Abstract:
:Many potent antiviral drugs have been developed against HIV-1, and their combined action is usually successful in achieving durable virus suppression in infected individuals. This success is based on two effects: additive or even synergistic virus inhibition and an increase in the genetic threshold for development of drug resistance. More recently, several genetic approaches have been developed to attack the HIV-1 genome in a gene therapy setting. We set out to test the combinatorial possibilities for a therapy based on the CRISPR-Cas9 and RNA interference (RNAi) mechanisms that attack the viral DNA and RNA, respectively. When two different sites in the HIV-1 genome were targeted, either with dual CRISPR-Cas9 antivirals or with a combination of CRISPR-Cas9 and RNAi antivirals, we observed additive inhibition, much like what was reported for antiviral drugs. However, when the same or overlapping viral sequence was attacked by the antivirals, rapid escape from a CRISPR-Cas9 antiviral, assisted by the error-prone nonhomologous end joining (NHEJ) DNA repair machinery, accelerated the development of cross-resistance to the other CRISPR-Cas9 or RNAi antiviral. Thus, genetic antiviral approaches can be combined, but overlap should be avoided.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Zhao N,Wang G,Das AT,Berkhout Bdoi
10.1128/AAC.01486-17subject
Has Abstractpub_date
2017-11-22 00:00:00issue
12eissn
0066-4804issn
1098-6596pii
AAC.01486-17journal_volume
61pub_type
杂志文章abstract::The aim of this analysis was to identify therapeutic micafungin regimens for children that produce the same micafungin exposures known to be effective for the prevention and treatment of Candida infections in adults. Pediatric pharmacokinetic data from 229 patients between the ages of 4 months and <17 years were obtai...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.03736-14
更新日期:2015-02-01 00:00:00
abstract::A-80556 is a novel fluoroquinolone with potent antibacterial activity against gram-positive, gram-negative, and anaerobic organisms. A-80556 was more active than ciprofloxacin, ofloxacin, lomefloxacin, and sparfloxacin against gram-positive bacteria. A-80556 was particularly active against Staphylococcus aureus (MIC f...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.5.1071
更新日期:1994-05-01 00:00:00
abstract::Surfing motility is a novel form of surface adaptation exhibited by the nosocomial pathogen Pseudomonas aeruginosa in the presence of the glycoprotein mucin, which is found in high abundance at mucosal surfaces, especially those of the lungs of cystic fibrosis and bronchiectasis patients. Here, we investigated the ada...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00848-18
更新日期:2018-08-27 00:00:00
abstract::Anidulafungin is an echinocandin with activity against Candida species and Aspergillus species. Adult dosages under study are 50 mg/day for esophageal candidiasis and 100 mg/day for invasive candidiasis and aspergillosis. Little is known, however, about the safety and pharmacokinetics of anidulafungin in children. A m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.50.2.632-638.2006
更新日期:2006-02-01 00:00:00
abstract::It remains controversial whether combination therapy, given empirically or as definitive treatment, for Pseudomonas aeruginosa bacteremia is associated with a better outcome than monotherapy. The aim of the present study was to compare the rates of survival among patients who received either combination therapy or mon...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.9.2756-2764.2003
更新日期:2003-09-01 00:00:00
abstract::An innovative liposomal formulation of meglumine antimoniate (LMA) was recently reported to promote both long-term parasite suppression and reduction of infectivity to sand flies in dogs with visceral leishmaniasis. However, 5 months after treatment, parasites were still found in the bone marrow of all treated dogs. I...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00208-12
更新日期:2012-06-01 00:00:00
abstract::The caspofungin clinical trial database offers an opportunity to assess susceptibility results for Candida pathogens obtained from patients with candidiasis and allows for correlations between efficacy outcomes and MICs. Candida isolates have been identified from patients enrolled in four studies of esophageal candidi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.9.3616-3623.2005
更新日期:2005-09-01 00:00:00
