In vitro and in vivo antibacterial activities of OPC-20011, a novel parenteral broad-spectrum 2-oxaisocephem antibiotic.

Abstract:

:OPC-20011, a new parenteral 2-oxaisocephem antibiotic, has an oxygen atom at the 2- position of the cephalosporin frame. OPC-20011 had the best antibacterial activities against gram-positive bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, and penicillin-resistant Streptococcus pneumoniae: MICs at which 90% of the isolates were inhibited were 6.25, 6.25, and 0.05 microg/ml, respectively. Its activity is due to a high affinity of the penicillin-binding protein 2' in MRSA, an affinity which was approximately 1,050 times as high as that for flomoxef. Against gram-negative bacteria, OPC-20011 also showed antibacterial activities similar to those of ceftazidime. The in vivo activities of OPC-20011 were comparable to or greater than those of reference compounds in murine models of systemic infection caused by gram-positive and -negative pathogens. OPC-20011 was up to 10 times as effective as vancomycin against MRSA infections in mice. This better in vivo efficacy is probably due to the bactericidal activity of OPC-20011, while vancomycin showed bacteriostatic activity against MRSA. OPC-20011 produced a significant decrease of viable counts in lung tissue at a dose of 2.5 mg/kg of body weight, an efficacy similar to that of ampicillin at a dose of 10 to 20 mg/kg on an experimental murine model of respiratory tract infection caused by non-ampicillin-susceptible S. pneumoniae T-0005. The better therapeutic efficacy of OPC-20011 was considered to be due to its potent antibacterial activity and low affinity for serum proteins of experimental animals (29% in mice and 6.4% in rats).

authors

Matsumoto M,Tamaoka H,Ishikawa H,Kikuchi M

doi

10.1128/AAC.42.11.2943

subject

Has Abstract

pub_date

1998-11-01 00:00:00

pages

2943-9

issue

11

eissn

0066-4804

issn

1098-6596

journal_volume

42

pub_type

杂志文章
  • Preclinical activity of VX-787, a first-in-class, orally bioavailable inhibitor of the influenza virus polymerase PB2 subunit.

    abstract::VX-787 is a novel inhibitor of influenza virus replication that blocks the PB2 cap-snatching activity of the influenza viral polymerase complex. Viral genetics and X-ray crystallography studies provide support for the idea that VX-787 occupies the 7-methyl GTP (m(7)GTP) cap-binding site of PB2. VX-787 binds the cap-bi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.04623-14

    authors: Byrn RA,Jones SM,Bennett HB,Bral C,Clark MP,Jacobs MD,Kwong AD,Ledeboer MW,Leeman JR,McNeil CF,Murcko MA,Nezami A,Perola E,Rijnbrand R,Saxena K,Tsai AW,Zhou Y,Charifson PS

    更新日期:2015-03-01 00:00:00

  • T-8581, a new orally and parenterally active triazole antifungal agent: in vitro and in vivo evaluations.

    abstract::T-8581 is a new water-soluble triazole antifungal agent. The geometric mean IC80s (GM-IC80S; where the IC80 is the lowest drug concentration which reduced the optical density at 630 nm by 80% compared with the optical density at 630 nm of the drug-free control) for Candida albicans were as follows: T-8581, 0.218 micro...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.41.1.30

    authors: Yotsuji A,Shimizu K,Araki H,Fujimaki K,Nishida N,Hori R,Annen N,Yamamoto S,Hayakawa H,Imaizumi H,Watanbe Y,Narita H

    更新日期:1997-01-01 00:00:00

  • Praziquantel in a clay nanoformulation shows more bioavailability and higher efficacy against murine Schistosoma mansoni infection.

    abstract::Consideration of existing compounds always simplifies and shortens the long and difficult process of discovering new drugs specifically for diseases of developing countries, an approach that may add to the significant potential cost savings. This study focused on improving the biological characteristics of the already...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.04875-14

    authors: El-Feky GS,Mohamed WS,Nasr HE,El-Lakkany NM,Seif El-Din SH,Botros SS

    更新日期:2015-01-01 00:00:00

  • Azasordarins: susceptibility of fluconazole-susceptible and fluconazole-resistant clinical isolates of Candida spp. to GW 471558.

