Abstract:
:Shiga toxin (Stx)-producing Escherichia coli (STEC) causes hemorrhagic colitis and hemolytic-uremic syndrome (HUS). The rates of STEC infection and complications, including death, are highest among young children and elderly individuals. There are no causal therapies. Because Stx is the primary pathological agent leading to organ injury in patients with STEC disease, therapeutic antibodies are being developed to neutralize systemically absorbed toxin during the early phase of the infection. Two phase I, single-dose, open-label, nonrandomized studies were conducted to evaluate the safety and pharmacokinetics of the chimeric monoclonal antibodies (antitoxins) against Stx 1 and 2 (calphaStx1 and calphaStx2, respectively). In the first study, 16 volunteers received 1 or 3 mg/kg of body weight of calphaStx1 or calphaStx2 as a single, short (1-h) intravenous infusion (n = 4 per group). In a second study, 10 volunteers received a 1-h infusion of calphaStx1 and calphaStx2 combined at 1 or 3 mg/kg (n = 5 per group). Treatment-emergent adverse events were mild, resolved spontaneously, and were generally unrelated to the antibody infusion. No serious adverse events were observed. Human antichimeric antibodies were detected in a single blood sample collected on day 57. Antibody clearance was slightly greater for calphaStx1 (0.38 +/- 0.16 ml/h/kg [mean +/- standard deviation]) than for calphaStx2 (0.20 +/- 0.07 ml/h/kg) (P = 0.0013, t test). The low clearance is consistent with the long elimination half-lives of calphaStx1 (190.4 +/- 140.2 h) and calphaStx2 (260.6 +/- 112.4 h; P = 0.151). The small volume of distribution (0.08 +/- 0.05 liter/kg, combined data) indicates that the antibodies are retained within the circulation. The conclusion is that calphaStx1 and calphaStx2, given as individual or combined short intravenous infusions, are well tolerated. These results form the basis for future safety and efficacy trials with patients with STEC infections to ameliorate or prevent HUS and other complications.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Bitzan M,Poole R,Mehran M,Sicard E,Brockus C,Thuning-Roberson C,Rivière Mdoi
10.1128/AAC.01661-08subject
Has Abstractpub_date
2009-07-01 00:00:00pages
3081-7issue
7eissn
0066-4804issn
1098-6596pii
AAC.01661-08journal_volume
53pub_type
杂志文章abstract::Fenpropimorph was shown to inhibit the accumulation of the pyrimidine bases uracil and cytosine from the growth media in Saccharomyces cerevisiae. Uracil prototrophs of S. cerevisiae were more resistant to the growth-inhibitory effects of fenpropimorph than were uracil auxotrophs. High concentrations of uracil rescued...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.5.1004
更新日期:1994-05-01 00:00:00
abstract::Pharmacodynamic parameters have become increasingly important for the determination of the optimal dosing schedules of antibiotics. In this study, the postantibiotic effects (PAEs), the postantibiotic sub-MIC effects (PA SMEs), and the sub-MIC effects (SMEs) of roxithromycin, clarithromycin, and azithromycin on refere...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.1.221
更新日期:1995-01-01 00:00:00
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pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.01031-09
更新日期:2009-12-01 00:00:00
abstract::In the eubacterial cell, the peptidoglycan is perpetually hydrolyzed throughout the cell cycle by different enzymes such as lytic transglycosylases, endopeptidases, and amidases. In Escherichia coli, four N-acetylmuramoyl-l-alanine amidases, AmiA, -B, -C, and -D, are present in the periplasm. AmiA, -B, and -C are solu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01520-07
更新日期:2009-07-01 00:00:00
abstract::Penetration of cefprozil into the middle ear fluid was investigated in patients with chronic otitis media. A total of 89 patients ranging from 7 months to 11 years old participated in the study. The middle ear fluid was removed by ventilation tubes inserted through the tympanic membrane at times ranging from 0.38 to 5...
