Abstract:
:Human cytomegalovirus (HCMV) infection does not generally cause problems in the immunocompetent adult but can result in severe clinical disease in the fetus, neonate, and immunocompromised host. Ganciclovir (GCV), the agent currently used to treat most HCMV infections, has resulted in much therapeutic success; however, efficacy remains suboptimal. Therefore, there is still a need to develop new compounds for use against HCMV infections. In the present study, several Z- and E-series methylenecyclopropane analogues and their phosphoroalaninate prodrugs were tested initially for activity against HCMV, strain AD169, and murine cytomegalovirus (MCMV) in vitro. Many were found to exhibit efficacy comparable to that of GCV against HCMV in plaque assays and were active against MCMV as well. The compounds were also tested for efficacy against herpes simplex virus types 1 and 2, varicella-zoster virus, and Epstein-Barr virus, and some had levels of activity that were comparable to that of acyclovir. In addition, the compounds synguanol (QYL-438) and 2-amino-6-cyclopropylamino analogue (QYL-769) were chosen for further evaluation and were found to be effective against additional laboratory and clinical isolates of HCMV and GCV-resistant isolates. QYL-438 and QYL-769 were found to be nontoxic in human and mouse fibroblasts and were considerably less toxic than GCV in granulocyte macrophage CFUs and erythroid burst-forming units. These results provide evidence for the high activity of some of these methylenecyclopropane analogues against various herpesviruses, particularly HCMV, in tissue culture and suggest that further evaluation is warranted to determine their potential for use in future clinical studies.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Rybak RJ,Hartline CB,Qiu YL,Zemlicka J,Harden E,Marshall G,Sommadossi JP,Kern ERdoi
10.1128/aac.44.6.1506-1511.2000subject
Has Abstractpub_date
2000-06-01 00:00:00pages
1506-11issue
6eissn
0066-4804issn
1098-6596journal_volume
44pub_type
杂志文章abstract::Penetration of fluconazole into female genital tissues was examined. Fluconazole was administered orally at a dose of 150 mg to patients undergoing total abdominal hysterectomy 1 to 151 h prior to surgery. During surgery, blood, uterus, ovary, and oviduct were sampled. Fluconazole concentrations in each tissue were de...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.43.1.148
更新日期:1999-01-01 00:00:00
abstract::Pulmonary infiltrates in neutropenic hosts with invasive aspergillosis are due to vascular invasion and hemorrhagic infarction. In order to measure the effect of antifungal compounds on this organism-mediated tissue injury, we monitored the course of pulmonary infiltrates by serial ultrafast computerized tomography (U...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.39.5.1065
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.50.1.73-79.2006
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abstract::Saccharomicins A and B, two new heptadecaglycoside antibiotics, were isolated from the fermentation broth of the rare actinomycete Saccharothrix espanaensis. They represent a novel class of bactericidal antibiotics that are active both in vitro and in vivo against bacteria and yeast (MICs: Staphylococcus aureus, <0.12...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.8.2154-2159.2000
更新日期:2000-08-01 00:00:00
abstract::Nucleobase and nucleoside transporters play central roles in the biochemistry of parasitic protozoa, as they lack the ability to synthesize purines de novo and are absolutely reliant upon purine salvage from their hosts. Furthermore, such transporters are potentially critical to the pharmacology of these important hum...
journal_title:Antimicrobial agents and chemotherapy
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abstract::Statins are inhibitors of cholesterol synthesis, but other biological properties, such as antimicrobial effects, have also been assigned to them, leading to their designation as pleiotropic agents. Our goal was to investigate the activity and selectivity of atorvastatin (AVA) against Trypanosoma cruzi by using in vitr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00979-18
更新日期:2018-08-27 00:00:00
abstract::Seventeen oral streptococci and 18 enterococci were tested for the presence of DNA sequences homologous to the conjugative transposon Tn916 encoding tetracycline resistance. All the strains were resistant to tetracyclines, including minocycline, and most of them were resistant to other antibiotics. Tn916-like structur...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.1.59
更新日期:1992-01-01 00:00:00
abstract::The pharmacokinetics of minocycline have been studied after single intravenous infusions and repeated oral doses to human subjects with varying degrees of renal impairment. There was no evidence of reduced drug clearance with reduced renal function after intravenous doses although there appeared to be an increase in t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.8.5.532
更新日期:1975-11-01 00:00:00
abstract::We conducted a randomized controlled trial of orally administered amifloxacin versus trimethoprimsulfamethoxazole (TMP-SMX) as treatments of acute uncomplicated urinary tract infection in women. Amifloxacin at a dosage of 200 mg twice a day appeared as safe and effective as TMP-SMX, but amifloxacin at 400 mg twice a d...
