Abstract:
:Bumped kinase inhibitors (BKIs) are effective against a variety of apicomplexan parasites. Fifteen BKIs with promising in vitro efficacy against Neospora caninum tachyzoites, low cytotoxicity in mammalian cells, and no toxic effects in non-pregnant BALB/c mice were assessed in pregnant mice. Drugs were emulsified in corn oil and were applied by gavage for 5 days. Five BKIs did not affect pregnancy, five BKIs exhibited ~15-35% neonatal mortality and five compounds caused strong effects (infertility, abortion, stillbirth and pup mortality). Additionally, the impact of these compounds on zebrafish (Danio rerio) embryo development was assessed by exposing freshly fertilised eggs to 0.2-50 μM of BKIs and microscopic monitoring of embryo development in a blinded manner for 4 days. We propose an algorithm that includes quantification of malformations and embryo deaths, and established a scoring system that allows the calculation of an impact score (Si) indicating at which concentrations BKIs visibly affect zebrafish embryo development. Comparison of the two models showed that for nine compounds no clear correlation between Si and pregnancy outcome was observed. However, the three BKIs affecting zebrafish embryos only at high concentrations (≥40 μM) did not impair mouse pregnancy at all, and the three compounds that inhibited zebrafish embryo development already at 0.2 μM showed detrimental effects in the pregnancy model. Thus, the zebrafish embryo development test has limited predictive value to foresee pregnancy outcome in BKI-treated mice. We conclude that maternal health-related factors such as cardiovascular, pharmacokinetic and/or bioavailability properties also contribute to BKI-pregnancy effects.
journal_name
Int J Antimicrob Agentsjournal_title
International journal of antimicrobial agentsauthors
Anghel N,Winzer PA,Imhof D,Müller J,Langa X,Rieder J,Barrett LK,Vidadala RSR,Huang W,Choi R,Hulverson MA,Whitman GR,Arnold SL,Van Voorhis WC,Ojo KK,Maly DJ,Fan E,Hemphill Adoi
10.1016/j.ijantimicag.2020.106099subject
Has Abstractpub_date
2020-09-01 00:00:00pages
106099issue
3eissn
0924-8579issn
1872-7913pii
S0924-8579(20)30280-6journal_volume
56pub_type
杂志文章abstract::Treatment options for multidrug-resistant (MDR) strains of Acinetobacter baumannii that acquire resistance to colistin are limited. Acinetobacter baumannii can become highly resistant to colistin through complete loss of lipopolysaccharide (LPS) owing to mutations in the genes encoding the first three enzymes involved...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2015.07.017
更新日期:2015-12-01 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::Recently, a novel coronavirus (2019-nCoV), officially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China. Despite drastic containment measures, the spread of this virus is ongoing. SARS-CoV-2 is the aetiological agent of coronavirus disease 2019 (COVID-19) characterised by pulmonar...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2020.105938
更新日期:2020-05-01 00:00:00
abstract::Other researchers have found that diethylcarbamazine (DEC) is effective treatment for filariasis despite a lack of demonstrated in vitro antifilarial activity. The results of our previous investigations using feline and murine leukemia virus models encouraged us to investigate the use of DEC with other infections. In ...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/0924-8579(92)90037-r
更新日期:1992-09-01 00:00:00
abstract::As shown in a previous study, the outcome of multidrug-resistant tuberculosis (MDR-TB) in France is not satisfactory (41% success rate). To improve the management and outcome of patients with MDR-TB, a prospective intervention study was carried out in 1998-1999 by National Reference Centre (NRC) staff. NRC staff conta...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2006.11.023
更新日期:2007-04-01 00:00:00
abstract::We evaluated the antimicrobial activity of fusidic acid (CEM-102) against 1140 clinical strains of Gram-positive bacteria obtained from patients with bacteraemia or skin and skin-structure infections collected in more than 30 medical centres in the USA and Canada over a 10-year period (1997-2006). Fusidic acid was ver...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2009.10.023
更新日期:2010-03-01 00:00:00
abstract::Molecular epidemiology studies aiming at understanding the acquisition of antimicrobial resistance by clinical isolates of Klebsiella pneumoniae are regularly published; however, information on the genes that contribute to its characteristic phenotype of resistance to antibiotics (intrinsic resistome) is scarce. To fi...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2018.09.012
更新日期:2019-01-01 00:00:00
abstract::Aspergillus flavus is the second most common Aspergillus spp. causing invasive infections in immunocompromised patients. Extensive prophylactic use of voriconazole (VCZ) in immunocompromised patients may enhance the selection of VCZ-resistant clinical isolates of A. flavus, compromising the effectiveness of this antif...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2008.06.018
更新日期:2008-12-01 00:00:00
abstract::The objective of this study was to better understand the in vitro activity of flomoxef against clinical extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae. A total of 401 ESBL-producing isolates, including 196 Escherichia coli, 124 Klebsiella pneumoniae and 81 Proteus mirabilis, were collected consecuti...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2014.11.012
