Abstract:
:The aim of this study was to determine the penetration of doripenem administered intravenously into the rabbit aqueous and vitreous humors. Nineteen New Zealand White rabbits received a 20-mg dose of doripenem intravenously over 60 min. Specimens of aqueous humor, vitreous humor, and blood were obtained 30 min (n = 5), 1 h (n = 5), 2 h (n = 5), and 3 h (n = 4) after the beginning of the infusion and analyzed by high-performance liquid chromatography (HPLC). A pharmacokinetic (PK) model was developed to fit the experimental data. Doripenem concentrations in aqueous humor were lower than those in plasma ultrafiltrates at all sampling times, with an average aqueous humor-to-plasma ultrafiltrate area under the concentration-time curve ratio estimated as 8.3%. A pharmacokinetic model with peripheral elimination described the data adequately and was tentatively used to predict concentration-versus-time profiles and pharmacokinetic-pharmacodynamic (PK-PD) target attainment in patients under various dosing regimens. In conclusion, systematically administered doripenem does not seem to be a promising approach for the treatment of intraocular infections, especially since it could not be detected in the vitreous humor. However, this study has provided an opportunity to develop a new PK modeling approach to characterize the intraocular distribution of doripenem administered intravenously to rabbits, with tentative extrapolation to humans.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Semoun O,Marchand S,Grégoire N,Lamarche I,Adier C,Laroche L,Goldschmidt P,Couet Wdoi
10.1128/AAC.06329-11subject
Has Abstractpub_date
2012-07-01 00:00:00pages
3531-4issue
7eissn
0066-4804issn
1098-6596pii
AAC.06329-11journal_volume
56pub_type
杂志文章abstract::Concomitant treatment of tuberculosis (TB) and HIV is recommended and improves outcomes. Bedaquiline is a novel drug for the treatment of multidrug-resistant (MDR) TB; combined use with antiretroviral drugs, nevirapine, or ritonavir-boosted lopinavir (LPV/r) is anticipated, but no clinical data from coinfected patient...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.03246-14
更新日期:2014-11-01 00:00:00
abstract::Liquid cultures of a Pseudomonas aeruginosa strain in Mueller-Hinton broth diluted at rates higher than the bacterial growth rate showed the expected decrease in CFU only for 1 to 2 h. Later the CFU started to increase. This phenomenon can be explained by a hypothesis that assumes that the bacteria multiply in two dif...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.5.765
更新日期:1986-05-01 00:00:00
abstract::Adult diabetic patients admitted to our Diabetes Center from September 1996 to January 1998 for severe, limb-threatening foot infection were consecutively enrolled in a prospective, randomized, controlled clinical study aimed at assessing the safety and efficacy of recombinant human granulocyte colony-stimulating fact...
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.45.4.1094-1098.2001
更新日期:2001-04-01 00:00:00
abstract::The antifolate activity and the transport characteristics of isoaminopterin (IA) in HeLa cells were studied and compared with those of methotrexate (MTX). Both IA and MTX inhibited the incorporation of [2-(14)C]deoxyuridine into HeLa cell DNA by 50% at a concentration of 0.09 muM by 8 h postaddition of the compounds. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.5.730
更新日期:1979-05-01 00:00:00
abstract::beta-Lactamases from Aeromonas hydrophila and A. sobria were purified and characterized. Both species produced beta-lactamases that were inducible by either cefoxitin or imipenem. These species were resistant to ampicillin and cephalothin but not imipenem. Isoelectric focusing of sonic extracts revealed one band at pI...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.1.44
更新日期:1990-01-01 00:00:00
abstract::Retrocyclins are humanized versions of the -defensin peptides expressed by the leukocytes of several nonhuman primates. Previous studies, performed in serum-free media, determined that retrocyclins 1 (RC1) and RC2 could prevent successful germination of Bacillus anthracis spores, kill vegetative B. anthracis cells, an...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00267-11
更新日期:2011-09-01 00:00:00
abstract::Since beta-lactam antibiotics have concentration-independent killing, bacterial eradication is a function of the time the serum drug concentration remains above the drug's MIC (T > MIC). We compared the serum bactericidal titers (SBTs) of ceftazidime given by continuous infusion (CI) or by intermittent bolus dosing (B...
