Abstract:
:WCK 5222 consists of cefepime combined with zidebactam, a bicyclo-acyl hydrazide β-lactam enhancer antibiotic with a dual action involving binding to Gram-negative bacterial PBP2 and β-lactamase inhibition. We evaluated the in vitro activity of cefepime-zidebactam against 7,876 contemporary (2015) clinical isolates of Enterobacteriaceae (n = 5,946), Pseudomonas aeruginosa (n = 1,291), and Acinetobacter spp. (n = 639) from the United States (n = 2,919), Europe (n = 3,004), the Asia-Pacific (n = 1,370), and Latin America (n = 583). The isolates were tested by a reference broth microdilution method for susceptibility against cefepime-zidebactam (1:1 and 2:1 ratios) and comparator agents. Cefepime-zidebactam was the most active compound tested against Enterobacteriaceae (MIC50/90, ≤0.03/0.12 μg/ml [1:1] and 0.06/0.25 μg/ml [2:1]; 99.9% of isolates were inhibited at ≤4 [1:1] and ≤8 μg/ml [2:1]). Cefepime-zidebactam was active against individual Enterobacteriaceae species (MIC50/90, ≤0.03 to 0.06/≤0.03 to 0.5 μg/ml [1:1]) and retained potent activity against carbapenem-resistant isolates (MIC50/90, 1/4 μg/ml; 99.3% of isolates were inhibited at ≤8 μg/ml [1:1]). Cefepime-zidebactam activity was consistent among geographic regions, and only one isolate showed MIC values of >8 μg/ml (1:1). Cefepime-zidebactam was also very active against P. aeruginosa with MIC50/90 values of 1/4 μg/ml, and 99.5% of isolates were inhibited at ≤8 μg/ml (1:1). The MIC values for cefepime-zidebactam at the 1:1 ratio were generally 2-fold lower than those for cefepime-zidebactam at the 2:1 ratio (MIC50/90, 2/8 μg/ml) and zidebactam alone (MIC50/90, 4/8 μg/ml). Against Acinetobacter spp., cefepime-zidebactam at 1:1 and 2:1 ratios (MIC50/90, 16/32 μg/ml for both) was 4-fold more active than cefepime or ceftazidime. Zidebactam exhibited potent in vitro antimicrobial activity against some organisms. These results support the clinical development of WCK 5222 for the treatment of Gram-negative bacterial infections, including those caused by multidrug-resistant isolates.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Sader HS,Castanheira M,Huband M,Jones RN,Flamm RKdoi
10.1128/AAC.00072-17subject
Has Abstractpub_date
2017-04-24 00:00:00issue
5eissn
0066-4804issn
1098-6596pii
AAC.00072-17journal_volume
61pub_type
杂志文章abstract::Two new fluorinated oxazolidinones, U-100592 and U-100766, were evaluated against more than 659 gram-positive and -negative organisms and compared with glycopeptides, erythromycin, clindamycin, clinafloxacin, and chloramphenicol. U-100592 and U-100766 were usually equally potent, but the MICs at which 90% of the isola...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.3.720
更新日期:1996-03-01 00:00:00
abstract::The therapeutic effect of intranasally administered enviroxime was tested against naturally occurring common colds. The double-blind evaluation was carried out in Tecumseh, Mich., during a period when rhinoviruses are usually the principal pathogen. Rhinovirus transmission followed the typical pattern during this peri...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.27.1.102
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abstract::Two methods for testing the susceptibility of Mycobacterium tuberculosis to rifapentine have been developed: the agar proportion method and the radiometric BACTEC technique. A critical concentration of 0.5 microg of rifapentine per ml is proposed for both methods since it provides a reliable means of distinguishing be...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.43.1.25
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abstract::MICs of daptomycin, linezolid, and vancomycin against 212 isolates, including Listeria monocytogenes and Pediococcus, Leuconostoc, Rhodococcus, and Nocardia spp., were determined by the broth microdilution method; daptomycin MICs were also determined by the Etest. Except with those for Leuconostoc spp., daptomycin Ete...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.01352-06
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abstract::We report the capacity of copper oxide-containing filters to reduce infectious titers of a panel of viruses spiked into culture media. Enveloped, nonenveloped, RNA, and DNA viruses were affected, suggesting the possibility of using copper oxide-containing devices to deactivate a wide spectrum of infectious viruses fou...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00125-07
