Abstract:
:The repurposing of existing drugs is being pursued as a means by which to accelerate the development of novel regimens for the treatment of drug-susceptible and drug-resistant tuberculosis (TB). In the current study, we assessed the activity of the antipsychotic drug thioridazine (TRZ) in combination with the standard regimen in a well-validated murine TB model. Single-dose and steady-state pharmacokinetic studies were performed in BALB/c mice to establish human-equivalent doses of TRZ. To determine the bactericidal activity of TRZ against TB in BALB/c mice, three separate studies were performed, including a dose-ranging study of TRZ monotherapy and efficacy studies of human-equivalent doses of TRZ with and without isoniazid (INH) or rifampin (RIF). Therapeutic efficacy was assessed by the change in mycobacterial load in the lung. The human-equivalent dose of thioridazine was determined to be 25 mg/kg of body weight, which was well tolerated in mice. TRZ was found to accumulate at high concentrations in lung tissue relative to serum levels. We observed modest synergy during coadministration of TRZ with INH, and the addition of TRZ reduced the emergence of INH-resistant mutants in mouse lungs. In conclusion, this study further illustrates the opportunity to reevaluate the contribution of TRZ to the sterilizing activity of combination regimens to prevent the emergence of drug-resistant M. tuberculosis.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Dutta NK,Pinn ML,Karakousis PCdoi
10.1128/AAC.02981-14subject
Has Abstractpub_date
2014-07-01 00:00:00pages
4048-53issue
7eissn
0066-4804issn
1098-6596pii
AAC.02981-14journal_volume
58pub_type
杂志文章abstract::Attachment of giardias to intestinal cells has been difficult to study because of a lack of a convenient in vitro model. We developed an assay for attachment of radiolabeled trophozoites to IEC-6 cells that can be done in microtiter trays. Attachment was confirmed by scanning and transmission electron microscopy. Trop...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.1.29
更新日期:1991-01-01 00:00:00
abstract::In vitro and in vivo studies were done on a herpes simplex virus type 2 strain recovered from a patient on acyclovir (ACV) which was ACV resistant but expressed thymidine (dThd) kinase (EC 2.7.1.21) activity. Plaque-purified clones derived from the original clinical sample were heterogeneous with respect to plaque siz...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.7.1117
更新日期:1987-07-01 00:00:00
abstract::Many successful antimicrobial drugs originate from synthetic dyes. This paper reports the in vitro activity of 14 fluorescent dyes against Plasmodium falciparum. Five of these dyes (Hoechst 33342, MitoRed, DiOC(6), SYTO 9, and rhodamine B) show activity at a low nanomolar concentration against two P. falciparum strain...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00709-12
更新日期:2012-11-01 00:00:00
abstract::The effect of protein binding on the activity of teicoplanin against Staphylococcus aureus was evaluated. Bactericidal rates of teicoplanin in cation-supplemented Mueller-Hinton broth (SMHB) and in a 1:1 mixture of pooled human serum and cation-supplemented Mueller-Hinton broth (PHS-SMHB) were compared with those of v...
