SeptiCyte® RAPID is a gene expression assay measuring the relative expression levels of host response genes PLA2G7 and PLAC8, indicative of a dysregulated immune response during sepsis. As severe forms of COVID-19 may be considered viral sepsis, we evaluated SeptiCyte RAPID in a series of 94 patients admitted to Foch Hospital (Suresnes, France) with proven SARS-CoV-2 infection. EDTA blood was collected in the emergency department (ED) in 67 cases, in the intensive care unit (ICU) in 23 cases and in conventional units in 4 cases. SeptiScore (0–15 scale) increased with COVID-19 severity. Patients in ICU had the highest SeptiScores, producing values comparable to 8 patients with culture-confirmed bacterial sepsis. Receiver operating characteristic (ROC) curve analysis had an area under the curve (AUC) of 0.81 for discriminating patients requiring ICU admission from patients who were immediately discharged or from patients requiring hospitalization in conventional units. SeptiScores increased with the extent of the lung injury. For 68 patients, a chest computed tomography (CT) scan was performed within 24 h of COVID-19 diagnosis. SeptiScore >7 suggested lung injury ≥50% (AUC = 0.86). SeptiCyte RAPID was compared to other biomarkers for discriminating Critical + Severe COVID-19 in ICU, versus Moderate + Mild COVID-19 not in ICU. The mean AUC for SeptiCyte RAPID was superior to that of any individual biomarker or combination thereof. In contrast to C-reactive protein (CRP), correlation of SeptiScore with lung injury was not impacted by treatment with anti-inflammatory agents. SeptiCyte RAPID can be a useful tool to identify patients with severe forms of COVID-19 in ED, as well as during follow-up.
Objectives To identify the genetic change responsible for resistance to penicillins, extended-spectrum cephalosporins (ESCs), aminoglycosides and ciprofloxacin in a Serratia marcescens clinical isolate recovered from a pancreatic abscess 6 weeks after a WT strain was isolated from the same patient. The impact on the fitness was also assessed. Methods The genomes of both S. marcescens isolates were sequenced using Illumina technology, assembled, annotated and compared with each other. PCR amplification followed by Sanger sequencing was carried out to confirm the mutation. Complementation of the resistant isolate with a recombinant plasmid harbouring the WT gene was performed. The growth rates were measured for both isolates in LB medium. Results Comparative genomic analysis disclosed only one frameshift mutation (690delG) in the cpxA gene, which codes for the histidine kinase of a two-component system (TCS). This change introduced a premature termination codon, leading to the truncated CpxA_HatR variant that contained 234 amino acids instead of 464. Complementation, which consisted of transfer of the WT cpxA into the resistant S. marcescens derivative, restored completely its susceptibility to ESCs, aminoglycosides and ciprofloxacin, thus confirming the contribution of the CpxA_HatR variant to resistance. Growth analysis showed that the fitness of the resistant isolate was unchanged. Conclusions This study shows for the first time that constitutive activation of the Cpx pathway can per se confer resistance to ESCs and ciprofloxacin, in addition to the aminoglycoside resistance usually described. It sheds new light on the role of altered TCSs in fostering bacterial survival.
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