Abstract:
:BAL5788 is the water-soluble prodrug of BAL9141, a novel broad-spectrum cephalosporin with potent bactericidal activities against methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae. We investigated the safety and pharmacokinetics of BAL5788 in a double-blind, single-ascending-dose study with 40 healthy male subjects. The subjects were randomized to receive placebo (n = 2 subjects per dose) or BAL5788 (n = 6 subjects per dose) as a 200-ml intravenous infusion over 30 min. The BAL5788 doses used were 125, 250, 500, 750, and 1,000 mg (BAL9141 equivalents). All doses were well tolerated, with no severe or serious adverse events (AEs). The most frequent AE was taste disturbance. No electrocardiographic abnormalities and no trends or clinically significant changes in laboratory parameters or vital signs were observed. The maximum concentration of drug in serum and the area under the concentration-time curve for BAL9141 were dose proportional over the dosing range. The elimination half-life of BAL9141 was about 3 h. The volume of distribution at steady state was equal to the volume of the adult extracellular water compartment, and the rate of renal clearance of free drug corresponded to the normal glomerular filtration rate for adults. More than 70% of the administered dose was excreted as BAL9141 in the urine, and almost no prodrug was detected. After the infusion of 750 mg, the mean plasma BAL9141 concentrations exceeded the MIC at which 100% of MRSA isolates are inhibited (4 microg/ml) for approximately 7 h, or 58% of a 12-h dosing interval. These results indicate that infusions of 750 mg twice a day should be adequate for the treatment of infections caused by MRSA.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Schmitt-Hoffmann A,Roos B,Schleimer M,Sauer J,Man A,Nashed N,Brown T,Perez A,Weidekamm E,Kovács Pdoi
10.1128/AAC.48.7.2570-2575.2004subject
Has Abstractpub_date
2004-07-01 00:00:00pages
2570-5issue
7eissn
0066-4804issn
1098-6596pii
48/7/2570journal_volume
48pub_type
临床试验,杂志文章,随机对照试验abstract::Use of combinations of antimicrobials that together achieve synergistic activities against targeted microorganisms is one potential strategy for overcoming bacterial resistance. As the incidence of infections caused by multidrug-resistant staphylococci and enterococci increases, the importance of devising additional s...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.8.2606-2612.2002
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abstract::The M184V substitution in human immunodeficiency virus type 1 reverse transcriptase (RT) is rapidly selected in tissue culture following serial passage of wild-type virus in the presence of increasing concentrations of lamivudine (3TC). M184V is also associated with several alterations of RT enzymatic function in vitr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.11.4189-4194.2004
更新日期:2004-11-01 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::The in vitro activity of tosufloxacin (A-61827; T-3262) against 15 clinical isolates of Chlamydia trachomatis and 31 recent clinical isolates of Neisseria gonorrhoeae, including 15 spectinomycin-resistant N. gonorrhoeae and 16 penicillinase-producing N. gonorrhoeae, was determined. Tosufloxacin was compared with doxyc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.6.971
更新日期:1990-06-01 00:00:00
abstract::Spider venoms are vast natural pharmacopoeias selected by evolution. The venom of the ant spider Lachesana tarabaevi contains a wide variety of antimicrobial peptides. We tested six of them (latarcins 1, 2a, 3a, 4b, 5, and cytoinsectotoxin 1a) for their ability to suppress Chlamydia trachomatis infection. HEK293 cells...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00449-11
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abstract::The susceptibilities of Streptococcus pneumoniae (1,476 strains) and untypeable Haemophilus influenzae (1,676 strains) to various oral beta-lactam, macrolide-azalide, and fluoroquinolone antimicrobial agents were determined by broth microdilution. Organisms were isolated from specimens obtained from outpatients in six...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.43.8.1901
更新日期:1999-08-01 00:00:00
abstract::The pharmacokinetics of cefprozil were determined with 12 volunteers (8 received cefprozil and 4 received a placebo) after oral administration of 500 mg every 12 h over an 8-day period in a randomized, double-blind, placebo-controlled design. Concentrations in serum and urine were measured by high-pressure liquid chro...
