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EditorialThe ASM Journals Committee Values the Contributions of Black Microbiologists
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Minireview周刊 - chinacourt.org:2021-10-24 · 群众反映问题，开通民意网上直通 车。黑龙江高院还制定了《“院长信 箱”所涉案件、事项办理工作的实施 细则》，规范信箱留言的梳理、批 转、办理和答复等流程。目前，全省 三级法院192个法院网站都开通了 “院长信箱”，极大地方便了当事人反 映诉求。Modern medicine is threatened by the global rise of antibiotic resistance, especially among Gram-negative bacteria. Metallo-β-lactamase (MBL) enzymes are a particular concern and are increasingly disseminated worldwide, though particularly in Asia. Many MBL producers have multiple further drug resistances, leaving few obvious treatment options. Nonetheless, and more encouragingly, MBLs may be less effective agents of carbapenem...
MinireviewEmerging Antimicrobial-Resistant High-Risk Klebsiella pneumoniae Clones ST307 and ST147There is an enormous global public health burden due to antimicrobial-resistant (AMR) Klebsiella pneumoniae high-risk clones. K. pneumoniae ST307 and ST147 are recent additions to the family of successful clones in the species. Both clones likely emerged in Europe during the early to mid-1990s and,...
网际直通车(p)ppGpp and Its Role in Bacterial Persistence: New ChallengesAntibiotic failure not only is due to the development of resistance by pathogens but can also often be explained by persistence and tolerance. Persistence and tolerance can be included in the “persistent phenotype,” with high relevance for clinics. Two of the most important molecular mechanisms involved in tolerance and persistence are toxin-antitoxin (TA) modules and signaling via guanosine pentaphosphate/tetraphosphate [(p)ppGpp],...
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Editor's Pick Challenging Clinical Case in Antimicrobial ResistanceGenomic Profiling of Evolving Daptomycin Resistance in a Patient with Recurrent Staphylococcus argenteus SepsisStaphylococcus argenteus is a novel staphylococcal species associated with invasive disease. We report the first case of daptomycin/vancomycin-resistant S. argenteus, initially speciated as Staphylococcus aureus, that developed...
Editor's Pick Challenging Clinical Case in Antimicrobial ResistanceCase Commentary: Daptomycin Resistance in Staphylococcus argenteus—from Northern Australia to San FranciscoStaphylococcus argenteus infection was initially described in Aboriginal patients in the Northern Territories of Australia as a predominant cause of skin infections and is rare outside Southeast Asia. A first well-characterized case of S. argenteus infection has now been described in the United...
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网际直通车Lactoferrin-Derived Peptide Lactofungin Is Potently Synergistic with Amphotericin BLactoferrin (LF) is an iron-binding glycoprotein with broad-spectrum antimicrobial activity. Previously, we discovered that LF synergistically enhanced the antifungal efficacy of amphotericin B (AMB) across a variety of yeast species and subsequently hypothesized that this synergy was enhanced by the presence of small peptides derived from the whole LF molecule. In this study, LF was digested with pepsin under a range of conditions. The...
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Editor's Pick Mechanisms of Action: Physiological EffectsUnexpected Cell Wall Alteration-Mediated Bactericidal Activity of the Antifungal Caspofungin against Vancomycin-Resistant Enterococcus faeciumEnterococcus faecium has become a major opportunistic pathogen with the emergence of vancomycin-resistant enterococci (VRE). As part of the gut microbiota, they have to cope with numerous stresses, including effects of antibiotics and other xenobiotics, especially in patients hospitalized in intensive care units (ICUs) who receive many medications. The aim of this...
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网际直通车Resistance to Ceftazidime/Avibactam plus Meropenem/Vaborbactam When Both Are Used Together Is Achieved in Four Steps in Metallo-β-Lactamase-Negative Klebsiella pneumoniaeSerine β-lactamases are dominant causes of β-lactam resistance in Klebsiella pneumoniae isolates. Recently, this has driven clinical deployment of the β-lactam–β-lactamase inhibitor pairs ceftazidime/avibactam and meropenem/vaborbactam. We show that four steps, i.e., 网际直通车 and ramR mutation plus carriage of OXA-232 and KPC-3-D178Y variant β-...
