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. Quantitation of colony counts in kidneys after 24 h of therapy with a wide range of doses and three dosing intervals was used to determine the dose required to achieve 50% of the maximal effect (ED(50)). The ED(50) was similar for each of the dosing intervals studied, supporting the area under the concentration-time curve (AUC) MIC ratio as the parameter that predicts the efficacy of fluconazole. Similar studies were performed with C. albicans strains for which fluconazole MICs are in the susceptible-dose-dependent range (MICs, 16 to 32 mg/liter). We found that the magnitude of the AUC/MIC ratio required to reach the ED(50) was similar for all three organisms studied, ranging from 12 to 25. When the pharmacokinetics of fluconazole in humans are considered, these AUC/MIC ratios would support in vitro susceptibility breakpoints of 8 mg/liter for dosages of 200 mg/day and susceptibility breakpoints of 16 to 32 mg/liter for dosages of 400 to 800 mg/day.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Andes D,van Ogtrop Mdoi
10.1128/AAC.43.9.2116subject
Has Abstractpub_date
1999-09-01 00:00:00pages
2116-20issue
9eissn
0066-4804issn
1098-6596journal_volume
43pub_type
杂志文章abstract::Fifty-seven Salmonella enterica serotype Typhimurium (S. typhimurium) isolates were collected from human patients in two French hospitals, Hôpital Antoine Béclère (Clamart, France) and Hôpital Bicêtre (Le Kremlin-Bicêtre, France), between 1996 and 1997. Thirty of them (52 percent) were resistant to amino-, carbeni-, a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.5.1098
更新日期:1999-05-01 00:00:00
abstract::TEM-1 hyperproduction in two ampicillin-sulbactam-resistant Shigella flexneri strains was studied. In both strains the blaTEM gene was encoded as a single copy on a large conjugatively transferable plasmid. A single G-->T transversion at position 1 of the -10 consensus sequence was identified to be the mechanism of TE...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.2.468
更新日期:1997-02-01 00:00:00
abstract::Cefiderocol is a siderophore cephalosporin active against many multidrug-resistant (MDR) Gram-negative pathogens. We examined the resistance mechanisms in 12 Acinetobacter baumannii strains with cefiderocol MICs ranging from ≤0.03 to >32 μg/ml. Cefiderocol resistance could not be explained by β-lactamase activity. Cef...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01221-20
更新日期:2020-10-20 00:00:00
abstract::Aminoglycoside acetyltransferase was detected in Mycobacterium kansasii and M. fortuitum but not in M. avium-M. intracellulare when they were screened by a radioassay. Aminoglycoside phosphotransferase and nucleotidyltransferase activities were absent from all three species tested. Acetyltransferases from both M. kans...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.1.39-42.2000
更新日期:2000-01-01 00:00:00
abstract::Susceptibilities of 121 clinical Helicobacter pylori strains to metronidazole were determined by both a 5-micrograms metronidazole disk diffusion test and a plate dilution method in duplicate and after different periods of incubation. The distribution of MICs of metronidazole against H. pylori among the strains was fo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.38.10.2357
更新日期:1994-10-01 00:00:00
abstract::Nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are important components of current combination therapies for human immunodeficiency virus type 1 (HIV-1) infection. In screening of chemical libraries, we found 6-azido-1-benzyl-3-(3,5-dimethylbenzyl)uracil (AzBBU) and 6-amino-1-benzyl-3-(3,5-dimethylbenzyl...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06307-11
更新日期:2012-05-01 00:00:00
abstract::Ciprofloxacin activity against Leptospira interrogans serogroup icterohaemorrhagiae was studied in vitro and in an animal model. The MBC of ciprofloxacin was 0.6 microgram/ml. Three of three Syrian hamsters died 8 to 9 days after intraperitoneal challenge with 10(6) leptospires. In contrast, five of six animals given ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.33.5.788
更新日期:1989-05-01 00:00:00
abstract::The in vivo activity of human immunoglobulin M monoclonal antibody IN-2A8, which is specific for flagellum type b of Pseudomonas aeruginosa, was evaluated in comparison to anti-O antigen (serotype B) MAb KO-2F2 and in combination with antibiotics. IN-2A8 showed stronger activity than KO-2F2 against subcutaneous infect...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.6.1290
