Phase I, open-label, safety and pharmacokinetic study to assess bronchopulmonary disposition of intravenous eravacycline in healthy men and women.

Abstract:

:This study evaluated the pulmonary disposition of eravacycline in 20 healthy adult volunteers receiving 1.0 mg of eravacycline/kg intravenously every 12 h for a total of seven doses over 4 days. Plasma samples were collected at 0, 1, 2, 4, 6, and 12 h on day 4, with each subject randomized to undergo a single bronchoalveolar lavage (BAL) at 2, 4, 6, or 12 h. Drug concentrations in plasma, BAL fluid, and alveolar macrophages (AM) were determined by liquid chromatography-tandem mass spectrometry, and the urea correction method was used to calculate epithelial lining fluid (ELF) concentrations. Pharmacokinetic parameters were estimated by noncompartmental methods. Penetration for ELF and AM was calculated by using a ratio of the area under the concentration time curve (AUC0-12) for each respective parameter against free drug AUC (fAUC0-12) in plasma. The total AUC0-12 in plasma was 4.56±0.94 μg·h/ml with a mean fAUC0-12 of 0.77±0.14 μg·h/ml. The eravacycline concentrations in ELF and AM at 2, 4, 6, and 12 h were means±the standard deviations (μg/ml) of 0.70±0.30, 0.57±0.20, 0.34±0.16, and 0.25±0.13 with a penetration ratio of 6.44 and 8.25±4.55, 5.15±1.25, 1.77±0.64, and 1.42±1.45 with a penetration ratio of 51.63, respectively. The eravacycline concentrations in the ELF and AM achieved greater levels than plasma by 6- and 50-fold, respectively, supporting further study of eravacycline for patients with respiratory infections.

authors

Connors KP,Housman ST,Pope JS,Russomanno J,Salerno E,Shore E,Redican S,Nicolau DP

doi

10.1128/AAC.02036-13

subject

Has Abstract

pub_date

2014-01-01 00:00:00

pages

2113-8

issue

4

eissn

0066-4804

issn

1098-6596

pii

AAC.02036-13

journal_volume

58

pub_type

杂志文章,随机对照试验
  • Comparative uptake of gentamicin, netilmicin, and amikacin in the guinea pig cochlea and vestibule.

    abstract::The kinetics of the entry of three aminoglycosides into inner-ear tissues of the guinea pig after acute and chronic administration were compared: gentamicin toxic to the cochlea and the vestibule, amikacin preferentially cochleotoxic, and netilmicin of low ototoxic liability. During constant intravenous infusion, leve...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.30.1.96

    authors: Dulon D,Aran JM,Zajic G,Schacht J

    更新日期:1986-07-01 00:00:00

  • Molecular evolution of beta-lactam-resistant Haemophilus influenzae: 9-year surveillance of penicillin-binding protein 3 mutations in isolates from Japan.

    abstract::A total of 621 clinical isolates of Haemophilus influenzae collected in Japan between 1995 and 2003 were studied for their susceptibilities to several antimicrobial agents, beta-lactamase production, and amino acid substitutions in penicillin-binding protein 3 (PBP 3). Over the four study periods (first period, 1995 t...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01316-05

    authors: Sanbongi Y,Suzuki T,Osaki Y,Senju N,Ida T,Ubukata K

    更新日期:2006-07-01 00:00:00

  • Molecular Basis for the Potent Inhibition of the Emerging Carbapenemase VCC-1 by Avibactam.

    abstract::In 2016, we identified a new class A carbapenemase, VCC-1, in a nontoxigenic Vibrio cholerae strain that had been isolated from retail shrimp imported into Canada for human consumption. Shortly thereafter, seven additional VCC-1-producing V. cholerae isolates were recovered along the German coastline. These isolates a...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02112-18

    authors: Mangat CS,Vadlamani G,Holicek V,Chu M,Larmour VLC,Vocadlo DJ,Mulvey MR,Mark BL

