Abstract:
:Alalevonadifloxacin (WCK 2349) is a novel l-alanine ester prodrug of levonadifloxacin that is being developed as an oral fluoroquinolone antibiotic. The primary objective of this study was to determine and compare plasma, epithelial lining fluid (ELF), and alveolar macrophage (AM) concentrations of levonadifloxacin following oral administration of alalevonadifloxacin to healthy adult subjects. Levonadifloxacin concentrations in plasma, ELF, and AM samples from 30 healthy subjects were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following oral dosing of alalevonadifloxacin (1,000 mg twice daily for 5 days). Six subjects were assigned to each bronchoalveolar lavage (BAL) fluid sampling time, i.e., 2, 4, 6, 8, or 12 h after the ninth oral dose. Noncompartmental pharmacokinetic (PK) parameters were determined from serial total plasma concentrations collected over a 12-h interval following the first and ninth oral doses. Penetration ratios were calculated from the areas under the concentration-time curves from 0 to 12 h (AUC0-12) for plasma, ELF, and AM by using mean (and median) concentrations at each BAL sampling time. Unbound plasma concentrations (∼85% plasma protein binding) were used to determine site-to-plasma penetration ratios. Plasma PK parameter values for levonadifloxacin were similar after the first and ninth doses. The respective AUC0-12 values based on mean ELF and AM concentrations were 172.6 and 35.3 mg · h/liter, respectively. The penetration ratios for ELF and AM levonadifloxacin concentrations to unbound plasma levonadifloxacin concentrations were 7.66 and 1.58, respectively. Similar penetration ratios were observed with median concentrations. The observed plasma, ELF, and AM concentrations of levonadifloxacin support further studies of alalevonadifloxacin for treatment of lower respiratory tract bacterial infections caused by susceptible pathogens. (This study has been registered at ClinicalTrials.gov under identifier NCT02253342.).
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Rodvold KA,Gotfried MH,Chugh R,Gupta M,Yeole R,Patel A,Bhatia Adoi
10.1128/AAC.02297-17subject
Has Abstractpub_date
2018-02-23 00:00:00issue
3eissn
0066-4804issn
1098-6596pii
AAC.02297-17journal_volume
62pub_type
杂志文章abstract::Against 307 pneumococci of various resistotypes, dalbavancin MICs were 0.008 to 0.125 microg/ml. All strains were susceptible to vancomycin, teicoplanin, linezolid, and quinupristin-dalfopristin. Dalbavancin at 2x MIC was bactericidal against all 10 pneumococci tested after 24 h. Vancomycin and teicoplanin killed 10 a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.12.5182-5184.2005
更新日期:2005-12-01 00:00:00
abstract::Using a rabbit model of methicillin-resistant Staphylococcus aureus knee-prosthesis infection, we studied the efficacy of teicoplanin cement alone or in combination with systemic intramuscular (i.m.) injections of teicoplanin. Seven days after infection, surgical debridement and removal of the infected prostheses were...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.10.3365-3367.2003
更新日期:2003-10-01 00:00:00
abstract::In this study, susceptibilities were determined for AZD0914, a spiropyrimidinetrione DNA gyrase inhibitor, azithromycin, doxycycline, and levofloxacin against Mycoplasma and Ureaplasma species. The activity of AZD0914 was comparable to that of levofloxacin and doxycycline against Mycoplasma genitalium and Mycoplasma p...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04945-14
更新日期:2015-01-01 00:00:00
abstract::The impact of acidification and alkalinization of the urine on the pharmacokinetics of cinoxacin was examined after single 500-mg oral doses were administered to nine healthy male volunteers. Acidic and alkaline conditions were achieved by repeated oral doses of ammonium chloride or sodium bicarbonate, respectively. P...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.3.472
更新日期:1982-03-01 00:00:00
abstract::The MICs and MBCs of the new difluorinated quinolone drug sparfloxacin against type strains belonging to 21 species of mycobacteria were screened. The MICs and MBCs were within the range of 0.1 to 2.0 and 0.1 to 4.0 micrograms/ml, respectively (with an MBC/MIC ratio of 1 to 2), and against 18 of the 21 species tested,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.12.2473
更新日期:1991-12-01 00:00:00
abstract::Pyrazinamide (PZA) is a first-line tuberculosis drug that inhibits the growth of Mycobacterium tuberculosis via an as yet undefined mechanism. An M. tuberculosis laboratory strain that was auxotrophic for pantothenate was found to be insensitive to PZA and to the active form, pyrazinoic acid (POA). To determine whethe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04028-14