abstract::Tiacumicins B and C are members of a novel group of 18-membered macrolide antibiotics with in vitro activity against Clostridium difficile. The MICs against 15 strains of C. difficile were 0.12 to 0.25 microgram/ml for tiacumicin B, 0.25 to 1 microgram/ml for tiacumicin C, and 0.5 to 1 microgram/ml for vancomycin. The...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.6.1108
更新日期:1991-06-01 00:00:00
abstract::The objective of this study was to determine risk factors for the development of resistance to β-lactams/β-lactamase inhibitors (βL/βLIs) and ertapenem among Bacteroides species bacteremia. We conducted a retrospective case-control study of 101 adult patients with Bacteroides species bacteremia at a 1,051-bed tertiary...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00046-15
更新日期:2015-08-01 00:00:00
abstract::We have previously shown that a series of nonnucleoside pyrrolo[2,3-d]pyrimidines selectively inhibit the replication of herpes simplex virus type 1 (HSV-1) and human cytomegalovirus (HCMV). These compounds act at the immediate-early or early stage of HCMV replication and have antiviral properties somewhat similar to ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.8.2470-2476.2002
更新日期:2002-08-01 00:00:00
abstract::Telavancin displays potent in vitro and in vivo activity against methicillin-resistant Staphylococcus aureus (MRSA), including strains with reduced susceptibility to vancomycin. We compared the efficacies of telavancin and vancomycin against MRSA strains with vancomycin MICs of ≥1 μg/ml in a neutropenic murine lung in...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00062-10
更新日期:2010-12-01 00:00:00
abstract::BO-1341, a new antipseudomonal semisynthetic cephalosporin, was evaluated for in vitro and in vivo antibacterial activities in comparison with ceftazidime, cefotaxime, and cefoperazone. The in vitro activity of BO-1341 was generally superior or comparable to the activities of the reference antibiotics against clinical...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.9.1423
更新日期:1989-09-01 00:00:00
abstract::The aims of the study were to investigate the prevalence of azole resistance among Aspergillus fumigatus clinical isolates. A total of 533 clinical isolates that had been collected between 1995 and 2006, from 441 patients, were screened. No resistance was detected in isolates collected between 1995 and 1997. Starting ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02234-15
更新日期:2015-11-09 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
abstract::An inhibitor-based characterization system which allowed the identification of beta-lactamases after isoelectric focusing on polyacrylamide gels was developed. This system, using potassium clavulanate and oxacillin, distinguished type I chromosomally mediated enzymes from other beta-lactamases of gram-negative bacteri...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.6.951
更新日期:1986-12-01 00:00:00
abstract::The activity of azlocillin and mezlocillin, new semisynthetic ureido penicillins, was investigated and compared with that of other known beta-lactam antibiotics. At a concentration of 25 mug/ml, azlocillin inhibited 74% of Enterobacter, 97% of Proteus mirabilis, 64% of Citrobacter, 91% of Pseudomonas aeruginosa, and 8...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.6.930
更新日期:1978-06-01 00:00:00
abstract::Conjugative transfer of R plasmids R64 and R64drd-11 has been compared in vitro and in vivo without selective pressure by antibiotics in a simplified experimental system; the ecosystem was the bowel of germfree chickens, with the host bacteria almost isogenic, and the plasmids differing only in their conjugative trans...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.17.3.327
更新日期:1980-03-01 00:00:00
abstract::Using an immunocompetent murine model of invasive aspergillosis (IA), we previously reported that the efficacy of liposomal amphotericin B (L-AmB) (Ambisome) is not hampered by the presence of azole resistance mutations in Aspergillus fumigatus (S. Seyedmousavi, W. J. G. Melchers, J. W. Mouton, and P. E. Verweij, Anti...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02479-16
更新日期:2017-05-24 00:00:00
abstract::This work reports, for the first time, the presence of New Delhi metallo-β-lactamase 1 (NDM-1) in Pseudomonas aeruginosa. Moreover, this is the first report of the NDM-1 presence in the Balkan region. Cosmid gene libraries of carbapenem-nonsusceptible Pseudomonas aeruginosa clinical isolates MMA83 and MMA533 were scre...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00226-11