    更新日期:2019-03-27 00:00:00

  • Selective antimicrobial modulation of the intestinal tract by norfloxacin in human volunteers and in gnotobiotic mice associated with a human fecal flora.

    abstract::Intestinal endogenous members of the family Enterobacteriaceae were eliminated in 12 human volunteers treated with 400 or 800 mg of oral norfloxacin per day for 5 days. No clones resistant to quinolone derivatives were isolated. Counts of aerotolerant streptococci were affected to various degrees, depending on their s...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.29.6.1047

    authors: Pecquet S,Andremont A,Tancrède C

    更新日期:1986-06-01 00:00:00

  • Fluoroquinolone and Third-Generation-Cephalosporin Resistance among Hospitalized Patients with Urinary Tract Infections Due to Escherichia coli: Do Rates Vary by Hospital Characteristics and Geographic Region?

    abstract::This analysis of nearly 10,000 hospital-associated urinary tract infection (UTI) episodes due to Escherichia coli showed that fluoroquinolone and third-generation-cephalosporin resistance rates were 34.5% and 8.6%, respectively; the rate of concurrent resistance to both agents was 7.3%. Fluoroquinolone resistance rate...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02505-15

    authors: Bidell MR,Palchak M,Mohr J,Lodise TP

    更新日期:2016-04-22 00:00:00

  • Identification and characterization of the anti-methicillin-resistant Staphylococcus aureus WAP-8294A2 biosynthetic gene cluster from Lysobacter enzymogenes OH11.

    abstract::Lysobactor enzymogenes strain OH11 is an emerging biological control agent of fungal and bacterial diseases. We recently completed its genome sequence and found it contains a large number of gene clusters putatively responsible for the biosynthesis of nonribosomal peptides and polyketides, including the previously ide...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.05370-11

    authors: Zhang W,Li Y,Qian G,Wang Y,Chen H,Li YZ,Liu F,Shen Y,Du L

    更新日期:2011-12-01 00:00:00

  • Regulation of heme polymerizing activity and the antimalarial action of chloroquine.

    abstract::Mice infected with Plasmodium berghei served as donors of erythrocytes with a high level of parasitemia for the study of ferriprotoporphyrin IX (FP) polymerization. Six hours after treatment of these mice with 3 micromol of chloroquine per 25 g of body weight, there were significant losses of heme polymerase I (HPA I)...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.41.11.2461

    authors: Fitch CD,Chou AC

    更新日期:1997-11-01 00:00:00

  • Ceftriaxone pharmacokinetics in patients with various degrees of renal impairment.

    abstract::The effects of renal impairment on the pharmacokinetics of ceftriaxone in humans were examined after intravenous infusion of a 1-g dose over 15 min to 30 renally impaired patients. The study included 12 dialysis patients and 18 patients with severe, moderate, or mild renal impairment. Plasma and, where appropriate, ur...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.25.4.438

    authors: Patel IH,Sugihara JG,Weinfeld RE,Wong EG,Siemsen AW,Berman SJ

    更新日期:1984-04-01 00:00:00

  • Efficacy of temafloxacin in experimental Streptococcus adjacens endocarditis and autoradiographic diffusion pattern of [14C]temafloxacin in cardiac vegetations.

    abstract::Temafloxacin, a new fluoroquinolone, alone or in combination with tobramycin, was compared with penicillin, tobramycin, and their combination in the therapy of rabbits with endocarditis caused by Streptococcus adjacens GaDT, a new species of nutritionally variant streptococci. Animals were injected intramuscularly for...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.36.10.2216

    authors: Cremieux AC,Saleh-Mghir A,Vallois JM,Maziere B,Muffat-Joly M,Devine C,Bouvet A,Pocidalo JJ,Carbon C

    更新日期:1992-10-01 00:00:00

  • Natural occurrence of structures in oral streptococci and enterococci with DNA homology to Tn916.

