Abstract:
:In our study we examined the anti-human immunodeficiency virus type 1 (anti-HIV-1) activity of a novel HIV-1 protease inhibitor, PNU-140690 (tipranavir), against patient-derived isolates resistant to multiple other protease inhibitors (PIs). The aim of our experiments was to investigate the genotypes and the in vitro phenotypes of drug resistance of PNU-140690. We carried out drug susceptibility tests with peripheral blood mononuclear cells and a fixed amount of infectious virus (1,000 50% tissue culture infective doses) to determine the 50% inhibitory concentration (IC(50)) and IC(90), PCR assays for the detection of drug resistance mutations in RNA in plasma, and direct sequencing of PCR products. Phenotypic resistance to PIs was invariably related to genotypic mutations. The substitutions among the amino acid residues of the protease included L10I, K20R, L24I, M36I, N37D, G48V, I54V, L63P, I64V, A71V, V77I, V82A, I84V, and L90M. Isolates from all of the patients had developed a maximal degree of resistance to indinavir, ritonavir, and nelfinavir (IC(50)s, >0.1 microM). We also compared these mutations with the amino acid changes previously described in association with in vivo tipranavir administration. The mutations included the following: I15V, E35D, N37D, R41K, D60E, and A71T. Infections with IIIB, 14aPre, and N70 were inhibited by an average drug IC(90) of 0.18 +/- 0.02 microM in multiple experiments. The average mean +/- standard error of mean IC(90) for the entire group of multidrug-resistant isolates derived from the mean values for two culture wells with p24 antigen supernatant appeared to be 0.619 +/- 0.055 microM (range, 0.31 to 0.86 microM). Tipranavir retained a sustained antiviral activity against PI-MDR clinical isolates and might be useful in combination regimens with other antiretroviral agents for patients who have already failed other PI-containing therapies.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Rusconi S,La Seta Catamancio S,Citterio P,Kurtagic S,Violin M,Balotta C,Moroni M,Galli M,d'Arminio-Monforte Adoi
10.1128/aac.44.5.1328-1332.2000subject
Has Abstractpub_date
2000-05-01 00:00:00pages
1328-32issue
5eissn
0066-4804issn
1098-6596journal_volume
44pub_type
杂志文章abstract::A single point mutation in the 23S rRNA gene of Helicobacter pylori is known to confer resistance to clarithromycin. Most prevalent among clarithromycin-resistant clinical H. pylori isolates are the mutations from A-2142 to G and A-2143 to G in the 23S rRNA gene. The bias in the 23S rRNA gene mutations conferring clar...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.10.2749
更新日期:1998-10-01 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 shown previously that high-dose lipid amphotericin preparations are not more efficacious than lower doses in aspergillosis. We studied toxicity, drug concentrations and localization, and quantitative infection concurrently, using a 4-day model of central nervous system (CNS) aspergillosis to assess early event...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06015-11
更新日期:2012-08-01 00:00:00
abstract::Combinations of caspofungin and posaconazole were evaluated by fractional inhibitory concentration index against 119 Candida glabrata isolates. Synergy was seen in 18% of all isolates and in 4% of fluconazole-resistant isolates at 48 h without evidence of antagonism. This antifungal combination may have utility agains...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.8.3544-3545.2005
更新日期:2005-08-01 00:00:00
abstract::Genes belonging to different erm DNA hybridization classes were selectively amplified by polymerase chain reaction with a pair of oligonucleotides that corresponded to conserved amino acid motifs in known ERM methylases. Identification of the resistance mechanism was possible despite substantial nucleotide sequence di...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.10.2024
更新日期:1990-10-01 00:00:00
abstract::Posaconazole and itraconazole were more potent inhibitors of ergosterol synthesis, in both intact cells and cell extracts from Absidia corymbifera and Rhizopus oryzae, than voriconazole and fluconazole. Similarly, expression of CYP51 from R. oryzae in Saccharomyces cerevisiae significantly increased resistance to fluc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00747-06
更新日期:2006-11-01 00:00:00
abstract::We report the ultrastructural alterations induced during the proliferative stages of Trypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas' disease, by two ergosterol biosynthesis inhibitors, ketoconazole and terbinafine, which had previously been shown to be potent growth inhibitors whose effects are pote...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.11.2097
