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BACKGROUND: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe disease with increased morbidity and mortality among certain risk groups. The presence of autoantibodies against type I interferons (aIFN-Abs) is one mechanism that contributes to severe coronavirus disease 2019 (COVID-19). METHODS: This study aimed to investigate the presence of aIFN-Abs in relation to the soluble proteome, circulating immune cell numbers, and cellular phenotypes, as well as development of adaptive immunity. RESULTS: aIFN-Abs were more prevalent in critical compared to severe COVID-19 but largely absent in the other viral and bacterial infections studied here. The antibody and T-cell response to SARS-CoV-2 remained largely unaffected by the presence aIFN-Abs. Similarly, the inflammatory response in COVID-19 was comparable in individuals with and without aIFN-Abs. Instead, presence of aIFN-Abs had an impact on cellular immune system composition and skewing of cellular immune pathways. CONCLUSIONS: Our data suggest that aIFN-Abs do not significantly influence development of adaptive immunity but covary with alterations in immune cell numbers.
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EUCAST rapid antimicrobial susceptibility testing (RAST) provides antibiotic susceptibility results after 4 to 8 h of incubation. This study assessed the diagnostic performance and clinical usefulness of EUCAST RAST after 4 h. This was a retrospective clinical study performed on blood cultures with Escherichia coli and Klebsiella pneumoniae complex (K. pneumoniae and Klebsiella variicola) at Karolinska University Laboratory (Stockholm, Sweden). The rate of categorized RAST results and the categorical agreement (CA) of RAST with the standard EUCAST 16-to-20-h disk diffusion (DD) method for piperacillin-tazobactam, cefotaxime, ceftazidime, meropenem, and ciprofloxacin were analyzed, as well as the utility of RAST for adjusting the empirical antibiotic therapy (EAT) and the combination of RAST with a lateral flow assay (LFA) for extended-spectrum ß-lactamase (ESBL) detection. A total of 530 E. coli and 112 K. pneumoniae complex strains were analyzed, generating 2,641 and 558 readable RAST zones, respectively. RAST results categorized according to antimicrobial sensitivity/resistance (S/R) were obtained for 83.1% (2,194/2,641) and 87.5% (488/558) of E. coli and K. pneumoniae complex strains, respectively. The RAST result categorization to S/R for piperacillin-tazobactam was poor (37.2% for E. coli and 66.1% for K. pneumoniae complex). CA with the standard DD method was over 97% for all tested antibiotics. Using RAST, we detected 15/26 and 1/10 of the E. coli and K. pneumoniae complex strains that were resistant to the EAT. For patients treated with cefotaxime, RAST was used to detect 13/14 cefotaxime-resistant E. coli strains and 1/1 cefotaxime-resistant K. pneumoniae complex strain. ESBL positivity was reported the same day as blood culture positivity with RAST and LFA. EUCAST RAST provides accurate and clinically relevant susceptibility results after 4 h of incubation and can accelerate the assessment of resistance patterns. IMPORTANCE Early effective antimicrobial treatment has been shown to be crucial for improving the outcome of bloodstream infections (BSI) and sepsis. In combination with the rise of antibiotic resistance, this calls for accelerated methods for antibiotic susceptibility testing (AST) for effective treatment of BSI. This study assesses EUCAST RAST, an AST method that yields results in 4, 6, or 8 h after blood culture positivity. We analyzed a high number of clinical samples of Escherichia coli and Klebsiella pneumoniae complex strains and confirm that the method delivers reliable results after 4 h of incubation for the relevant antibiotics for treating E. coli and K. pneumoniae complex bacteremia. Furthermore, we conclude that it is an important tool for antibiotic treatment decision-making and early detection of ESBL-producing isolates.
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The performance of blood cultures (BCs) relies on optimal sampling. Sepsis guidelines do not specify which sampling protocol to use but recommend two sets of BC bottles, each set containing one aerobic and one anaerobic bottle. For the single-site sampling (SSS) protocol, only one venipuncture is performed for all four bottles. The predominating multisite sampling (MSS) protocol implies that BC bottles are collected from two separate venipuncture sites. The aim of this study was to compare SSS and MSS. Primary outcomes were number of BC sets collected, sample volume, and diagnostic performance. This was a retrospective clinical study comparing BC results in an emergency department before and after changing the sampling protocol to SSS from MSS. All BC samples were incubated in the BacT/Alert BC system. The analysis included 5,248 patients before and 5,364 patients after the implementation of SSS. There was a significantly higher proportion of positive BCs sampled with SSS compared with MSS, 1,049/5,364 (19.56%) and 932/5,248 (17.76%), respectively (P = 0.018). This difference was due to a higher proportion of solitary BC sets (two BC bottles) in MSS. Analyzing only patients with the recommended four BC bottles, there was no difference in positivity. SSS had a higher proportion of BC bottles with the recommended sample volumes of 8-12 ml than MSS (P < 0.001). Changing the sampling protocol to SSS from MSS resulted in higher positivity rates, higher sample volume and fewer solitary BC sets. These advantages of SSS should be considered in future sepsis guidelines.
