Abstract：
:The fungal pathogen Cryptococcus neoformans poses a major threat to immunocompromised patients and is a leading killer of human immunodeficiency virus (HIV)-infected patients worldwide. Cryptococci are known to manipulate host macrophages and can either remain latent or proliferate intracellularly within the host phagocyte, a favourable niche that also renders them relatively insensitive to antifungal agents. Here we report an attempt to address this limitation by using a fluorescence-based drug screening method to identify potential inhibitors of intracellular proliferation of C. neoformans. The Prestwick Chemical Library(®) of FDA-approved small molecules was screened for compounds that limit the intracellular replication of a fluorescently-tagged C. neoformans reference strain (H99-GFP) in macrophages. Preliminary screening revealed 19 of 1200 compounds that could significantly reduce intracellular growth of the pathogen. Secondary screening and host cell cytotoxicity assays highlighted fendiline hydrochloride as a potential drug candidate for the development of future anticryptococcal therapies. Live cell imaging demonstrated that this Ca(2+) channel blocker strongly enhanced phagosome maturation in macrophages leading to improved fungal killing and reduced intracellular replication. Whilst the relatively high dose of fendiline hydrochloride required renders it unfit for clinical deployment against cryptococcosis, this study highlights a novel approach for identifying new lead compounds and unravels a pharmacologically promising scaffold towards the development of novel antifungal therapies for this neglected disease.
journal_name
Int J Antimicrob Agentsjournal_title
International journal of antimicrobial agentsauthors
Samantaray S,Correia JN,Garelnabi M,Voelz K,May RC,Hall RAdoi
10.1016/j.ijantimicag.2016.04.018subject
Has Abstractpub_date
2016-07-01 00:00:00pages
69-77issue
1eissn
0924-8579issn
1872-7913pii
S0924-8579(16)30096-6journal_volume
48pub_type
杂志文章abstract：:Macrolides have been reported to modify the host immune and inflammatory responses both in vivo and in vitro. We examined the in vitro effect of the macrolides tilmicosin and tylosin, which are only used in the veterinary clinic, on the production of nitric oxide (NO), prostaglandin E(2) (PGE(2)) and cytokines by lipo...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2005.12.010
更新日期：2006-05-01 00:00:00
abstract：:Recent studies have found an association between piperacillin/tazobactam when added to vancomycin and acute kidney injury (AKI) risk. However, studies were limited by the small sample size and residual confounding. The aim of this study was to compare the risk of AKI with vancomycin plus piperacillin/tazobactam (VPT) ...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2017.02.023
更新日期：2017-07-01 00:00:00
abstract：:Knowing the ability of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to bind to the angiotensin-converting enzyme 2 (ACE2) receptor and to enter cells via endocytosis paved the way for repositioning of old drugs as potential treatment of COVID-19, the disease caused by SARS-CoV-2 infection. This paper h...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2020.106192
更新日期：2020-12-01 00:00:00
abstract：:The epidemiology of multidrug-resistant bacteria (MDRB) has changed significantly in European healthcare settings, with a decrease in frequency of meticillin-resistant Staphylococcus aureus and an increase in extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. Little is known about the effects of these ...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2015.07.010
更新日期：2015-11-01 00:00:00
abstract：:There is strong evidence that self-monitoring and feedback are effective behaviour change techniques (BCTs) across a range of healthcare interventions and that their effectiveness is enhanced by goal setting and action planning. Here we report a summary of the update of a systematic review assessing the application of...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,评审
doi：10.1016/j.ijantimicag.2014.11.014
更新日期：2015-03-01 00:00:00
abstract：:Pseudomonas aeruginosa (PA) is a major cause of healthcare-associated infections. Antipseudomonal carbapenems are among the antimicrobial agents used to treat PA infections, but several mechanisms of resistance, including the production of a carbapenemase (CP), may compromise their clinical efficacy. The objectives of...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2020.105959
更新日期：2020-06-01 00:00:00
abstract：:New initiatives have been introduced in Europe and the USA to encourage more rapid development of antibiotics. The need to ensure these new antibiotics can be safely used in children, and especially neonates, is important owing to high antimicrobial resistance in these patient groups. This review aims to determine wha...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,评审
doi：10.1016/j.ijantimicag.2013.05.001
更新日期：2013-08-01 00:00:00
abstract：:Carbapenemase-producing (CP) Pseudomonas aeruginosa is rare compared with mutation-driven carbapenem-resistance, but this situation may be changing. A collection of CP P. aeruginosa isolates was characterized in this study. In 2016, 232 unduplicated carbapenem-resistant P. aeruginosa isolates, of which 71 (30.6%) carr...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2020.106026