Mechanisms of ResistanceRelationship between Gepotidacin Exposure and Prevention of On-Therapy Resistance Amplification in a Neisseria gonorrhoeae Hollow-Fiber In Vitro Infection ModelMultidrug-resistant Neisseria gonorrhoeae has emerged as a threat to global health. The relationship between gepotidacin exposure and prevention of on-therapy amplification of drug-resistant 网际直通车 was examined using a 7-day hollow-fiber in vitro infection model. The study design...
网际直通车Associations between Aminoquinoline Resistance Genotypes and Clinical Presentations of Plasmodium falciparum Infection in UgandaMutations that mediate resistance of Plasmodium falciparum to aminoquinoline antimalarials are selected by prior drug use and may alter parasite fitness, but associations with clinical presentations are uncertain. We evaluated genotypes in samples from a case-control study of determinants of severe malaria in Ugandan children 4 months to 10 years of age. We studied...
Mechanisms of ResistanceAspergillus fumigatus Cyp51A and Cyp51B Proteins Are Compensatory in Function and Localize Differentially in Response to Antifungals and Cell Wall InhibitorsTriazole antifungals are the primary therapeutic option against invasive aspergillosis. However, resistance to azoles has increased dramatically over the last decade. Azole resistance is known to primarily occur due to point mutations in the azole target protein Cyp51A, one of two paralogous 14-α sterol demethylases found in Aspergillus fumigatus. Despite the...
Mechanisms of ResistanceRNA Sequencing Identifies a Common Physiology in Vancomycin- and Ciprofloxacin-Tolerant Staphylococcus aureus Induced by ileS MutationsLittle is known about the mechanisms by which ileS mutations induce vancomycin tolerance in Staphylococcus aureus. This study showed that transcriptome profiles were similar in vancomycin-tolerant mutants and the IleRS-inhibitor-treated parent. Notably, ileS and relA, which induce a stringent response, were upregulated. The same mechanism...
网际直通车IS网际直通车-Mediated Mobilization of the Colistin Resistance Gene mcr-3.11 in Escherichia coliThe mobile colistin resistance gene mcr-3 has globally disseminated since it was first reported in 2017 in 网际直通车. In vitro mobilization assays in this study demonstrate the functionality of the composite transposon structure ISKpn40-mcr-3.11-dgkA-ISKpn40 in wild-type and recA−...
Mechanisms of ResistanceScarless Removal of Large Resistance Island AbaR Results in Antibiotic Susceptibility and Increased Natural Transformability in Acinetobacter baumanniiWith a great diversity in gene composition, including multiple putative antibiotic resistance genes, AbaR islands are potential contributors to multidrug resistance in 网际直通车. However, the effective contribution of AbaR to antibiotic resistance and bacterial physiology remains elusive. To address this, we sought to accurately remove AbaR islands and...
Mechanisms of ResistanceramR Deletion in an 网际直通车 Isolate as a Consequence of Therapeutic Failure of Key Antibiotics in a Long-Term Hospitalized PatientGenome changes are central to the adaptation of bacteria, especially under antibiotic pressure. The aim of this study was to report phenotypic and genomic adaptations undergone by an Enterobacter hormaechei clinical strain that became highly resistant to key antimicrobials during a 4-month period in a patient hospitalized in an intensive care unit (ICU). All six...
Mechanisms of ResistanceFirst Report of Candidemia Clonal Outbreak Caused by Emerging Fluconazole-Resistant Candida parapsilosis Isolates Harboring Y132F and/or Y132F+K143R in TurkeyClonal outbreaks of fluconazole-resistant (FLZR) Candida parapsilosis isolates have been reported in several countries. Despite its being the second leading cause of candidemia, the azole resistance mechanisms and the clonal expansion of FLZR 网际直通车 blood isolates have not been reported in...
Mechanisms of ResistanceStrong Environment-Genotype Interactions Determine the Fitness Costs of Antibiotic Resistance In Vitro and in an Insect Model of InfectionThe acquisition of antibiotic resistance commonly imposes fitness costs, a reduction in the fitness of bacteria in the absence of drugs. These costs have been quantified primarily using in vitro experiments and a small number of in vivo studies in mice, and it is commonly assumed that these diverse methods are consistent. Here, we used an insect model of infection to compare the fitness costs of antibiotic resistance...