更新日期:2011-08-01 00:00:00
abstract::A two-compartment pharmacokinetic (PK) population model of anidulafungin was fitted to PK data from 23 critically ill patients (age, 65 years [range, 28 to 81 years]; total body weight [TBW], 75 kg [range, 54 to 168 kg]). TBW was associated with clearance and incorporated into a final population PK model. Simulations ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00378-19
更新日期:2019-06-24 00:00:00
abstract::Resistance to daptomycin in enterococcal clinical isolates remains rare but is being increasingly reported in the United States and worldwide. There are limited data on the genetic relatedness and microbiological and clinical characteristics of daptomycin-nonsusceptible enterococcal clinical isolates. In this study, w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02683-14
更新日期:2014-08-01 00:00:00
abstract::The in vitro activity of the aminoglycoside 6'-N-acetyltransferase type Ib [AAC(6')-Ib] was inhibited by CuCl2 with a 50% inhibitory concentration (IC50) of 2.8 μM. The growth of an amikacin-resistant Klebsiella pneumoniae strain isolated from a neonate with meningitis was inhibited when amikacin was supplemented by t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01106-15
更新日期:2015-09-01 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
pub_type: 杂志文章
doi:10.1128/AAC.49.9.3682-3689.2005
更新日期:2005-09-01 00:00:00
abstract::Since November 1982 at the Sainte-Justine Hospital in Montreal, ampicillin and cefotaxime were used in association as initial treatment (greater than or equal to 48 h) for childhood bacterial meningitis. In this report is described the in vitro interaction of the new regimen in comparison with that of the previous amp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.4.594
更新日期:1986-04-01 00:00:00
abstract::In vivo antiherpesvirus effects of 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (brovavir) were tested in two mouse model infections with herpes simplex virus type 1 (HSV-1) strains which showed different degrees of virulence in mice. Successful efficacies of oral and intraperitoneal (i.p.) treatments with brova...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.5.691
更新日期:1990-05-01 00:00:00
abstract::Of five parenteral cephalosporins tested against 43 lactobacilli, cephaloridine, cefazolin, and cefamandole were the most active inhibitory and bactericidal agents. Timed-kill analysis revealed a slow bactericidal effect, with significant declines in mean minimal bactericidal concentration values at 48 h versus 24 h. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.16.1.112
更新日期:1979-07-01 00:00:00
abstract::Since human cytomegalovirus (HCMV) does not infect or replicate in nonhuman cells and tissues, there are few animal models currently available for evaluation of antiviral therapies for these infections. In the present studies, we utilized two different models in which severe combined immunodeficient (SCID) mice were i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.5.1749-1755.2004
更新日期:2004-05-01 00:00:00
abstract::The emergence of human immunodeficiency virus type 1 (HIV-1) strains resistant to highly active antiretroviral therapy necessitates continued drug discovery for the treatment of HIV-1 infection. Most current drug discovery strategies focus upon a single aspect of HIV-1 replication. A virus-cell-based assay, which can ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.2.501-508.2003
更新日期:2003-02-01 00:00:00
abstract::Miconazole, a broad-spectrum antimycotic agent with some antibacterial activity, has recently become available for experimental parenteral use in the United States. Its efficacy as an anticandidal drug was tested in adult Wistar rats. A previously established infectious dose of 5 x 10(6)Candida albicans was intravenou...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.2.321
更新日期:1978-02-01 00:00:00
abstract::Pseudomonas putida is well known for its metabolic capabilities, but recently, it has been shown to exhibit resistance to a wide range of antibiotics. In P. putida DOT-T1E, the TtgABC efflux pump, which has a broad substrate specificity, extrudes antibiotics such as ampicillin, carbenicillin, tetracycline, nalidixic a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.10.3067-3072.2003
更新日期:2003-10-01 00:00:00