更新日期:2015-05-01 00:00:00
abstract::The aim of this study was to develop an in-vitro topical treatment for Acanthamoeba keratitis (AK) effective against cysts and trophozoites. Qualitative assays were performed with voriconazole, chlorhexidine, propamidine, cellulase, tobramycin, ciprofloxacin and paromomycin as monotherapy and various combinations. Rib...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2017.03.033
更新日期:2017-09-01 00:00:00
abstract::The in vitro susceptibilities to several antibiotics of 136 Escherichia coli strains containing virulence factors isolated from children with urinary tract infection were analysed. Escherichia coli strains were analysed by multiplex polymerase chain reaction for genes encoding the following virulence factors: pyelonep...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2007.07.030
更新日期:2008-02-01 00:00:00
abstract::Escherichia coli O25b-B2-ST131 isolates harbouring bla(CTX-M-15) are distributed worldwide. The bla(CTX-M-15) transposition unit has often been found on plasmids and the genetic contexts have been examined; however, less is known about the frequency and contexts of the bla(CTX-M-15) transposition unit on the chromosom...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2013.08.005
更新日期:2013-12-01 00:00:00
abstract::Cross-protection by anti-lipid A antibodies may be mediated by contribution to host defence mechanisms such as enhancement of bactericidal activity and phagocytosis. The lipid A-specific murine monoclonal antibody (mAb) E5 was evaluated in vitro for its ability to enhance antibacterial effects in concert with antibiot...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/0924-8579(94)90008-6
更新日期:1994-08-01 00:00:00
abstract::Although the vancomycin minimum inhibitory concentration (VMIC) susceptibility breakpoint for Staphylococcus aureus was recently lowered to ≤2 mg/L, it is argued that isolates in the higher levels of the susceptible range may bear adverse clinical outcomes. Clinical outcomes (all-cause mortality and treatment failure)...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.ijantimicag.2012.07.023
更新日期:2012-12-01 00:00:00
abstract::The aim of this review was to evaluate the susceptibility of contemporary Gram-positive and Gram-negative bacteria to fosfomycin. PubMed and Scopus databases were systematically searched to identify studies published in print or electronically from January 2010 until June 2015. In total, 84 studies were selected. Susc...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章,评审
doi:10.1016/j.ijantimicag.2016.02.001
更新日期:2016-04-01 00:00:00
abstract::In this study, 2275 clinical isolates of 49 species of non-tuberculous mycobacteria isolated in The Netherlands were subjected to standardised drug susceptibility testing using the Middlebrook 7H10 agar dilution method. Clarithromycin and rifabutin were most active, with 87% and 83% of all isolates, respectively, bein...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2009.09.023
更新日期:2010-02-01 00:00:00
abstract::With the abuse of macrolide, lincosamide, and streptogramin (MLS), the traditionally safe bifidobacterial strains in the human intestine could serve as a reservoir of MLS resistance genes. In this study, the erm(X) gene was detected in 29 MLS-resistant strains and one MLS-susceptible strain among 92 bifidobacterial st...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2017.04.007
更新日期:2017-10-01 00:00:00
abstract::Infestation with parasitic helminths is a common problem in human populations of third world countries and is ubiquitous in livestock and other domestic animals. The cell-membrane efflux pump, P-glycoprotein (Pgp), appears to contribute to anthelmintic resistance. Pgp have been identified from both phyla of parasitic ...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章,评审
doi:10.1016/s0924-8579(03)00221-8
更新日期:2003-09-01 00:00:00
abstract::Integrase strand transfer inhibitors (INSTIs) are the most recent class of antiretroviral drugs with potent and durable antiviral activity used to treat human immunodeficiency virus type 1 (HIV-1) infection. However, development of drug resistance increases the risk of treatment failure, disease progression and mortal...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.ijantimicag.2019.08.008
更新日期:2019-11-01 00:00:00
abstract::This study aimed to identify factors associated with virological response (VR) to raltegravir (RAL)-containing regimens in 468 treatment-experienced but integrase inhibitor-naive HIV-1 patients receiving a RAL-containing regimen. VR was defined at Month 6 (M6) as HIV-1 RNA viral load (VL) <50 copies/mL. The impacts on...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2013.02.016
更新日期:2013-07-01 00:00:00
abstract::The epidemiology of invasive fungal infections is currently at a crucial stage. Potentially fatal fungal strains are emerging that are resistant to many commonly used antifungal agents. It is therefore important to recognize and minimize the major risk factors associated with infection. This paper summarizes the key e...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章,评审
doi:10.1016/j.ijantimicag.2006.03.006
更新日期:2006-06-01 00:00:00
abstract::The bactericidal activity and resistance selectivity of garenoxacin against Streptococcus pneumoniae with mutations in ParC (S79F) or both GyrA (S81F) and ParC (D83Y and K137N) were investigated using in vitro pharmacokinetic models simulating plasma concentrations for a standard clinical regimen [400mg once daily (q....
