A new SARS-CoV-2 variant with high lethality poorly detected by RT-PCR on nasopharyngeal samples: an observational study.

OBJECTIVES: In early January 2021 an outbreak of nosocomial cases of coronavirus disease 2019 (COVID-19) emerged in Western France; RT-PCR tests were repeatedly negative on nasopharyngeal samples but positive on lower respiratory tract samples. Whole-genome sequencing (WGS) revealed a new variant, currently defining a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.616. In March, the WHO classified this as a 'variant under investigation' (VUI). We analysed the characteristics and outcomes of COVID-19 cases related to this new variant. METHODS: Clinical, virological, and radiological data were retrospectively collected from medical charts in the two hospitals involved. We enrolled those inpatients with: (a) positive SARS-CoV-2 RT-PCR on a respiratory sample, (b) seroconversion with anti-SARS-CoV-2 IgG/IgM, or (c) suggestive symptoms and typical features of COVID-19 on a chest CT scan. Cases were categorized as B.1.616, a variant of concern (VOC), or unknown. RESULTS: From 1st January to 24th March 2021, 114 patients fulfilled the inclusion criteria: B.1.616 (n = 39), VOC (n = 32), and unknown (n = 43). B.1.616-related cases were older than VOC-related cases (81 years, interquartile range (IQR) 73-88 versus 73 years, IQR 67-82, p < 0.05) and their first RT-PCR tests were rarely positive (6/39, 15% versus 31/32, 97%, p < 0.05). The B.1.616 variant was independently associated with severe disease (multivariable Cox model HR 4.0, 95%CI 1.5-10.9) and increased lethality (28-day mortality 18/39 (46%) for B.1.616 versus 5/32 (16%) for VOC, p = 0.006). CONCLUSION: We report a nosocomial outbreak of COVID-19 cases related to a new variant, B.1.616, which is poorly detected by RT-PCR on nasopharyngeal samples and is associated with high lethality.

In vitro bactericidal activity of amoxicillin combined with different cephalosporins against endocarditis-associated Enterococcus faecalis clinical isolates.

BACKGROUND: The combination of amoxicillin with cefazolin could be an interesting regimen for the empirical therapy of severe infective endocarditis, but its activity against enterococci is unknown. OBJECTIVES: To evaluate in vitro the bactericidal activity of the combination of amoxicillin with different cephalosporins including cefazolin. METHODS: Combinations of amoxicillin (at MIC×») with cefazolin, cefotaxime, ceftriaxone, cefepime, ceftaroline or ceftobiprole (at the mean free plasma concentration) were studied using time-kill experiments for 10 endocarditis-associated Enterococcus faecalis strains and 2 reference strains. RESULTS: The combinations amoxicillin/cefazolin, amoxicillin/cefotaxime, amoxicillin/ceftriaxone and amoxicillin/cefepime were synergistic at 12 and 24 h against 12/12 strains and amoxicillin/ceftobiprole and amoxicillin/ceftaroline against 10/12 strains. The combination amoxicillin/cefepime was bactericidal at 24 h against 9/12 strains, the combination amoxicillin/cefazolin against 8/12 strains, the combinations amoxicillin/ceftaroline, amoxicillin/cefotaxime and amoxicillin/ceftobiprole against 7/12 strains and the combination amoxicillin/ceftriaxone against 6/12 strains. CONCLUSIONS: The combination amoxicillin/cefazolin is as synergistic and bactericidal in vitro as amoxicillin/cefotaxime or amoxicillin/ceftriaxone against E. faecalis.