Abstract:
:The nucleotide phosphonates cidofovir (CDV) and cyclic cidofovir (cCDV) are potent antiviral compounds when administered parenterally but are not well absorbed orally. These compounds have been reported to have activity against orthopoxvirus replication in vitro and in animal models when administered parenterally or by aerosol. To obtain better oral activity, we synthesized a novel series of analogs of CDV and cCDV by esterification with two long-chain alkoxyalkanols, 3-hexadecyloxy-1-propanol (HDP-CDV; HDP-cCDV) or 3-octadecyloxy-1-ethanol (ODE-CDV; ODE-cCDV). Their activities were evaluated and compared with those of CDV and cCDV in human foreskin fibroblast (HFF) cells infected with vaccinia virus (VV) or cowpox virus (CV) using a plaque reduction assay. The 50% effective concentrations (EC(50)s) against VV in HFF cells for CDV and cCDV were 46.2 and 50.6 microM compared with 0.84 and 3.8 microM for HDP-CDV and HDP-cCDV, respectively. The EC(50)s for ODE-CDV and ODE-cCDV were 0.20 and 1.1 microM, respectively. The HDP analogs were 57- and 13-fold more active than the parent nucleotides, whereas the ODE analogs were 231- and 46-fold more active than the unmodified CDV and cCDV. Similar results were obtained using CV. Cytotoxicity studies indicated that although the analogs were more toxic than the parent nucleotides, the selective index was increased by 4- to 13-fold. These results indicate that the alkoxyalkyl esters of CDV and cCDV have enhanced activity in vitro and need to be evaluated for their oral absorption and efficacy in animal models.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Kern ER,Hartline C,Harden E,Keith K,Rodriguez N,Beadle JR,Hostetler KYdoi
10.1128/aac.46.4.991-995.2002subject
Has Abstractpub_date
2002-04-01 00:00:00pages
991-5issue
4eissn
0066-4804issn
1098-6596journal_volume
46pub_type
杂志文章abstract::Chronic airway infection and inflammation contribute to the progressive loss of lung function and shortened survival of patients with cystic fibrosis (CF). Rhesus theta defensin-1 (RTD-1) is a macrocyclic host defense peptide with antimicrobial and immunomodulatory activities. Combined with favorable preclinical safet...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00154-17
更新日期:2017-07-25 00:00:00
abstract::Invasive pulmonary aspergillosis (IPA) is a devastating disease of immunocompromised patients. Pharmacodynamic (PD) examination of antifungal drug therapy in IPA is one strategy that may improve outcomes. The current study explored the PD target of posaconazole in an immunocompromised murine model of IPA against 10 A....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01279-12
更新日期:2013-01-01 00:00:00
abstract::We report the identification of a carbapenem-resistant, hypervirulent Klebsiella pneumoniae (hvKp) strain which produced the carbapenemase VIM-1. Genomic analysis showed that the strain belonged to sequence type ST23 and serotype K1, a major hvKp clone, and harbored three resistance-encoding plasmids. Among them, a bl...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01056-19
更新日期:2019-08-23 00:00:00
abstract::The potential of bacteriophage therapy to treat infections caused by antibiotic-resistant bacteria has now been well established using various animal models. While numerous newly isolated bacteriophages have been claimed to be potential therapeutic candidates on the basis of in vitro observations, the parameters used ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01596-13
更新日期:2013-12-01 00:00:00
abstract::The in vitro activities of the new triazole, ravuconazole (BMS-207147), were compared to those of fluconazole and itraconazole against 541 clinical isolates of Cryptococcus neoformans. Isolates were obtained from cerebrospinal fluid (396), blood (116), and miscellaneous clinical specimens (29). Overall, ravuconazole (...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.10.2883-2886.2000
更新日期:2000-10-01 00:00:00
abstract::The susceptibilities of 87 periodontitis-associated strains of Actinobacillus actinomycetemcomitans to clarithromycin and erythromycin were determined by standard methodology recommended for Haemophilus influenzae. For clarithromycin the MIC at which 90% of the isolates were inhibited was =2.0 microg/ml and the mini...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.11.3000
更新日期:1998-11-01 00:00:00
abstract::The epileptogenic activity of imipenem was investigated in rats with experimental renal failure induced by uranyl nitrate injection by using electroencephalogram (EEG) recording and a pharmacokinetic-pharmacodynamic model including an effect compartment. Results previously obtained with healthy rats were used to estim...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.12.3607-3609.2001
