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 models to identify optimal doses currently are lacking. We developed a novel hollow fiber system model of intracellular M. kansasii infection. We indexed the efficacy of the standard combination regimen, which was a kill rate of -0.08 ± 0.05 log10 CFU/ml/day (r(2) = 0.99). We next performed moxifloxacin dose-effect and dose-scheduling studies at a half-life of 11.1 ± 6.47 h. Some systems also were treated with the efflux pump inhibitor reserpine. The highest moxifloxacin exposure, as well as lower exposures plus reserpine, sterilized the cultures by day 7. This suggests that efflux pump-mediated tolerance at low ratios of the area under the concentration-time curve from 0 to 24 h (AUC0 - 24) to MICs is an early bacterial defense mechanism but is overcome by higher exposures. The highest rate of moxifloxacin monotherapy sterilization was -0.82 ± 0.15 log10 CFU/ml/day (r(2) = 0.97). The moxifloxacin exposure associated with 80% of maximal kill (EC80) was an AUC0-24/MIC of 317 (the non-protein-bound moxifloxacin AUC0-24/MIC was 158.5). We performed Monte Carlo simulations of 10,000 patients in order to identify the moxifloxacin dose that would achieve or exceed the EC80. The simulations revealed an optimal moxifloxacin dose of 800 mg a day. The MIC susceptibility breakpoint at this dose was 0.25 mg/liter. Thus, moxifloxacin, at high enough doses, is suitable to study in patients for the potential to add rapid sterilization to the standard regimen.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Srivastava S,Pasipanodya J,Sherman CM,Meek C,Leff R,Gumbo Tdoi
10.1128/AAC.04441-14subject
Has Abstractpub_date
2015-04-01 00:00:00pages
2273-9issue
4eissn
0066-4804issn
1098-6596pii
AAC.04441-14journal_volume
59pub_type
杂志文章abstract::Optimal doses for antituberculosis (anti-TB) drugs in children have yet to be established. In 2010, the World Health Organization (WHO) recommended revised dosages of the first-line anti-TB drugs for children. Pharmacokinetic (PK) studies that investigated the adequacy of the WHO revised dosages to date have yielded c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.00008-18
更新日期:2018-08-27 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::Nitazoxanide (NTZ), a drug currently being tested in human clinical trials for efficacy against chronic cryptosporidiosis, was assessed in cell culture and in two animal models. The inhibitory activity of NTZ was compared with that of paromomycin (PRM), a drug that is partially effective against Cryptosporidium parvum...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.8.1959
更新日期:1998-08-01 00:00:00
abstract::Streptococcus pneumoniae, a major cause of human disease, produces a 17-mer autoinducer peptide pheromone (competence-stimulating peptide [CSP]) for the control of competence for genetic transformation. Due to previous work linking CSP to stress phenotypes, we set up an in vivo sepsis model to assay its effect on viru...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.12.4725-4732.2004
更新日期:2004-12-01 00:00:00
abstract::Diethylpyrocarbonate (DEPC) treatment of interferon (IF) inducers was studied both in vitro and in vivo. DEPC did not affect the antiviral activity of poly(I.C), statolon, or reovirus in cultured chicken embryo fibroblast cells, but the activities of poly(I.C), statolon, and MU9 replicative form in cultured mouse embr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.4.675
更新日期:1976-04-01 00:00:00
abstract::The aim of the study was to identify the plasmid-encoded factors contributing to the emergence and spread of epidemic IncI1-Iγ plasmids obtained from Escherichia coli and Salmonella enterica isolates from animal and human reservoirs. For this, 251 IncI1-Iγ plasmids carrying various extended-spectrum β-lactamase (ESBL)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05006-14
更新日期:2015-09-01 00:00:00
abstract::The cell wall composition and autolytic properties of passage-selected glycopeptide-intermediate Staphylococcus aureus (GISA) isolates and their parent strains were studied in order to investigate the mechanism of decreased vancomycin susceptibility. GISA had relatively modest changes in peptidoglycan composition invo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.10.3749-3757.2004
更新日期:2004-10-01 00:00:00
abstract::This study determined the pharmacokinetic disposition of cefonicid. A single dose of 7.5 mg/kg of body weight was administered to five healthy volunteers as a 5-min intravenous infusion. Multiple plasma and urine samples were collected for 48 h. Peak plasma concentrations ranged from 95 to 156 micrograms/ml and fell s...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.6.935
更新日期:1982-06-01 00:00:00
abstract::Meropenem is a broad-spectrum carbapenem antibacterial agent. In order to optimize levels in plasma relative to the MICs, the ideal dose level and dosage regimen need to be determined. The pharmacokinetics of meropenem were studied in two groups, each comprising eight healthy volunteers who received the following dose...
