Abstract:
:Meropenem-vaborbactam (Vabomere) is highly active against Gram-negative pathogens, especially Klebsiella pneumoniae carbapenemase (KPC)-producing, carbapenem-resistant Enterobacteriaceae The objective of these studies was to evaluate the efficacy of meropenem alone and in combination with vaborbactam in mouse thigh and lung infection models. Thighs or lungs of neutropenic mice were infected with KPC-producing carbapenem-resistant Enterobacteriaceae, with meropenem MICs ranging from ≤0.06 to 8 mg/liter in the presence of 8 mg/liter vaborbactam. Mice were treated with meropenem alone or meropenem in combination with vaborbactam every 2 h for 24 h to provide exposures comparable to 2-g doses of each component in humans. Meropenem administered in combination with vaborbactam produced bacterial killing in all strains tested, while treatment with meropenem alone either produced less than 0.5 log CFU/tissue of bacterial killing or none at all. In the thigh model, 11 strains were treated with the combination of meropenem plus vaborbactam (300 plus 50 mg/kg of body weight). This combination produced from 0.8 to 2.89 logs of bacterial killing compared to untreated controls at the start of treatment. In the lung infection model, two strains were treated with the same dosage regimen of meropenem and vaborbactam. The combination produced more than 1.83 logs of bacterial killing against both strains tested compared to untreated controls at the start of treatment. Overall, these data suggest that meropenem-vaborbactam may have utility in the treatment of infections due to KPC-producing carbapenem-resistant Enterobacteriaceae.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Sabet M,Tarazi Z,Nolan T,Parkinson J,Rubio-Aparicio D,Lomovskaya O,Dudley MN,Griffith DCdoi
10.1128/AAC.01446-17subject
Has Abstractpub_date
2017-12-21 00:00:00issue
1eissn
0066-4804issn
1098-6596pii
AAC.01446-17journal_volume
62pub_type
杂志文章abstract::Clinical isolates of Klebsiella pneumoniae resistant to carbapenems are being isolated with increasing frequency. Loss of the expression of the major nonspecific porins OmpK35/36 is a frequent feature in these isolates. In this study, we looked for porins that could compensate for the loss of the major porins in carba...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00309-11
更新日期:2011-10-01 00:00:00
abstract::In 2002, the first two clinical isolates of vancomycin-resistant Staphylococcus aureus (VRSA) containing vanA were recovered in Michigan and Pennsylvania. Tn1546, a mobile genetic element that encodes high-level vancomycin resistance in enterococci, was present in both isolates. With PCR and DNA sequence analysis, we ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.1.470-472.2005
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abstract::Although the clinical correlates of the reference antifungal susceptibility test results in hematogenous and deep-seated Candida infection are still controversial, we evaluated the clinical correlates of this test in deep-seated Candida infections in non-AIDS patients. Thirty-two non-AIDS patients with hematogenous or...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.44.10.2715-2718.2000
更新日期:2000-10-01 00:00:00
abstract::Enviroxime, an inhibitor of rhinovirus replication, was studied in a double-blind, placebo-controlled trial with 99 volunteers. The efficacy of a nasal-spray formulation of enviroxime was tested as pretreatment or as postchallenge treatment for rhinovirus type 4 infection. In the regimens used, drug administration nei...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,随机对照试验
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abstract::Low-level vancomycin-resistant Staphylococcus aureus (vancomycin-intermediate S. aureus [VISA] and heterogenous VISA [hVISA]) is increasingly reported and leads to glycopeptide treatment failure. Various phenotypic features have been reported for these isolates, but the genetic changes leading to hVISA and VISA have y...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.00422-06
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abstract::The in vitro activities of CG400549, a novel FabI inhibitor, were compared to those of linezolid and commonly used antimicrobials against recent bacterial isolates. CG400549 had an MIC(90) of 0.5 microg/ml for Staphylococcus aureus strains and was more potent than either linezolid or vancomycin. ...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.01562-06
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abstract::Increasing mobile colistin resistance, mediated by the mcr gene family, in Enterobacteriaceae has become a global concern. Among the 10 reported mcr genes, mcr-8 was first identified in Klebsiella pneumoniae, which could cause severe infections with high mortality. Information about the prevalence and genetic context ...