    abstract::The in vitro activity of the azasordarin GW 471558 was compared with those of amphotericin B, flucytosine, itraconazole, and ketoconazole against 177 clinical isolates of Candida spp. GW 471558 showed potent activity against Candida albicans, Candida glabrata, and Candida tropicalis, even against isolates with decreas...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.45.6.1905-1907.2001

    authors: Cuenca-Estrella M,Mellado E,Díaz-Guerra TM,Monzón A,Rodríguez-Tudela JL

    更新日期:2001-06-01 00:00:00

  • Potentiation of the antimalarial agent rufigallol.

    abstract::We have discovered a remarkable synergistic antimalarial interaction between rufigallol and the structurally similar compound exifone. The synergistic effects were produced in chloroquine-susceptible and chloroquine-resistant clones of Plasmodium falciparum. The degree of potentiation as estimated by standard isobolar...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.40.6.1408

    authors: Winter RW,Cornell KA,Johnson LL,Ignatushchenko M,Hinrichs DJ,Riscoe MK

    更新日期:1996-06-01 00:00:00

  • Distribution of amoxicillin and clavulanic acid in infected animals and efficacy against experimental infections.

    abstract::The therapeutic effects produced by formulations of amoxicillin plus clavulanic acid (BRL 25 000A and BRL 25 000G) were compared with those of amoxicillin and clavulanic acid separately against a variety of infections produced by amoxicillin-susceptible and beta-lactamase-producing (amoxicillin-resistant) bacteria. Th...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.22.3.369

    authors: Boon RJ,Beale AS,Comber KR,Pierce CV,Sutherland R

    更新日期:1982-09-01 00:00:00

  • Comparison of daclatasvir resistance barriers on NS5A from hepatitis C virus genotypes 1 to 6: implications for cross-genotype activity.

    abstract::A comparison of the daclatasvir (DCV [BMS-790052]) resistance barrier on authentic or hybrid replicons containing NS5A from hepatitis C virus (HCV) genotypes 1 to 6 (GT-1 to -6) was completed using a replicon elimination assay. The data indicated that genotype 1b (GT-1b) has the highest relative resistance barrier and...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02788-14

    authors: Wang C,Jia L,O'Boyle DR 2nd,Sun JH,Rigat K,Valera L,Nower P,Huang X,Kienzle B,Roberts S,Gao M,Fridell RA

    更新日期:2014-09-01 00:00:00

  • In vitro antibacterial activity of SM-1652, a new broad-spectrum cephalosporin with antipseudomonal activity.

    abstract::SM-1652 (sodium 7-[D(-)-alpha-(4-hydroxy-6-methylpyridine-3-carboxamido)-alpha-(4-hydroxyphenyl)acetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate) is a new semisynthetic cephalosporin derivative with a broad spectrum of antibacterial activity. Its in vitro activity against gram-positive bact...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.23.2.195

    authors: Fukasawa M,Noguchi H,Okuda T,Komatsu T,Yano K

    更新日期:1983-02-01 00:00:00

  • Characterization of the inhibition mechanism of HIV-1 nucleocapsid protein chaperone activities by methylated oligoribonucleotides.

    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

    authors: Avilov SV,Boudier C,Gottikh M,Darlix JL,Mély Y

    更新日期:2012-02-01 00:00:00

  • UPC2A is required for high-level azole antifungal resistance in Candida glabrata.

    abstract::Candida glabrata, the second most common cause of Candida infections, is associated with high rates of mortality and often exhibits resistance to the azole class of antifungal agents. Upc2 and Ecm22 in Saccharomyces cerevisiae and Upc2 in Candida albicans are the transcriptional regulators of ERG11, the gene encoding ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02217-13

    authors: Whaley SG,Caudle KE,Vermitsky JP,Chadwick SG,Toner G,Barker KS,Gygax SE,Rogers PD

    更新日期:2014-08-01 00:00:00

  • Molecular Analysis of a blaIMP-1-Harboring Class 3 Integron in Multidrug-Resistant Pseudomonas fulva.