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.36.1.144
更新日期:1992-01-01 00:00:00
abstract::Two bla(OXA-48)-like-positive isolates (Klebsiella pneumoniae and Enterobacter cloacae) were recovered in Argentina in 2008 as part of a large-scale survey focused on multidrug resistance in Enterobacteriaceae. In both cases, sequencing identified β-lactamase OXA-163, differing from OXA-48 by a single amino substituti...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00022-11
更新日期:2011-06-01 00:00:00
abstract::The effects of binding and the bactericidal action of vancomycin on the arrangement and mobilities of cell wall polymers in Bacillus licheniformis were investigated by (15)N nuclear magnetic resonance spectroscopy. The bactericidal action of vancomycin led to reduced mobilities of cell wall teichoic acid and teichuron...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.14.5.695
更新日期:1978-11-01 00:00:00
abstract::The use of dialysis fermentation with the continuous extraction of the dialysate has resulted in a twofold increase in the cycloheximide titer due to relief from product inhibition. Continuous extraction of the dialysate has eliminated the necessity for large reservoir volumes of fermentation medium normally used in d...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.7.6.861
更新日期:1975-06-01 00:00:00
abstract::Given the greater than 90% lethality of clinical central nervous system (CNS) aspergillosis despite current therapies, there is a need for an animal model to study therapeutic strategies. We previously established a model of CNS aspergillosis by intracerebral infection and report here the results of treatment with the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.2.813-815.2003
更新日期:2003-02-01 00:00:00
abstract::The antimicrobial activity of cinoxacin, 1-ethyl-4(1H)-oxo-[1,3]dioxolo[4,5-g]cinnoline-3-carboxylic acid, previously reported as compound 64716, was determined and compared with other antimicrobial agents at a dosage of 12 mg/kg once daily in a descending pyelonephritis rat model with Escherichia coli and Proteus mir...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.6.4.432
更新日期:1974-10-01 00:00:00
abstract::The pharmacokinetic properties of an everninomicin antibiotic (SCH27899; Ziracin) were studied with healthy Japanese male volunteers by single (1, 3, 6, and 9 mg/kg of body weight) and multiple 60-min intravenous infusions (3, 6, and 9 mg/kg once daily for 10 consecutive days following a 2-day interval after the initi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.45.3.917-921.2001
更新日期:2001-03-01 00:00:00
abstract::A Cedecea davisae isolate, which was intermediate or resistant to third-generation cephalosporins and carbapenems, was recovered from a urine sample. Susceptibility testing, isoelectric focusing, and analysis of outer membrane proteins showed that AmpC β-lactamase expression combined with porin deficiency accounted fo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03237-14
更新日期:2014-11-01 00:00:00
abstract::Macrolide-resistant Mycoplasma pneumoniae (MR M. pneumoniae) has been isolated from clinical specimens in Japan since 2000. A comparative study was carried out to determine whether or not macrolides are effective in treating patients infected with MR M. pneumoniae. The clinical courses of 11 patients with MR M. pneumo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.2.709-712.2006
更新日期:2006-02-01 00:00:00
abstract::The in vitro antifungal activities of two N-aminoacyl derivatives of amphotericin B methyl ester (AME) were compared by tube dilution with those of amphotericin B and AME, using 60 isolates representing 10 yeast species. A total of 70% of the strains were inhibited by concentrations of the N-aminoacyl AME derivatives ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.19.1.106
更新日期:1981-01-01 00:00:00
abstract::Pyrazinamide (PZA) has important sterilizing activity in tuberculosis (TB) chemotherapy. We describe trends, risk factors, and molecular epidemiology associated with PZA-resistant (PZA(r)) Mycobacterium tuberculosis in New York City (NYC). From 2001 to 2008, all incident culture-positive TB cases reported by the NYC D...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00764-15
更新日期:2015-10-01 00:00:00
abstract::Ceftolozane is a novel cephalosporin with activity against drug-resistant pathogens, including Pseudomonas aeruginosa and Streptococcus pneumoniae. The in vivo investigation reported here tested the limits of this drug against 20 P. aeruginosa and S. pneumoniae isolates across a wide MIC range and defined resistance m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03572-14
更新日期:2014-10-01 00:00:00
