Abstract:
:Clostridium difficile causes antibiotic-associated diarrhea and is a major public health concern. Current therapies disrupt the protective intestinal flora, do not reliably prevent recurrent infections, and will be decreasingly effective should less susceptible strains emerge. CRS3123 is an oral agent that inhibits bacterial methionyl-tRNA synthetase and has potent activity against C. difficile and aerobic Gram-positive bacteria but little activity against Gram-negative bacteria, including anaerobes. This first-in-human, double-blind, placebo-controlled, dose escalation study evaluated the safety and systemic exposure of CRS3123 after a single oral dose in healthy adults. Five cohorts of eight subjects each received CRS3123 or placebo in a 3:1 ratio. Doses for the respective active arms were 100 mg, 200 mg, 400 mg, 800 mg, and 1,200 mg. Blood and urine were collected for pharmacokinetic analysis. CRS3123 concentrations were measured with validated LC-MS/MS techniques. There were no serious adverse events or immediate allergic reactions during administration of CRS3123. In the CRS3123-treated groups, the most frequent adverse events were decreased hemoglobin, headache, and abnormal urine analysis; all adverse events in the active-treatment groups were mild to moderate, and their frequency did not increase with dose. Although CRS3123 systemic exposure increased at higher doses, the increase was less than dose proportional. The absorbed drug was glucuronidated at reactive amino groups on the molecule, which precluded accurate pharmacokinetic analysis of the parent drug. Overall, CRS3123 was well tolerated over this wide range of doses. This safety profile supports further investigation of CRS3123 as a treatment for C. difficile infections. (This study has been registered at ClinicalTrials.gov under identifier NCT01551004.).
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Nayak SU,Griffiss JM,Blumer J,O'Riordan MA,Gray W,McKenzie R,Jurao RA,An AT,Le M,Bell SJ,Ochsner UA,Jarvis TC,Janjic N,Zenilman JMdoi
10.1128/AAC.02760-16subject
Has Abstractpub_date
2017-07-25 00:00:00issue
8eissn
0066-4804issn
1098-6596pii
AAC.02760-16journal_volume
61pub_type
杂志文章abstract::We tested 32 Candida isolates recovered in the early 1990s from the bloodstreams of patients with candidemia for in vitro susceptibility to fluconazole and determined if MIC and/or the daily dose of fluconazole/MIC ratio correlated with the response to therapy. This is a unique data set since 87.5% (28/32) of patients...
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.49.8.3171-3177.2005
更新日期:2005-08-01 00:00:00
abstract::The antimicrobial activity of CS-940, a new trifluorinated quinolone drug, was tested against 761 clinical isolates. CS-940 activity against members of the family Enterobacteriaceae was most similar to that of ciprofloxacin and ofloxacin, with a large range of MICs inhibiting 90% of isolates tested (MIC90S) of 0.015 t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.10.2325
更新日期:1995-10-01 00:00:00
abstract::Bovicin HC5, a broad-spectrum lantibiotic produced by Streptococcus bovis HC5, catalyzed the efflux of intracellular potassium from Streptococcus bovis JB1, a sensitive strain. The level of ATP also decreased, but this decline appeared to be caused by the activity of the F(1)F(0) ATPase rather than efflux per se. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00109-08
更新日期:2008-06-01 00:00:00
abstract::A sensitive and specific high-pressure liquid chromatographic method is described for the determination of the antibacterial drug flumequine and a major metabolite, 7-hydroxyflumequine, in human plasma and urine. The assay was linear over a concentration range of 1 to 120 micrograms/ml for both compounds. This method ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.3.301
更新日期:1984-03-01 00:00:00
abstract::We have used the endogenous reverse transcriptase reaction of viral core particles from duck liver to elucidate the mechanism of inhibition of duck hepatitis B virus (DHBV) replication by the nucleoside analog (-)-beta-L-2',3'-dideoxy-3'-thiacytidine (3TC). As is the case in human immunodeficiency virus replication, 3...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.7.1430
更新日期:1995-07-01 00:00:00
abstract::This work in conjunction with the results presented in an earlier report (M. A. Purdy and K. L. Yielding, Antimicrob. Agents Chemother. 10:182--184, 1976) showed the following. (i) Nalidixic acid and novobiocin could inhibit post-ultraviolet and post-X-ray survival, implicating gyrase function in deoxyribonucleic acid...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.16.3.247