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.40.1.61
更新日期:1996-01-01 00:00:00
abstract::PSI-352938 is a novel cyclic phosphate prodrug of β-D-2'-deoxy-2'-α-fluoro-2'-β-C-methylguanosine 5'-monophosphate that has potent activity against hepatitis C virus (HCV) in vitro. The studies described here characterize the in vitro anti-HCV activity of PSI-352938, alone and in combination with other inhibitors of H...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00032-11
更新日期:2011-06-01 00:00:00
abstract::Determination of the neutrophil gelatinase-associated lipocalin (NGAL) level can be used to detect acute kidney injury (AKI) earlier than determination of the serum creatinine (SCr) level in settings such as cardiac surgery, contrast nephropathy, and intensive care units. We hypothesized that urine NGAL (UrNGAL) would...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01079-15
更新日期:2015-11-01 00:00:00
abstract::We determined the pharmacodynamic parameter and the magnitude of that parameter that was predictive of the efficacy of fluconazole in the treatment of disseminated candidiasis. We used a neutropenic murine model of disseminated Candida albicans infection to characterize the time course of activity of fluconazole. Quan...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.9.2116
更新日期:1999-09-01 00:00:00
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
更新日期:2015-02-01 00:00:00
abstract::The distribution of subclasses mefA and mefE of the mefA gene among 116 M-phenotype streptococci was as follows: pneumococci (38 strains had mefE and 4 mefA), viridans streptococci (49 mefE and 1 mefA), and Streptococcus pyogenes (24 mefA). Spain(9V)-3-14 and England(14)-9 clones of serotype 14 were dominant among pne...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.2.827-829.2005
更新日期:2005-02-01 00:00:00
abstract::A case-control study of the effect of antiretroviral therapy (ART) on apoptosis pathway genes comprising 16 cases (HIV infected with mitochondrial toxicity) and 16 controls (HIV uninfected) was conducted. A total of 26 of 84 genes of the apoptosis pathway were differentially expressed. Two of the upregulated genes, DF...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00522-17
更新日期:2017-07-25 00:00:00
abstract::We evaluated MEDI8852, a human IgG1 monoclonal antibody that binds a highly conserved influenza A hemagglutinin stalk epitope, in outpatients with uncomplicated influenza A infection. A total of 126 subjects aged 18 to 65 years were enrolled during the 2015 to 2016 Northern and 2016 Southern Hemisphere seasons. Subjec...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.00694-18
更新日期:2018-10-24 00:00:00
abstract::Rifampin was shown in vitro to decrease the amphotericin B minimal inhibitory concentrations of all of 10 strains of Coccidioides immitis tested. These decreases ranged from two- to fourfold and occurred with rifampin concentrations of 10 to 40 mug/ml. Rifampin alone was without effect. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.6.6.783
更新日期:1974-12-01 00:00:00
abstract::A combination of 3 g of ticarcillin and 200 mg of clavulanic acid was administered intravenously to six healthy male volunteers, after which the concentrations of these agents in serum and blister fluid were measured. The ratio of the two drugs in serum varied from 15:1 (ticarcillin-clavulanic acid) at the time of adm...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.6.831
更新日期:1983-06-01 00:00:00
abstract::A number of proflavine (PF)-resistant mutants of Escherichia coli B were also resistant to penicillin and cephalothin. Mutants resistant to 1.0 mM PF were 10 times more penicillin resistant than were the PF-susceptible, wild-type cells. Single-step mutants selected for resistance to either PF or penicillin were also r...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.10.4.765
更新日期:1976-10-01 00:00:00
abstract::Broth dilution minimal inhibitory concentration (MIC) readings were compared after different incubation periods and with different inoculum concentrations. The purpose was to determine the best conditions for obtaining early results as close as possible to overnight readings. Initially, 76 antibiotic-organism combinat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.8.4.429
更新日期:1975-10-01 00:00:00