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.38.9.2210
更新日期:1994-09-01 00:00:00
abstract::The two groups of chromosomal beta-lactamases from Klebsiella oxytoca (OXY-1 and OXY-2) can be overproduced 73- to 223-fold, due to point mutations in the consensus sequences of their promoters. The different versions of promoters from blaOXY-1 and blaOXY-2 were cloned upstream of the chloramphenicol acetyltransferase...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.4.850
更新日期:1999-04-01 00:00:00
abstract::We report a case of accelerated metabolism of voriconazole during therapy for invasive pulmonary aspergillosis, resulting in subtherapeutic levels. Target voriconazole levels were restored with high dosages of voriconazole (up to 40 mg/kg of body weight/day) and the addition of cimetidine as a cytochrome P450 enzyme i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01221-08
更新日期:2009-04-01 00:00:00
abstract::9-Deoxy-Delta(9),Delta(12)-13,14-dihydro-prostaglandin D(2) (Delta(12)-PGJ(2)), a natural cyclopentenone metabolite of prostaglandin D(2), is shown to possess therapeutic efficacy against influenza A virus A/PR8/34 (H1N1) infection in vitro and in vivo. The results indicate that the antiviral activity is associated wi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.1.200-204.2000
更新日期:2000-01-01 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::Coresistance to human reserve antibiotics can be selected by antibiotics used in veterinary medicine. A Clostridium perfringens strain isolated from pig manure was resistant to the reserve drug linezolid and, simultaneously, resistant against florfenicol and erythromycin. We detected a new mutation in a highly conserv...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01208-09
更新日期:2010-03-01 00:00:00
abstract::PER-1 extended-spectrum β-lactamase-producing Gram-negative bacilli are resistant to oxyimino-cephalosporins. However, the bla(PER-1) gene has never been reported in Klebsiella pneumoniae. Here, we studied interspecies dissemination of the bla(PER-1) gene by horizontal transfer of Tn1213 among Acinetobacter baumannii,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00994-10
更新日期:2011-03-01 00:00:00
abstract::The macrolide resistance gene erm(T) was identified for the first time in a porcine Erysipelothrix rhusiopathiae isolate from swine in China. The novel 3,749-bp small plasmid pER29, which carries erm(T), had a G+C content of 31% and four distinct open reading frames. The presence of pER29 increased by at least 128-fol...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00228-15
更新日期:2015-04-01 00:00:00
abstract::Mycograb (NeuTec Pharma plc) is a human genetically recombinant antibody against fungal heat shock protein 90 (HSP90). Antibody to HSP90 is closely associated with recovery in patients with invasive candidiasis who are receiving amphotericin B (AMB). Using in vitro assays developed for efficacy assessment of chemother...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.7.2208-2216.2003
更新日期:2003-07-01 00:00:00
abstract::The activities of sparfloxacin, azithromycin, temafloxacin, and rifapentine against two virulent strains of the Mycobacterium avium complex isolated from patients with AIDS were evaluated in a model of intracellular infection and were compared with that of clarithromycin. Human monocyte-derived macrophages were infect...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.7.1356
更新日期:1991-07-01 00:00:00
abstract::A woman in her late 60s with disseminated histoplasmosis was treated with posaconazole because first-line therapies were not tolerated. She subsequently presented with decompensated heart failure, hypertension, and hypokalemia. Laboratory tests revealed low renin and aldosterone levels. A potential mechanism is inhibi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02130-17
更新日期:2018-04-26 00:00:00
abstract::Zika virus (ZIKV) has been linked to the development of microcephaly in newborns, as well as Guillain-Barré syndrome. There are currently no drugs available to treat ZIKV infection, and accordingly, there is an unmet medical need for the discovery of new therapies. High-throughput drug screening efforts focusing on in...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00725-18
更新日期:2018-09-24 00:00:00
abstract::A novel plasmid-mediated metallo-beta-lactamase (IMP-9) is described in seven isolates of Pseudomonas aeruginosa from Guangzhou, China, isolated in 2000. The gene was carried on a large (approximately 450-kb) IncP-2 conjugative plasmid. This is the first report of carriage of bla(IMP) genes on such large plasmids. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.1.355-358.2006