journal_title:Antimicrobial agents and chemotherapy
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abstract::MICs of a set of cephalosporins against a variety of gram-positive and gram-negative pathogens showed no strong correlations with the rate at which these inhibitors acylate or are deacylated by beta-lactam-sensitive DD-peptidases excreted by Streptomyces sp. strain R61 and Actinomadura sp. strain R39. ...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.29.5.774
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abstract::Primaquine is currently the only drug available for radical cure of Plasmodium vivax and P. ovale liver infection stages, but limited safety data exist for children <10 years of age. Detailed daily assessments of side effects in glucose-6-phosphate dehydrogenase (G6PD)-normal children treated with 14 days of primaquin...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.05566-11
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abstract::Nalidixic acid-resistant derivatives of Neisseria gonorrhoeae WR302 were identified and categorized into two classes on the basis of their susceptibilities to this antimicrobial agent. The MIC of nalidixic acid for the derivative strain MUG116 was fourfold greater than that for its isogenic parental strain WR302 (2 ve...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.4.622
更新日期:1991-04-01 00:00:00
abstract::The aromatic diamidines represent a class of compounds with broad-spectrum antimicrobial activity; however, their development is hindered by a lack of understanding of their mechanism of antimicrobial action. DB75 [2,5-bis(4-amidinophenyl)furan] is a trypanocidal aromatic diamidine that was originally developed as a s...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.10.3968-3974.2004
更新日期:2004-10-01 00:00:00
abstract::The creation of new chemotherapeutic regimens that permit shortening the duration of treatment is a major priority for antituberculosis drug development. In this study, we used the murine model of experimental tuberculosis therapy to determine whether incorporation of the investigational new nitroimidazopyran PA-824 i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00451-06
更新日期:2006-08-01 00:00:00
abstract::The VanA ligase encoded by the vancomycin resistance plasmid pIP816 of Enterococcus faecium BM4147 condenses D-alanine with various D-2-hydroxy and D-2-amino acids in vitro. D-Lactate added to the culture medium restored the vancomycin resistance of a strain that does not produce the VanH dehydrogenase and therefore a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.4.867
更新日期:1992-04-01 00:00:00
abstract::Escherichia coli MRE 600 is a colicinogenic bacterium. Its colicinogenic activity may be ascribed mostly to colicin E1, although it produces a small amount of another, as yet unidentified, colicin. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.14.5.797
更新日期:1978-11-01 00:00:00
abstract::The activity of gemifloxacin against Haemophilus influenzae and Moraxella catarrhalis was compared to those of 11 other agents. All quinolones were very active (MICs, =0.125 microgram/ml) against 248 quinolone-susceptible H. influenzae isolates (40.7% of which were beta-lactamase positive); cefixime (MICs, =0.125 ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.3.633-639.2000
更新日期:2000-03-01 00:00:00
abstract::Bacterial adaptation to external stresses and toxic compounds is a key step in the emergence of multidrug-resistant strains that are a serious threat to human health. Although some of the proteins and regulators involved in antibiotic resistance mechanisms have been described, no information is available to date conce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01481-06
更新日期:2007-09-01 00:00:00
abstract::The MIC of an antimalarial drug for a particular infection is the drug level associated with a net parasite multiplication rate of one per asexual cycle. To ensure the cure of malaria, the MIC must be exceeded until all parasites have been eliminated. The development of highly sensitive and accurate PCR quantitation o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.01940-16
更新日期:2017-01-24 00:00:00
abstract::The effects of an antacid containing magnesium and aluminum hydroxide on the pharmacokinetics of pefloxacin in 10 healthy volunteers were investigated. In a randomized crossover design, each subject received an oral dose of 400 mg of pefloxacin either with or without multiple doses of the antacid. The concentrations o...
