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Purpose: We determined the phenotypic resistance to third-generation cephalosporins, phenotypic extended spectrum beta-lactamase (ESBL) prevalence, and genotypic prevalence of ESBL-encoding genes blaCTX-M, blaTEM, and blaSHV in Enterobacteriaceae isolated from hematologic cancer patients with febrile neutropenia and bacteremia at the Uganda Cancer Institute (UCI). Patients and Methods: Blood cultures from hematologic cancer patients with febrile neutropenia were processed in BACTEC 9120. E. coli, K. pneumoniae, and Enterobacter spp. isolates were identified using conventional biochemical methods. Antimicrobial susceptibility tests, phenotypic ESBL characterization, and genotypic characterization of the ESBL-encoding genes blaCTX-M, blaTEM, and blaSHV were determined for pure isolates of E. coli, K. pneumoniae, and Enterobacter spp. Results: Two hundred and two patients were included in the study. Median age of patients was 19 years (IQR: 10-30 years). Majority (N=119, 59%) were male patients. Sixty (30%) of the participants had at least one febrile episode due to Enterobacteriaceae. Eighty-three organisms were isolated with E. coli being predominant (45, 54%). Seventy-nine (95%) Enterobacteriaceae were multidrug resistant. The ESBL phenotype was detected in 54/73 (74%) of Enterobacteriaceae that were resistant to third-generation cephalosporins. A higher proportion of Enterobacteriaceae with ESBL-positive phenotype were resistant to piperacillin-tazobactam (p=0.024), gentamicin (p=0.000), ciprofloxacin (p=0.000), and cotrimoxazole (p=0.000) compared to Enterobacteriaceae, which were sensitive to third-generation cephalosporins. The organisms were more susceptible to carbapenems and chloramphenicol than resistant. ESBL-encoding genes (blaCTX-M, blaTEM, and blaSHV) were detected in 55 (75%) of the 73 Enterobacteriaceae that were resistant to third-generation cephalosporins. BlaCTX-M, was the most common ESBL-encoding gene identified with 50 (91%). Conclusion: ESBL-producing Enterobacteriaceae are a predominant cause of bacteremia in hematologic cancer patients at UCI. The most common ESBL-encoding gene identified in the ESBL-PE was blaCTX-M. Resistance to imipenem and meropenem was low.
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Summary: Human immunodeficiency virus (HIV) remains a public health threat, with drug resistance being a major concern in HIV treatment. Next-generation sequencing (NGS) is a powerful tool for identifying low-abundance drug resistance mutations (LA-DRMs) that conventional Sanger sequencing cannot reliably detect. To fully understand the significance of LA-DRMs, it is necessary to integrate NGS data with clinical and demographic data. However, freely available tools for NGS-based HIV-1 drug resistance analysis do not integrate these data. This poses a challenge in interpretation of the impact of LA-DRMs, mainly for resource-limited settings due to the shortage of bioinformatics expertise. To address this challenge, we present HIVseqDB, a portable, secure, and user-friendly resource for integrating NGS data with associated clinical and demographic data for analysis of HIV drug resistance. HIVseqDB currently supports uploading of NGS data and associated sample data, HIV-1 drug resistance data analysis, browsing of uploaded data, and browsing and visualizing of analysis results. Each function of HIVseqDB corresponds to an individual Django application. This ensures efficient incorporation of additional features with minimal effort. HIVseqDB can be deployed on various computing environments, such as on-premises high-performance computing facilities and cloud-based platforms. Availability and implementation: HIVseqDB is available at https://github.com/AlfredUg/HIVseqDB. A deployed instance of HIVseqDB is available at https://hivseqdb.org.