    abstract::A multidrug-resistant (MDR) Pseudomonas fulva strain was isolated in 2006 from a urine sample. The isolate harbored the blaIMP-1 gene, which was located in a chromosomal Tn402-like class 3 integron as a gene cassette array of aacA31-fosE-blaIMP-1 Two mutations in gyrA and one mutation in parC were detected in quinolon...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00701-18

    authors: Yamamoto M,Matsumura Y,Gomi R,Matsuda T,Nakano S,Nagao M,Tanaka M,Ichiyama S

    更新日期:2018-07-27 00:00:00

  • Dosing regimen matters: the importance of early intervention and rapid attainment of the pharmacokinetic/pharmacodynamic target.

    abstract::To date, the majority of pharmacokinetic/pharmacodynamic (PK/PD) discussions have focused on PK/PD relationships evaluated at steady-state drug concentrations. However, a concern with reliance upon steady-state drug concentrations is that it ignores events occurring while the pathogen is exposed to intermittent subopt...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,评审

    doi:10.1128/AAC.05360-11

    authors: Martinez MN,Papich MG,Drusano GL

    更新日期:2012-06-01 00:00:00

  • Host biomarkers of invasive pulmonary aspergillosis to monitor therapeutic response.

    abstract::Invasive pulmonary aspergillosis (IPA) is a life-threatening disease of immunocompromised patients that requires aggressive therapy. Detection of the disease and monitoring of the therapeutic response during IPA are complex, and current molecular diagnostics are not suitably robust. Here, we explored proteomic profile...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02482-14

    authors: Krel M,Petraitis V,Petraitiene R,Jain MR,Zhao Y,Li H,Walsh TJ,Perlin DS

    更新日期:2014-06-01 00:00:00

  • Expression of the essential Kinase PfCDPK1 from Plasmodium falciparum in Toxoplasma gondii facilitates the discovery of novel antimalarial drugs.

    abstract::We have previously shown that genetic disruption of Toxoplasma gondii calcium-dependent protein kinase 3 (TgCDPK3) affects calcium ionophore-induced egress. We examined whether Plasmodium falciparum CDPK1 (PfCDPK1), the closest homolog of TgCDPK3 in the malaria parasite P. falciparum, could complement a TgCDPK3 mutant...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02261-13

    authors: Gaji RY,Checkley L,Reese ML,Ferdig MT,Arrizabalaga G

    更新日期:2014-05-01 00:00:00

  • Echinocandin susceptibility testing of Candida spp. Using EUCAST EDef 7.1 and CLSI M27-A3 standard procedures: analysis of the influence of bovine serum albumin supplementation, storage time, and drug lots.

    abstract::The MICs of echinocandins against Candida isolates with fks mutations are higher than those for wild-type (WT) isolates. However, the MIC ranges for susceptible and mutant populations overlap or are poorly separated. It was recently reported that a greater separation could be achieved in the presence of serum. To more...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01364-10

    authors: Arendrup MC,Rodriguez-Tudela JL,Park S,Garcia-Effron G,Delmas G,Cuenca-Estrella M,Gomez-Lopez A,Perlin DS

    更新日期:2011-04-01 00:00:00

  • Influence of inoculum size and marbofloxacin plasma exposure on the amplification of resistant subpopulations of Klebsiella pneumoniae in a rat lung infection model.

    abstract::We tested the hypothesis that the bacterial load at the infection site could impact considerably on the pharmacokinetic/pharmacodynamic (PK/PD) parameters of fluoroquinolones. Using a rat lung infection model, we measured the influence of different marbofloxacin dosage regimens on selection of resistant bacteria after...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00608-09

    authors: Kesteman AS,Ferran AA,Perrin-Guyomard A,Laurentie M,Sanders P,Toutain PL,Bousquet-Mélou A

    更新日期:2009-11-01 00:00:00

  • In vitro induction of human immunodeficiency virus type 1 variants resistant to 2'-beta-Fluoro-2',3'-dideoxyadenosine.

    abstract::2'-beta-Fluoro-2',3'-dideoxyadenosine (F-ddA) is an acid-stable purine dideoxynucleoside analog active against a wide spectrum of human immunodeficiency virus type 1 (HIV-1) and HIV-2 strains in vitro. F-ddA is presently undergoing a phase I clinical trial at the National Cancer Institute. We induced HIV-1 variants re...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.41.6.1313

    authors: Tanaka M,Srinivas RV,Ueno T,Kavlick MF,Hui FK,Fridland A,Driscoll JS,Mitsuya H