更新日期:1992-06-01 00:00:00
abstract::Helicobacter pylori is a major etiological agent in gastroduodenal disorders. The adhesion of H. pylori to human gastric epithelial cells is the initial step of H. pylori infection. Inhibition of H. pylori adhesion is thus a therapeutic target in the prevention of H. pylori infection. Experiments were performed to eva...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.8.1895
更新日期:1998-08-01 00:00:00
abstract::In this study, we synthesized antisense oligodeoxynucleotides (ODNs) with phosphodiester, phosphorothioate (S-ODNs), or methylphosphonate linkages complementary to the splicing acceptor site of immediate-early pre-mRNA 5 of herpes simplex virus type 1 (HSV-1). The antiviral activity of each analog on cytopathic effect...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.7.1670
更新日期:1996-07-01 00:00:00
abstract::Mycobacterium abscessus is intrinsically resistant to many antimycobacterial antibiotics, which presents serious problems in therapy. Here, we describe the development of a novel phenotype-based microscopic and computerized imaging drug screening approach. A pilot screen of 568 compounds from two libraries identified ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00828-18
更新日期:2018-08-27 00:00:00
abstract::Here we completely sequenced four mcr-1-haboring plasmids, isolated from two extended-spectrum-β-lactamase (ESBL)-producing Escherichia coli and two carbapenemase-producing Klebsiella pneumoniae clinical isolates. The mcr-1-harboring plasmids from an E. coli sequence type 2448 (ST2448) isolate and two K. pneumoniae ST...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00550-16
更新日期:2016-06-20 00:00:00
abstract::The antibacterial drug nalidixic acid (Nal) can suppress the growth of Candida albicans at levels of the drug normally found in urine. Growth suppression increases as drug levels are increased, and Nal also causes a similar proportional inhibition of the synthesis of all cellular macromolecules. However, growth temper...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.3.485
更新日期:1976-03-01 00:00:00
abstract::Therapeutic options for severe infections caused by strains of oxacillin-resistant Staphylococcus aureus (ORSA) and coagulase-negative staphylococci (ORSE) are very limited. With the increasing resistance of such strains to aminoglycosides, rifampin, and currently available quinolone agents, as well as the recent docu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.7.1837
更新日期:1998-07-01 00:00:00
abstract::The ultrastructural alterations induced in vitro by ICI 195,739, a recently developed bis-triazole derivative with potent antiproliferative effects on Trypanosoma (Schizotrypanum) cruzi, are reported. On epimastigotes, the triazole at its minimum growth-inhibitory concentration (0.1 microM) produced immediately (withi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.4.736
更新日期:1991-04-01 00:00:00
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
更新日期:2016-04-22 00:00:00
abstract::Polymyxin B nonapeptide, derived by cleavage of the fatty acyl diaminobutyric acid from polymyxin B, is considerably less toxic, lacks bactericidal activity, and retains its ability to render gram-negative bacteria susceptible to several antibiotics by permeabilizing their outer membranes. The peptide rendered all 53 ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.2.374
更新日期:1994-02-01 00:00:00
abstract::Antibiotic therapy with penicillin, doxycycline, and ceftriaxone has proven to be effective for the treatment of Lyme borreliosis. In some patients, however, it was noticed that borreliae can survival in the tissues in spite of seemingly adequate therapy. For a better understanding of this phenomenon, we investigated ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.5.1127
更新日期:1995-05-01 00:00:00
abstract::Tafenoquine is a novel 8-aminoquinoline antimalarial drug recently approved by the U.S. Food and Drug Administration (FDA) for the radical cure of acute Plasmodium vivax malaria, which is the first new treatment in almost 60 years. A population pharmacokinetic (POP PK) analysis was conducted with tafenoquine exposure ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00711-18
更新日期:2018-10-24 00:00:00