更新日期：2020-07-01 00:00:00
abstract：:Exposure of Aspergillus fumigatus to stressful antifungal therapies may result in decreased susceptibility. The aim of the present work was to evaluate the susceptibility to azole and non-azole antifungals of 159 isolates of A. fumigatus collected from cystic fibrosis (CF) patients receiving azole antifungal therapy. ...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2009.12.007
更新日期：2010-04-01 00:00:00
abstract：:To describe the relationship between the ratio of the 24-h area under the concentration-time curve (AUC(24)) to minimum inhibitory concentration (MIC) as well as the effect of linezolid on Staphylococcus aureus, the killing kinetics of three S. aureus strains was studied by in vitro simulation of 5-day antibiotic dosi...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2008.09.006
更新日期：2009-03-01 00:00:00
abstract：:Mechanisms leading to carbapenem and cephalosporin resistance were sought in Enterobacter aerogenes isolates that were highly resistant to carbapenems but had no known carbapenemase. Results were compared with recent work examining carbapenem-resistant Enterobacter cloacae. Eighteen carbapenem-resistant E. aerogenes w...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2016.07.021
更新日期：2016-11-01 00:00:00
abstract：:Antimicrobial resistance is a major health problem worldwide, but marked variations in the resistance profiles of bacterial pathogens are found between countries and in different patient settings, especially in Asia. In Taiwan, the strikingly high prevalence of resistance to macrolides and streptogramins in clinical i...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,评审
doi：10.1016/S0924-8579(08)70023-2
更新日期：2008-11-01 00:00:00
abstract：:Antimicrobial susceptibility testing plays a key role in clinical microbiology. The disk diffusion test dates back to the 1940s and became standardised from the 1950s, with the International Collaborative Study (ICS) and National Committee for Clinical Laboratory Standards (NCCLS) as the two major standards. Interlabo...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,评审
doi：10.1016/j.ijantimicag.2011.04.006
更新日期：2011-10-01 00:00:00
abstract：:The celestial rise in antibiotic resistance among Gram-negative bacteria has challenged both the scientific and pharmaceutical sectors. The hallmark of this general increase is the unbridled dissemination of carbapenem resistance genes, namely KPC, OXA and metallo-β-lactamase variants. In particular, the media attenti...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章,评审
doi：10.1016/S0924-8579(10)70004-2
更新日期：2010-11-01 00:00:00
abstract：:Biofilms are complex bacterial structures protected by a self-produced polymer matrix that enables survival in hostile environments. Biofilms are more resistant to antibiotics than their planktonic counterparts and are therefore more difficult to eradicate. The aim of this study was to investigate the influence of van...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2013.12.003
更新日期：2014-03-01 00:00:00
abstract：:In this study, 183 Salmonella enterica isolates were characterised for integrons and virulence genes. Among the isolates, 46% were positive for intI1, but no isolates carried intI2 or intI3. Eighteen class 1 integrons (21%) contained resistance gene cassettes (i.e. dfrA1-orfC, dfrA12-aadA2, bla(PSE-1) and aadA2) and f...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2010.12.001
更新日期：2011-05-01 00:00:00
abstract：:The pharmacokinetic/pharmacodynamic (PK/PD) index for the efficacy of linezolid is a 24-h area under the plasma drug concentration-time curve (AUC₂₄)/minimum inhibitory concentration (MIC) ratio of ≥100. The main adverse event associated with administration of linezolid is thrombocytopenia. Therefore, the aims of the ...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2014.05.010
更新日期：2014-09-01 00:00:00
abstract：:The infecting pathogen and its susceptibility to antibiotics is used to suggest prognosis in endocarditis. A case study was performed in a tertiary referral cardiology centre to assess the contribution of the measurement of minimum inhibitory concentration (MIC) to the decision to treat endocarditis surgically. The re...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2003.08.012
更新日期：2004-04-01 00:00:00
abstract：:Nationwide monitoring of antimicrobial resistance in Campylobacter isolated from food-producing animals on farms was performed in Japan. A total of 468 Campylobacter isolates were obtained during the period from June 1999 to March 2001. Campylobacter species showed high frequencies of resistance to oxytetracycline and...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2004.03.017
更新日期：2004-09-01 00:00:00
abstract：:Consecutive adult patients admitted to the hospital with community-acquired pneumonia from January 2000 to September 2003 were included in this prospective observational cohort study. A total of 459 patients, 259 treated with levofloxacin in single drug therapy at a dose of 500 mg once a day and 209 with the combinati...