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
更新日期:1997-04-01 00:00:00
abstract::The rpoB gene encodes the beta subunit of the DNA-dependent RNA polymerase of bacteria. Mutations in defined areas result in resistance to rifampin. Mycobacterium smegmatis is naturally resistant to rifampin, but analysis of the rpoB gene revealed no identifiable rifampin resistance mutations. Another mechanism of res...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.9.2164
更新日期:1995-09-01 00:00:00
abstract::In a sample of 6,156 sequences from 4,183 persons, the top 30 patterns of protease inhibitor, nucleoside reverse transcriptase (RT) inhibitor, and nonnucleoside RT inhibitor mutations accounted for 55, 46, and 66%, respectively, of sequences with drug resistance mutations. Characterization of the phenotypic and clinic...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.8.3122-3126.2004
更新日期:2004-08-01 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 effectiveness of gatifloxacin therapy (15 mg/kg every 5 h [q5h]) was compared with that of meropenem (75 mg/kg q5h) and cefotaxime (75 mg/kg q5h) therapy in experimental meningitis caused by a beta-lactamase-producing strain of Escherichia coli. Gatifloxacin therapy was more rapidly bactericidal than cefotaxime bu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.7.1805
更新日期:1999-07-01 00:00:00
abstract::Mupirocin is a topical antimicrobial used to decolonize patients who carry methicillin-resistant Staphylococcus aureus (MRSA), and the topical agent retapamulin may be a potential alternative therapy. The goal of this study was to determine the in vitro activity of retapamulin as well as a panel of 15 antimicrobial ag...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01568-15
更新日期:2015-12-14 00:00:00
abstract::The in vitro activities of magainin analogs against Blastocystis hominis, Entamoeba histolytica, and Trypanosoma cruzi were assessed by protozoan morphological integrity and motility. The antiprotozoan activities in descending order were magainin B greater than G greater than H, the same order as the alpha-helix conte...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.9.1824
更新日期:1990-09-01 00:00:00
abstract::Difloxacin, A-56620, cefazolin, cefotaxime, ceftizoxime, cephapirin, SK&F 88070, and spectinomycin were used to compare the in vitro susceptibilities of Mycobacterium avium-M. intracellular isolates from patients with acquired immunodeficiency syndrome (AIDS), patients without AIDS, and diseased animals. Against the i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.7.1390
更新日期:1990-07-01 00:00:00
abstract::The disposition of caspofungin, a parenteral antifungal drug, was investigated. Following a single, 1-h, intravenous infusion of 70 mg (200 microCi) of [(3)H]caspofungin to healthy men, plasma, urine, and feces were collected over 27 days in study A (n = 6) and plasma was collected over 26 weeks in study B (n = 7). Su...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.48.3.815-823.2004
更新日期:2004-03-01 00:00:00
abstract::Shigella flexneri continues to be a major cause of diarrhea-associated illness, and increasing resistance to first-line antimicrobials complicates the treatment of infections caused by this pathogen. We investigated the pharmacodynamics of current antimicrobial treatments for shigellosis to determine the likelihood of...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00086-17
更新日期:2017-06-27 00:00:00
abstract::An inhibitor-based characterization system which allowed the identification of beta-lactamases after isoelectric focusing on polyacrylamide gels was developed. This system, using potassium clavulanate and oxacillin, distinguished type I chromosomally mediated enzymes from other beta-lactamases of gram-negative bacteri...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.6.951
更新日期:1986-12-01 00:00:00
abstract::Although often dismissed as contaminants when isolated from blood cultures, Bacillus spp. are increasingly recognized as capable of causing serious systemic infections. As part of a clinical-microbiological study, 89 strains of Bacillus spp. isolated from clinical blood cultures between 1981 and 1985 had their species...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.5.642
更新日期:1988-05-01 00:00:00