Abstract:
:Topical blockade of the gp41 fusogenic protein of HIV-1 is one possible strategy by which microbicides could prevent HIV transmission, working early against infection, by inhibiting viral entry into host cells. In this study, we examined the potential of gp41 fusion inhibitors (FIs) as candidate anti-HIV microbicides. Preclinical evaluation of four FIs, C34, T20, T1249, and L'644, was performed using cellular and ex vivo genital and colorectal tissue explant models. Increased and sustained activity was detected for L'644, a cholesterol-derivatized version of C34, relative to the other FIs. The higher potency of L'644 was further increased with sustained exposure of cells or tissue to the compound. The activity of L'644 was not affected by biological fluids, and the compound was still active when tissue explants were treated after viral exposure. L'644 was also more active than other FIs against a viral escape mutant resistant to reverse transcriptase inhibitors (RTIs), demonstrating the potential of L'644 to be included as part of a multiactive antiretroviral (ARV) combination-based microbicide. These data support the further development of L'644 for microbicide application.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Harman S,Herrera C,Armanasco N,Nuttall J,Shattock RJdoi
10.1128/AAC.06108-11subject
Has Abstractpub_date
2012-05-01 00:00:00pages
2347-56issue
5eissn
0066-4804issn
1098-6596pii
AAC.06108-11journal_volume
56pub_type
杂志文章abstract::The pharmacokinetics and bacteriological effect of ceftazidime were evaluated in rabbits experimentally infected with Streptococcus pneumoniae, Haemophilus influenzae type b, and Escherichia coli K1. The mean penetration of ceftazidime into cerebrospinal fluid after single-dose or constant-infusion administration rang...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.2.213
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abstract::Forty years after the last endemic smallpox case, variola virus (VARV) is still considered a major threat to humans due to its possible use as a bioterrorism agent. For many years, the risk of disease reemergence was thought to solely be through deliberate misuse of VARV strains kept in clandestine laboratories. Howev...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,评审
doi:10.1128/AAC.01683-19
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abstract::The dynamic interaction of planktonic and biofilm cells of mucoid Pseudomonas aeruginosa with tobramycin and piperacillin was investigated in a chemostat system. The results indicated that planktonic and young biofilm cells of the 2-day-old chemostat culture of P. aeruginosa were susceptible to killing by chemostat-co...
journal_title:Antimicrobial agents and chemotherapy
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abstract::The intrinsic mechanisms of resistance to beta-lactam antibiotics in Serratia marcescens IFO 12648 were investigated, comparing the action of benzylpenicillin, apalcillin, cefazolin, and ceftizoxime. The minimal inhibitory concentrations for this strain were 1,600, 3.13, 6,400, and 0.05 microgram/ml, respectively. The...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.19.3.397
更新日期:1981-03-01 00:00:00
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::The in vitro activity of GR-20263, a new aminothiazolyl cephalosporin, was compared with the activities of other beta-lactam antibiotics by using 800 clinical bacterial isolates. GR-20263 was highly active (inhibition of 90% of the isolates between 0.03 and 1 microgram/ml) against the common Enterobacteriaceae and 5 t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.17.5.807
更新日期:1980-05-01 00:00:00
abstract::Sordarin and its derivatives are antifungal compounds of potential clinical interest. Despite the highly conserved nature of the fungal and mammalian protein synthesis machineries, sordarin is a selective inhibitor of protein synthesis in fungal organisms. In cells sensitive to sordarin, its mode of action is through ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01603-07
更新日期:2008-05-01 00:00:00
abstract::The postantibiotic subminimum inhibitory concentration effect (PA SME) may simulate in vivo drug exposure more accurately than the postantibiotic effect (PAE) since subinhibitory concentrations of drug persist between antibiotic dosings. In this study, we compared the PAEs and PA SMEs of levofloxacin and ciprofloxacin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.5.950
更新日期:1997-05-01 00:00:00
abstract::Human immunodeficiency virus (HIV) type 1 (HIV-1) variants were selected for resistance to the (+) and (-) enantiomers of a novel nucleoside analogue, 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine (dOTFC), by use of the infectious molecular clone HIV HXB2D and the human T-cell line MT-4. The dOTFC-resistant variants that w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.5.1127-1131.2000
更新日期:2000-05-01 00:00:00
abstract::A novel gene encoding an aminoglycoside 3-N-acetyltransferase, which confers resistance to gentamicin, astromicin, and sisomicin, was cloned from Pseudomonas aeruginosa Stone 130. Its sequence was determined and found to show considerable similarity to an aac(3)-I gene previously cloned from R plasmids from Enterobact...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.8.1790
更新日期:1995-08-01 00:00:00
abstract::Ceftaroline is a new cephalosporin with bactericidal activity against resistant Gram-positive organisms, including methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae, as well as common Gram-negative organisms. This study tested the prodrug, ceftaroline fosamil, against...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00286-13
更新日期:2013-10-01 00:00:00
abstract::The in vitro activities of eight antifungal drugs against clinical isolates of Fonsecaea pedrosoi (n = 21), Fonsecaea monophora (n = 25), and Fonsecaea nubica (n = 9) were tested. The resulting MIC(90)s for all strains (n = 55) were as follows, in increasing order: posaconazole, 0.063 microg/ml; itraconazole, 0.125 mi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01655-09
更新日期:2010-04-01 00:00:00
abstract::Antimicrobial proteins and peptides (AMPs) are essential effectors of innate immunity, acting as a first line of defense against bacterial infections. Many AMPs exhibit high affinity for cell wall structures such as lipopolysaccharide (LPS), a potent endotoxin able to induce sepsis. Hence, understanding how AMPs can i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06107-11
更新日期:2012-05-01 00:00:00