Mechanisms of ResistanceRapid Increase of CTX-M-Producing Shigella sonnei Isolates in Switzerland Due to Spread of Common Plasmids and International ClonesThe Swiss Centre for Antibiotic Resistance (ANRESIS) has recently noted an increase of extended-spectrum cephalosporin-resistant (ESC-R) Shigella sonnei isolates nationwide (3.8% in 2016 versus 37.5% in 2019). To understand this phenomenon, we analyzed 25 representative isolates (of which 14 were ESC-R) collected in Switzerland during 2016 to 2019. Whole-genome...
Mechanisms of ResistanceEffect of Sub-MICs of Macrolides on the Sensitivity of Pseudomonas aeruginosa to Nitrosative Stress: Effectiveness against P. aeruginosa with and without Multidrug ResistanceSub-MICs of the 14-membered macrolides erythromycin (EM) and clarithromycin (CAM) decreased the growth of 网际直通车 PAO1 and increased its sensitivity to endogenous and exogenous nitrosative stress. However, a 16-membered macrolide, josamycin (JM), was not or less effective. In 9 of 13 non-multidrug-resistant...
Mechanisms of ResistanceCombination of Miconazole and Domiphen Bromide Is Fungicidal against Biofilms of Resistant Candida spp.The occurrence and recurrence of mucosal biofilm-related Candida infections, such as oral and vulvovaginal candidiasis, are serious clinical issues. Vaginal infections caused by Candida spp., for example, affect 70 to 75% of women at least once during their lives. Miconazole (MCZ) is the preferred topical treatment against these fungal infections, yet it has only moderate antibiofilm activity. Through screening of a...
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SusceptibilityManogepix (APX001A) In Vitro Activity against Candida auris: Head-to-Head Comparison of EUCAST and CLSI MICsFosmanogepix is a novel prodrug in a new class of antifungal agents. Manogepix is the active moiety. We evaluated the CLSI and EUCAST MICs of manogepix and eight comparators against Candida auris. CLSI M27-A3 susceptibility testing of manogepix was performed for 122 C. auris isolates and compared to...
SusceptibilityCaenorhabditis elegans as a Model System To Assess Candida glabrata, 网际直通车, and Candida bracarensis Virulence and Antifungal EfficacyAlthough 网际直通车 remains the major etiological agent of invasive candidiasis, Candida glabrata and other emerging species of Candida are increasingly isolated. This species is the second most prevalent cause of candidiasis in many regions of the world. However, clinical isolates of...
SusceptibilityFive-Year Survey (2014 to 2018) of Azole Resistance in Environmental Aspergillus fumigatus Isolates from ChinaA total of 191 soil samples from Hangzhou, China, were submitted to detect non-wild-type (non-WT) Aspergillus fumigatus and its associated mechanisms. There were 2 (4.7%), 13 (12.4%), and 31 (23.1%) isolates identified as non-WT in 2014, 2016, and 2018, respectively. The resistant mutations of TR34/L98H, TR46/Y121F/T289A, and TR34/L98H/S297T/F495I were found in 3, 5,...
网际直通车 SusceptibilityIn Vitro Susceptibility of Treponema pallidum subsp. pallidum to DoxycyclineDoxycycline is regarded as an effective therapy for early syphilis, and there is increasing interest in using doxycycline for prophylaxis of this infection. However, the MIC of doxycycline for Treponema pallidum subsp. pallidum has not been reported previously. In this study, an in vitro culture system was utilized to determine that the MIC of...
Antiviral Agents
Antiviral AgentsThe Clinically Approved Antifungal Drug Posaconazole Inhibits Human Cytomegalovirus ReplicationPosaconazole (PCZ) is a clinically approved drug used predominantly for prophylaxis and salvage therapy of fungal infections. Here, we report its previously undescribed anti-human cytomegalovirus (HCMV) activity. By using antiviral assays, we demonstrated that PCZ, along with other azolic antifungals, has a broad anti-HCMV activity, being active against different strains, including low-passage-number clinical isolates and strains...
Antiviral AgentsInhibitory Effect of PIK-24 on Respiratory Syncytial Virus Entry by Blocking Phosphatidylinositol-3 Kinase SignalingPhosphoinositide-3 kinase signaling modulates many cellular processes, including cell survival, proliferation, differentiation, and apoptosis. Currently, it is known that the establishment of respiratory syncytial virus infection requires phosphoinositide-3 kinase signaling. However, the regulatory pattern of phosphoinositide-3 kinase signaling or its corresponding molecular mechanism during respiratory syncytial virus entry remains...