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.34.4.665
更新日期:1990-04-01 00:00:00
abstract::Oral Fusobacterium nucleatum populations from 20 young, healthy children were examined for beta-lactamase production. Ten children (50%) harbored, altogether, 25 beta-lactamase-positive F. nucleatum isolates that were identified as F. nucleatum subsp. polymorphum, F. nucleatum subsp. nucleatum, and F. nucleatum subsp....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.5.1270
更新日期:1999-05-01 00:00:00
abstract::Ga(3+) is a semimetal element that competes for the iron-binding sites of transporters and enzymes. We investigated the activity of gallium maltolate (GaM), an organic gallium salt with high solubility, against laboratory and clinical strains of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resista...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00700-09
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abstract::There has been a resurgence of interest in aerosolization of antibiotics for treatment of patients with severe pneumonia caused by multidrug-resistant pathogens. A combination formulation of amikacin-fosfomycin is currently undergoing clinical testing although the exposure-response relationships of these drugs have no...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01763-16
更新日期:2016-12-27 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.12.3053
更新日期:1998-12-01 00:00:00
abstract::Effervescent lozenges containing 10 mg of zinc acetate were evaluated as a treatment of upper respiratory tract infections in a double-blind randomized trial by using a placebo which was indistinguishable to most observers in taste and appearance from the active material. Of the 70 treatment courses used by 55 individ...
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.31.8.1263
更新日期:1987-08-01 00:00:00
abstract::Macrolide-resistant Mycoplasma pneumoniae (MR M. pneumoniae) has been isolated from clinical specimens in Japan since 2000. A comparative study was carried out to determine whether or not macrolides are effective in treating patients infected with MR M. pneumoniae. The clinical courses of 11 patients with MR M. pneumo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.2.709-712.2006
更新日期:2006-02-01 00:00:00
abstract::Triple antifungal combinations are used against refractory invasive aspergillosis without an adequate understanding of their pharmacodynamic interactions. We initially studied the in vitro triple combination of voriconazole, amphotericin B, and caspofungin against Aspergillus fumigatus, A. flavus, and A. terreus by a ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00873-06
更新日期:2007-06-01 00:00:00
abstract::A mouse model of cystitis caused by uropathogenic Escherichia coli was used to study the distribution of gallium in bladder tissue following oral administration of gallium maltolate during urinary tract infection. The median concentration of gallium in homogenized bladder tissue from infected mice was 1.93 μg/g after ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00616-13
更新日期:2013-11-01 00:00:00
abstract::Spectinomycin resistance in clinical isolates of Neisseria meningitidis and Neisseria gonorrhoeae was found to be due to mutations G1064C and C1192U (Escherichia coli numbering) in 16S rRNA genes, respectively. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.5.1365-1366.2000
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abstract::A potential pharmacokinetic interaction between rifampin (Rimactan, Rifadin) and zidovudine (AZT, Retrovir) was investigated in the population of human immunodeficiency virus-infected patients at our hospital. The results from four patients who were on long-term (> or = 6 months) combination therapy with zidovudine an...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.37.7.1426
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abstract::The mycobacterial phosphoglycosyltransferase WecA, which initiates arabinogalactan biosynthesis in Mycobacterium tuberculosis, has been proposed as a target of the caprazamycin derivative CPZEN-45, a preclinical drug candidate for the treatment of tuberculosis. In this report, we describe the functional characterizati...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.01310-17
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abstract::Solithromycin (CEM-101) is a new antibiotic that is highly potent against Ureaplasma and Mycoplasma spp. and active against many other antibiotic-resistant organisms. We have explored the maternal-amniotic-fetal pharmacokinetics of CEM-101 in a pregnant sheep model to assess its potential for treating intrauterine and...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.5.2.139
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00086-17
更新日期:2017-06-27 00:00:00
abstract::A novel stilbene glycoside [piceid-(1-->6)-beta-d-glucopyranoside; PBG] from Parthenocissus tricuspidata was tested in vivo against Plasmodium berghei. PBG exhibited significant blood schizontocidal activity in a 4-day early infection, a repository evaluation, and an established infection, with a significant mean surv...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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abstract::One hundred thirty nonimmune subjects living in Yaoundé, Cameroon, completed an 18-month prospective study on the efficacy and safety of weekly chloroquine and daily proguanil (chloroguanide) (Ch-P) in malaria prevention. A total of 9 of 78 Ch-P-treated subjects and 26 of 52 subjects who received no prophylaxis contra...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
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更新日期:1991-02-01 00:00:00
abstract::In patients with polytrauma or major surgery, severe bacterial infections leading to septic shock and multiorgan failure are still a major cause of death. Prevention of septic shock in patients at risk would be an alternative to treatment of patients with overt septic shock. We therefore conducted a trial with the mon...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.11.2535
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03408-14
更新日期:2014-09-01 00:00:00
abstract::Febrifugine is the active principal isolated 50 years ago from the Chinese herb chang shan (Dichroa febrifuga Lour), which has been used as an antimalarial in Chinese traditional medicine for more than 2,000 years. However, intensive study of the properties of febrifugine has been hindered for decades due to its side ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.3.1169-1176.2005
更新日期:2005-03-01 00:00:00
abstract::beta-Lactamases from Aeromonas hydrophila and A. sobria were purified and characterized. Both species produced beta-lactamases that were inducible by either cefoxitin or imipenem. These species were resistant to ampicillin and cephalothin but not imipenem. Isoelectric focusing of sonic extracts revealed one band at pI...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.1.44
更新日期:1990-01-01 00:00:00