abstract::aac(6')-Ib-cr is a plasmid-mediated quinolone resistance gene embedded within a gene cassette, most often within an integron. It confers resistance to quinolones and aminoglycosides. We investigated the role of a 101-bp fragment frequently present upstream of the aac(6')-Ib-cr gene cassette and found that it contribut...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02704-16
更新日期:2017-04-24 00:00:00
abstract::Though the primary action of the cationic antibiotic polymyxin B is against the membrane of susceptible bacteria, severe morphological changes are detected in the cytoplasm. Using fluorescence microscopy and a mono-N-dansyl-polymyxin B derivative, we could demonstrate aggregations of the antibiotic with cellular mater...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.8.1.95
更新日期:1975-07-01 00:00:00
abstract::Rifabutin pharmacokinetics were studied by the population approach (NONMEM) with 40 human immunodeficiency virus-infected patients receiving rifabutin at different doses for prophylaxis or therapy of mycobacterial infections. A two-compartment open model with first-order absorption was used as the structural pharmacok...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.8.2017
更新日期:1998-08-01 00:00:00
abstract::For treatment of mild to moderate Clostridium difficile-associated disease (CDAD), oral metronidazole has been recommended as the preferred agent, in part due to concern that vancomycin may be more likely to promote colonization by vancomycin-resistant enterococci (VRE). We performed a prospective observational study ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00090-08
更新日期:2008-07-01 00:00:00
abstract::Linezolid is the first synthetic oxazolidone agent to treat infections caused by Gram-positive pathogens. Infected patients with liver dysfunction (LD) are more likely to suffer from adverse reactions, such as thrombocytopenia, when standard-dose linezolid is used than patients with LD who did not use linezolid. Curre...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00133-20
更新日期:2020-05-21 00:00:00
abstract::Desbutyl-benflumetol (DBB) is a novel antimalarial compound closely related to benflumetol (lumefantrine), of which it is a putative metabolite. The in vitro response of Plasmodium falciparum to DBB was studied in Mae Hong Son and Mae Sot, in northwest Thailand, in 1997 and 1998. In total, 155 fresh isolates were succ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.7.2106-2109.2001
更新日期:2001-07-01 00:00:00
abstract::Antibiotics disrupt the intestinal microbiota, rendering patients vulnerable to colonization by exogenous pathogens. Intermicrobial interactions may attenuate this effect. Incubation with ceftriaxone-resistant, ccrA-positive, β-lactamase-producing Bacteroides strains raised the minimum bactericidal concentration of ce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03719-14
更新日期:2015-01-01 00:00:00
abstract::Olorofim is a novel antifungal drug in phase 2 trials. It has shown promising in vitro activity against various molds, except for Mucorales. Initially, we observed a broad range of EUCAST MICs for Aspergillus fumigatus Here, we explored the MIC variability in more detail and prospectively investigated the susceptibili...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01527-20
更新日期:2020-12-16 00:00:00
abstract::Thirty-nine patients with uncomplicated gonorrhea were randomized to receive single, oral 50-, 100-, or 200-mg doses of trovafloxacin (CP-99,219), a new quinolone antibiotic. All 31 evaluable patients were cured of infection. Trovafloxacin was well tolerated. The trovafloxacin MICs at which 50 and 90% of 36 Neisseria ...
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.40.7.1720
更新日期:1996-07-01 00:00:00
abstract::This phase 1, open-label, single-dose, parallel-group study evaluated the pharmacokinetics (PK) of isavuconazole after a single oral dose of the prodrug isavuconazonium sulfate in healthy nonelderly (age, 18 to 45 years) and elderly (age, ≥65 years) males and females. Overall, 48 subjects were enrolled in the study (n...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02629-18
更新日期:2019-05-24 00:00:00
abstract::Pharmacokinetic modeling has often been applied to evaluate vancomycin pharmacokinetics in neonates. However, clinical application of the model-based personalized vancomycin therapy is still limited. The objective of the present study was to evaluate the clinical utility and safety of a model-based patient-tailored do...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02214-15
更新日期:2016-03-25 00:00:00