Antiviral AgentsTargeting the Respiratory Syncytial Virus N0-P Complex with Constrained α-Helical Peptides in Cells and MiceRespiratory syncytial virus (RSV) is the main cause of severe respiratory infection in young children worldwide, and no therapies have been approved for the treatment of RSV infection. Data from recent clinical trials of fusion or L polymerase inhibitors for the treatment of RSV-infected patients revealed the emergence of escape mutants, highlighting the need for the discovery of inhibitors with novel mechanisms of action. Here we...
网际直通车Atazanavir, Alone or in Combination with Ritonavir, Inhibits SARS-CoV-2 Replication and Proinflammatory Cytokine ProductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is already responsible for far more deaths than previous pathogenic coronaviruses (CoVs) from 2002 and 2012. The identification of clinically approved drugs to be repurposed to combat 2019 CoV disease (COVID-19) would allow the rapid implementation of potentially life-saving procedures. The major protease (Mpro) of SARS-CoV-2 is considered a promising target, based on previous...
Antiviral AgentsNucleocapsid Protein Precursors NCp9 and NCp15 Suppress ATP-Mediated Rescue of AZT-Terminated Primers by HIV-1 Reverse TranscriptaseIn HIV-1, development of resistance to AZT (3′-azido-3′-deoxythymidine) is mediated by the acquisition of thymidine analogue resistance mutations (TAMs) (i.e., M41L, D67N, K70R, L210W, T215F/Y, and K219E/Q) in the viral reverse transcriptase (RT). Clinically relevant combinations of TAMs, such as M41L/T215Y or D67N/K70R/T215F/K219Q, enhance the ATP-mediated excision of AZT monophosphate (AZTMP) from the 3′ end of the primer, allowing...
Epidemiology and Surveillance
Epidemiology and SurveillanceHIV Coinfection Is Associated with Low-Fitness 网际直通车 Variants in Rifampicin-Resistant Mycobacterium tuberculosisWe analyzed 312 drug-resistant genomes of 网际直通车 isolates collected from HIV-coinfected and HIV-negative TB patients from nine countries with a high tuberculosis burden. We found that rifampicin-resistant 网际直通车 strains isolated from HIV-coinfected patients carried...
Epidemiology and SurveillanceActivity of Cefiderocol, Ceftazidime-Avibactam, and Eravacycline against Carbapenem-Resistant Escherichia coli Isolates from the United States and International Sites in Relation to Clonal Background, Resistance Genes, Coresistance, and RegionEmerging carbapenem resistance in Escherichia coli, including sequence type 131 (ST131), the leading cause of extraintestinal E. coli infections globally, threatens therapeutic efficacy. Accordingly, we determined broth microdilution MICs for three distinctive newer agents, i.e., cefiderocol (CFDC...
网际直通车 Epidemiology and SurveillanceA Diverse Panel of Clinical Acinetobacter baumannii for Research and DevelopmentOver the past two decades, 网际直通车 has emerged as a leading cause of nosocomial infections worldwide. Of particular concern are panresistant strains, leading the World Health Organization (WHO) to designate carbapenem-resistant A. baumannii as a priority 1 (critical) pathogen for...
网际直通车Escherichia coli Resistance to Fluoroquinolones in Community-Acquired Uncomplicated Urinary Tract Infection in Women: a Systematic ReviewAntibiotic resistance is a threat to public health, and uncomplicated urinary tract infections (uUTIs) are an example of this concern. This systematic review (International Prospective Register of Systematic Reviews [PROSPERO] ID: CRD42020156674) is the first to determine the prevalence of Escherichia coli resistance to fluoroquinolones in women with community-...
Epidemiology and SurveillancePrevalence and Antimicrobial Susceptibility of Mycoplasma hominis and Ureaplasma Species in Nonpregnant Female Patients in South Korea Indicate an Increasing Trend of Pristinamycin-Resistant IsolatesMycoplasma hominis and Ureaplasma species, commonly found in the lower urogenital tract, have been associated with various urogenital infections. This study aimed to estimate the prevalence and antimicrobial susceptibility trend of M. hominis and Ureaplasma sp. in female patients...