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.35.6.1089
更新日期:1991-06-01 00:00:00
abstract::The pharmacokinetics of azlocillin were investigated in five healthy subjects and in 16 subjects with chronic renal failure. After intravenous bolus injection of a single dose of 30 mg/kg in normal subjects, pharmacokinetic data were calculated, using a two-compartment open body model. The mean distribution serum half...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.17.3.344
更新日期:1980-03-01 00:00:00
abstract::We report patient-to-patient transmission of Enterobacter hormaechei isolates with reduced susceptibility to ceftazidime-avibactam due to production of KPC-40, a variant of KPC-3 with a two-amino-acid insertion in the Ω-loop region (L167_E168dup). The index patient had received a prolonged course of ceftazidime-avibac...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00955-19
更新日期:2019-09-23 00:00:00
abstract::A mouse model of cystitis caused by uropathogenic Escherichia coli was used to study the distribution of gallium in bladder tissue following oral administration of gallium maltolate during urinary tract infection. The median concentration of gallium in homogenized bladder tissue from infected mice was 1.93 μg/g after ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00616-13
更新日期:2013-11-01 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::The Autobac I system was used to evaluate the antibiotic susceptibility pattern of methicillin-resistant Staphylococcus aureus isolates. The results of the Autobac I were compared with the results of the disk diffusion method. The disk diffusion susceptibility pattern showed resistance to methicillin/oxacillin, penici...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.13.5.837
更新日期:1978-05-01 00:00:00
abstract::Human immunodeficiency virus (HIV) type 1 (HIV-1) variants were selected for resistance to the (+) and (-) enantiomers of a novel nucleoside analogue, 2'-deoxy-3'-oxa-4'-thio-5-fluorocytidine (dOTFC), by use of the infectious molecular clone HIV HXB2D and the human T-cell line MT-4. The dOTFC-resistant variants that w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.5.1127-1131.2000
更新日期:2000-05-01 00:00:00
abstract::A portion of the Mycobacterium tuberculosis gene encoding the beta subunit of RNA polymerase (rpoB) was amplified by PCR using degenerate oligonucleotides and used as a hybridization probe to isolate plasmid clones carrying the entire rpoB gene of M. tuberculosis H37Rv, a virulent, rifampin-susceptible strain. Sequenc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.4.805
更新日期:1994-04-01 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::The in vitro activities of LY146032 and seven comparative antimicrobial agents against 14 species of staphylococci, streptococci, and enterococci were studied. MICs of LY146032 were less than or equal to 0.5 microgram/ml for all staphylococci, including oxacillin-resistant strains; less than or equal to 0.25 microgram...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.5.781
更新日期:1986-11-01 00:00:00
abstract::For 177 gram-negative isolates, the MICs for ciprofloxacin ranged from 0.02 microgram/ml (Escherichia coli) to 0.31 microgram/ml (Pseudomonas aeruginosa). In time-kill curves, ciprofloxacin at 8 X the MIC almost completely killed 10(6) CFU of P. aeruginosa by 24 h. Ciprofloxacin at 4 X the MIC allowed bacterial regrow...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.4.597
更新日期:1984-10-01 00:00:00
abstract::The multidrug resistance profiles of Klebsiella pneumoniae carbapenemase (KPC) producers have led to increased clinical polymyxin use. Combination therapy with polymyxins may improve treatment outcomes, but it is uncertain which combinations are most effective. Clinical successes with intravenous minocycline-based com...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00073-17
更新日期:2017-06-27 00:00:00
abstract::Robust determination of the concentration-time profile of anti-infective agents in certain specialized compartments is often limited by the inability to obtain more than a single sample from such a site in any one subject. Vitreous humor and cerebrospinal fluid are obvious examples for which the determination of conce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.8.1683
更新日期:1995-08-01 00:00:00
abstract::The in vitro activity of BMS-207147 against 80 clinical isolates of Aspergillus was compared with that of itraconazole and amphotericin B, using a validated microtiter method. Geometric mean MICs (in microg/ml) were as follows: 1.71 for BMS-207147, 0.67 for itraconazole, and 0.63 for amphotericin B. The range of conce...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.2.441-443.2000