    更新日期:1997-06-01 00:00:00

  • Possible reason for preferential damage to renal tubular epithelial cells evoked by amphotericin B.

    abstract::An important determinant of nephrotoxicity, which is the major complication of long-term amphotericin B treatment, is dysfunction of distal tubular epithelial cells. The underlying cause for this rather selective damage to the cells is unknown. In the present investigation, it was shown that kidney epithelial cells we...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.40.5.1116

    authors: Walev I,Bhakdi S

    更新日期:1996-05-01 00:00:00

  • Effect of liposome-entrapped ampicillin on survival of Listeria monocytogenes in murine peritoneal macrophages.

    abstract::The effect of liposomal encapsulation of ampicillin on the antibacterial activity against intracellular Listeria monocytogenes was studied by comparing survival of L. monocytogenes within peritoneal mouse macrophages in the presence of free ampicillin alone or in combination with liposome-entrapped ampicillin. In the ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.30.2.295

    authors: Bakker-Woudenberg IA,Lokerse AF,Vink-van den Berg JC,Roerdink FH,Michel MF

    更新日期:1986-08-01 00:00:00

  • Correlation of β-Lactamase Production and Colistin Resistance among Enterobacteriaceae Isolates from a Global Surveillance Program.

    abstract::The increasing use of carbapenems for treating multidrug-resistant (MDR) Gram-negative bacterial infections has contributed to the global dissemination of carbapenem-resistant Enterobacteriaceae (CRE). Serine and metallo-β-lactamases (MBLs) that hydrolyze carbapenems have become prevalent and endemic in some countries...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01870-15

    authors: Bradford PA,Kazmierczak KM,Biedenbach DJ,Wise MG,Hackel M,Sahm DF

    更新日期:2015-12-14 00:00:00

  • In vitro cytotoxicity and mitochondrial toxicity of tenofovir alone and in combination with other antiretrovirals in human renal proximal tubule cells.

    abstract::We assessed the in vitro toxicity of tenofovir (TFV) and compared it with those of zidovudine (AZT), didanosine (ddI), ritonavir (RTV), and lopinavir (LPV) alone and in combination in human renal proximal tubule epithelial cells (RPTECs). The cells were treated with various concentrations and combinations of the teste...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00437-06

    authors: Vidal F,Domingo JC,Guallar J,Saumoy M,Cordobilla B,Sánchez de la Rosa R,Giralt M,Alvarez ML,López-Dupla M,Torres F,Villarroya F,Cihlar T,Domingo P

    更新日期:2006-11-01 00:00:00

  • Screening and Characterization of Multidrug-Resistant Gram-Negative Bacteria from a Remote African Area, São Tomé and Príncipe.

    abstract::The occurrence of resistance to last-resort antibiotics was evaluated among Enterobacteriaceae isolates recovered from hospitalized children in a remote African archipelago, São Tomé and Príncipe, where there is limited access to those antibiotics. Fifty patients were screened for colonization by carbapenem-, pan-amin...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01021-18

    authors: Poirel L,Aires-de-Sousa M,Kudyba P,Kieffer N,Nordmann P

    更新日期:2018-08-27 00:00:00

  • Effects of probiotics on acquisition and spread of multiresistant enterococci.

    abstract::Ampicillin-resistant Enterococcus faecium (ARE) and vancomycin-resistant E. faecium (VRE) are important nosocomial pathogens. We quantified effects of probiotics and antibiotics on intestinal acquisition of ARE colonization in patients hospitalized in two non-intensive care unit (non-ICU) wards with high ARE prevalenc...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01765-09

    authors: de Regt MJ,Willems RJ,Hené RJ,Siersema PD,Verhaar HJ,Hopmans TE,Bonten MJ

    更新日期:2010-07-01 00:00:00

  • Molecular characterization of multidrug-resistant Mycobacterium tuberculosis isolated in Nepal.

