Abstract:
:The relative therapeutic effects of vidarabine (9-beta-D-arabinofuranosyladenine), cyclaradine (the adenosine deaminase-resistant carbocyclic analog of vidarabine), and cyclaradine-5'-methoxyacetate in the parenteral treatment of systemic herpes simplex virus type 1 infections in Swiss mice were determined. Among control mice inoculated intraperitoneally with virus, a mortality rate of 95% was observed. The intraperitoneal administration of nontoxic doses of vidarabine (125 to 250 mg/kg per day) or cyclaradine (113 to 450 mg/kg per day), by daily injections for 7 days beginning 4 h after virus inoculation, reduced mortality to 0 to 10%. Among control animals inoculated intracerebrally with 32 50% lethal doses of virus, 100% mortality was observed, with a mean survival time of 4.6 days. Treatment with either drug at equimolar dose levels ranging from ca. 32 to 750 mg/kg per day produced significant (P less than 0.0005), dose-dependent increases in the mean survival time of animals dying of herpesvirus encephalitis. Mice inoculated intracerebrally with 10 50% lethal doses of virus exhibited 97% mortality and a mean survival time of 5.5 to 6.4 days. Treatment with vidarabine, cyclaradine, or cyclaradine-5'-methoxyacetate significantly increased the mean survival time of dying animals and, at doses ranging from 250 to 750 mg/kg per day, produced significant increases in survival. The three drugs displayed equivalent antiviral efficacy in vivo. Drug toxicity (measured by weight loss) was not detected in mice treated with cyclaradine or cyclaradine-5'-methoxyacetate at 750 mg/kg per day, whereas severe toxicity (weight loss of greater than or equal to 3 g) was observed in mice treated with vidarabine at an equivalent dose level. Thus, cyclaradine or its 5'-methoxyacetic acid ester may possess some advantage over vidarabine in the treatment of severe herpesvirus infections and should therefore be considered for clinical trials in humans.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Shannon WM,Westbrook L,Arnett G,Daluge S,Lee H,Vince Rdoi
10.1128/aac.24.4.538subject
Has Abstractpub_date
1983-10-01 00:00:00pages
538-43issue
4eissn
0066-4804issn
1098-6596journal_volume
24pub_type
杂志文章abstract::The antibacterial activity of RU 64004, a new ketolide, was evaluated against more than 600 bacterial strains and was compared with those of various macrolides and pristinamycin. RU 64004 had good activity against multiresistant pneumococci, whether they were erythromycin A resistant or not, including penicillin-resis...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.10.2149
更新日期:1997-10-01 00:00:00
abstract::The susceptibility of Saccharomyces cerevisiae JG436 multidrug transporter deletion mutant, Deltapdr5, to several antifungal agents was compared to that of JG436-derived JGCDR1 and JGCaMDR1 transformants, harboring the CDR1 and CaMDR1 genes, encoding the main drug-extruding membrane proteins of Candida albicans. The J...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.1.223-228.2001
更新日期:2001-01-01 00:00:00
abstract::A basic, random copolymer of l-ornithine and l-leucine (OL; molar ratios 1:1) was bactericidal to a sensitive (S) strain of Staphylococcus aureus at low concentration. Resistant cells (R) were selected from the culture medium and, after serial transfers to solutions containing increasing amounts of the polymer, grew w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.5.2.179
更新日期:1974-02-01 00:00:00
abstract::The effects on Staphylococcus aureus viability and beta-lactamase activity of concentrations that simulated those in human serum after a combined dose of 875 mg of amoxicillin and 125 mg of clavulanic acid were studied in an in vitro pharmacodynamic model. Six hours of preexposure to concentrations of the amoxicillin-...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.6.1403
更新日期:1997-06-01 00:00:00
abstract::A method utilizing immobilized major group rhinoviruses and biotinylated soluble intercellular adhesion molecule 1 has been developed for the detection of capsid binders. Binding measurements indicate a loss in relative affinity of biotinylated soluble intercellular adhesion molecule 1 for rhinoviruses by capsid binde...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.8.1693
更新日期:1993-08-01 00:00:00
abstract::Although information about the efficacy and safety experience with caspofungin at 50 mg/m(2) daily is available for children and adolescents, the dosing regimen in infants and toddlers 3 to 24 months of age has yet to be established. We studied the pharmacokinetics and safety of caspofungin at 50 mg/m(2) once daily in...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1128/AAC.01027-08
