Abstract:
:The oxazolidinone linezolid represents a new antibacterial class of potential benefit in managing multidrug-resistant gram-positive infections, including those caused by Streptococcus pneumoniae. In a gerbil model of acute otitis media (AOM) induced by either penicillin-resistant S. pneumoniae (PRSP; amoxicillin MIC = 8 micro g/ml, linezolid MIC = 1 micro g/ml) or penicillin-susceptible S. pneumoniae (PSSP; amoxicillin MIC = 0.015 micro g/ml, linezolid MIC = 1 micro g/ml), we explored the plasma and ear fluid levels of linezolid required to demonstrate efficacy. Threshold pathogen doses required to induce bilateral AOM (1,500 CFU/ear with PRSP; 30 CFU/ear with PSSP) were administered to gerbils by intrabullar injection on day 0. At peak infection ( approximately 10(6) to 10(7) CFU/ear flush; day 2 for PRSP-AOM and day 3 for PSSP-AOM), twice-a-day oral doses of linezolid, amoxicillin, or vehicle were administered over 4.5 days prior to collection and assay of middle ear effluents for S. pneumoniae content. Linezolid doses of >/=10 mg/kg of body weight induced significant cure rates of >/=72% versus both PRSP and PSSP infections, whereas amoxicillin at =100 mg/kg was consistently effective only versus PSSP-AOM. Plasma and ear fluid levels of linezolid necessary to elicit pneumococcal eradication from the middle ear were measured by high-performance liquid chromatography-tandem mass spectrometry and found to be similar both within and between each infection protocol. The plasma-ear fluid pharmacodynamic profile associated with linezolid efficacy was a T>MIC of >/=42%, a C(max)/MIC ratio of >/=3.1, and a (24-h area under the curve)/MIC ratio of >/=30 h. Application of this model will be useful in defining preclinical pharmacodynamic relationships of novel antibiotics necessary to cure S. pneumoniae-induced AOM.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Humphrey WR,Shattuck MH,Zielinski RJ,Kuo MS,Biermacher JJ,Smith DP,Jensen JL,Schaadt RD,Zurenko GE,Richards IMdoi
10.1128/aac.47.4.1355-1363.2003subject
Has Abstractpub_date
2003-04-01 00:00:00pages
1355-63issue
4eissn
0066-4804issn
1098-6596journal_volume
47pub_type
杂志文章abstract::Many Pseudomonas aeruginosa isolates from the airways of patients with cystic fibrosis (CF) are sensitive to antibiotics in susceptibility testing, but eradication of the infection is difficult. The main reason is the biofilm formation in the airways of patients with CF. The pharmacokinetics (PKs) and pharmacodynamics...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06486-11
更新日期:2012-05-01 00:00:00
abstract::The indinavir dosage regimen currently used for human immunodeficiency virus (HIV)-infected children is not based on pharmacokinetic data obtained in the target patient population. The purpose of our study was to characterize indinavir pharmacokinetics and pharmacodynamics in HIV-infected children. Eleven children (ag...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.44.3.752-755.2000
更新日期:2000-03-01 00:00:00
abstract::The Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) offer different recommendations for carbapenem MIC susceptibility breakpoints for Acinetobacter species. In addition, the clinical efficacy of the intermediate category remains uncertain. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.00661-17
更新日期:2017-08-24 00:00:00
abstract::A biodegradable system of poly-D,L-dilactide releasing ciprofloxacin was assessed in a Pseudomonas aeruginosa osteomyelitis model after inoculation of the test pathogen into the left tibia of 76 New Zealand White rabbits; 31 were controls (group A), and 45 were implanted with the polymer at the infection site (group B...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01360-07
更新日期:2008-07-01 00:00:00
abstract::A mixed culture of an hypermutable hexA Streptococcus pneumoniae mutant strain and its hexA(+) isogenic ancestor was challenged with low cefotaxime concentrations. Despite identical original cefotaxime MICs, the hexA mutant population was significantly selected at very low concentrations, and all of the tested selecte...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.2.528-530.2002
更新日期:2002-02-01 00:00:00
abstract::An agar dilution method was employed to test the susceptibility of 12 strains of Coccidioides immitis to polymyxin B (PB). After 3 days of incubation, eight strains were markedly inhibited by 5.0 mug of PB per ml and four strains did not grow. PB at 10 mug/ml inhibited the growth of all strains through 20 days of incu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.10.2.318