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.38.5.1129
更新日期:1994-05-01 00:00:00
abstract::Management of coinfection with malaria and HIV is a major challenge to public health in developing countries, and yet potential drug-drug interactions between antimalarial and antiviral regimens have not been adequately investigated in people with both infections. Each of the constituent components of artemether-lumef...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02508-12
更新日期:2013-09-01 00:00:00
abstract::This study was undertaken to investigate biochemical, genetic, and epidemiological aspects of resistance to aminoglycoside antibiotics among 650 consecutive isolates of Pseudomonas aeruginosa from Parkland Memorial Hospital, Dallas, Tex. In 364 strains, minimal inhibitory concentrations were 25 mug/ml or greater for g...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.6.3.253
更新日期:1974-09-01 00:00:00
abstract::The efficacy of atovaquone alone or combined with pyrimethamine, sulfadiazine, clarithromycin, and minocycline was examined in vitro and in a murine model of acute toxoplasmosis. In vitro studies were performed with MRC5 fibroblast tissue cultures, with quantification of Toxoplasma growth by an enzyme-linked immunosor...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.11.2371
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abstract::In a previous study we have shown that cultured epithelial cell lines can be used to measure the transepithelial passage of antimicrobial agents across the intestine and to obtain information on the mechanisms of transport utilized and predict the bioavailability of the antimicrobial agents after oral administration. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.6.1239
更新日期:1994-06-01 00:00:00
abstract::Hepatitis C virus (HCV) is the major cause of non-A, non-B hepatitis worldwide. Current treatments are not curative for most infected individuals, and there is an urgent need for both novel therapeutic agents and small-animal models which can be used to evaluate candidate drugs. A small-animal model of HCV gene expres...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.43.2.347
更新日期:1999-02-01 00:00:00
abstract::Spontaneous mutants of susceptible clinical and laboratory isolates of Streptococcus pneumoniae exhibiting reduced susceptibility to evernimicin (SCH27899; MIC, 0.5 to 4.0 mg/liter) were selected on plates containing evernimicin. Four isolates that did not harbor mutations in rplP (which encodes ribosomal protein L16)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.11.3101-3106.2000
更新日期:2000-11-01 00:00:00
abstract::lacZ fusion strains were constructed using the promoters of five cell wall stress stimulon genes: pbp2, tcaA, vraSR, sgtB, and lytR. All fusion strains were induced only in the presence of cell wall-active antibiotics, suggesting the potential of these strains for use in high-throughput screening for new cell wall-act...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00273-08
更新日期:2008-08-01 00:00:00
abstract::This study investigates the role of active efflux system MexXY in the emergence of aminoglycoside (AG) resistance among cystic fibrosis (CF) isolates of Pseudomonas aeruginosa. Three genotypically related susceptible and resistant (S/R) bacterial pairs and three other AG-resistant CF strains were compared to four non-...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.5.1676-1680.2004
更新日期:2004-05-01 00:00:00
abstract::Twenty-four Staphylococcus species and their subspecies were examined for their susceptibilities to teicoplanin by disk diffusion (30-micrograms disk) and agar dilution for the determination of MICs. Moderately susceptible and resistant clinical strains were further tested for their susceptibilities to oxacillin and v...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.9.1919
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abstract::The activities of trimethoprim (TMP) and sulfamethoxazole (SMZ), alone and in combination (SMZ-TMP), and of the following antibiotics were tested against 115 clinical isolates of nontyphoid Salmonella species: tobramycin, gentamicin, ampicillin, amoxicillin, neomycin, kanamycin, chloramphenicol, and tetracycline. The ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.4.5.555
更新日期:1973-11-01 00:00:00
abstract::Deciphering the mode of action (MOA) of new antibiotics discovered through phenotypic screening is of increasing importance. Metabolomics offers a potentially rapid and cost-effective means of identifying modes of action of drugs whose effects are mediated through changes in metabolism. Metabolomics techniques also co...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2016-03-25 00:00:00
abstract::The quinolones inhibit the A subunit of DNA gyrase in the presence of Mg2+ by interrupting the DNA breakage and resealing steps, and the latter step is also retarded without quinolones if Mg2+ is replaced by Ca2+. Pyrimido[1,6-a]benzimidazoles have been found to represent a new class of potent DNA gyrase inhibitors wh...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.1.163
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