Abstract:
:Cytomegalovirus can cause debilitating and life-threatening disease in newborns infected in utero and immunocompromised individuals, including transplant recipients. RG7667 is a unique combination of two monoclonal antibodies that binds glycoprotein complexes on the surface of cytomegalovirus and inhibits its entry into host cells. A phase 1 first-in-human, randomized, double-blind, placebo-controlled, dose-escalation study of RG7667 given intravenously was conducted in 181 healthy adults. The study involved a single ascending dose stage (1, 3, 5, and 10 mg/kg each antibody; n = 21), a multiple ascending dose stage (5 and 10 mg/kg each antibody monthly for 3 doses; n = 10), and a multiple dose expansion stage (10 mg/kg each antibody monthly for 3 doses; n = 150). Subjects were followed for 85 to 141 days to evaluate safety, tolerability, pharmacokinetics, and immunogenicity. Most adverse events were mild, and the incidence of adverse events was similar among the RG7667 and placebo groups. RG7667 had dose-proportional pharmacokinetics in all three dosing stages, a mean terminal half-life of 20 to 30 days, and an overall pharmacokinetic profile consistent with that of a human monoclonal antibody that lacks endogenous host targets. The proportion of subjects developing an antitherapeutic antibody response was not higher in the RG7667 group than in the placebo group. In summary, single and multiple doses of RG7667 were found to be safe and well-tolerated in healthy adults and had a favorable pharmacokinetic and immunogenicity profile. This study supports further development of RG7667 as a therapy for the prevention and treatment of cytomegalovirus infection in susceptible populations. (This study has been registered at ClinicalTrials.gov under registration no. NCT01496755.).
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Ishida JH,Burgess T,Derby MA,Brown PA,Maia M,Deng R,Emu B,Feierbach B,Fouts AE,Liao XC,Tavel JAdoi
10.1128/AAC.00523-15subject
Has Abstractpub_date
2015-08-01 00:00:00pages
4919-29issue
8eissn
0066-4804issn
1098-6596pii
AAC.00523-15journal_volume
59pub_type
杂志文章,多中心研究,随机对照试验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::Changes in plasmid DNA supercoiling were measured following treatment of Escherichia coli cells, carrying topoisomerase mutations, with the quinolone ciprofloxacin. In quinolone-susceptible cells (top+ gyr+) as well as in topA mutants and in gyrB mutants, plasmid DNA was relaxed after the addition of ciprofloxacin. In...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.1.20
更新日期:1991-01-01 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::Berberine sulfate is an alkaloid extracted from the roots and bark of various plants and possesses antibacterial, antifungal, and antiprotozoal activities. Most studies have focused on the bacteriostatic or bactericidal activities of this compound. In this study, we report that berberine sulfate is bacteriostatic for ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.9.1370
更新日期:1988-09-01 00:00:00
abstract::Here, we report the first autochthonous cases of infections caused by blaNDM-5 New Delhi metallo-β-lactamase-producing Escherichia coli strains recovered from urine and blood specimens of three patients from Algeria between January 2012 and February 2013. The three isolates belong to sequence type 2659 and they coexpr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02818-13
更新日期:2014-09-01 00:00:00
abstract::To study whether the capability of horizontal DNA transfer is associated with metronidazole resistance in Helicobacter pylori, a total of 81 clinical isolates were tested for MICs of metronidazole (MTZ). The MIC assays were performed by using the E-test and reconfirmed by the agar dilution method. Natural competence a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.5.1564-1567.2002
更新日期:2002-05-01 00:00:00
abstract::The in vitro activity of ketolide HMR 3647 against coryneform bacteria isolated from clinical samples was evaluated. Except against Corynebacterium jeikeium and C. urealyticum, HMR 3647 showed high activity against Corynebacterium spp., being more active than 14- and 16-membered macrolides, azithromycin, or clindamyci...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.12.3290
更新日期:1998-12-01 00:00:00
abstract::The susceptibilities of 216 strains of Neisseria gonorrhoeae to a new fluoroquinolone, CP-99,219 were determined. For strains for which the MICs of ciprofloxacin were < or = 0.06 microgram/ml, the MICs at which 90% of the isolates are inhibited (MIC90s) of CP-99,219, ciprofloxacin, and ofloxacin were 0.008, 0.015, and...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.4.987
更新日期:1995-04-01 00:00:00