Epidemiology and SurveillanceDecreased Incidence of Methicillin-Resistant Staphylococcus aureus Bacteremia in Intensive Care Units: a 10-Year Clinical, Microbiological, and Genotypic Analysis in a Tertiary HospitalThere are limited long-term data on the trends in incidence and characteristics of methicillin-resistant 网际直通车 (MRSA) bacteremia (MRSAB) in intensive care units (ICUs) in which infection control measures have been adopted. We evaluated the trend of incidence and changes in characteristics of MRSA bacteremia in ICUs at a tertiary-care hospital over 10 ...
Epidemiology and SurveillanceNational Surveillance of Antimicrobial Susceptibility of Bacteremic Gram-Negative Bacteria with Emphasis on Community-Acquired Resistant Isolates: Report from the 2019 Surveillance of Multicenter Antimicrobial Resistance in Taiwan (SMART)A multicenter collection of bacteremic isolates of 网际直通车 (n = 423), 网际直通车 (n = 372), Pseudomonas aeruginosa (n = 300), and...
Experimental Therapeutics
Experimental TherapeuticsDiscovery and Preclinical Development of Antigiardiasis Fumagillol DerivativesGiardiasis, caused by the intestinal parasite Giardia lamblia, is a severe diarrheal disease, endemic in poverty-stricken regions of the world, and also a common infection in developed countries. The available therapeutic options are associated with adverse effects, and G. lamblia resistance to the...
Experimental TherapeuticsZebrafish Embryo Model for Assessment of Drug Efficacy on Mycobacterial PersistersTuberculosis continues to kill millions of people each year. The main difficulty in eradication of the disease is the prolonged duration of treatment, which takes at least 6 months. Persister cells have long been associated with failed treatment and disease relapse because of their phenotypical, though transient, tolerance to drugs. By targeting these persisters, the duration of treatment could be shortened, leading to improved...
Experimental TherapeuticsEfficacy of Ibrexafungerp (SCY-078) against Candida auris in an In Vivo Guinea Pig Cutaneous Infection ModelCandida auris has been shown to have a high risk of skin colonization in hospitalized patients, possibly contributing to nosocomial spread. In a guinea pig skin model, animals were evaluated for clinical appearance, tissue fungal burden, histology, and pharmacokinetics. Oral dosing with 10 mg/kg ibrexafungerp (IBX) reduced the severity of lesions and significantly...
Experimental TherapeuticsAntifungal Activity of Gepinacin Scaffold Glycosylphosphatidylinositol Anchor Biosynthesis Inhibitors with Improved Metabolic StabilityThe glycosylphosphatidylinositol anchor biosynthesis inhibitor gepinacin demonstrates broad-spectrum antifungal activity and negligible mammalian toxicity in culture but is metabolically labile. The stability and bioactivity of 39 analogs were tested 网际直通车 to identify LCUT-8, a stabilized lead with increased potency and promising single-dose pharmacokinetics. Unfortunately, no antifungal activity was seen at the maximum...
网际直通车
网际直通车Topical Antibiotic Elution in a Collagen-Rich Hydrogel Successfully Inhibits Bacterial Growth and Biofilm Formation In VitroChronic wounds are a prominent concern, accounting for $25 billion of health care costs annually. Biofilms have been implicated in delayed wound closure, but they are susceptible to developing antibiotic resistance and treatment options continue to be limited. A novel collagen-rich hydrogel derived from human extracellular matrix presents an avenue for treating chronic wounds by providing appropriate extracellular proteins for healing...
Clinical TherapeuticsAfabicin, a First-in-Class Antistaphylococcal Antibiotic, in the Treatment of Acute Bacterial Skin and Skin Structure Infections: Clinical Noninferiority to Vancomycin/LinezolidAfabicin (formerly Debio 1450, AFN-1720) is a prodrug of afabicin desphosphono, an enoyl-acyl carrier protein reductase (FabI) inhibitor, and is a first-in-class antibiotic with a novel mode of action to specifically target fatty acid synthesis in 网际直通车 spp. The efficacy, safety, and tolerability of afabicin were compared with those of vancomycin/linezolid in the treatment of acute bacterial skin and skin structure...
Clinical TherapeuticsStructural Basis and Binding Kinetics of Vaborbactam in Class A β-Lactamase InhibitionClass A β-lactamases are a major cause of β-lactam resistance in Gram-negative bacteria. The recently FDA-approved cyclic boronate vaborbactam is a reversible covalent inhibitor of class A β-lactamases, including CTX-M extended-spectrum β-lactamase and KPC carbapenemase, both frequently observed in the clinic. Intriguingly, vaborbactam displayed different binding kinetics and cell-based activity for these two enzymes, despite their...