更新日期:1976-08-01 00:00:00
abstract::R plasmids from chloramphenicol-resistant salmonella from Ontario are shown to belong to the H(2) incompatibility subgroup and to mediate a broad-spectrum, phage inhibition function. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.10.4.762
更新日期:1976-10-01 00:00:00
abstract::Five isoforms of protein mannosyltransferase (Pmt) O-mannosylate secretory proteins in Candida albicans. pmt mutants were differentially defective for biofilm formation on plastic in static and flow-through systems, and a Pmt inhibitor blocked early stages of biofilm formation. Conceptually, Pmt inhibition may prevent...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00606-06
更新日期:2006-10-01 00:00:00
abstract::The objective of this study was to quantitate cefotaxime and its active metabolite, desacetyl cefotaxime, in the distal airways and to compare these levels to concentrations in plasma. Respiratory secretions were obtained from the subsegmental level in 17 adult patients undergoing fiber-optic bronchoscopy within 2 h a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.5.815
更新日期:1987-05-01 00:00:00
abstract::The dependence of microbial killing on chloride ions present in solutions undergoing iontophoresis is addressed. A 400-microA current was applied to vials containing synthetic urine or saline, and the production of chlorine-based substances (CBSs) was detected by the N,N-diethyl-p-phenylene diamine colorimetric method...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.12.2768
更新日期:1994-12-01 00:00:00
abstract::The in vitro susceptibility of Mycobacterium fortuitum and Mycobacterium chelonei to cefmetazole was studied by the agar dilution method. At a concentration of 16 micrograms/ml or lower, 44 isolates (96%) of M. fortuitum and 8 isolates (40%) of M. chelonei were inhibited. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.27.2.282
更新日期:1985-02-01 00:00:00
abstract::Resistance-nodulation-division (RND) efflux pumps are important contributors to bacterial antibiotic resistance. In this study, we combined evolutionary sequence analyses, computational structural modeling, and ligand docking to develop a framework that can explain the known antibiotic substrate selectivity difference...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00496-20
更新日期:2020-07-22 00:00:00
abstract::Antimicrobial peptides (AMPs) are effective antibiotic agents commonly found in plants, animals, and microorganisms, and they have been suggested as the future of antimicrobial chemotherapies. It is vital to understand the molecular details that define the mechanism of action of resistance to AMPs for a rational plann...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05558-11
更新日期:2012-04-01 00:00:00
abstract::The potent antiretroviral pyrimidinediones IQP-0528 (PYD1) and IQP-0532 (PYD2) were formulated in polyurethane intravaginal rings (IVRs) as prophylactic drug delivery systems to prevent the sexual transmission of HIV-1. To aid in the selection of a pyrimidinedione candidate and the optimal loading of the drug in the I...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05721-11
更新日期:2012-03-01 00:00:00
abstract::Magainins are novel polycationic peptides with broad-spectrum antimicrobial activity, including activity against gram-negative bacteria. Gram-negative bacteremia can elicit endotoxic shock that is associated with the increased formation of eicosanoids. Inhibition of eicosanoid synthesis has been shown to improve the o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.3.393
更新日期:1993-03-01 00:00:00
abstract::Posaconazole (POS) is a new antifungal agent for prevention and therapy of mycoses in immunocompromised patients. Variable POS pharmacokinetics after oral dosing may influence efficacy: a trough threshold of 0.5 μg/ml has been recently proposed. Measurement of POS plasma concentrations by complex chromatographic techn...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00022-10
更新日期:2010-12-01 00:00:00
abstract::We undertook a prospective, randomized comparison of oral ciprofloxacin with standard parenteral therapies for the treatment of biopsy-proven osteomyelitis caused by susceptible organisms. Following surgical debridement, the ciprofloxacin patients received 750 mg twice a day, and the other patients received a broad-sp...