    abstract::Seventeen oral streptococci and 18 enterococci were tested for the presence of DNA sequences homologous to the conjugative transposon Tn916 encoding tetracycline resistance. All the strains were resistant to tetracyclines, including minocycline, and most of them were resistant to other antibiotics. Tn916-like structur...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.36.1.59

    authors: Bentorcha F,Clermont D,de Cespédès G,Horaud T

    更新日期:1992-01-01 00:00:00

  • Delta(12)-prostaglandin J(2) is a potent inhibitor of influenza A virus replication.

    abstract::9-Deoxy-Delta(9),Delta(12)-13,14-dihydro-prostaglandin D(2) (Delta(12)-PGJ(2)), a natural cyclopentenone metabolite of prostaglandin D(2), is shown to possess therapeutic efficacy against influenza A virus A/PR8/34 (H1N1) infection in vitro and in vivo. The results indicate that the antiviral activity is associated wi...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.44.1.200-204.2000

    authors: Pica F,Palamara AT,Rossi A,De Marco A,Amici C,Santoro MG

    更新日期:2000-01-01 00:00:00

  • Proof-of-Principle Study in a Murine Lung Infection Model of Antipseudomonal Activity of Phage PEV20 in a Dry-Powder Formulation.

    abstract::Bacteriophage therapy is a promising alternative treatment to antibiotics, as it has been documented to be efficacious against multidrug-resistant bacteria with minimal side effects. Several groups have demonstrated the efficacy of phage suspension in vivo to treat lung infections using intranasal delivery; however, p...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01714-17

    authors: Chang RYK,Chen K,Wang J,Wallin M,Britton W,Morales S,Kutter E,Li J,Chan HK

    更新日期:2018-01-25 00:00:00

  • Erythromycin esterase gene ere(A) is located in a functional gene cassette in an unusual class 2 integron.

    abstract::The gene ere(A) of the plasmid pIP1100 is larger than originally reported and is organized as an integron gene cassette. The ere(A) gene cassette carries its own promoter and is propagated by a class 2 integron with an insertion sequence element, IS1, inserted upstream of the intI2 gene. The mobility of the ere(A) cas...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.47.10.3326-3331.2003

    authors: Biskri L,Mazel D

    更新日期:2003-10-01 00:00:00

  • Population pharmacokinetics of micafungin and its metabolites M1 and M5 in children and adolescents.

    abstract::The aim of this analysis was to identify therapeutic micafungin regimens for children that produce the same micafungin exposures known to be effective for the prevention and treatment of Candida infections in adults. Pediatric pharmacokinetic data from 229 patients between the ages of 4 months and <17 years were obtai...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章,随机对照试验

    doi:10.1128/AAC.03736-14

    authors: Hope WW,Kaibara A,Roy M,Arrieta A,Azie N,Kovanda LL,Benjamin DK Jr

    更新日期:2015-02-01 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

  • Resistance trends of Neisseria gonorrhoeae in the Republic of Korea.

    abstract::Penicillinase-producing Neisseria gonorrhoeae has increased in the Far East to the point that penicillin can no longer be recommended as the drug of choice, mandating a change to spectinomycin. As part of an ongoing surveillance of antibiotic susceptibilities, minimal inhibitory concentrations of penicillin, tetracycl...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.25.1.7

    authors: Piziak MV,Woodbury C,Berliner D,Takafuji E,Kirkpatrick J,Opal S,Tramont E

    更新日期:1984-01-01 00:00:00

  • Fenpropimorph affects uptake of uracil and cytosine in Saccharomyces cerevisiae.

    abstract::Fenpropimorph was shown to inhibit the accumulation of the pyrimidine bases uracil and cytosine from the growth media in Saccharomyces cerevisiae. Uracil prototrophs of S. cerevisiae were more resistant to the growth-inhibitory effects of fenpropimorph than were uracil auxotrophs. High concentrations of uracil rescued...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.38.5.1004

    authors: Crowley JH,Lorenz RT,Parks LW

    更新日期:1994-05-01 00:00:00

  • Rapid direct method for monitoring antibiotics in a mouse model of bacterial biofilm infection.