更新日期:1979-09-01 00:00:00
abstract::Yersinia enterocolitica has emerged as an enteropathogen associated with several types of human infections that often require antimicrobial therapy, but little is known about the antimicrobial susceptibilities of pathogenic strains isolated from humans in Canada. To determine the present patterns of antimicrobial susc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.9.2121
更新日期:1994-09-01 00:00:00
abstract::As a relationship between nelfinavir antiretroviral efficacy and plasma concentrations has been previously established, nelfinavir pharmacokinetics was investigated in order to optimize the individual treatment schedule in a pediatric population. A population pharmacokinetic model was developed to describe the concent...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.3.910-916.2006
更新日期:2006-03-01 00:00:00
abstract::Cinodine, a broad-spectrum glycocinnamoylspermidine antibiotic, binds to DNA and irreversibly inhibits bacterial and phase DNA synthesis. Cinodine was found to inhibit the activity of Micrococcus luteus DNA gyrase in vitro, but it did not inhibit the activities of two other DNA-binding enzymes, namely, topoisomerase I...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.7.1450
更新日期:1990-07-01 00:00:00
abstract::Food for human consumption is screened widely for the presence of antibiotic-resistant bacteria to assess the potential for transfer of resistant bacteria to the general population. Here, we describe an Enterobacter cloacae complex isolated from imported seafood that encodes two carbapenemases on two distinct plasmids...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02338-18
更新日期:2019-05-24 00:00:00
abstract::Sixteen healthy male volunteers participated in a randomized, balanced, three-way crossover study comparing the pharmacokinetics of cefmetazole, cefoxitin, and cefmetazole with probenecid pretreatment. Single 2-g doses of cefmetazole sodium and cefoxitin sodium were given intravenously as a 5-min infusion. Concentrati...
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.33.3.356
更新日期:1989-03-01 00:00:00
abstract::Macrolide antibiotics are used as anti-inflammatory agents, e.g., for prevention of exacerbations in chronic obstructive pulmonary disease and cystic fibrosis. Several studies have shown improved outcomes after the addition of macrolides to β-lactam antibiotics for treatment of severe community-acquired pneumonia. How...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02761-16
更新日期:2017-08-24 00:00:00
abstract::To date, there is only one drug in use, praziquantel, to treat more than 250 million people afflicted with schistosomiasis, a debilitating parasitic disease. The aryl hydantoin Ro 13-3978 is a promising drug candidate with in vivo activity superior to that of praziquantel against both adult and juvenile Schistosoma ma...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01142-17
更新日期:2017-11-22 00:00:00
abstract::We developed a multiplex real-time SYBR green-based PCR assay for rapid detection of tet(X) and its variants, including tet(X1) and tet(X2) and high-level tigecycline resistance genes tet(X3), tet(X4), and tet(X5). We showed that the real-time PCR assay developed had high linearity (R2 ≥ 0.996), sensitivity (low detec...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02292-19
更新日期:2020-03-24 00:00:00
abstract::The outer membrane of gram-negative cells excludes hydrophobic molecules and is responsible for the resistance of these cells to a number of dyes, detergents, and antibiotics. We describe a test for hydrophobic permeability in which a series of tetracyclines with various hydrophobicities are used. Normal Escherichia c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.5.539
更新日期:1984-05-01 00:00:00
abstract::We characterized the genetic environment of mcr-1 in colistin-resistant Escherichia coli strains isolated in Switzerland during 2014 to 2016 from humans (n = 3) and chicken meat (n = 6). Whole-genome and plasmid sequencing identified the mcr-1 gene integrated in IncX4 (of which, one strain carried the mcr-1.2 variant)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01245-17
更新日期:2017-10-24 00:00:00
abstract::Doripenem, a parenteral carbapenem, exhibited high affinity for penicillin-binding protein 2 (PBP2) and PBP3 in Pseudomonas aeruginosa and PBP2 in Escherichia coli, the primary PBPs whose inhibition leads to cell death. This PBP affinity profile correlates with the broad-spectrum gram-negative activity observed with d...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01529-07
更新日期:2008-04-01 00:00:00
