drug resistance
Experimental TherapeuticsDelamanid Central Nervous System Pharmacokinetics in Tuberculous Meningitis in Rabbits and HumansCentral nervous system tuberculosis (TB) is devastating and affects vulnerable populations. Multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculous meningitis (TBM) specifically are nearly uniformly fatal, with little information being available to guide the treatment of these patients. Delamanid (DLM), a nitro-dihydro-imidazooxazole, is a new, well-tolerated anti-TB drug with a low MIC (1 to 12 ng/ml) against...
Epidemiology and SurveillanceMolecular Surveillance of Drug Resistance of Plasmodium falciparum Isolates Imported from Angola in Henan Province, ChinaAngola was the main origin country for the imported malaria in Henan Province, China. Antimalarial drug resistance has posed a threat to the control and elimination of malaria. Several molecular markers were confirmed to be associated with the antimalarial drug resistance, such as pfcrt, pfmdr1, pfdhfr, pfdhps, and K13. This study evaluated the drug resistance of the 180 imported...
![1<em>H</em>-Benzo[<em>d</em>]Imidazole Derivatives Affect MmpL3 in <span class="named-content genus-species" id="named-content-1">Mycobacterium tuberculosis</span>](https://aac.asm.org/sites/default/files/styles/thumbnail/public/externals/0284aba2d9c90d343ecad3753723bc65.jpg?itok=g4CsECuU)
Mechanisms of Action: Physiological Effects1H-Benzo[d]Imidazole Derivatives Affect MmpL3 in Mycobacterium tuberculosis1H-benzo[d]imidazole derivatives exhibit antitubercular activity in vitro at a nanomolar range of concentrations and are not toxic to human cells, but their mode of action remains unknown. Here, we showed that these compounds are active against intracellular Mycobacterium tuberculosis.
Clinical TherapeuticsEfficacy and Safety of Pyronaridine-Artesunate plus Single-Dose Primaquine for the Treatment of Malaria in Western CambodiaThis single-arm trial (n = 104) in western Cambodia showed high efficacy for 3-day treatment with pyronaridine-artesunate plus single-dose primaquine in Plasmodium falciparum malaria.
Antiviral AgentsPatient-Derived Cytomegaloviruses with Different Ganciclovir Sensitivities from UL97 Mutation Retain Their Replication Efficiency and Some Kinase Activity In VitroMutations in the cytomegalovirus UL97 kinase gene contribute to antiviral resistance. Mutations A594S and G598D from two clinical isolates were analyzed, and bacterial artificial chromosome (BAC)-engineered A594S recombinant cytomegalovirus exhibited a ganciclovir-resistant phenotype on plaque reduction. Viral replication was comparable to that of the wild type. Cell-based kinase activity and autophosphorylation of ectopically expressed...
Mechanisms of Action: Physiological EffectsVerapamil Improves the Activity of Bedaquiline against Mycobacterium abscessus In Vitro and in MacrophagesDue to intrinsic multidrug resistance, pulmonary infections with Mycobacterium abscessus are extremely difficult to treat. Previously, we demonstrated that bedaquiline is highly effective against Mycobacterium abscessus both in vitro and in vivo. Here, we report that verapamil...
Mechanisms of ResistanceGenomewide Elucidation of Drug Resistance Mechanisms for Systemically Used Antifungal Drugs Amphotericin B, Caspofungin, and Voriconazole in the Budding YeastThere are only a few antifungal drugs used systemically in treatment, and invasive fungal infections that are resistant to these drugs are an emerging problem in health care. In this study, we performed a high-copy-number genomic DNA (gDNA) library screening to find and characterize genes that reduce susceptibility to amphotericin B, caspofungin, and voriconazole in ...
Antiviral AgentsNovel Central Nervous System (CNS)-Targeting Protease Inhibitors for Drug-Resistant HIV Infection and HIV-Associated CNS ComplicationsThere is currently no specific therapeutics for the HIV-1-related central nervous system (CNS) complications. Here we report that three newly designed CNS-targeting HIV-1 protease inhibitors (PIs), GRL-083-13, GRL-084-13, and GRL-087-13, which contain a P1-3,5-bis-fluorophenyl or P1-para-monofluorophenyl ring, and P2-bis-tetrahydrofuran (bis-THF) or P2-tetrahydropyrano-tetrahydrofuran (Tp-THF...
Experimental TherapeuticsIn Vitro and In Vivo Activities of Zinc Linolenate, a Selective Antibacterial Agent against Helicobacter pyloriHelicobacter pylori is a major global pathogen, and its infection represents a key factor in the etiology of various gastric diseases, including gastritis, peptic ulcers, and gastric carcinoma. The efficacy of current standard treatment for H. pylori infection including two broad-spectrum...