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2011.09.021
更新日期:2012-02-01 00:00:00
abstract::Recent basic and clinical research efforts have shed more light on the taxonomy, microbiology, epidemiology, antimicrobial susceptibility and treatment of Bacteroides, Prevotella, and Porphyromonas species. Of all anaerobic bacteria, Bacteroides is the most frequently isolated pathogen from clinical specimens, includi...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章,评审
doi:10.1016/s0924-8579(99)00164-8
更新日期:2000-06-01 00:00:00
abstract::Therapeutic drug monitoring for critically ill patients receiving piperacillin/tazobactam is described as a useful tool. However, the minimum inhibitory concentration of piperacillin depends on a sufficiently high concentration of tazobactam in case of β-lactamase-producing strains. Therefore, the relationship between...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2016.06.013
更新日期:2016-10-01 00:00:00
abstract::Triple therapy combining the protease inhibitor telaprevir with interferon-α and ribavirin is a promising new option for long-term treatment of hepatitis C. The interaction potential of telaprevir has not yet been fully elucidated. The in vitro potency of telaprevir to inhibit P-glycoprotein (P-gp, ABCB1) and breast c...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2013.10.003
更新日期:2014-02-01 00:00:00
abstract::A gerbil model of acute otitis media induced by Streptococcus pneumoniae plus Haemophilus influenzae was used to assess the efficacy of amoxicillin/clavulanic acid (A/C) (1.5/0.3, 2.5/0.5 and 10/2 mg/kg) and erythromycin (2.5, 10, 20 and 50 mg/kg) with or without acetaminophen. The amoxicillin/clavulanic acid MIC was ...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2003.05.016
更新日期:2004-01-01 00:00:00
abstract:OBJECTIVES:To compare the in vitro activity of linezolid with 12 other antimicrobials against 190 strains of the coryneform bacteria, including 60 strains of C. amycolatum, 30 of C. striatum, 30 of C. jeikeium, 10 of C. urealyticum, 20 of B. casei, 20 of D. hominis and 20 of T. otitidis. METHODS:Minimum inhibitory con...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2006.11.032
更新日期:2007-06-01 00:00:00
abstract::In this study, the prevalence and characteristics of metallo-β-lactamase (MBL)-producing Pseudomonas aeruginosa isolates in South Korea were investigated. Among 215 P. aeruginosa isolates collected from eight hospitals, 77 (35.8%) and 72 (33.5%) were resistant to imipenem and meropenem, respectively. Of the 77 imipene...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2017.01.023
更新日期:2017-06-01 00:00:00
abstract:BACKGROUND:Tuberculosis (TB) causes 25% of all deaths among individuals infected with human immunodeficiency virus (HIV). Rifampicin (RIF) is a potent inducer of drug metabolizing enzymes and drug transporters, and co-administration with dolutegravir (DTG) reduces DTG exposure; this can be overcome by doubling the DTG ...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/j.ijantimicag.2019.04.009
更新日期:2019-08-01 00:00:00
abstract::Methicillin-resistant Staphylococcus aureus (MRSA) is a worldwide important pathogen in nosocomial infections. To investigate the extent of the problem in Taiwan, analysis for the period of 1981-1994 was carried out of prospective surveillance data from the National Taiwan University Hospital, a major university teach...
journal_title:International journal of antimicrobial agents
pub_type: 杂志文章
doi:10.1016/s0924-8579(96)00360-3
更新日期:1997-03-01 00:00:00