    abstract::We have developed a rapid, continuous method for monitoring the effectiveness of several antibacterial agents in real time, noninvasively, by using a recently described mouse model of chronic biofilm infection (J. L. Kadurugamuwa et al., Infect. Immun. 71:882-890, 2003), which relies on biophotonic imaging of biolumin...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.47.10.3130-3137.2003

    authors: Kadurugamuwa JL,Sin LV,Yu J,Francis KP,Kimura R,Purchio T,Contag PR

    更新日期:2003-10-01 00:00:00

  • Extension of Pharmacokinetic/Pharmacodynamic Time-Kill Studies To Include Lipopolysaccharide/Endotoxin Release from Escherichia coli Exposed to Cefuroxime.

    abstract::The release of inflammatory bacterial products, such as lipopolysaccharide (LPS)/endotoxin, may be increased upon the administration of antibiotics. An improved quantitative understanding of endotoxin release and its relation to antibiotic exposure and bacterial growth/killing may be gained by an integrated analysis o...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02070-19

    authors: Thorsted A,Tano E,Kaivonen K,Sjölin J,Friberg LE,Nielsen EI

    更新日期:2020-03-24 00:00:00

  • Enhanced Efflux Pump Expression in Candida Mutants Results in Decreased Manogepix Susceptibility.

    abstract::Manogepix is a broad-spectrum antifungal agent that inhibits glycosylphosphatidylinositol (GPI) anchor biosynthesis. Using whole-genome sequencing, we characterized two efflux-mediated mechanisms in the fungal pathogens Candida albicans and Candida parapsilosis that resulted in decreased manogepix susceptibility. In C...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00261-20

    authors: Liston SD,Whitesell L,Kapoor M,Shaw KJ,Cowen LE

    更新日期:2020-04-21 00:00:00

  • Commensal streptococci serve as a reservoir for β-lactam resistance genes in Streptococcus pneumoniae.

    abstract::Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, septicemia, and middle ear infections. The incidence of S. pneumoniae isolates that are not susceptible to penicillin has risen worldwide and may be above 20% in some countries. Beta-lactam antibiotic resistance in pneumococci is associated with sig...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.00429-15

    authors: Jensen A,Valdórsson O,Frimodt-Møller N,Hollingshead S,Kilian M

    更新日期:2015-01-01 00:00:00

  • Pentamidine is active in a neutropenic murine model of acute invasive pulmonary fusariosis.

    abstract::We studied the efficacy of pentamidine (PNT) as prophylaxis or early treatment in acute pulmonary fusariosis in neutropenic mice. PNT-preexposed mice had significantly improved survival and reduced fungal burden compared to amphotericin B-preexposed and untreated mice. PNT-treated mice had increased survival but no di...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.50.1.294-297.2006

    authors: Lionakis MS,Chamilos G,Lewis RE,Wiederhold NP,Raad II,Samonis G,Kontoyiannis DP

    更新日期:2006-01-01 00:00:00

  • Phase I, single-dose, dose-escalating study of inhaled dry powder capreomycin: a new approach to therapy of drug-resistant tuberculosis.

    abstract::Multidrug-resistant tuberculosis (MDR-TB) threatens global TB control. The lengthy treatment includes one of the injectable drugs kanamycin, amikacin, and capreomycin, usually for the first 6 months. These drugs have potentially serious toxicities, and when given as intramuscular injections, dosing can be painful. Adv...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.02346-12

    authors: Dharmadhikari AS,Kabadi M,Gerety B,Hickey AJ,Fourie PB,Nardell E

    更新日期:2013-06-01 00:00:00

  • Azlocillin pharmacokinetics in patients with cystic fibrosis.

    abstract::The pharmacokinetics of azlocillin were studied in 10 cystic fibrosis patients, ranging in age from 11 to 28 years. The patients received a 9- to 23-day course of 350 mg of azlocillin per kg in four or six divided daily doses in combination with am aminoglycoside. Blood and urine samples were collected at specified ti...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.25.5.630

    authors: Bosso JA,Saxon BA,Herbst JJ,Matsen JM

    更新日期:1984-05-01 00:00:00

  • Cefoxitin inactivation by Bacteroides fragilis.