abstract::Gatifloxacin (GTX), a new fluoroquinolone with extended antibacterial activity, is an interesting candidate for the treatment of chronic bacterial prostatitis (CBP). Besides the antibacterial spectrum, the concentrations in the target tissues and fluids are crucial for the treatment of CBP. Thus, it was of interest to...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.45.1.293-297.2001
更新日期:2001-01-01 00:00:00
abstract::The DNA sequences of two IncHI2 plasmids, pEC-IMP and pEC-IMPQ, from metallo-beta-lactamase-producing Enterobacter cloacae clinical isolates were determined. The two conjugative plasmids are almost identical, but pEC-IMPQ carries an additional segment containing an orf513 (ISCR1), a truncated 3' conserved sequence, an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00970-08
更新日期:2009-03-01 00:00:00
abstract::Here we completely sequenced four mcr-1-haboring plasmids, isolated from two extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli and two carbapenemase-producing Klebsiella pneumoniae clinical isolates. The mcr-1-harboring plasmids from an E. coli sequence type 2448 (ST2448) isolate and two K. pneumoniae ST...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00550-16
更新日期:2016-06-20 00:00:00
abstract::The National Committee for Clinical Laboratory Standards has proposed a reference broth macrodilution method for in vitro antifungal susceptibility testing of yeasts (the M27-P method). This method is cumbersome and time-consuming and includes MIC endpoint determination by visual and subjective inspection of growth in...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.9.1998
更新日期:1996-09-01 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::Macrolides are the antimicrobials of choice for treating human campylobacteriosis. The recent emergence of erm(B) in Campylobacter bacteria threatens the utility of this class of antibiotics. Here we report the constitutive and inducible expression of erm(B) in Campylobacter isolates derived from diarrheal patients an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01103-15
更新日期:2015-10-01 00:00:00
abstract::The activity of methacycline against microbial L-forms and their parent bacteria was compared with that of oxytetracycline, chlortetracycline, tetracycline, and demethylchlortetracycline, as well as with that of 22 other antibiotics which included examples of major groups of antibiotics. The L-forms and bacteria used ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.2.4.276
更新日期:1972-10-01 00:00:00
abstract::Miltefosine (MT) is a membrane-active alkylphospholipid licensed for the topical treatment of breast cancer skin metastases and the oral treatment of leishmaniasis, although its mechanism of action remains unclear. Electron paramagnetic resonance (EPR) spectroscopy of a spin-labeled lipid and a thiol-specific spin lab...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01332-13
更新日期:2014-06-01 00:00:00
abstract::Cyclacillin, a new aminosalicylic semisynthetic penicillin, was compared with amoxicillin for the therapy of acute bacterial maxillary sinusitis in 80 patients (ages, 12 to 70 years) in a prospective, double-blind, randomized clinical trial. Direct sinus aspirations for quantitative culture were done for all patients ...
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.30.3.350
更新日期:1986-09-01 00:00:00
abstract::We examined an E-test-based strategy for testing the combination of itraconazole and amphotericin B, the latter given either sequentially or concomitantly, in isolates of Aspergillus fumigatus. An antagonistic interaction between the two drugs was noted, especially with the sequential administration of amphotericin B....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.10.2915-2918.2000
更新日期:2000-10-01 00:00:00
abstract::The activity of cefbuperazone against 266 strains of anaerobic bacteria was determined by the agar dilution method and compared with cefoxitin, moxalactam, piperacillin, and clindamycin. All strains were recent clinical isolates from community hospitals. All agents tested showed good activity against Bacteroides fragi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.27.2.162
更新日期:1985-02-01 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::Minibacterium massiliensis strain CIP107820 is a recently discovered waterborne Gram-negative rod isolated from hospital water samples. It harbors a chromosomally located gene encoding an Ambler class A extended-spectrum β-lactamase termed MIN-1, sharing 56%, 54%, and 51% amino acid identities with β-lactamases LUT-1,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06401-11
更新日期:2012-07-01 00:00:00