更新日期:2001-12-01 00:00:00
abstract::The use of gentamicin to control contamination in a tissue culture system for the isolation of Chlamydia was investigated. Gentamicin, at concentrations up to 100 mug/ml, did not appear to inhibit the growth of stock chlamydial strains, as judged by assays for iodine-staining inclusions. When 343 cervical and urethral...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.3.6.698
更新日期:1973-06-01 00:00:00
abstract::The spectrum of activity of levofloxacin was initially determined against 29 strains belonging to 16 species of atypical mycobacteria by measuring radiometric MICs. Levofloxacin MICs were 1 to 2 dilutions lower compared with those obtained for ofloxacin and 8 to 64 dilutions lower compared with those obtained for its ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.11.2483
更新日期:1996-11-01 00:00:00
abstract::Mycobacterium abscessus is increasingly recognized as an emerging opportunistic pathogen causing severe lung diseases. As it is intrinsically resistant to most conventional antibiotics, there is an unmet medical need for effective treatments. Repurposing of clinically validated pharmaceuticals represents an attractive...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00363-20
更新日期:2020-10-20 00:00:00
abstract::Compounds that interact with DNA or RNA generally act as inhibitors of enzymes that unwind DNA or RNA. In the present study we describe the synthesis and properties of some nucleoside analogues that interact with double-stranded DNA but that, in contrast, facilitate the unwinding reaction mediated by West Nile (WN) vi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.5.1231-1239.2002
更新日期:2002-05-01 00:00:00
abstract::A practical preclinical model for the hyperbilirubinemia produced by human immunodeficiency virus protease inhibitors has been developed. Indinavir and atazanavir produced significant hyperbilirubinemia, whereas amprenavir, the negative control, was indistinguishable from the ritonavir booster dose. This model was use...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.2.762-764.2006
更新日期:2006-02-01 00:00:00
abstract::The JAK-STAT pathway is activated in both macrophages and lymphocytes upon human immunodeficiency virus type 1 (HIV-1) infection and thus represents an attractive cellular target to achieve HIV suppression and reduced inflammation, which may impact virus sanctuaries. Ruxolitinib and tofacitinib are JAK1/2 inhibitors t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02496-13
更新日期:2014-01-01 00:00:00
abstract::Of the 176 randomly selected, commensal, gram-negative bacteria isolated from healthy children with low exposure to antibiotics, 138 (78%) carried one or more of the seven macrolide resistance genes tested in this study. These isolates included 79 (91%) isolates from the oral cavity and 59 (66%) isolates from urine sa...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.9.3451-3456.2004
更新日期:2004-09-01 00:00:00
abstract::The recent escalation of occurrences of carbapenem-resistant Pseudomonas aeruginosa has been recognized globally and threatens to erode the widespread clinical utility of the carbapenem class of compounds for this prevalent health care-associated pathogen. Here, we compared the in vitro inhibitory activity of ceftazid...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.00875-17
更新日期:2017-09-22 00:00:00
abstract::Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the last remaining options for first-line gonorrhea treatment, was isolated in Japan. Here, we confirm and characterize a second strain (F89) with high-level cefix...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05760-11
更新日期:2012-03-01 00:00:00
abstract::The biological availability of cefoxitin administered rectally in the form of suppositories was examined in six human subjects by a cross-over design. Four different suppository systems containing adjuvants expected to enhance the absorption of the drug were studied. The presence of sodium salicylate and a nonionic su...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/aac.28.2.211
更新日期:1985-08-01 00:00:00
abstract::Strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger were tested for in vitro susceptibility to amphotericin B alone and in combination with fixed concentrations of tetracycline, doxycycline, or minocycline, using buffered minimal essential medium in microtiter plates. Enhanced inhibitory activi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.6.837
更新日期:1984-12-01 00:00:00
abstract::A brief therapeutic regimen of praziquantel, reduced to a single day, has been effective for treatment of neurocysticercosis. To study its pharmacokinetic characteristics, levels of praziquantel in plasma were determined for eight healthy volunteers after the administration of three oral doses of 25 mg/kg of body weig...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1128/AAC.41.6.1256