Clinical TherapeuticsSafety and Pharmacokinetics of Recombinant Human Plasma Gelsolin in Patients Hospitalized for Nonsevere Community-Acquired PneumoniaThere remains an unmet need to address the substantial morbidity and mortality associated with severe community-acquired pneumonia (sCAP). Recombinant human plasma gelsolin (rhu-pGSN) improves disease outcomes in diverse animal models of infectious and noninfectious inflammation. This blinded dose-escalation safety study involved non-intensive care unit (ICU) patients admitted for mild CAP and randomized 3:1 to receive adjunctive rhu-...
Clinical TherapeuticsPhase I EnACT Trial of the Safety and Tolerability of a Novel Oral Formulation of Amphotericin BAmphotericin B deoxycholate (AMB) has substantial toxicities. A novel encochleated amphotericin B deoxycholate (cAMB) formulation has oral bioavailability, efficacy in an animal model, and minimal toxicity due to targeted drug delivery into macrophages, where intracellular fungi reside. We conducted a phase I, ascending-dose trial of cAMB administered at 1.0 g, 1.5 g, or 2.0 g per day in 4 to 6 divided doses among HIV-positive survivors...
Clinical TherapeuticsPopulation Pharmacokinetics of Linezolid in Tuberculosis Patients: Dosing Regimen Simulation and Target Attainment AnalysisThe prolonged treatment duration for multidrug-resistant tuberculosis (MDR-TB) makes linezolid dosing difficult because of adverse effects associated with long-term use. We sought to find the optimal dosing regimen for linezolid across different MIC values. Pharmacokinetic (PK) data from TB patients were included from Brazil, Georgia, and two U.S. sites. Population PK modeling and simulation were performed. We used an fAUC (...
Clinical TherapeuticsEffect of Vancomycin-Associated Acute Kidney Injury on Incidence of 30-Day Readmissions among Hospitalized Veterans Affairs Patients with Skin and Skin Structure Infections胡锦涛开通“网络民意直通车”-东北网国内-东北网:2021-6-28 · 早在2021年，胡锦涛、温家宝就公开了网民身份，向外界展现对互联网的重视；2021至2021年，温家宝连续四年在“两会”中外记者招待会上主动问候中国网民，并感谢网民分忧，公开肯定了这种“民意直达高层直通车”的沟通方式；去年初，中共中央政治局集体学习
Pharmacology
Pharmacology人民法院报 - chinacourt.org:2021-10-27 · “院长信箱”是黑龙江法院网69个栏目中的重要栏目之一，旨在便利群众反映问题，开通民意网上直通车。黑龙江高院还制定了《“院长信箱”所涉案件、事项办理工作的实施细则》，规范信箱留言的梳理、批转、办理和答复等流程。This study aimed to evaluate the antimicrobial activity of the novel monosulfactam 0073 against multidrug-resistant Gram-negative bacteria in vitro and in vivo and to characterize the mechanisms underlying 0073 activity. The in vitro activities of 0073, aztreonam, and the combination with avibactam were assessed by MIC and time-kill assays. The safety of 0073 was evaluated using 3-(4,5-dimethylthizol-2-yl)-2,5...
PharmacologyEffect of Pregnancy on Unbound Raltegravir Concentrations in the ANRS 160 RalFe TrialA population pharmacokinetic model was developed to explore the pharmacokinetics modification of unbound raltegravir during pregnancy. The RalFe ANRS160 study was a nonrandomized, open-label, multicenter trial enrolling HIV-infected pregnant women receiving a combined antiretroviral regimen containing 400 mg raltegravir twice daily. Biological samples were collected during the third trimester of pregnancy (between 30 and 37 weeks of...
PharmacologyComparison of a Novel Regimen of Rifapentine, Tedizolid, and Minocycline with Standard Regimens for Treatment of Pulmonary Mycobacterium kansasiiThe combination of isoniazid, rifampin, and ethambutol is recommended by the American Thoracic Society (ATS) for treatment of pulmonary Mycobacterium kansasii, while the British Thoracic Society (BTS) recommends clarithromycin, rifampin and ethambutol. Unfortunately, therapy duration for both regimens lasts for years. In this study, we administered tedizolid,...
