Multiple drug resistant

Among hospitalized patients worldwide, infections caused by multidrug-resistant (MDR) bacteria are a major cause of morbidity and mortality. This study aimed to isolate MDR bacteria from five intensive care units (ICUs) at Tripoli University Hospital (TUH). A prospective cross-sectional study was conducted over a seven-month period (September 2022 to March 2023) across five ICUs at TUH. A total of 197 swabs were collected from Patients', healthcare workers' and ICUs equipment. Samples collected from patients were nasal swabs, oral cavity swabs, hand swabs, sputum specimens, skin swabs, umbilical venous catheter swabs, and around cannula...

Currently, although some antibody-drug conjugates have been shown to be safe and effective in the treatment of drug-resistant relapsed human epidermal growth factor receptor 2 (HER2)-positive (IHC 3+ or IHC 2+/fluorescence in situ hybridization+) breast cancer, they are already approved for clinical use in China. But the clinical needs of advanced HER2-positive patients cannot be met due to adverse reactions, drug resistance, drug accessibility and other problems, thus affecting the prognosis of patients. In particular, the representation of elderly and frail patients in randomized clinical trials is significantly under-represented...

PURPOSE: Cystatin SA (CST2) belongs to the superfamily of cysteine protease inhibitors. Emerging research indicates that CST2 is often dysregulated across various cancers. Its role and molecular mechanisms in gastric cancer remain underexplored. This study aims to explore the expression and function of CST2 in gastric cancer. METHODS: CST2 expression was analyzed and validated through Western blot. CST2 overexpression was induced by lentivirus in GC cells, and the correlation between CST2 expression levels and downstream signaling pathways was assessed...

The current tuberculosis (TB) treatment is challenged by a complex first-line treatment for drug-sensitive (DS) TB. Additionally, the prevalence of multidrug (MDR)- and extensively drug (XDR)-resistant TB necessitates the search for new drug prototypes. We synthesized and screened 30 hybrid compounds containing aminopyridine and 2-chloro-3-formyl quinoline to arrive at a compound with potent antimycobacterial activity, UH-NIP-16. Subsequently, antimycobacterial activity against DS and MDR Mycobacterium tuberculosis ( M...

To combat the global burden of malaria, development of new drugs to replace or complement current therapies is urgently required. Here, we show that the compound MMV1557817 is a selective, nanomolar inhibitor of both Plasmodium falciparum and Plasmodium vivax aminopeptidases M1 and M17, leading to inhibition of end-stage hemoglobin digestion in asexual parasites. MMV1557817 can kill sexual-stage P. falciparum , is active against murine malaria, and does not show any shift in activity against a panel of parasites resistant to other antimalarials...

This review covers the most recent advances in the development of inhibitors for the bacterial enzyme sortase A (SrtA). Sortase A (SrtA) is a critical virulence factor present ubiquitously in Gram-positive bacteria of which many are considered pathogenic. Sortases are key enzymes regulating bacterial adherence to host cells, by anchoring extracellular matrix-binding proteins to the bacterial outer cell wall. By targeting virulence factors, effective treatment can be achieved, without inducing antibiotic resistance to the treatment...

This study utilized integrative bioinformatics' tools together with phenotypic assays to understand the whole-genome features of a carbapenem-resistant international clone II Acinetobacter baumannii AB073. Overall, we found the isolate to be resistant to seven antibiotic classes, penicillins, β -lactam/ β -lactamase inhibitor combinations, cephalosporins, carbapenems, aminoglycosides, fluoroquinolones, and folate pathway antagonists. These resistance phenotypes are related to various chromosomal-located antibiotic resistance determinants involved in different mechanisms such as reduced permeability, antibiotic target protection, antibiotic target alteration, antibiotic inactivation, and antibiotic efflux...

BACKGROUND: Routine surveillance for antimalarial drug resistance is critical to sustaining the efficacy of artemisinin-based Combination Therapies (ACTs). Plasmodium falciparum kelch-13 (Pfkelch-13) and non- Pfkelch-13 artemisinin ( ART) resistance-associated mutations are uncommon in Africa. We investigated polymorphisms in Plasmodium falciparum actin-binding protein (Pfcoronin ) associated with in vivo reduced sensitivity to ART in Nigeria. METHODS: Fifty-two P...

BACKGROUND: The World Health Organization (WHO) has classified carbapenem-resistant Enterobacteriaceae, Pseudomonas aeruginosa ( P. aeruginosa ), and Acinetobacter baumannii ( A. baumannii ) as high-priority pathogens, and carbapenem-resistant bacteria (CRB) have been reported to spread between humans, animals, and the environment. OBJECTIVE: This study aimed to conduct a systematic review of carbapenem resistance in animals, foods, and the environment on the African continent and to provide recommendations and perspectives for better prevention and control of carbapenem resistance in Africa...