abstract::The activity of the siderophore cephalosporin cefiderocol is targeted against carbapenem-resistant Gram-negative bacteria. In this study, the activity of cefiderocol against characterized carbapenem-resistant Acinetobacter baumannii complex, Stenotrophomonas maltophilia, Pseudomonas aeruginosa, and Enterobacteriaceae ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01801-18
更新日期:2018-12-21 00:00:00
abstract::The topical delivery of liposomally encapsulated interferon was evaluated in the cutaneous herpes simplex virus guinea pig model. Application of liposomally entrapped interferon caused a reduction of lesion scores, whereas application of interferon formulated as a solution or as an emulsion was ineffective. The method...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.8.1217
更新日期:1989-08-01 00:00:00
abstract::Ethambutol (EMB) plays a pivotal role in the chemotherapy of drug-resistant tuberculosis (TB), including multidrug-resistant tuberculosis (MDR-TB). Resistance to EMB is considered to be caused by mutations in the embCAB operon (embC, embA, and embB). In this study, we analyzed the embCAB mutations among 139 MDR-TB iso...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04933-14
更新日期:2015-04-01 00:00:00
abstract::We describe a primary high-throughput screen that uses the reporter strain Bacillus subtilis BAU-102 to identify antibiotics that induce autolysis. The screen measures autolysis in terms of the incipient release of recombinant Escherichia coli beta-galactosidase (beta-Gal) from the periplasmic space of B. subtilis owi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01597-09
更新日期:2010-09-01 00:00:00
abstract::In 1891 Guttmann and Ehrlich (P. Guttmann and P. Ehrlich, Berlin Klin. Wochenschr. 28:953-956, 1891) were the first to report the antimalarial properties of a synthetic, rather than a natural, material when they described the clinical cure of two patients after oral administration of a thiazine dye, methylene blue. Si...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.12.2671
更新日期:1995-12-01 00:00:00
abstract::Tilorone is a 50-year-old synthetic small-molecule compound with antiviral activity that is proposed to induce interferon after oral administration. This drug is used as a broad-spectrum antiviral in several countries of the Russian Federation. We have recently described activity in vitro and in vivo against the Ebola...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00440-20
更新日期:2020-04-21 00:00:00
abstract::Echinocandins are important in the prevention and treatment of invasive candidiasis but limited by current dosing regimens that include daily intravenous administration. The novel echinocandin CD101 has a prolonged half-life of approximately 130 h in humans, making it possible to design once-weekly dosing strategies. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02154-17
更新日期:2018-01-25 00:00:00
abstract::Quinolones, in addition to their antibacterial activities, act as immunomodulators. Osteopontin (OPN), a member of the extracellular matrix proteins, was found to play a role in the immune and inflammatory response. We found that quinolones significantly enhanced OPN secretion, namely, garenoxacin (220%), moxifloxacin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06062-11
更新日期:2012-06-01 00:00:00
abstract::Despite the documented benefit of voriconazole therapeutic drug monitoring, nonlinear pharmacokinetics make the timing of steady-state trough sampling and appropriate dose adjustments unpredictable by conventional methods. We developed a nonparametric population model with data from 141 previously richly sampled child...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.00032-15
更新日期:2015-01-01 00:00:00
abstract::We have discovered a remarkable synergistic antimalarial interaction between rufigallol and the structurally similar compound exifone. The synergistic effects were produced in chloroquine-susceptible and chloroquine-resistant clones of Plasmodium falciparum. The degree of potentiation as estimated by standard isobolar...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.6.1408
更新日期:1996-06-01 00:00:00
abstract::An oligonucleoside methylphosphonate (ONMP) complementary to the splice acceptor site of immediate-early (IE) pre-mRNAs 4 and 5 (IE4,5SA) inhibits herpes simplex virus type 1 (HSV-1) growth in vitro and in infected animals. The antiviral effect appears to be due to inhibition of IE pre-mRNA 4 and 5 splicing and/or IE4...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.4.675
更新日期:1994-04-01 00:00:00
abstract::Piperaquine (PQ) is an antimalarial drug whose high lipid solubility suggests that its absorption can be increased by a high-fat meal. We examined the pharmacokinetics of PQ phosphate (500 mg given orally) in the fasting state and after a high-fat meal in eight healthy Caucasian volunteers (randomized crossover). Plas...