更新日期:2014-12-01 00:00:00
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
pub_type: 杂志文章
doi:10.1128/aac.17.2.273
更新日期:1980-02-01 00:00:00
abstract::The 8-aminoquinoline tafenoquine showed significant in vitro activity against Leishmania species, including L. donovani amastigotes in macrophages, with 50% inhibitory concentrations (IC(50)s) between 0.1 and 4.0 μM for both pentavalent antimony (SbV)-sensitive and SbV-resistant strains and by oral administration in B...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00985-10
更新日期:2010-12-01 00:00:00
abstract::Ciprofloxacin, clinafloxacin, PD 131628, sparfloxacin, and trovafloxacin were tested against 236 strains of Streptococcus pneumoniae, most of which were resistant to other agents. Resistance to multiple antibiotics did not affect the organism's susceptibility to the fluoroquinolones. The fluoroquinolones with in vitro...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.10.2431
更新日期:1996-10-01 00:00:00
abstract::The pharmacokinetics of oral and intravenous ofloxacin (7.5 mg.kg of body weight-1 given over 30 min) were studied in an open crossover study of 17 Vietnamese children, aged between 5 and 14 years, with acute uncomplicated typhoid fever. Following oral administration, the median (95% confidence interval [CI]) time to ...
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.40.9.2167
更新日期:1996-09-01 00:00:00
abstract::Polymyxins are often the only option to treat acquired multidrug-resistant Pseudomonas aeruginosa. Polymyxin susceptibility in P. aeruginosa PAO1 is associated with the lipopolysaccharide structure that is determined by arnBCADTEF and modulated by phoPQ and pmrAB. We examined five clonally unrelated clinical isolates ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00893-09
更新日期:2009-12-01 00:00:00
abstract::The present population pharmacokinetic (PK) and pharmacodynamic (PD) study modeled the effects of covariates including drug adherence and the coadministration of protease inhibitors (PIs) on the pharmacokinetics of efavirenz (EFV) and the relationship between EFV exposure and virological failure in patients who failed...
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.47.1.130-137.2003
更新日期:2003-01-01 00:00:00
abstract::The pharmacokinetics and penetration into a cantharidine-induced inflammatory exudate of meropenem was studied in six volunteers following a single 1-g intravenous dose. Concentrations in plasma, urine, and the inflammatory exudate were determined by a microbiological assay. The mean elimination half-life of meropenem...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.8.1515
更新日期:1990-08-01 00:00:00
abstract::The isolation of trimethoprim-resistant, sulfonamide-susceptible Enterobacteriaceae causing urinary tract infections is reported. The appearance of these strains followed the introduction of trimethoprim alone for use as treatment. Trimethoprim resistance was attributable to plasmids or transposons less frequently in ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.4.617
更新日期:1983-04-01 00:00:00
abstract::An in vitro pharmacodynamic model was used to simulate the in vivo pharmacokinetics of clarithromycin and 14-hydroxyclarithromycin in order to generate time-kill curves for three clinical isolates of Haemophilus influenzae (isolates 2019, 91-183, and 1746). Representative concentrations in serum or lung tissue and the...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.9.2003
更新日期:1994-09-01 00:00:00
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
更新日期:1986-07-01 00:00:00
abstract::Antimicrobial resistance (AMR) is an ever-growing public health problem worldwide. The low rate of antibiotic discovery coupled with the rapid spread of drug-resistant bacterial pathogens is causing a global health crisis. To facilitate the drug discovery processes, we present a large-scale study of reference antibiot...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01207-19
更新日期:2020-02-21 00:00:00
abstract::[14C]aztreonam was administered intramuscularly (50 mg/kg) to male and female rats. Groups of 10 rats (five male and five female) were sacrificed at 0.25, 2, 6, and 24 h after dosing. Blood and various tissues were removed from six rats (three male and three female) in each group for determination of total radioactivi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.2.127
更新日期:1984-08-01 00:00:00
abstract::The apicomplexan parasites that cause malaria and babesiosis invade and proliferate within erythrocytes. To assess the potential for common antiparasitic treatments, we measured the sensitivities of multiple species of Plasmodium and Babesia parasites to the chemically diverse collection of antimalarial compounds in t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00928-16