更新日期:1997-06-01 00:00:00
abstract::Exposure of any of six clinical isolates of Staphylococcus aureus to daptomycin alone or in combination with vancomycin or oxacillin (compared with vancomycin or oxacillin alone) led to a dampened macrophage inflammatory response with diminished tumor necrosis factor secretion and reduced accumulation of inducible nit...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01559-05
更新日期:2006-06-01 00:00:00
abstract::Prior investigations have suggested the use of a dosing weight correction factor of ideal body weight (IBW) plus 40% excess body weight (EBW, where EBW = total body weight [TBW] - IBW) to determine the weight to use for aminoglycoside dosing in morbidly obese (TBW/IBW ratio, > 2) patients. Little data are available to...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.2.545
更新日期:1995-02-01 00:00:00
abstract::The global spread of carbapenem-resistant Klebsiella pneumoniae (CR-Kp) has been largely associated with sequence type 258 (ST258) and its related variants (clonal group 258 [CG258]). Here we describe the molecular epidemiology of CR-Kp from five tertiary care hospitals in Medellín, the second largest city in Colombia...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.01775-15
更新日期:2015-10-26 00:00:00
abstract::Viridin B, a bacteriocin produced by Streptococcus mitis, copurified with the alpha-hemolysin after ammonium sulfate precipitation and gel filtration on Sephadex G-200. The bacteriocin and hemolysin were separated in some instances by ion-exchange chromatography on diethylaminoethyl-Sephadex A-50, but the two substanc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.3.436
更新日期:1979-03-01 00:00:00
abstract::Despite being genetically monomorphic, the limited genetic diversity within the Mycobacterium tuberculosis complex (MTBC) has practical consequences for molecular methods for drug susceptibility testing and for the use of current antibiotics and those in clinical trials. It renders some representatives of MTBC intrins...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,评审
doi:10.1128/AAC.01641-12
更新日期:2012-12-01 00:00:00
abstract::Platelet microbicidal proteins (PMPs) are believed to be integral to host defense against endovascular infection. We previously demonstrated that susceptibility to thrombin-induced PMP 1 (tPMP-1) in vitro negatively influences Candida albicans virulence in the rabbit model of infective endocarditis (IE). This study ev...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.8.3051-3056.2004
更新日期:2004-08-01 00:00:00
abstract::Ciprofloxacin, a fluorinated 4-quinolone, is useful for the clinical treatment of infections due to its antibacterial properties and also modulates the immune response of monocytes isolated from human peripheral blood mononuclear cells. In the present study, we found that ciprofloxacin induced the production of prosta...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.8.3228-3233.2005
更新日期:2005-08-01 00:00:00
abstract::The in vitro susceptibility of 406 clinical isolates to BMY-28142, a new semisynthetic cephem, was evaluated and compared with cefpimizole, HR 810, ceftazidime, cefotaxime, moxalactam, and cefoperazone in a broth microdilution assay. On a weight basis, the activity of BMY-28142 against Escherichia coli, Proteus specie...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.27.4.515
更新日期:1985-04-01 00:00:00
abstract::Macrolide-resistant group A streptococci (MRGAS) have been recovered from many countries worldwide. However, the strain typing information that is available has been insufficient for estimating the total number of macrolide-resistant clones, their geographic distributions, and their evolutionary relationships. In this...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00325-06
更新日期:2006-09-01 00:00:00
abstract::The in vitro activities of ceftaroline and comparators, using broth microdilution, were determined against 1,066 Staphylococcus aureus isolates from hospitalized patients. Seventeen medical centers from Latin American countries contributed isolates. Methicillin-resistant S. aureus (MRSA) percentages ranged from 46% (B...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.01833-15
更新日期:2015-12-01 00:00:00
abstract::The mechanism of penetration of quinolones through the bacterial outer membrane was studied with lipopolysaccharide-deficient and porin-deficient mutants. The data indicated that the lipopolysaccharide layer might form a permeability barrier for hydrophobic quinolones such as nalidixic acid but not for hydrophilic qui...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.3.535
更新日期:1986-03-01 00:00:00