更新日期:1990-11-01 00:00:00
abstract::We describe the first IMP metallo-beta-lactamase in Aeromonas caviae: IMP-19, which differed from IMP-2 by a single amino acid change (Arg to Ala at position 38). bla(IMP-19) was found within a class 1 integron located on a 35-kb plasmid. This is also the first description of an IMP producer in France. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01462-06
更新日期:2007-12-01 00:00:00
abstract::Since currently available therapies against HIV/AIDS still show important drawbacks, the development of novel anti-HIV treatments is a key issue. We recently characterized methylated oligoribonucleotides (mONs) that extensively inhibit HIV-1 replication in primary T cells at nanomolar concentrations. The mONs were sho...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05614-11
更新日期:2012-02-01 00:00:00
abstract::Two genes (rpsL and rrs) with mutations associated with streptomycin resistance in Mycobacterium tuberculosis were characterized in 78 streptomycin-resistant and 61 streptomycin-susceptible isolates recovered from patients living in the United States, South America, Europe, Africa, and Asia. Fifty-four percent of the ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.4.1024
更新日期:1996-04-01 00:00:00
abstract::We investigated the efficacies of cefotaxime (CTX) and amoxicillin (AMX)-clavulanate (CLA) (AMC) against extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli in vitro and in a murine model of urinary tract infection (UTI). MICs, the checkerboard dilution method, and time-kill curves were used to explore the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02018-15
更新日期:2015-11-02 00:00:00
abstract::Two specific inhibitors of herpes simplex virus thymidine kinase, N2-phenyl-2'-deoxyguanosine and N2-(m-trifluoromethylphenyl)guanine, were tested for their ability to inhibit the reactivation of virus from explant cultures of latently infected murine trigeminal ganglia. Both compounds significantly diminished the fre...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.6.1285
更新日期:1990-06-01 00:00:00
abstract::FCE 22891 is the oral prodrug of FCE 22101, a new broad-spectrum penem. The pharmacokinetics of FCE 22891 after single-dose administration, its absolute bioavailability, and the effect of food intake on its absorption were investigated in three different randomized crossover studies in healthy volunteers. Drug levels ...
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.34.6.1001
更新日期:1990-06-01 00:00:00
abstract::Bacteriophage therapy of bacterial infections has received renewed attention owing to the increasing prevalence of antibiotic-resistant pathogens. A side effect of many antibiotics as well as of phage therapy with lytic phage is the release of cell wall components, e.g., endotoxins of gram-negative bacteria, which med...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.10.3817-3822.2004
更新日期:2004-10-01 00:00:00
abstract::TEM-24 remains one of the most widespread TEM-type extended-spectrum beta-lactamases (ESBLs) among Enterobacteriaceae. To analyze the reasons influencing its spread and persistence, a multilevel population genetics study was carried out on 28 representative TEM-24 producers from Belgium, France, Portugal, and Spain (1...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00959-09
更新日期:2010-02-01 00:00:00
abstract::Neisseria meningitidis has been relatively slow to acquire resistance to penicillin. We previously reported an increase in the incidence of invasive meningococcal disease (IMD) strains with decreased susceptibility to penicillin (DSP) in Ontario. Our objectives were to evaluate trends in IMD with DSP, to identify case...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01077-09
更新日期:2010-03-01 00:00:00
abstract::Toxoplasma gondii and Cryptosporidium parvum, members of the phylum Apicomplexa, are significant pathogens of both humans and animals worldwide for which new and effective therapeutics are needed. Here we describe the activity of the antibiotic boromycin against Toxoplasma and Cryptosporidium Boromycin potently inhibi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01278-20
更新日期:2021-01-19 00:00:00
abstract::Retrocyclins are humanized versions of the -defensin peptides expressed by the leukocytes of several nonhuman primates. Previous studies, performed in serum-free media, determined that retrocyclins 1 (RC1) and RC2 could prevent successful germination of Bacillus anthracis spores, kill vegetative B. anthracis cells, an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00267-11
