Uhlemann, Anne‐Catrin

Introduction: Sarcopenia, characterized by loss of muscle mass and function, is prevalent in heart failure (HF) and associated with poor outcomes. We investigated alterations in sarcopenia index (SI), a surrogate marker of skeletal muscle mass, in HF, left ventricular assist device (LVAD) and heart transplant (HT) and assessed its relationship with inflammation and digestive tract (gut and oral) microbiota. Hypothesis: Sarcopenia will be associated with increased inflammation, dysbiotic microbial signatures, higher HF class, and earlier time post-HT or post LVAD. Methods: We enrolled 460 HF, LVAD and HT patients. Repeated measures pre and post procedures were obtained in a subset of LVAD and HT patients. Sarcopenia index (serum Creatinine/Cystatin C) and inflammatory biomarkers (C-reactive protein, interleukin-6, tumor necrosis factor-alpha) were measured in 271 and 622 blood samples, respectively. Gut and saliva microbiota were assessed via 16S rRNA sequencing among 335 stool and 341 saliva samples. Multivariable regression models were used to assess the relationship between SI and i) New York Heart Association class; ii) pre- vs. post-LVAD or HT; iii) biomarkers of inflammation and microbial diversity. Results: Median (interquartile range) ln-SI was -0.13(-0.32,0.05). Ln-SI decreased across worsening HF class, further declined within the 1-month after LVAD and HT and rebounded over time to the levels of symptomatic HF. Ln-SI demonstrated an inverse correlation with inflammation (r=-0.28, p<0.0001), and a positive correlation with gut (r=0.26, p<0.0001) and oral microbial diversity (r=0.24, p<0.0001). Presence of the gut taxa Roseburia inulinivorans was associated with increased SI. Conclusions: SI levels decreased in symptomatic HF and remained decreased long-term after LVAD and HT. SI levels covaried with inflammation, gut and oral microbiota in a similar fashion.

Plasmid-mediated colistin resistance (PMCR) is a global public health concern, given its ease of transmissibility. The purpose of this study was to evaluate two methods for the detection of PMCR from bacterial colonies: (i) the NG-Test MCR-1 lateral flow immunoassay (LFA; NG Biotech, Guipry, France) and (ii) the EDTA-colistin broth disk elution (EDTA-CBDE) screening test method. These methods were evaluated using a cohort of contemporary, clinical Gram-negative bacillus isolates from 3 U.S. academic medical centers (126 isolates of the Enterobacterales , 50 Pseudomonas aeruginosa isolates, and 50 Acinetobacter species isolates; 1 isolate was mcr positive) and 12 mcr -positive CDC-FDA Antibiotic Resistance (AR) Isolate Bank isolates for which reference broth microdilution colistin susceptibility results were available.

Despite the increasing reliance on polymyxin antibiotics (polymyxin B and colistin) for treatment of multidrug-resistant Gram-negative infections, many clinical laboratories are unable to perform susceptibility testing due to the lack of accurate and reliable methods. Although gradient agar diffusion is commonly performed for other antimicrobials, its use for polymyxins is discouraged due to poor performance characteristics.

Susceptibility testing of the polymyxins (colistin and polymyxin B) is challenging for clinical laboratories. The Clinical and Laboratory Standards Institute (CLSI) Antimicrobial Susceptibility Testing Subcommittee evaluated two methods to enable accurate testing of these agents. These methods were a colistin broth disk elution (CBDE) and a colistin agar test (CAT), the latter of which was evaluated using two inoculum volumes, 1 μl (CAT-1) and 10 μl (CAT-10).