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abstract::E5531, a novel synthetic lipid A analogue, antagonizes the toxic effects of lipopolysaccharide, making it a potential intravenously administered therapeutic agent for the treatment of sepsis. This report describes the distribution of E5531 in human blood and its activity when it is associated with different lipoprotei...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.3.504-510.2000
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abstract::The introduction of reactive thiol groups in recombinant human tumor necrosis factor (TNF) alpha (rhTNF-alpha) by the reagent succinimidyl-S-acetylthioacetate resulted in the formation of a chemically stabilized rhTNF-alpha trimer (rhTNFalpha-AT; as determined by sodium dodecyl sulfate-polyacrylamide gel electrophores...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.43.5.1027
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abstract::Although controversial, it has been suggested that antibiotic treatment of laboratory animals infected with Borrelia burgdorferi often leads to the persistence of residual spirochetes that are claimed to be viable but noncultivable. If viable cells of B. burgdorferi do persist following antibiotic therapy, one possibl...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.03751-14
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abstract::Potential alternatives, including linezolid, adjunctive rifampin, and moxifloxacin, were evaluated against vancomycin-tolerant (P9802-020) and vancomycin-susceptible clinical isolates of Streptococcus pneumoniae in an in vitro pharmacodynamic model. Vancomycin exhibited maximal killing of 2-log(10) CFU/ml against P980...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.47.6.1984-1987.2003
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abstract::Activity of the new antiviral compound selenazofurin was compared with the known active compounds ribavirin and amantadine against influenza A and B viruses. In experiments with Madin Darby canine kidney cells, selenazofurin inhibited the cytopathic effect and yield of influenza A/NWS/33 virus, with 50% effective dose...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.28.3.375
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abstract::We analyzed the relationship between itraconazole (ITZ) and hydroxy-itraconazole (OH-ITZ) levels in 1223 human samples. Overall, there was a statistically significant correlation between ITZ and OH-ITZ levels (correlation coefficient 0.7838), and OH-ITZ levels were generally higher than that of ITZ (median OH-ITZ:ITZ ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02353-20
更新日期:2021-01-19 00:00:00
abstract::A total of 18 strains of Mycobacterium fortuitum, 15 strains of M. chelonei, and 31 strains of M. chelonei-like organisms were tested by both broth microdilution and agar dilution to determine their susceptibility to 34 antimicrobial agents. All strains grew well enough in cation-supplemented Mueller-Hinton broth for ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.22.2.186
更新日期:1982-08-01 00:00:00
abstract::Hemolytic-uremic syndrome (HUS) is a serious complication of infection by Shiga toxin-producing Escherichia coli. Shiga toxin type 2 (Stx2) is responsible for the renal toxicity that can follow intestinal infection and hemorrhagic colitis due to E. coli. A chimeric mouse-human antibody, designated c alpha Stx2, that h...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.49.5.1808-1812.2005
更新日期:2005-05-01 00:00:00
abstract::Hypermutable Pseudomonas aeruginosa strains are prevalent in patients with cystic fibrosis and rapidly become resistant to antibiotic monotherapies. Combination dosage regimens have not been optimized against such strains using mechanism-based modeling (MBM) and the hollow-fiber infection model (HFIM). The PAO1 wild-t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02055-17
更新日期:2018-03-27 00:00:00
abstract::Amoxicillin and ampicillin were compared at a dose of 250 mg twice daily for 4 weeks to treat Salmonella typhi or Salmonella paratyphi A chronic bacteriuria with intermittent bacteremia. Eleven patients received amoxicillin, and 15 received ampicillin. Concentrations of the two drugs were measured in the urine and ser...
