The Occurrence of Type I, II, and III Integrons in Multi-drug Resistance and Methicillin-Resistant Staphylococcus aureus Isolates in Iran

Integrons are mobilizable platforms-DNA elements with impacts on moving antibiotic resistance genes among bacteria and capable of spreading multi-drug resistance (MDR) in pathogens. Methicillin-resistant Staphylococcus aureus (MRSA) strains are the main cause of community-acquired and nosocomial infections with high mortality and morbidity rates worldwide. This work is mainly aimed at calculating the frequency of Type I, II, and III integrons within multi-drug resistance and Methicillin-resistant S. aureus Isolates in Iran. In this cross-sectional study, 230 clinical isolates of S. aureus were gathered from patients of educational hospitals in the provinces of Iran. These isolates were verified utilizing particular biochemical examinations and then assessed for antibiotic susceptibility through disk diffusion technique and standard procedures were done. Genomic and plasmid DNA of all isolates were extracted using Extraction Kit and PCR assay was used for the detection of Type I, II and III integrons genes. Out of the 230 S. aureus isolates, 136 (59.1) isolates were MRSA and 141 (61.3) isolates exhibited the MDR pattern. PCR and sequencing showed that 57 (24.8) of tested isolates carry Type I integron. Among the isolates investigated, MRSA and MDR isolates showed frequencies of 56.1 and 57.9, respectively. Type II and III integrons were found in none of 230 isolates. The IntI I gene was present in approximately one-quarter of this study isolates. The great prevalence rate of MDR and MRSA isolates and concurrently the existence of Type I integron among those isolates have been considered an important concern in medical society. © 2020, Springer Science+Business Media, LLC, part of Springer Nature

Assessment of the Efficacy of Therapies Following Venetoclax Discontinuation in CLL Reveals BTK inhibition as an Effective Strategy.

PURPOSE: Venetoclax-based therapy is a standard of care option in front-line and relapsed/refractory CLL. Patient management following venetoclax discontinuation remains non-standard and poorly understood. EXPERIMENTAL DESIGN: To address this, we conducted a large international study to identify a cohort of 326 patients who discontinued venetoclax and have been subsequently treated. Co-primary endpoints were overall response rate (ORR) and progression free survival (PFS) for the post-venetoclax treatments stratified by treatment type (BTKi, PI3Ki, and cellular therapies). RESULTS: We identified CLL patients who discontinued venetoclax in the front-line (4%) and relapsed/refractory settings (96%). Patients received a median of three therapies prior to venetoclax; 40% were BTKi naïve (n=130), and 81% were idelalisib naïve (n=263). ORR to BTKi was 84% (n=44) in BTKi-naïve patients vs. 54% (n=30) in BTKi-exposed patients. We demonstrate therapy selection following venetoclax requires prior novel agent exposure consideration and discontinuation reasons. CONCLUSIONS: For BTKi naïve patients, selection of covalently binding BTKis results in high ORR and durable remissions. For BTKi exposed patients, covalent BTK inhibition is not effective in the setting of BTKi resistance. PI3Kis following venetoclax do not appear to result in durable remissions. We conclude that BTKi in naïve or previously responsive patients and cellular therapies following venetoclax may be the most effective strategies