Abstract:
:A pyridodiazepine amine inhibitor of Helicobacter pylori glutamate racemase (MurI) was characterized. The compound was selectively active against H. pylori, and growth suppression was shown to be mediated through the inhibition of MurI by several methods. In killing kinetics experiments, the compound showed concentration-independent activity, with about a 2-log loss of viability in 24 h. A demonstration of efficacy in a mouse infection model was attempted but not achieved, and this was attributed to the failure to attain extended exposure levels above the MIC for >95% of the time. This index and magnitude were derived from pharmacokinetic-pharmacodynamic (PK-PD) studies with amoxicillin, another inhibitor of peptidoglycan biosynthesis that showed slow killing kinetics similar to those of the pyridodiazepine amines. These studies indicate that MurI and other enzymes involved in peptidoglycan biosynthesis may be less desirable targets for monotherapy directed against H. pylori if once-a-day dosing is required.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
de Jonge BL,Kutschke A,Newman JV,Rooney MT,Yang W,Cederberg Cdoi
10.1128/AAC.04410-14subject
Has Abstractpub_date
2015-04-01 00:00:00pages
2337-42issue
4eissn
0066-4804issn
1098-6596pii
AAC.04410-14journal_volume
59pub_type
杂志文章abstract::A beta-lactam-sensitive strain (C152) of Shigella dysenteriae showed two major outer membrane proteins (OMPs) with M(r)s of 43,000 and 38,000, while the clinical isolate M2 lacked the 43,000-Mr OMP, which acted as a channel for beta-lactam antibiotics. Permeability of beta-lactams across the outer membrane (OM) of M2 ...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.41.10.2302
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abstract::Forty-one children <8 years of age treated for brucellosis with oral minocycline (2.5 mg/kg) twice daily for 3 weeks were recalled and examined to check for dental staining and defects. Dental staining and defects were found in 14 of 41 exposed children (34.1%) and in 30 of 82 matched controls (36.6%), respectively (P...
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pub_type: 杂志文章
doi:10.1128/AAC.48.7.2739-2741.2004
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doi:10.1128/aac.24.2.305
更新日期:1983-08-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00208-12
更新日期:2012-06-01 00:00:00
abstract::Lethal mutagenesis is an antiviral approach that consists in extinguishing a virus by an excess of mutations acquired during replication in the presence of a mutagenic agent, often a nucleotide analogue. One of its advantages is its broad spectrum nature that renders the strategy potentially effective against emergent...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01653-19
更新日期:2019-09-30 00:00:00
abstract::Broth dilution minimal inhibitory concentration (MIC) readings were compared after different incubation periods and with different inoculum concentrations. The purpose was to determine the best conditions for obtaining early results as close as possible to overnight readings. Initially, 76 antibiotic-organism combinat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.8.4.429
更新日期:1975-10-01 00:00:00
abstract::Botulinum neurotoxin A is a category A bioterrorism agent. Current antitoxin therapies are scarce and produce adverse reactions. XOMA 3AB consists of 3 IgG1 monoclonal antibodies (MAbs), each with a distinct human or humanized variable region, which bind to distinct epitopes on botulinum neurotoxin serotype A. This fi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
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更新日期:2014-09-01 00:00:00
abstract::The role of mutations in the genes for GyrA and ParC in quinolone resistance in Mycoplasma hominis was studied. Selection with sparfloxacin gave mutations at GyrA83 (Ser-->Leu; Escherichia coli numbering) or GyrA87 (Glu-->Lys), and mutants had increased levels of resistance to sparfloxacin (8- to 16-fold) but not to o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.10.2493
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abstract::Viridin B, a bacteriocin produced by Streptococcus mitis, copurified with the alpha-hemolysin after ammonium sulfate precipitation and gel filtration on Sephadex G-200. The bacteriocin and hemolysin were separated in some instances by ion-exchange chromatography on diethylaminoethyl-Sephadex A-50, but the two substanc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:1979-03-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00732-11
更新日期:2012-01-01 00:00:00
abstract::Daptomycin pharmacokinetics were evaluated for burn patients. Burn patients had decreases in the maximum concentration of the drug in serum (44%) and the area under the concentration-time curve (47%) and increases in the volume of distribution (64%) and total clearance (77%) compared to healthy volunteers. In burn pat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.01321-07
更新日期:2008-05-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00185-19