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.20.5.630
更新日期:1981-11-01 00:00:00
abstract::Previous studies showed an increased prevalence of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) thumb subdomain polymorphisms Pro272, Arg277, and Thr286 in patients failing therapy with nucleoside analogue combinations. Interestingly, wild-type HIV-1(BH10) RT contains Pro272, Arg277, and Thr2...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00716-10
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abstract::The susceptibilities of 52 clinical isolates of Bacteroides fragilis to five monoanionic cephalosporins were examined. Cefoperazone showed the highest antibacterial activity, followed by ceftezole, cefazolin, cefamandole, and cephalothin. There were two groups of resistant strains: one group (ca. 15%), of which B. fra...
journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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abstract::Bacterial resistance studies using in vitro dynamic models are highly dependent on the starting inoculum that might or might not contain spontaneously resistant mutants (RMs). To delineate concentration-resistance relationships with linezolid-exposed Staphylococcus aureus, a mixed inoculum containing both susceptible ...
journal_title:Antimicrobial agents and chemotherapy
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abstract::EDP-239, a novel hepatitis C virus (HCV) inhibitor targeting nonstructural protein 5A (NS5A), has been investigated in vitro and in vivo EDP-239 is a potent, selective inhibitor with potency at picomolar to nanomolar concentrations against HCV genotypes 1 through 6. In the presence of human serum, the potency of EDP-2...
journal_title:Antimicrobial agents and chemotherapy
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abstract::The effect of ganciclovir [9-(1,3-dihydroxy-2-propoxymethyl)guanine] on herpes simplex virus type 1 DNA and protein synthesis was studied. Ganciclovir markedly inhibited the synthesis of viral DNA and gamma proteins in a dose-dependent manner. However, the synthesis of viral beta proteins was significantly increased b...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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abstract::A total of 91 multiply resistant bacterial strains, including Klebsiella pneumoniae (32 strains), Pseudomonas aeruginosa (16 strains), and Serratia marcescens (43 strains), were collected during hospital epidemics of nosocomial infection from 1975 to 1979. These strains were resistant to gentamicin, tobramycin, cephal...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.17.2.273
更新日期:1980-02-01 00:00:00
abstract::The cattle trypanocide, isometamidium, was readily taken up by inactivated Trypanosoma brucei, while its uptake by living parasites was reduced or inhibited by plasma. In both respects isometamidium differs from diminazene. ...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.6.3.372
更新日期:1974-09-01 00:00:00
abstract::The objective of this study was to determine the population pharmacokinetic parameters of levofloxacin, gatifloxacin, and moxifloxacin following multiple oral doses. Twenty-nine patients with tuberculosis at the University Hospital in Vitória, Brazil, participated. Subjects received multiple doses of one drug (levoflo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
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更新日期:2008-03-01 00:00:00
abstract::Oral Fusobacterium nucleatum populations from 20 young, healthy children were examined for beta-lactamase production. Ten children (50%) harbored, altogether, 25 beta-lactamase-positive F. nucleatum isolates that were identified as F. nucleatum subsp. polymorphum, F. nucleatum subsp. nucleatum, and F. nucleatum subsp....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.5.1270
更新日期:1999-05-01 00:00:00
abstract::Strains of Aspergillus fumigatus, Aspergillus flavus, and Aspergillus niger were tested for in vitro susceptibility to amphotericin B alone and in combination with fixed concentrations of tetracycline, doxycycline, or minocycline, using buffered minimal essential medium in microtiter plates. Enhanced inhibitory activi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.6.837
更新日期:1984-12-01 00:00:00
abstract::AmBisome (ABLP) is a unilamellar liposomal preparation of amphotericin B that has demonstrated an improved safety profile compared to conventional amphotericin B. Single- and multiple-dose pharmacokinetics were determined by using noncompartmental methods for rats administered ABLP at 1, 3, 9, and 20 mg/kg/day. The to...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:
更新日期:1998-02-01 00:00:00
abstract::Linezolid is the first member of the oxazolidinones and is active against drug-resistant Gram-positive pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA). Additionally, linezolid shows an immunomodulatory effect, such as inhibition of inflammatory cytokine production. In this study, we examined the ...
journal_title:Antimicrobial agents and chemotherapy
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abstract::With the rapid spread of antimicrobial resistance in Gram-negative pathogens, biofilm-associated infections are increasingly harder to treat and combination therapy with colistin has become one of the most efficient therapeutic strategies. Our study aimed to evaluate the potential for the synergy of colistin combined ...
journal_title:Antimicrobial agents and chemotherapy
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abstract::In vitro susceptibility tests were performed on 84 strains of Clostridium difficile to 11 antimicrobial agents. All isolates were from the stools of patients with antibiotic-associated diarrhea or colitis in which there was a cytopathic toxin that was neutralized by Clostridium sordellii antitoxin. Over 95% of the str...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:1980-04-01 00:00:00