abstract::Despite the marketing of a series of new antibiotics for antibiotic-resistant gram-positive bacteria, no new agents for multiple-antibiotic-resistant gram-negative infections will be available for quite some time. Clinicians will need to find more effective ways to utilize available agents. Colistin is an older but no...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.3.905-909.2003
更新日期:2003-03-01 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
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doi:10.1128/AAC.02761-16
更新日期:2017-08-24 00:00:00
abstract::All known DNA ligases catalyze the formation of a phosphodiester linkage between adjacent termini in double-stranded DNA via very similar mechanisms. The ligase family can, however, be divided into two classes: eubacterial ligases, which require NAD(+) as a cofactor, and other ligases, from viruses, archaea, and eukar...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.11.2766
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abstract::BO-2727, a new 1-beta-methyl-carbapenem, was active at concentrations of 6.25 micrograms/ml or less against gram-positive and gram-negative bacteria, including some imipenem- and/or meropenem-resistant (MICs, > or = 12.5 micrograms/ml) Pseudomonas aeruginosa strains, against which it proved generally fourfold more act...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.12.2756
更新日期:1993-12-01 00:00:00
abstract::The effects of 6-amino-2-n-pentylthiobenzothiazole (APB), a new antifungal agent, on ergosterol biosynthesis in Candida albicans and Saccharomyces cerevisiae were studied, using [14C]acetate incorporation. In C. albicans, the inhibition of growth was accompanied by a marked inhibition of acetate incorporation in 4-des...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.7.1538
更新日期:1995-07-01 00:00:00
abstract::A group H1 R factor encoding resistance to chloramphenicol, streptomycin, sulfonamide, and tetracycline was transferred into Salmonella typhimurium LT-2. The virulence of LT-2 for mice, as assessed by intraperitoneal 50% lethal dose and the number of organisms in the spleen, was not affected by the R factor. On the ot...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.3.478
更新日期:1979-03-01 00:00:00
abstract::Methionine gamma-lyase, the enzyme which catalyzes the single-step conversion of methionine to alpha-ketobutyrate, ammonia, and methanethiol, is highly active in many anaerobic pathogenic microorganisms but has no counterpart in mammals. This study tested the hypothesis that this pathogen-specific enzyme can be exploi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.6.1743-1745.2001
更新日期:2001-06-01 00:00:00
abstract::A model of orogastric candidosis in SCID mice, which mimics disease seen in AIDS patients, was used to evaluate ravuconazole in comparison with fluconazole for treatment. Mice were infected orally with Candida albicans and received either no treatment or oral treatment once daily for 12 days with 1, 5, or 25 mg of rav...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.12.3433-3436.2001
更新日期:2001-12-01 00:00:00
abstract::Carbovir is a novel carbocyclic nucleoside which has been shown to have potent in vitro activity against human immunodeficiency virus, the causative agent of acquired immunodeficiency syndrome. Sprague-Dawley male rats were used to investigate the pharmacokinetics and bioavailability of carbovir. Six rats received car...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.2.171
更新日期:1989-02-01 00:00:00
abstract::Ceftriaxone in short courses has emerged as an effective alternative to chloramphenicol for the treatment of typhoid fever. To study the pharmacokinetics of ceftriaxone in acute typhoid fever, 10 febrile Nepalese adolescents and young adults with blood culture-positive illness were treated with 3 g of ceftriaxone (int...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.10.2415
更新日期:1994-10-01 00:00:00
abstract::We evaluated phage therapy in experimental infections due to S242, a fatal neonatal meningitis Escherichia coli strain belonging to the worldwide-distributed O25b:H4-ST131 clone that produces extended-spectrum beta-lactamase CTX-M-15. A lytic phage, EC200(PP), active against S242, was isolated from environmental water...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06330-11
更新日期:2012-07-01 00:00:00
abstract::Thirty-two strains of Trichophyton rubrum and 16 strains of Trichophyton mentagrophytes isolated from patients with tinea unguium in various parts of Germany were subjected to a microdilution test with six systemic or topical antimycotic agents. Apart from griseofulvin, there were no species-specific differences betwe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/aac.39.5.1206
更新日期:1995-05-01 00:00:00