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.49.6.2407-2411.2005
更新日期:2005-06-01 00:00:00
abstract::Flaviviruses comprise several medically important viruses, including Japanese encephalitis virus, West Nile virus, dengue virus (DENV), yellow fever virus, and Zika virus (ZIKV). A large outbreak of DENV and ZIKV occurred recently, leading to many cases of illness and death. However, despite decades of effort, we have...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00941-19
更新日期:2019-12-20 00:00:00
abstract::The anti-influenza drug oseltamivir is an ester prodrug activated by hepatic carboxylesterases. Plasma esterases also convert up to 31.8% of the parent compound to the active metabolite after 4 h ex vivo, with wide interindividual variation. This source of error is removed by adding the esterase inhibitor dichlorvos t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00500-06
更新日期:2006-09-01 00:00:00
abstract::Though the primary action of the cationic antibiotic polymyxin B is against the membrane of susceptible bacteria, severe morphological changes are detected in the cytoplasm. Using fluorescence microscopy and a mono-N-dansyl-polymyxin B derivative, we could demonstrate aggregations of the antibiotic with cellular mater...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.8.1.95
更新日期:1975-07-01 00:00:00
abstract::An association exists between respiratory viruses and bacterial infections. Prevention or treatment of the preceding viral infection is a logical goal for reducing this important cause of morbidity and mortality. The ability of the novel, selective parainfluenza virus hemagglutinin-neuraminidase inhibitor BCX 2798 to ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.1.398-405.2005
更新日期:2005-01-01 00:00:00
abstract::The aim of this open-label, fixed-sequence study was to investigate the potential of the botanical supplement Echinacea purpurea to interact with etravirine, a nonnucleoside reverse transcriptase inhibitor of HIV. Fifteen HIV-infected patients receiving antiretroviral therapy with etravirine (400 mg once daily) for at...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.01205-12
更新日期:2012-10-01 00:00:00
abstract::The in vitro activity of cefaclor against 556 clinical isolates of gram-positive and gram-negative bacteria was compared with that of other cephalosporins. Cefaclor had activity similar to that of cephalexin against gram-positive bacteria. It showed greater activity against Haemophilus strains than did cephalexin and ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.4.584
更新日期:1978-04-01 00:00:00
abstract::Occidiofungin is a cyclic glyco-lipopeptide produced by Burkholderia contaminans. MICs against Candida species were between 0.5 and 2.0 μg/ml. Occidiofungin retains its in vitro potency in the presence of 5% and 50% human serum with a minimal lethal concentration (MLC) of 2 and 4 μg/ml, respectively. Time-kill and pos...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05231-11
更新日期:2012-02-01 00:00:00
abstract::Candida lusitaniae is usually susceptible to echinocandins. Beta-1,3-glucan synthase encoded by FKS genes is the target of echinocandins. A few missense mutations in the C. lusitaniae FKS1 hot spot 1 (HS1) have been reported. We report here the rapid emergence of antifungal resistance in C. lusitaniae isolated during ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02204-15
更新日期:2015-12-01 00:00:00
abstract::Extensive biochemical testing and 16S rRNA and rpoB sequence analysis revealed that clinical strain CF01Ent1, initially identified as Buttiauxella agrestis by the use of Api 32 biochemical strips, is a new organism in the Enterobacteriaceae family. It produced an inducible AmpC-type beta-lactamase whose sequence share...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.10.3316-3319.2002
更新日期:2002-10-01 00:00:00
abstract::An important determinant of nephrotoxicity, which is the major complication of long-term amphotericin B treatment, is dysfunction of distal tubular epithelial cells. The underlying cause for this rather selective damage to the cells is unknown. In the present investigation, it was shown that kidney epithelial cells we...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.5.1116
更新日期:1996-05-01 00:00:00