abstract::Six strains of Staphylococcus aureus isolated from cystic fibrosis patients after treatment with azithromycin were cross-resistant to azithromycin and erythromycin. None of the isolates contained erm or msr(A) genes, but they all carried either A2058G/U or A2059G mutations within the rrl genes, with a majority of the ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.9.3054-3056.2002
更新日期:2002-09-01 00:00:00
abstract::SCY-078 is an orally active antifungal whose target is the β-(1,3)-d-glucan synthase (GS). We evaluated the spontaneous emergence of SCY-078-resistant Candida glabrata isolates following drug exposure in vitro Resistant isolates were analyzed using broth microdilution methodology and FKS sequencing. The kinetic inhibi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00833-17
更新日期:2017-08-24 00:00:00
abstract::The in vitro susceptibility to linezolid shown by nine Greek isolates of Coxiella burnetii derived from patients with acute Q fever was investigated. MICs of linezolid were compared with those of pefloxacin, ciprofloxacin, ofloxacin, trovafloxacin, doxycycline, and clarithromycin using the shell vial assay. MICs of li...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.11.3276-3278.2001
更新日期:2001-11-01 00:00:00
abstract::There has been major interest by the scientific community in antivirulence approaches against bacterial infections. However, partly due to a lack of viable lead compounds, antivirulence therapeutics have yet to reach the clinic. Here we investigate the development of an antivirulence lead targeting quorum sensing sign...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00263-17
更新日期:2017-07-25 00:00:00
abstract::Omadacycline is a first-in-class aminomethylcycline antibiotic with microbiological activity against Gram-positive and Gram-negative aerobes and anaerobes and atypical bacteria that is being developed for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
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更新日期:2016-11-21 00:00:00
abstract::The telithromycin susceptibility of 210 erythromycin-resistant pneumococci was tested with the agar diffusion method. Twenty-six erm(B)-positive isolates showed heterogeneous resistance to telithromycin, which was manifested by the presence of colonies inside the inhibition zone. When these cells were cultured and tes...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:1985-08-01 00:00:00
abstract::Methicillin-resistant Staphylococcus aureus (MRSA) is a multidrug-resistant pathogen that poses a significant risk to global health today. We have developed a promising new FtsZ-targeting agent (TXA707) with potent activity against MRSA isolates resistant to current standard-of-care antibiotics. We present here result...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2017-08-24 00:00:00
abstract::A broad-spectrum vaginal microbicide must be effective against a variety of sexually transmitted disease pathogens and be minimally toxic to the cell types found within the vaginal epithelium, including vaginal keratinocytes. We assessed the sensitivity of primary human vaginal keratinocytes to potential topical vagin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.7.1954-1960.2000
更新日期:2000-07-01 00:00:00
abstract::When developing novel microbicide products for the prevention of HIV infection, the preclinical safety program must evaluate not only the active pharmaceutical ingredient but also the product itself. To that end, we applied several relatively standard toxicology study methodologies to female sheep, incorporating an as...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04954-14
更新日期:2015-07-01 00:00:00
abstract::The in vitro activities of seven fluoroquinolones against 290 anaerobes were determined by agar dilution. CI-960 and WIN 57273 inhibited greater than 95% of the strains at less than or equal to 2 micrograms/ml. CI-990 required less than or equal to 16 micrograms/ml. Clustering around 2 to 4 micrograms/ml was noted for...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.5.1158
更新日期:1992-05-01 00:00:00
abstract::The biosynthetic gene cluster of the aminocoumarin antibiotic coumermycin A(1) was cloned by screening of a cosmid library of Streptomyces rishiriensis DSM 40489 with heterologous probes from a dTDP-glucose 4,6-dehydratase gene, involved in deoxysugar biosynthesis, and from the aminocoumarin resistance gyrase gene gyr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.11.3040-3048.2000
更新日期:2000-11-01 00:00:00
abstract::Carbapenemase-producing Gram-negative bacteria (CP-GNB) have increasingly spread worldwide, and different families of carbapenemases have been identified in various bacterial species. Here, we report the identification of five VIM metallo-β-lactamase-producing Alcaligenes faecalis isolates associated with a small outb...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2017-10-24 00:00:00
abstract::Visceral leishmaniasis is a neglected tropical disease that causes significant morbidity and mortality worldwide. Characterization of the pharmacokinetics and pharmacodynamics of antileishmanial drugs in preclinical models is important for drug development and use. Here we investigated the pharmacodynamics and drug di...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2017-08-24 00:00:00
abstract::The novel 6-substituted acyclouridine derivatives 1-[(2-hydroxyethoxy)methyl]-6-phenylthiothymine (HEPT), 1-[(2-hydroxyethoxy)methyl]-6-(3-methylphenylthio)thymine (HEPT-M), 6-cyclohexylthio-1-[(2-hydroxyethoxy) methyl]thymine (HEPT-H), and 1-[(2-hydroxyethoxy)methyl]-6-phenylthio-2- thiothymine (HEPT-S) have proved t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.12.2358
更新日期:1990-12-01 00:00:00
abstract::Yersinia pestis is the etiologic agent of the plague. Reports of Y. pestis strains that are resistant to each of the currently approved first-line and prophylactic treatments point to the urgent need to develop novel antibiotics with activity against the pathogen. We previously reported that Y. pestis strain KIM6+, un...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00181-15
更新日期:2015-07-01 00:00:00
abstract::Staphylococcus aureus is a bacterial pathogen responsible for the majority of skin and soft tissue infections. Antibiotics are losing their efficacy as treatment for skin and soft tissue infections as a result of increased resistance in a variety of pathogens, including S. aureus It is thus imperative to explore alter...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2016-06-20 00:00:00