更新日期:2006-01-01 00:00:00
abstract::The occurrence and diversity of vancomycin-resistant Enterococcus faecium (VREF) were investigated in 100 Danish broiler flocks 15 years after the avoparcin ban. VREF occurred in 47 flocks at low fecal concentrations detectable only by selective enrichment. Vancomycin resistance was prevalently associated with a trans...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05072-14
更新日期:2015-05-01 00:00:00
abstract::Candida albicans is an opportunistic human fungal pathogen and a causative agent of oropharyngeal candidiasis (OPC), the most frequent opportunistic infection among patients with AIDS. Fluconazole and other azole antifungal agents have proven effective in the management of OPC; however, with increased use of these age...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.4.1220-1227.2003
更新日期:2003-04-01 00:00:00
abstract::Clinical isolates of Trichomonas vaginalis were obtained from women consecutively enrolled in a study of partner notification. Testing of susceptibility to metronidazole and tinidazole was performed. Resistance to metronidazole and tinidazole was present in 17/178 (9.6%) and 1/178 (0.56%) strains, respectively. In vit...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00814-06
更新日期:2006-12-01 00:00:00
abstract::Bactericidal activity in serum produced after administration of 1-g intravenous doses of cefoperazone, cefotaxime, ceftizoxime, and moxalactam was ascertained in six healthy subjects. The assay organisms were a strain of Staphylococcus aureus which was moderately susceptible to the drugs (MBC, 2 to 8 micrograms/ml) an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.1.55
更新日期:1985-07-01 00:00:00
abstract::Ajoene (4,5,9-trithiadodeca-1,6,11-triene 9-oxide), a product initially isolated from extracts of garlic (Allium sativum), was tested for its antimalarial activity in vivo in a well-characterized murine model. A single ajoene dose of 50 mg/kg, on the day of infection, suppressed the development of parasitemia; there w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.2.337
更新日期:1994-02-01 00:00:00
abstract::In a previous work, we described the possible relationship between a defect of purine-cytosine permease and the acquisition of a cross-resistance to the antifungal combination flucytosine (5FC) and fluconazole (FLC) in Candida lusitaniae (T. Noël, F. François, P. Paumard, C. Chastin, D. Brethes, and J. Villard, Antimi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.8.3101-3108.2005
更新日期:2005-08-01 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::Lipids in fresh human milk do not inactivate viruses but become antiviral after storage of the milk for a few days at 4 or 23 degrees C. The appearance of antiviral activity depends on active milk lipases and correlates with the release of free fatty acids in the milk. A number of fatty acids which are normal componen...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.1.27
更新日期:1987-01-01 00:00:00
abstract::Amphotericin B (AMB) has been a mainstay therapy for fungal infections of the central nervous system, but its use has been limited by its poor penetration into the brain, the mechanism of which remains unclear. In this study, we aimed to investigate the role of P-glycoprotein (P-gp) in AMB crossing the blood-brain bar...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02535-14
更新日期:2014-08-01 00:00:00
abstract::The antileishmanial efficacies of four proprietary amphotericin B (AmB) formulations (Fungizone, AmBisome, Abelcet, and Amphocil) and an experimental nonionic surfactant vesicle (NIV) formulation were compared in a murine model of acute visceral leishmaniasis. By a multiple-dosing regimen, groups of Leishmania donovan...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.10.2089
更新日期:1997-10-01 00:00:00
abstract::Several fast-growing Mycobacterium strains were found to inactivate rifampin. Two inactivated compounds (RIP-Ma and RIP-Mb) produced by these organisms were different from previously reported derivatives, i.e., phosphorylated or glucosylated derivatives, of the antibiotic. The structures of RIP-Ma and RIP-Mb were dete...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.4.1007
更新日期:1995-04-01 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:UNLABELLED:Peramivir is an intravenous anti-influenza agent that inhibits viral growth by selectively inhibiting neuraminidase in human influenza A and B viruses. To characterize its pharmacokinetics, a population pharmacokinetic analysis of peramivir was performed using 3,199 plasma concentration data samples from 332...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00799-15
更新日期:2015-11-01 00:00:00