    abstract::We have surveyed the susceptibility of 1,575 clinical isolates of the Bacteroides fragilis group of organisms to cefoxitin and eight other antimicrobial agents. Eleven isolates, 0.7% of the total, were highly cefoxitin resistant and had minimum inhibitory concentrations of greater than or equal to 64 micrograms/ml. Th...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/aac.24.6.936

    authors: Cuchural GJ Jr,Tally FP,Jacobus NV,Marsh PK,Mayhew JW

    更新日期:1983-12-01 00:00:00

  • OXA-15, an extended-spectrum variant of OXA-2 beta-lactamase, isolated from a Pseudomonas aeruginosa strain.

    abstract::Pseudomonas aeruginosa AH, isolated in Ankara, Turkey, was highly resistant to ceftazidime (MIC, 128 microg/ml) and produced a beta-lactamase that gave a doublet of bands at pIs 8.7 and 8.9. beta-Lactamase production was transferable to P. aeruginosa PU21 by conjugation and was determined by a ca. 450-kb plasmid, pMLH...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.41.4.785

    authors: Danel F,Hall LM,Gur D,Livermore DM

    更新日期:1997-04-01 00:00:00

  • A chemical genomic screen in Saccharomyces cerevisiae reveals a role for diphthamidation of translation elongation factor 2 in inhibition of protein synthesis by sordarin.

    abstract::Sordarin and its derivatives are antifungal compounds of potential clinical interest. Despite the highly conserved nature of the fungal and mammalian protein synthesis machineries, sordarin is a selective inhibitor of protein synthesis in fungal organisms. In cells sensitive to sordarin, its mode of action is through ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01603-07

    authors: Botet J,Rodríguez-Mateos M,Ballesta JP,Revuelta JL,Remacha M

    更新日期:2008-05-01 00:00:00

  • Comparison of Cytomegalovirus Terminase Gene Mutations Selected after Exposure to Three Distinct Inhibitor Compounds.

    abstract::Letermovir, GW275175X (a benzimidazole), and tomeglovir (Bay38-4766) are chemically unrelated human cytomegalovirus (CMV) terminase complex inhibitors that have been tested in human subjects. UL56 gene mutations are the dominant pathway of letermovir resistance, while UL89 and UL56 mutations are known to confer benzim...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.01325-17

    authors: Chou S

    更新日期:2017-10-24 00:00:00

  • Microplate alamar blue assay versus BACTEC 460 system for high-throughput screening of compounds against Mycobacterium tuberculosis and Mycobacterium avium.

    abstract::In response to the need for rapid, inexpensive, high-throughput assays for antimycobacterial drug screening, a microplate-based assay which uses Alamar blue reagent for determination of growth was evaluated. MICs of 30 antimicrobial agents against Mycobacterium tuberculosis H37Rv, M. tuberculosis H37Ra, and Mycobacter...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:10.1128/AAC.41.5.1004

    authors: Collins L,Franzblau SG

    更新日期:1997-05-01 00:00:00

  • Antibiotic susceptibility of enterohemorrhagic Escherichia coli O157:H7 isolated from an outbreak in Japan in 1996.

    abstract::The antibiotic susceptibilities of 43 strains of Escherichia coli O157:H7 identified in the summer of 1996 in Japan were investigated. Growth of 90% of O157 strains was inhibited at a concentration of < or = 0.5 micro/ml by several agents including fosfomycin with glucose-6-phosphate. ...

    journal_title:Antimicrobial agents and chemotherapy

    pub_type: 杂志文章

    doi:

    authors: Tsuboi I,Ida H,Yoshikawa E,Hiyoshi S,Yamaji E,Nakayama I,Nonomiya T,Shigenobu F,Shimizu M,O'Hara K,Sawai T,Mizuoka K

    更新日期:1998-02-01 00:00:00