更新日期:2011-09-01 00:00:00
abstract::Liposomal formulations of rifabutin were developed, and the effects of some parameters on the incorporation efficiency were studied. The antimycobacterial activity of rifabutin incorporated into liposomes prepared with phosphatidylcholine and phosphatidylserine (molar ratio, 7:3) was evaluated in a murine model of inf...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.9.2424-2430.2000
更新日期:2000-09-01 00:00:00
abstract::The intrapulmonary pharmacokinetics of azithromycin, clarithromycin, ciprofloxacin, and cefuroxime were studied in 68 volunteers who received single, oral doses of azithromycin (0.5 g), clarithormycin (0.5 g), ciprofloxacin (0.5 g), or cefuroxime (0.5 g). In subgroups of four subjects each, the subjects underwent bron...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.7.1617
更新日期:1996-07-01 00:00:00
abstract::Antibiotic resistance in bacteria is ever changing and adapting, as once-novel β-lactam antibiotics are losing their efficacy, primarily due to the production of β-lactamases. Metallo-β-lactamases (MBLs) efficiently inactivate a broad range of β-lactam antibiotics, including carbapenems, and are often coexpressed with...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01651-15
更新日期:2015-12-01 00:00:00
abstract::A total of 6,991 unique patient isolates of Streptococcus pneumoniae were collected from October 1997 to June 2002 from 25 medical centers in 9 of the 10 Canadian provinces. Among these isolates, 20.2% were penicillin nonsusceptible, with 14.6% being penicillin intermediate (MIC, 0.12 to 1 microg/ml) and 5.6% being pe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.6.1867-1874.2003
更新日期:2003-06-01 00:00:00
abstract::Disk diffusion antibiotic susceptibility tests as performed by the hospital diagnostic microbiology laboratory were read at 4, 8, and 12 h of incubation and compared to the traditional 18-h readings. Both the zone size in millimeters and a judgement of susceptible or resistant were recorded by the investigator at each...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.8.2.139
更新日期:1975-08-01 00:00:00
abstract::Colistin is an old antibiotic that has recently gained a considerable renewal of interest for the treatment of pulmonary infections due to multidrug-resistant Gram-negative bacteria. Nebulization seems to be a promising form of administration, but colistin is administered as an inactive prodrug, colistin methanesulfon...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03510-14
更新日期:2014-12-01 00:00:00
abstract::The genetic basis of erythromycin resistance in cutaneous propionibacteria was determined by comparing the nucleotide sequences of the peptidyl transferase region in the 23S rRNAs from 9 susceptible and 26 resistant clinical isolates as well as 4 laboratory-selected erythromycin-resistant mutants of a susceptible stra...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.5.1162
更新日期:1997-05-01 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 vitro selection of mutants with decreased susceptibility to ertapenem was performed using Escherichia coli and Klebsiella pneumoniae clinical strains producing either the bla(CTX-M-2), bla(CTX-M-3), bla(CTX-M-9), or bla(CTX-M-15) gene. Frequencies of mutants with decreased susceptibilities to ertapenem were similar...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01007-08
更新日期:2009-02-01 00:00:00
abstract::Infection caused by Mycobacterium avium is common in AIDS patients who do not receive treatment with highly active antiretroviral therapy (HAART) or who develop resistance to anti-HIV therapy. Mefloquine, a racemic mixture used for malaria prophylaxis and treatment, is bactericidal against M. avium in mice. MICs of (+...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00320-12
更新日期:2012-08-01 00:00:00
abstract::Daptomycin is a lipopeptide antibiotic with potent in vitro activity against gram-positive cocci, including Staphylococcus aureus. This study evaluated the in vitro and in vivo efficacies of daptomycin against two clinical isolates: methicillin-resistant S. aureus (MRSA) 277 (vancomycin MIC, 2 microg/ml) and glycopept...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00510-07
更新日期:2008-07-01 00:00:00
abstract::The MICs for 90% of the organisms tested (MIC90S) of 11 antibiotics against 24 clinical isolates of Actinobacillus actinomycetemcomitans were determined by the MIC 2000 system. The lowest MIC90S (16 micrograms/ml) were observed with ceftriaxone and rifampin. The next lowest MIC90S were found with cephapirin, tetracycl...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.1.179
更新日期:1986-01-01 00:00:00