vitro translation assays. In vivo, delayed renal toxicity occurred at >10-fold higher doses of S-F compared with S-D. Substantial treatment effect of S-F in the murine thigh model was observed against the otherwise pandrug-resistant, NDM-1-expressing Klebsiella pneumoniae Nevada strain with minimal or no toxicity. Cryo-EM characterization of S-F bound to the A. baumannii 70S ribosome defines extensive hydrogen bonding of the S-F steptolidine moiety, as a guanine mimetic, to the 16S rRNA C1054 nucleobase (Escherichia coli numbering) in helix 34, and the carbamoylated gulosamine moiety of S-F with A1196, explaining the high-level resistance conferred by corresponding mutations at the residues identified in single rrn operon E. coli. Structural analysis suggests that S-F probes the A-decoding site, which potentially may account for its miscoding activity. Based on unique and promising activity, we suggest that the streptothricin scaffold deserves further preclinical exploration as a potential therapeutic for drug-resistant, gram-negative pathogens.
Pathogen inactivation is a strategy to enhance the safety of transfused blood products. We identify the compound, amotosalen, widely used for pathogen inactivation, as a bacterial multidrug efflux substrate.
Recent work indicates that heightened nasal innate immunity in children may impact SARS-CoV-2 pathogenesis. Here, we identified drivers of nasal innate immune activation in children using cytokine profiling and multiplex pathogen detection in 291 pediatric nasopharyngeal samples from the 2022 Omicron surge. Nasal viruses and bacterial pathobionts were highly prevalent, especially in younger children (81% of symptomatic and 37% asymptomatic children overall; 91% and 62% in subjects <5 yrs). For SARS-CoV-2, viral load was highest in young children, and viral load in single infections or combined viral loads in coinfections best predicted nasal CXCL10, a biomarker of the mucosal interferon response. Bacterial pathobionts correlated with high nasal IL-1 beta and TNF, but not CXCL10, and viral-bacterial coinfections showed a combined immunophenotype. These findings reveal virus and bacteria as drivers of heightened nasal innate immunity in children and suggest that frequent host-pathogen interactions shape responses to respiratory viruses in this age group
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