更新日期:2000-02-01 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::Pneumonia occurring outside of the hospital setting has traditionally been categorized as community-acquired pneumonia (CAP). However, when pneumonia is associated with health care risk factors (prior hospitalization, dialysis, residing in a nursing home, immunocompromised state), it is now more appropriately classifi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00851-07
更新日期:2007-10-01 00:00:00
abstract::The antimicrobial activity of carumonam (formerly RO-17-2301), a monocyclic beta-lactam antibiotic, was compared with those of aztreonam, cefotaxime, cefoperazone, ceftazidime, piperacillin, and gentamicin against 455 bacterial isolates. Carumonam did not possess activity against gram-positive cocci and was generally ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.2.346
更新日期:1986-02-01 00:00:00
abstract::With the rapid spread of antimicrobial resistance in Gram-negative pathogens, biofilm-associated infections are increasingly harder to treat and combination therapy with colistin has become one of the most efficient therapeutic strategies. Our study aimed to evaluate the potential for the synergy of colistin combined ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02223-16
更新日期:2017-06-27 00:00:00
abstract::This study was directed at characterizing the genetic elements carrying the methylase gene erm(B), encoding ribosome modification-mediated resistance to macrolide, lincosamide, and streptogramin B (MLS) antibiotics, in Streptococcus pyogenes. In this species, erm(B) is responsible for MLS resistance in constitutively ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01484-06
更新日期:2007-04-01 00:00:00
abstract::Cytochrome aa3 concentrations in the cytoplasmic membrane of Bacillus subtilis were altered by growth conditions, and the effects on the membrane potential (delta psi) in whole cells were measured. When cytochrome aa3 was absent, the magnitude of delta psi was not diminished by comparison with the delta psi measured i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.1.141
更新日期:1986-01-01 00:00:00
abstract::Low-level vancomycin-resistant Staphylococcus aureus (vancomycin-intermediate S. aureus [VISA] and heterogenous VISA [hVISA]) is increasingly reported and leads to glycopeptide treatment failure. Various phenotypic features have been reported for these isolates, but the genetic changes leading to hVISA and VISA have y...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00422-06
更新日期:2006-09-01 00:00:00
abstract::TAN 1057-resistant Staphylococcus aureus and Escherichia coli strains were selected to elucidate the mechanism of resistance and the mode of action of this dipeptide antibiotic. Cell-free translation with isolated ribosomes and S150 fractions from sensitive and resistant S. aureus strains demonstrated that alterations...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.2.619-622.2004
更新日期:2004-02-01 00:00:00
abstract::Spider venoms are vast natural pharmacopoeias selected by evolution. The venom of the ant spider Lachesana tarabaevi contains a wide variety of antimicrobial peptides. We tested six of them (latarcins 1, 2a, 3a, 4b, 5, and cytoinsectotoxin 1a) for their ability to suppress Chlamydia trachomatis infection. HEK293 cells...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00449-11
更新日期:2011-11-01 00:00:00
abstract::The residual antibiotic concentration of vancomycin (2 mg/ml)- or ceftazidime (2 mg/ml)-heparin solutions instilled in ports in pediatric hematology-oncology patients 1 to 34 days earlier was measured. Antibiotic concentrations of > or = 100 microg of either antibiotic per ml persisted for at least 21 days. For treatm...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.5.1565-1567.2001
更新日期:2001-05-01 00:00:00
abstract::Pseudomonas aeruginosa infections represent a serious threat to worldwide health. Proline-rich antimicrobial peptides (PR-AMPs), a particular group of peptide antibiotics, have demonstrated in vitro activity against P. aeruginosa strains. Here we show that the mammalian PR-AMP Bac7(1-35) is active against some multidr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01660-16
更新日期:2017-03-24 00:00:00
abstract::The main aim of this study was to develop a standardized experimental assay to enable differential antimicrobial comparisons of test biocidal aerosols. This study represents the first chlorine-matched comparative assessment of the antimicrobial activities of aerosolized sodium hypochlorite, chlorine dioxide, and elect...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02589-12
更新日期:2013-05-01 00:00:00
abstract::The in vitro activity of LY 146032, a cyclic lipopeptide antibiotic belonging to the class of agents designated A21978C, was compared with those of vancomycin, cefpirome, cefotaxime, and clindamycin against selected gram-positive bacteria. The new drug inhibited all staphylococcal isolates, including methicillin-resis...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.4.532
更新日期:1986-10-01 00:00:00