更新日期:2019-04-25 00:00:00
abstract::We previously showed that the mouse inorganic phosphate transporter Npt1 operates in the hepatic sinusoidal membrane transport of anionic drugs such as benzylpenicillin and mevalonic acid. In the present study, the mechanism of renal secretion of penem antibiotics was examined by using a Xenopus oocyte expression syst...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.3.574-577.2000
更新日期:2000-03-01 00:00:00
abstract::Most surveys for class 1 integrons are at least partly predicated on PCR screening that targets integron conserved regions. However, class 1 integrons are structurally diverse, so dependence on conserved regions may lead to missing clinically relevant examples of class 1 integrons. Here, we surveyed a commensal popula...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01831-10
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abstract::The response of tolerant Streptococcus sanguis and nontolerant Streptococcus mitis infections to penicillin therapy was compared in the rabbit model of endocarditis. The minimal inhibitory and bactericidal concentrations of penicillin were 0.1 and 0.1 mug/ml, respectively, for S. mitis and 0.05 and 6.2 mug/ml, respect...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.1.67
更新日期:1983-01-01 00:00:00
abstract::Resistance to metronidazole, clarithromycin, and amoxicillin (amoxicilline) was found in 82, 3.8, and 1.9% of 106 Helicobacter pylori isolates, respectively. No tetracycline-resistant isolates were found. In all of the clarithromycin-resistant isolates, only one point mutation was present, either A2143G or A2142G. Our...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00145-09
更新日期:2009-09-01 00:00:00
abstract::Heat shock protein 90 (Hsp90) is an essential chaperone involved in the fungal stress response that can be harnessed as a novel antifungal target for the treatment of invasive aspergillosis. We previously showed that genetic repression of Hsp90 reduced Aspergillus fumigatus virulence and potentiated the effect of the ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02286-13
更新日期:2014-01-01 00:00:00
abstract::Because of the potential for an interaction between cephalosporins and aminoglycosides leading to renal injury, an evaluation of the effect of a new cephalosporin, cefamandole nafate, on the toxicity of the aminoglycoside tobramycin was performed in laboratory animals. High doses of cefamandole nafate did not increase...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.12.4.465
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:1996-05-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01014-08
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abstract::Pyronaridine, a Mannich base antimalarial, has demonstrated high in vivo and in vitro efficacy against chloroquine-resistant Plasmodium falciparum. Although this drug has the potential to become a prominent artemisinin combination therapy, little is known about its efficacy against drug-resistant Plasmodium vivax. The...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00801-10
更新日期:2010-12-01 00:00:00
abstract::We applied in vitro evolution to an Escherichia coli strain containing bla(CTX-M-2) and obtained 10 independent mutant bla(CTX-M-2) alleles that confer elevated resistance to ceftazidime (MIC > or = 32 microg/ml) but lost the ability to confer resistance to cefepime. All alleles had a Pro-to-Ser substitution at positi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.3.1242-1244.2005
更新日期:2005-03-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
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更新日期:2018-12-21 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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abstract::Isavuconazole is a novel, broad-spectrum, antifungal azole. In order to evaluate its interactions with known azole resistance mechanisms, isavuconazole susceptibility among different yeast models and clinical isolates expressing characterized azole resistance mechanisms was tested and compared to those of fluconazole,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02157-15
更新日期:2015-10-19 00:00:00
abstract::Mycobacteria grew rapidly in FST medium (tissue culture medium F12 supplemented with 5% serum and 0.05% Tween 80). Growth of Mycobacterium tuberculosis and other niacin-negative mycobacteria in flat-bottomed, 96-well tissue culture plates was estimable by the naked eye within 3 to 5 days when mycobacteria were inocula...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.24.2.268
更新日期:1983-08-01 00:00:00
abstract::The gram-positive bacterium Staphylococcus epidermidis is the most common cause of infections associated with catheters and other indwelling medical devices. S. epidermidis produces an extracellular slime that enables it to form adherent biofilms on plastic surfaces. We found that a biofilm-releasing enzyme produced b...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.7.2633-2636.2004
更新日期:2004-07-01 00:00:00