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.34.1.40
更新日期:1990-01-01 00:00:00
abstract::Granulocytopenia is a complication of human immunodeficiency virus disease, as well as a toxic manifestation of zidovudine therapy. To evaluate pharmacokinetic and pharmacodynamic relationships, 11 AIDS-AIDS-related complex patients who had developed zidovudine-associated granulocytopenia (mean absolute neutrophil cou...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.3.512
更新日期:1993-03-01 00:00:00
abstract::The in vitro activities of sparfloxacin, temafloxacin, ciprofloxacin, ofloxacin, clarithromycin, erythromycin, tetracycline, cephalothin, penicillin G, and amoxicillin-clavulanic acid against 173 recent clinical bite wound isolates were determined by agar dilution. Sparfloxacin was active against all strains (MIC for ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.5.1150
更新日期:1993-05-01 00:00:00
abstract::A series of 3,5-dioxopyrazolidines was identified as novel inhibitors of UDP-N-acetylenolpyruvylglucosamine reductase (MurB). Compounds 1 to 3, which are 1,2-bis(4-chlorophenyl)-3,5-dioxopyrazolidine-4-carboxamides, inhibited Escherichia coli MurB, Staphyloccocus aureus MurB, and E. coli MurA with 50% inhibitory conce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.2.556-564.2006
更新日期:2006-02-01 00:00:00
abstract::The rabbit kidney cell line LLC-RK1 was tested for its ability to discriminate the toxicities of six cephalosporin antibiotics according to their in vivo nephrotoxic potentials in rabbits. With the exception of cephalothin, which was markedly toxic to kidney cells in vitro, a good correlation between in vitro toxicity...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.32.3.314
更新日期:1988-03-01 00:00:00
abstract::We conducted time-kill studies to evaluate the inhibitory activities of either cefotaxime or minocycline alone and the two drugs in combination against a clinical strain of Vibrio vulnificus. The MICs of cefotaxime and minocycline were 0.03 and 0.06 microg/ml, respectively. When approximately 5 x 10(5) CFU of V. vulni...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.10.2214
更新日期:1997-10-01 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::Mutants of attenuated Bacillus anthracis with high-level ciprofloxacin resistance were isolated using a three-step in vitro selection. Ciprofloxacin MICs were 0.5 micro g/ml for first-step mutants, which had one of two gyrA quinolone resistance-determining region (QRDR) mutations. Ciprofloxacin MICs were 8 and 16 micr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.7.2362-2365.2003
更新日期:2003-07-01 00:00:00
abstract::Pregnancy alters the pharmacokinetic properties of many drugs used in the treatment of malaria, usually resulting in lower drug exposures. This increases the risks of treatment failure, adverse outcomes for the fetus, and the development of resistance. The pharmacokinetic properties of artemether and its principal met...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00683-13
更新日期:2013-10-01 00:00:00
abstract::Rifalazil, also known as KRM-1648 or benzoxazinorifamycin, is a new semisynthetic rifamycin with a long half-life of approximately 60 h. Rifalazil has potent bactericidal activity against Mycobacterium tuberculosis in vitro and in animal models of tuberculosis (TB). Prior studies in healthy volunteers showed that once...
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.45.7.1972-1976.2001
更新日期:2001-07-01 00:00:00
abstract::A vancomycin-resistant Staphylococcus aureus (VRSA) isolate was obtained from a patient in Pennsylvania in September 2002. Species identification was confirmed by standard biochemical tests and analysis of 16S ribosomal DNA, gyrA, and gyrB sequences; all of the results were consistent with the S. aureus identification...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.1.275-280.2004
更新日期:2004-01-01 00:00:00
abstract::Identifying and understanding potential drug-drug interactions (DDIs) are vital for the treatment of human immunodeficiency virus type 1 (HIV-1) infection. This article discusses DDIs between doravirine, a nonnucleoside reverse transcriptase inhibitor (NNRTI), and cytochrome P450 3A (CYP3A) substrates and drugs that m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02016-18
更新日期:2019-04-25 00:00:00
abstract::The following compounds, which possess anti-R-plasmid activity (Hahn and Ciak, 1976) in decreasing order, were shown by viscometric titration to change systematically the superhelical density of closed circular PM2 deoxyribonucleic acid in the manner of intercalators: ethidium bromide, quinacrine, acridine orange, qui...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.11.2.251
更新日期:1977-02-01 00:00:00
abstract::Antibacterial compounds with novel modes of action are needed for management of bacterial infections. Here we describe a high-content screen of 9,800 compounds identifying acylated sulfonamides as novel growth inhibitors of the sexually transmitted pathogen Chlamydia trachomatis. The effect was bactericidal and distin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02015-13
更新日期:2014-05-01 00:00:00