journal_title：International journal of antimicrobial agents
pub_type： 临床试验,杂志文章
doi：10.1016/j.ijantimicag.2004.07.013
更新日期：2005-01-01 00:00:00
abstract：:The antibacterial effects of six inorganic antibacterial agents were assessed using broth dilution and agar dilution tests on six pathogenic bacteria associated with oral infectious diseases: Streptococcus mutans (ATCC 25175), S. mutans (Ingbritt), Actinomyces viscosus (ATCC 15987), Lactobacillus casei (ATCC 393), Sta...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2006.01.008
更新日期：2006-06-01 00:00:00
abstract：:The pharmacodynamic profile of modithromycin (EDP-420, EP-013420, S-013420), a novel bicyclolide, was evaluated in a neutropenic pneumococcal murine pneumonia model. Streptococcus pneumoniae median minimum inhibitory concentrations (MICs) for five genotypically diverse isolates ranged from 0.016 μg/mL to 0.125 μg/mL a...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2014.01.029
更新日期：2014-06-01 00:00:00
abstract：:The emergence of multidrug-resistant (MDR) Gram-negative bacteria has become a major public health problem, eliciting renewed interest in colistin, an old antibiotic that is now routinely used to treat MDR bacterial infections. Here we investigated whether colistin use has affected the prevalence of infections due to ...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2014.10.010
更新日期：2015-02-01 00:00:00
abstract：:One hundred and seventy-seven strains of Streptococcus pneumoniae derived from respiratory specimens between 1987 and 2001 were evaluated for their antimicrobial susceptibilities and distribution of genes related to penicillin and macrolide resistance. Resistance rates tended to be higher for the 1996-2001 isolates th...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2004.02.024
更新日期：2004-08-01 00:00:00
abstract：:Strains of Salmonella typhi resistant to chloramphenicol and ampicillin have been isolated in several countries. This study compares treatment of Salmonella infection using ciprofloxacin (500 mg twice daily) for 10 days with chloramphenicol (50 mg/kg per day divided into four doses) for 14 days. The pathogen eradicati...
journal_title：International journal of antimicrobial agents
pub_type： 临床试验,杂志文章
doi：10.1016/s0924-8579(00)00262-4
更新日期：2000-11-01 00:00:00
abstract：:Lactoferrin is a glycoprotein and plays an important role in defence against pathogens. Although the antiviral activity of lactoferrin is one of the major biological functions of such protein, the mechanism of action is still under debate. The effect of lactoferrin on echovirus 6 infection in vitro was analysed and re...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2005.02.011
更新日期：2005-05-01 00:00:00
abstract：:Visceral leishmaniasis (VL), caused by the protozoan Leishmania sp., affects 500000 people annually, with the Indian subcontinent contributing a significant proportion of these cases. Emerging refractoriness to conventional antimony therapy has emphasised the need for safer yet effective antileishmanial drugs. Artemis...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2010.03.008
更新日期：2010-07-01 00:00:00
abstract：:The objective of this study was to comprehensively identify the target genes regulated by the two-component regulatory system VraSR in Staphylococcus aureus and to clarify the role of VraSR in low-level vancomycin resistance. Expression of vraS was determined by real-time quantitative reverse transcriptase PCR (qRT-PC...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2016.02.003
更新日期：2016-05-01 00:00:00
abstract：:Depending on the severity of the clinical syndrome, acute pyelonephritis may require more extensive imaging diagnostics. In the uncomplicated form of the disease, ultrasonography does not appear to be absolutely necessary. In clinically severe cases, however, which fail to respond to antibiotic therapy, ultrasound is ...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/s0924-8579(99)00026-6
更新日期：1999-05-01 00:00:00
abstract：:Although cephalosporins are recommended as primary agents, moxifloxacin may be a suitable second-line antibiotic in cardiac surgery, especially if additional Gram-negative coverage is warranted. Cardiopulmonary bypass (CPB) may alter the pharmacokinetics of drugs in numerous ways. Since no such data exist, the aim of ...
journal_title：International journal of antimicrobial agents
pub_type： 杂志文章
doi：10.1016/j.ijantimicag.2013.01.017
更新日期：2013-05-01 00:00:00