OBJECTIVES: Tuberous sclerosis complex (TSC) is a genetic disorder caused by a TSC1 or TSC2 gene variation characterized by widespread hamartomas in organs such as the skin, brain, heart, lungs, liver, and kidneys. METHODS: We report a case of a patient with TSC who presented with broad clinical manifestations, including epilepsy. RESULTS: An 18-year-old man was diagnosed with recurrent drug-resistant epilepsy. Neuroimaging revealed bilateral cortical and subcortical tubers with multiple calcified subependymal nodules...

BACKGROUND/AIMS: Improved knowledge of local epidemiology and predicting risk factors of multidrug-resistant (MDR) bacteria are required to optimize the management of infections. This study examined local epidemiology and antibiotic resistance patterns of liver cirrhosis (LC) patients and evaluated the predictors of MDR bacteremia in Korea. METHODS: This was a retrospective study including 140 LC patients diagnosed with bacteremia between January 2017 and December 2022...

Major histocompatibility complex (MHC) could serve as a potential biomarker for tumor immunotherapy, however, it is not yet known whether MHC could distinguish potential beneficiaries. Single-cell RNA sequencing datasets derived from patients with immunotherapy were collected to elucidate the association between MHC and immunotherapy response. A novel MHCsig was developed and validated using large-scale pan-cancer data, including The Cancer Genome Atlas and immunotherapy cohorts. The therapeutic value of MHCsig was further explored using 17 CRISPR/Cas9 datasets...

AXL, a receptor tyrosine kinase (RTK), plays a pivotal role in various cellular functions. It is primarily involved in processes such as epithelial-mesenchymal transition (EMT) in tumor cells, angiogenesis, apoptosis, immune regulation, and chemotherapy resistance mechanisms. Therefore, targeting AXL is a promising therapeutic approach for the treatment of cancer. AXL inhibitors that have entered clinical trials, such as BGB324(1), have shown promising efficacy in the treatment of melanoma and non-small cell lung cancer...

BACKGROUND: Multidrug resistance Salmonellosis remains an important public health problem globally. The disease is among the leading causes of morbidity and mortality in developing countries, but there have been limited recent studies about the prevalence, antimicrobial resistance, and multidrug resistance patterns of Salmonella isolates from various clinical specimens. OBJECTIVE: Aimed to assess the prevalence, antimicrobial resistance, and multidrug resistance patterns of Salmonella isolates from clinical specimens at the University of Gondar Comprehensive Specialised Hospital, northwestern Ethiopia...

With high incidence of hepatocarcinoma and limited effective treatments, most patients suffer in pain. Antitumor drugs are single-targeted, toxicity, causing adverse side effects and resistance. Dihydroartemisinin (DHA) inhibits tumor through multiple mechanisms effectively. This study explores and evaluates safety and potential mechanism of DHA towards human hepatocarcinoma based on network pharmacology in a comprehensive way. Adsorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of DHA were evaluated with pkCSM, SwissADME, and ADMETlab...

Targeted therapies directed against oncogenic signaling addictions, such as inhibitors of ALK in ALK+ NSCLC often induce strong and durable clinical responses. However, they are not curative in metastatic cancers, as some tumor cells persist through therapy, eventually developing resistance. Therapy sensitivity can reflect not only cell-intrinsic mechanisms but also inputs from stromal microenvironment. Yet, the contribution of tumor stroma to therapeutic responses in vivo remains poorly defined. To address this gap of knowledge, we assessed the contribution of stroma-mediated resistance to therapeutic responses to the frontline ALK inhibitor alectinib in xenograft models of ALK+ NSCLC...

BACKGROUND: Infections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistant Klebsiella pneumoniae as a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology of Klebsiella pneumoniae can inform management strategies but data from sub-Saharan Africa are lacking...

Although bortezomib (BTZ) is the cornerstone of anti-multiple myeloma (MM) therapy, the inevitable primary and secondary drug resistance still seriously affects the prognosis of patients. New treatment strategies are in need. Sodium-calcium exchanger 1 (NCX1) is a calcium-permeable ion transporter on the membrane, and our previous studies showed that low NCX1 confers inferior viability in MM cells and suppressed osteoclast differentiation. However, the effect of NCX1 on BTZ sensitivity of MM and its possible mechanism remain unclear...

Fibroblast growth factor receptor (FGFR) alterations drive oncogenesis in multiple tumor types. Here we studied pemigatinib, a selective, potent, oral FGFR1-FGFR3 inhibitor, in the phase 2 FIGHT-207 basket study of FGFR-altered advanced solid tumors. Primary end points were objective response rate (ORR) in cohorts A (fusions/rearrangements) and B (activating non-kinase domain mutations). Secondary end points were progression-free survival, duration of response and overall survival in cohorts A and B, and safety...

Cortical malformations such as focal cortical dysplasia type II (FCDII) are associated with pediatric drug-resistant epilepsy that necessitates neurosurgery. FCDII results from somatic mosaicism due to post-zygotic mutations in genes of the PI3K-AKT-mTOR pathway, which produce a subset of dysmorphic cells clustered within healthy brain tissue. Here we show a correlation between epileptiform activity in acute cortical slices obtained from human surgical FCDII brain tissues and the density of dysmorphic neurons...