更新日期:2016-07-22 00:00:00
abstract::Retrospective analysis of 189 nonredundant strains of Pseudomonas aeruginosa sequentially recovered from the sputum samples of 46 cystic fibrosis (CF) patients over a 10-year period (1998 to 2007) revealed that 53 out of 189 (28%) samples were hypersusceptible to the beta-lactam antibiotic ticarcillin (MIC < or = 4 mi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01024-08
更新日期:2009-05-01 00:00:00
abstract::Echinocandins are recommended as the first-line drugs for the treatment of systemic candidiasis. Cas5 is a key transcription factor involved in the response to cell wall damage induced by echinocandins. In this study, through a genetic screen, we identified a second transcription factor, Efg1, that is also crucial for...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01584-20
更新日期:2021-01-20 00:00:00
abstract::We previously showed that simian immunodeficiency virus-infected macaque macrophages contacting uninfected CD4+ lymphocytes caused extensive cell fusion and synthesis of phlogistic cytokines. In this study, macaque macrophage cultures inoculated with SIVmac251 and treated simultaneously with 10 microM 3'-azidothymidin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.2.360
更新日期:1993-02-01 00:00:00
abstract::Mycobacterium kansasii is the second most common mycobacterial cause of lung disease. Standard treatment consists of rifampin, isoniazid, and ethambutol for at least 12 months after negative sputum. Thus, shorter-duration therapies are needed. Moxifloxacin has good MICs for M. kansasii. However, good preclinical model...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04441-14
更新日期:2015-04-01 00:00:00
abstract::Molecular studies have shown that the majority of azole resistance in Aspergillus fumigatus is associated with amino acid substitutions in the cyp51A gene. To obtain insight into azole resistance mutations, the cyp51A gene of 130 resistant and 76 susceptible A. fumigatus isolates was sequenced. Out of 130 azole-resist...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01599-09
更新日期:2010-06-01 00:00:00
abstract::A carbapenem-resistant Serratia marcescens strain, 10mdr148, was identified in a Japanese hospital in 2010. The carbapenem resistance of this strain was attributed to the production of a novel metallo-β-lactamase (MBL), named SMB-1 (Serratia metallo-β-lactamase). SMB-1 possessed a zinc binding motif, H(Q)XHXDH (residu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05045-11
更新日期:2011-11-01 00:00:00
abstract::The effects of free amphotericin B (as Fungizone) and amphotericin B (AMB) incorporated into liposomes on the proliferation of lymphocytes were determined. Freshly obtained guinea pig and rat antigen-specific lymphocytes were compared with rat T-lymphocyte cell lines cultured for a long period of time. Incorporation o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.5.879
更新日期:1991-05-01 00:00:00
abstract::The in vitro activity of tosufloxacin (A-61827; T-3262) against 15 clinical isolates of Chlamydia trachomatis and 31 recent clinical isolates of Neisseria gonorrhoeae, including 15 spectinomycin-resistant N. gonorrhoeae and 16 penicillinase-producing N. gonorrhoeae, was determined. Tosufloxacin was compared with doxyc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.6.971
更新日期:1990-06-01 00:00:00
abstract::Anidulafungin is an echinocandin with activity against Candida species and Aspergillus species. Adult dosages under study are 50 mg/day for esophageal candidiasis and 100 mg/day for invasive candidiasis and aspergillosis. Little is known, however, about the safety and pharmacokinetics of anidulafungin in children. A m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.50.2.632-638.2006
更新日期:2006-02-01 00:00:00
abstract::The presence and genetic content of integrons were investigated for 37 epidemiologically unrelated multiple-drug-resistant strains of Salmonella enterica serotype Typhimurium from humans. All isolates were resistant to ampicillin, chloramphenicol, kanamycin, streptomycin, sulfonamides, and trimethoprim, as well as to ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.12.3053
更新日期:1998-12-01 00:00:00
abstract::Mycoplasma hominis was highly susceptible to two new quinolones, with MICs for 90% of isolates tested of 0.004 micrograms/ml for WIN 57273 and 0.063 micrograms/ml for sparfloxacin, which were activities much greater than the 1 microgram/ml found for ofloxacin and tetracycline. Although Ureaplasma urealyticum was less ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.7.1515
更新日期:1991-07-01 00:00:00