    abstract::Despite the fact that Nepal is one of the first countries globally to introduce multidrug-resistant tuberculosis (MDR-TB) case management, the number of MDR-TB cases is continuing to rise in Nepal. Rapid molecular tests applicable in this setting to identify resistant organisms would be an effective tool in reversing ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.06418-11

    authors: Poudel A,Nakajima C,Fukushima Y,Suzuki H,Pandey BD,Maharjan B,Suzuki Y

    更新日期:2012-06-01 00:00:00

  • Integration of pT181-like tetracycline resistance plasmids into large staphylococcal plasmids involves IS257.

    abstract::Four large staphylococcal plasmids ranging in size from 31 to 82 kbp have been shown to mediate tetracycline resistance via an integrated copy of the tet(K)-encoding plasmid pT181 which was flanked by copies of the insertion element IS257. In two cases, IS257 elements interrupted the repC reading frame of pT181 and an...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.40.11.2542

    authors: Werckenthin C,Schwarz S,Roberts MC

    更新日期:1996-11-01 00:00:00

  • Antibiofilm Activity and Synergistic Inhibition of Staphylococcus aureus Biofilms by Bactericidal Protein P128 in Combination with Antibiotics.

    abstract::P128 is an antistaphylococcal protein, comprising a cell wall-degrading enzymatic region and a Staphylococcus-specific binding region, which possesses specific and potent bactericidal activity against sensitive and drug-resistant strains of Staphylococcus aureus To explore P128's ability to kill S. aureus in a range o...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01118-16

    authors: Nair S,Desai S,Poonacha N,Vipra A,Sharma U

    更新日期:2016-11-21 00:00:00

  • Frequency of voriconazole resistance in vitro among Spanish clinical isolates of Candida spp. According to breakpoints established by the Antifungal Subcommittee of the European Committee on Antimicrobial Susceptibility Testing.

    abstract::A total of 4,226 Spanish clinical isolates of Candida spp. were analyzed to assess resistance to voriconazole according to breakpoints established by the European Committee for Antimicrobial Susceptibility Testing (where susceptibility [S] to voriconazole corresponds to a MIC of ≤ 0.12 mg/liter). Resistance was uncomm...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01757-10

    authors: Cuenca-Estrella M,Gomez-Lopez A,Cuesta I,Zaragoza O,Mellado E,Rodriguez-Tudela JL,Antifungal Subcommittee of European Committee on Antimicrobial Susceptibility Testing.

    更新日期:2011-04-01 00:00:00

  • Renal glycosuria as a novel early sign of colistin-induced kidney damage in mice.

    abstract::The polymixin colistin represents a last resort antibiotic for multidrug resistant infections, but its use is limited by the frequent onset of acute drug-induced kidney injury (DIKI). It is essential to closely monitor kidney function prior to and during colistin treatment in order to pinpoint early signs of injury an...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01650-19

    authors: Samodelov SL,Visentin M,Gai Z,Häusler S,Kullak-Ublick GA

    更新日期:2019-10-07 00:00:00

  • Mutations in pepQ Confer Low-Level Resistance to Bedaquiline and Clofazimine in Mycobacterium tuberculosis.

    abstract::The novel ATP synthase inhibitor bedaquiline recently received accelerated approval for treatment of multidrug-resistant tuberculosis and is currently being studied as a component of novel treatment-shortening regimens for drug-susceptible and multidrug-resistant tuberculosis. In a limited number of bedaquiline-treate...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00753-16

    authors: Almeida D,Ioerger T,Tyagi S,Li SY,Mdluli K,Andries K,Grosset J,Sacchettini J,Nuermberger E

    更新日期:2016-07-22 00:00:00

  • A Choline-Recognizing Monomeric Lysin, ClyJ-3m, Shows Elevated Activity against Streptococcus pneumoniae.

    abstract::Streptococcus pneumoniae is a leading pathogen for bacterial pneumonia, which can be treated with bacteriophage lysins harboring a conserved choline binding module (CBM). Such lysins regularly function as choline-recognizing dimers. Previously, we reported a pneumococcus-specific lysin ClyJ comprising the binding doma...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00311-20

    authors: Luo D,Huang L,Gondil VS,Zhou W,Yang W,Jia M,Hu S,He J,Yang H,Wei H

    更新日期:2020-11-17 00:00:00