PharmacologyPopulation Pharmacokinetic Study of Ceftriaxone in Elderly Patients, Using Cystatin C-Based Estimates of Renal Function To Account for Frailty周刊 - chinacourt.org:2021-10-24 · 群众反映问题，开通民意网上直通 车。黑龙江高院还制定了《“院长信 箱”所涉案件、事项办理工作的实施 细则》，规范信箱留言的梳理、批 转、办理和答复等流程。目前，全省 三级法院192个法院网站都开通了 “院长信箱”，极大地方便了当事人反 映诉求。
Pharmacology中国行业云安全PCSF论坛推动私有云等级保护升级－企业 ...:2021-10-26 · 联系我们 邮箱登录 通行证登录 网站地图Single nucleotide polymorphisms in the OATP1B1 transporter have been suggested to partially explain the large interindividual variation in rifampicin exposure. HEK293 cells overexpressing wild-type (WT) or OATP1B1 variants *1b, *4, *5, and *15 were used to determine the 网际直通车 rifampicin intrinsic clearance. For OATP1B1*5 and *15, a 36% and 42% reduction in intrinsic clearance, respectively, compared to WT was found. We...
PharmacologySuboptimal Dosing of Fluconazole in Critically Ill Patients: Time To Rethink DosingFluconazole is frequently used for the treatment of invasive 网际直通车 infections in critically ill patients. However, alterations in renal functions might influence fluconazole clearance. Therefore, our objective was to study the impact of renal function on the population pharmacokinetics of fluconazole in critically ill patients with various degrees of renal function or undergoing continuous renal replacement therapy (CRRT)....
PharmacologyPreserved Efficacy and Reduced Toxicity with Intermittent Linezolid Dosing in Combination with Bedaquiline and Pretomanid in a Murine Tuberculosis ModelThe novel regimen of bedaquiline, pretomanid, and linezolid (BPaL) is highly effective against drug-resistant tuberculosis, but linezolid toxicities are frequent. We hypothesized that, for a similar total weekly cumulative dose, thrice-weekly administration of linezolid would preserve efficacy while reducing toxicity compared with daily dosing, in the context of the BPaL regimen. Using C3HeB/FeJ and BALB/c mouse models of tuberculosis...
PharmacologyAntiretroviral Penetration and Drug Transporter Concentrations in the Spleens of Three Preclinical Animal Models and HumansAdequate antiretroviral (ARV) concentrations in lymphoid tissues are critical for optimal antiretroviral therapy (ART). While the spleen contains 25% of the body’s lymphocytes, there are minimal data on ARV penetration in this organ. This study quantified total and protein-unbound splenic ARV concentrations and determined whether drug transporters, sex, or infection status were modifiers of these concentrations in animal models and...
PharmacologySafety, Tolerability, and Pharmacokinetics of a Novel Oral Amphotericin B Formulation (iCo-019) following Single-Dose Administration to Healthy Human Subjects: an Alternative Approach to Parenteral Amphotericin B AdministrationThis study evaluated the safety, tolerability, and pharmacokinetics of a novel oral amphotericin B (AmB) formulation (iCo-019) following single doses to healthy humans. The data from this study suggest that iCo-019 has a long circulation time and systemic exposure without the associated gastrointestinal, liver, and kidney toxicity associated with AmB. This novel oral AmB formulation can serve as a new treatment strategy to overcome the...
PharmacologyPharmacokinetic-Pharmacodynamic Target Attainment Analyses To Support Dose Selection for ME1100, an Arbekacin Inhalation SolutionME1100 (arbekacin inhalation solution) is an inhaled aminoglycoside that is being developed to treat patients with hospital-acquired and ventilator-associated bacterial pneumonia (HABP and VABP, respectively). Pharmacokinetic-pharmacodynamic (PK-PD) target attainment analyses were undertaken to evaluate ME1100 regimens for the treatment of patients with HABP/VABP. The data used included a population pharmacokinetic (PPK) 4-compartment...
Letters to the Editor
网际直通车Amphotericin B Inhibits 网际直通车 Infection of Human Alveolar Type II Epithelial A549 Cells
Letter to the EditorDetection of Mobile Colistin Resistance Gene mcr-10.1 in a Conjugative Plasmid from Enterobacter roggenkampii of Chicken Origin in China
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