更新日期:2009-04-01 00:00:00
abstract::In an effort to discover novel, noncarbohydrate inhibitors of influenza virus neuraminidase we hypothesized that compounds which contain positively charged amino groups in an appropriate position to interact with the Asp 152 or Tyr 406 side chains might be bound tightly by the enzyme. Testing of 300 alpha- and beta-am...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.45.9.2563-2570.2001
更新日期:2001-09-01 00:00:00
abstract::The aminoglycoside Geneticin (G418) is known to inhibit cell culture proliferation, via virus-specific mechanisms, of two different virus genera from the family Flaviviridae. Here, we tried to determine whether Geneticin can selectively alter the switching of the nucleotide 1 to 570 RNA region of hepatitis C virus (HC...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02511-15
更新日期:2015-11-30 00:00:00
abstract::The opportunistic apicomplexan parasite Toxoplasma gondii damages fetuses in utero and threatens immunocompromised individuals. The toxicity associated with standard antitoxoplasmal therapies, which target the folate pathway, underscores the importance of examining alternative pharmacological strategies. Parasitic pro...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.6.2172-2179.2005
更新日期:2005-06-01 00:00:00
abstract::Spontaneous mutants of susceptible clinical and laboratory isolates of Streptococcus pneumoniae exhibiting reduced susceptibility to evernimicin (SCH27899; MIC, 0.5 to 4.0 mg/liter) were selected on plates containing evernimicin. Four isolates that did not harbor mutations in rplP (which encodes ribosomal protein L16)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.11.3101-3106.2000
更新日期:2000-11-01 00:00:00
abstract::The mycobacterial embCAB operon encodes arabinosyl transferases, putative targets of the antimycobacterial agent ethambutol (EMB). Mutations in embB lead to resistance to EMB in Mycobacterium tuberculosis. The basis for natural, intrinsic resistance to EMB in nontuberculous mycobacteria (NTM) is not known; neither is ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.10.2270
更新日期:1997-10-01 00:00:00
abstract::Mycobacterium simiae is a rare species of slow-growing nontuberculous mycobacteria (NTM). From 2002 to 2017, we conducted a retrospective study that included all patients with NTM-positive respiratory samples detected in two university hospitals of the French overseas department of Reunion Island. We recorded the prev...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00395-18
更新日期:2018-06-26 00:00:00
abstract::Isavuconazole is a novel, broad-spectrum, antifungal azole. In order to evaluate its interactions with known azole resistance mechanisms, isavuconazole susceptibility among different yeast models and clinical isolates expressing characterized azole resistance mechanisms was tested and compared to those of fluconazole,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02157-15
更新日期:2015-10-19 00:00:00
abstract::Vulvovaginal candidiasis (VVC) is a global health problem affecting ∼75% of women at least once in their lifetime. Here we examined the epidemiology of VVC in a patient cohort to identify the causative organisms associated with VVC. Biofilm-forming capacity and antifungal sensitivity profiles were also assessed. We re...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01065-17
更新日期:2017-08-24 00:00:00
abstract::Current data indicate that once-daily aminoglycoside therapy is as efficacious as traditional multiple daily dosing and equally or less toxic. Our experience with once-daily gentamicin, 6 mg/kg of body weight led to a 10% (3 of 33 patients) occurrence of documented ototoxicity after prolonged aminoglycoside exposure. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.9.2209
更新日期:1996-09-01 00:00:00
abstract::Daptomycin is a lipopeptide antibiotic with activity against gram-positive bacteria, including Staphylococcus aureus. We defined the pharmacodynamic parameters that determine the activity of daptomycin for S. aureus using in vitro methods and the Craig (W. A. Craig, J. Redington, and S. C. Ebert, J. Antimicrob. Chemot...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.3.845-851.2001
更新日期:2001-03-01 00:00:00
abstract::Ninety-four patients with recurrences of genital herpes were randomized in a double-blind trial to receive topical therapy for 5 days with either alpha-2a interferon at 30 X 10(6) IU/ml or 10 X 10(6) IU/ml or placebo six times daily. No differences were noted between either interferon dose and placebo with respect to ...
