Trends in the activity of mold-active azole agents against Aspergillus fumigatus clinical isolates with and without cyp51 alterations from Europe and North America (2017-2021).

Azole resistance in Aspergillus fumigatus (AFM) is increasing and often associated with cyp51 alterations. We evaluated the activity of isavuconazole and other mold-active azoles against 731 AFM isolates causing invasive aspergillosis collected in Europe (EU; n = 449) and North America (NA; n = 282). Isolates were submitted to CLSI susceptibility testing and epidemiological cutoff value (ECV) criteria. A posaconazole ECV of 0.5 mg/L was used as no CLSI ECV was determined. Azole non-wild-type (NWT) isolates were submitted for cyp51 sequencing by whole genome sequencing. Overall, isavuconazole activity (92.7%/94.0% WT in EU/NA) was comparable to other azoles (WT rate range, 90.9%-96.4%/91.8%-98.6%, respectively), regardless of the region. A total of 79 (10.8%) azole NWT isolates were detected, and similar rates of these isolates were noted in EU (10.7%) and NA (11.0%). Although most AFM were WT to azoles, increasing azole NWT rates were observed in NA (from 6.0% in 2017 to 29.3% in 2021). Azole NWT rates varied from 4.9% (2019) to 20.6% (2018) in EU without an observed trend. cyp51 alterations occurred in 56.3%/54.8% of azole NWT from EU/NA, respectively. The cyp51A TR34/L98H alteration was observed only in EU isolates (72.0% of EU isolates), while cyp51A I242V occurred only in NA isolates (58.3%). Isavuconazole remained active (MIC, ≤1 mg/L) against 18.5/47.1% of azole NWT AFM exhibiting cyp51 alterations in EU/NA, along with voriconazole (29.6/82.4%; MIC, ≤1 mg/L) and posaconazole (48.1/88.2%; MIC, ≤0.5 mg/L). Fourteen different cyp51 alterations were detected in 44 of 79 NWT isolates. The in vitro activity of the azoles varied in AFM that displayed cyp51 alterations. IMPORTANCE A few microbiology laboratories perform antifungal susceptibility testing locally for systemically active antifungal agents. The identification of emerging azole-resistant Aspergillus fumigatus is worrisome. As such, there is a critical role for antifungal surveillance in tracking emerging resistance among both common and uncommon opportunistic fungi. Differences in the regional prevalence and antifungal resistance of these fungi render local epidemiological knowledge essential for the care of patients with a suspected invasive fungal infection.

Oritavancin in vitro activity against Gram-positive organisms from European medical centers: a 10-year longitudinal overview from the SENTRY Antimicrobial Surveillance Program (2010-2019).

To assess oritavancin in vitro activity against clinically relevant Gram-positive pathogens in European (EU) hospitals, a total of 51,531 consecutive and unique clinical isolates collected in 2010-2019 were evaluated. All isolates were tested by CLSI broth microdilution methods. The key resistance phenotypes differed considerably between Eastern Europe (E-EU) and Western Europe (W-EU), respectively: methicillin-resistant (MR) Staphylococcus aureus 27.7%/22.9%; multidrug resistant (MDR) S. aureus, 19.7%/15.2%; MR coagulase-negative staphylococci, 77.3%/61.9%; vancomycin-resistant enterococci (E. faecium), 44.2%/20.9%; and MDR E. faecium, 63.8%/55.4%. There were no substantive differences in oritavancin minimum inhibitory concentration (MIC) values for the different species/organism groups over time or by EU region. Oritavancin inhibited 99.9% and 99.1% of all S. aureus and coagulase-negative staphylococci at 0.12 mg/L, respectively, and all isolates of E. faecalis and E. faecium at ≤0.5 mg/L. Oritavancin susceptibility rates against ß-hemolytic and Viridans group streptococci isolates were 98.1% and 99.4%, respectively. Oritavancin had potent activity in vitro against this contemporary collection of European Gram-positive isolates from 2010 to 2019.

The joint use of the tangential electric field and surface Laplacian in EEG classification.

We investigate the joint use of the tangential electric field (EF) and the surface Laplacian (SL) derivation as a method to improve the classification of EEG signals. We considered five classification tasks to test the validity of such approach. In all five tasks, the joint use of the components of the EF and the SL outperformed the scalar potential. The smallest effect occurred in the classification of a mental task, wherein the average classification rate was improved by 0.5 standard deviations. The largest effect was obtained in the classification of visual stimuli and corresponded to an improvement of 2.1 standard deviations.