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.31.7.1137
更新日期:1987-07-01 00:00:00
abstract::Time-kill studies were used to examine the in vitro activities of penicillin G, RP 59500, erythromycin, ciprofloxacin, sparfloxacin, and vancomycin against 10 pneumococci expressing various degrees of susceptibility to penicillin and erythromycin. RP 59500 MICs for all strains were 0.5 to 2.0 micrograms/ml, while eryt...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.9.2065
更新日期:1994-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00533-15
更新日期:2015-08-01 00:00:00
abstract::The efficacy of clarithromycin in a murine model of acute toxoplasmosis was studied. Clarithromycin was administered alone and concurrently with minocycline, and efficacy was assessed by survival rates and sequential determination of parasite burden in blood, brains, and lungs. Limited protection resulted from adminis...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.12.2852
更新日期:1992-12-01 00:00:00
abstract::Replication of hepatitis C virus (HCV) RNA is catalyzed by the virally encoded RNA-dependent RNA polymerase NS5B. It is believed that the viral polymerase utilizes a de novo or primer-independent mechanism for initiation of RNA synthesis. Our previous work has shown that dinucleotides were efficient initiation molecul...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.8.2674-2681.2003
更新日期:2003-08-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02656-16
更新日期:2017-04-24 00:00:00
abstract::Subtherapeutic levels of oxytetracycline plus neomycin in animal feeds did not bring about increases in the quantity, prevalence, or shedding of Salmonella typhimurium in swine, calves, or chickens. In fact, the medication generally reduced the proportion of animals carrying S. typhimurium. The medicated groups were f...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.10.1.89
更新日期:1976-07-01 00:00:00
abstract::Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections in young children and other high-risk populations. RSV nucleoprotein (N) is essential for virus assembly and replication as part of the viral ribonucleoprotein (RNP) complex. RSV604 was a putative N inhibitor in phase 2 ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04119-14
更新日期:2015-02-01 00:00:00
abstract::Interactions between bacterial biofilms formed by Pseudomonas aeruginosa and clarithromycin, a macrolide having no anti-P. aeruginosa activity, were investigated. P. aeruginosa incubated for 10 days on membrane filters formed biofilms on the surfaces of the filters. The biofilms were characterized by dense colonizatio...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.9.1749
更新日期:1993-09-01 00:00:00
abstract::The combination of liposomal amphotericin B (LAMB) and caspofungin (CAS) holds promise to improve the outcome of opportunistic invasive mycoses with poor prognosis. Little is known, however, about the safety and pharmacokinetics of the combination in patients at high risk for these infections. The safety and pharmacok...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1128/AAC.00425-10
更新日期:2010-10-01 00:00:00
abstract::The effect of a selected tripeptide, Z-d-Phe-Phe-Arg(NO(2)) (SV-4814) on the kinetics of lysis of green monkey erythrocytes by measles virus hemolysin suggested conditions of competitive inhibition. SV-4814 prevented not only hemoglobin release, but also the preceding leakage of K(+) through the cell membrane. The cap...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.5.4.426
更新日期:1974-04-01 00:00:00
abstract::Amphotericin B derivatives, such as MS-8209, have been evaluated as a therapeutic approach to human immunodeficiency virus (HIV) infection. We show that MS-8209, like amphotericin B, increases tumor necrosis factor alpha (TNF-alpha) mRNA expression and TNF-alpha production and consequently HIV replication in human mac...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.2.405-407.2000
更新日期:2000-02-01 00:00:00
abstract::Chagas disease is a parasitic infection that leads to a significant public health problem in countries where the disease is endemic and where it is nonendemic. Benznidazole is the most commonly used drug for the etiological treatment of Chagas disease. Patients treated with benznidazole suffer frequent adverse drug re...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04078-14
更新日期:2015-01-01 00:00:00
abstract::R4.0, a synthetic CCL5/RANTES-derived peptide, exerts potent anti-HIV-1 activity via its nonactivating interaction with CCR5, the major HIV-1 coreceptor. CCR5 chronic activation may promote undesirable inflammatory effects and enhance viral infection; thus, receptor antagonism is a necessary requisite. HIV-1 gp120, CC...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03559-14
更新日期:2014-10-01 00:00:00