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.49.5.1881-1889.2005
更新日期:2005-05-01 00:00:00
abstract::BEL-1 is an acquired class A extended-spectrum β-lactamase (ESBL) found in Pseudomonas aeruginosa clinical isolates from Belgium which is divergent from other ESBLs (maximum identity of 54% with GES-type enzymes). This enzyme is efficiently inhibited by clavulanate, imipenem, and moxalactam. Crystals of BEL-1 were obt...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00936-16
更新日期:2016-11-21 00:00:00
abstract::A group H1 R factor encoding resistance to chloramphenicol, streptomycin, sulfonamide, and tetracycline was transferred into Salmonella typhimurium LT-2. The virulence of LT-2 for mice, as assessed by intraperitoneal 50% lethal dose and the number of organisms in the spleen, was not affected by the R factor. On the ot...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.3.478
更新日期:1979-03-01 00:00:00
abstract::To compare the in vitro antibacterial efficacies and resistance profiles of rifampin-based combinations against methicillin-resistant Staphylococcus aureus (MRSA) in a biofilm model, the antibacterial activities of vancomycin, teicoplanin, daptomycin, minocycline, linezolid, fusidic acid, fosfomycin, and tigecycline a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01236-13
更新日期:2013-11-01 00:00:00
abstract::The effect of moxalactam and cefuroxime on mitogen-stimulated human peripheral blood mononuclear leukocytes was studied. Mononuclear leukocytes, mitogen, and antibiotic were added to microtiter wells. Cells were cultured for 3 days, pulsed with tritiated thymidine, and then counted. Compared with control cell cultures...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.23.3.360
更新日期:1983-03-01 00:00:00
abstract::Ribonucleoside analog inhibitors (rNAI) target the hepatitis C virus (HCV) RNA-dependent RNA polymerase nonstructural protein 5B (NS5B) and cause RNA chain termination. Here, we expand our studies on β-d-2'-C-methyl-2,6-diaminopurine-ribonucleotide (DAPN) phosphoramidate prodrug 1 (PD1) as a novel investigational inhi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00318-16
更新日期:2016-07-22 00:00:00
abstract::Miltefosine (MT) is a membrane-active alkylphospholipid licensed for the topical treatment of breast cancer skin metastases and the oral treatment of leishmaniasis, although its mechanism of action remains unclear. Electron paramagnetic resonance (EPR) spectroscopy of a spin-labeled lipid and a thiol-specific spin lab...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01332-13
更新日期:2014-06-01 00:00:00
abstract::Drug exposure or pharmacodynamic breakpoints refer to a magnitude of drug exposure which separates a population into groups with high and low probabilities of attaining a desired outcome. We used a pharmacodynamic model of disseminated candidiasis to define an in vivo drug exposure breakpoint for flucytosine (5FC) aga...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00369-06
更新日期:2006-11-01 00:00:00
abstract::Pentamidine is a second-line agent in the treatment of leishmaniasis whose mode of action and resistance mechanism are not well understood. In this work, we show that the intracellular ABC protein PRP1 (pentamidine resistance protein 1) (ABCC7) can confer resistance to pentamidine in Leishmania sp. parasites in the in...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00404-07
更新日期:2007-08-01 00:00:00
abstract::Genome studies suggest that DNA gyrase is the sole type II topoisomerase and likely the unique target of quinolones in Mycobacterium tuberculosis. Despite the emerging importance of quinolones in the treatment of mycobacterial disease, the slow growth and high pathogenicity of M. tuberculosis have precluded direct pur...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.4.1281-1288.2004
更新日期:2004-04-01 00:00:00
abstract::Invasive and allergic infections by Aspergillus flavus are more common in tropical and subtropical countries. The emergence of voriconazole (VRC) resistance in A. flavus impacts the management of aspergillosis, as azoles are used as the first-line and empirical therapy. We screened 120 molecularly confirmed A. flavus ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01928-17
更新日期:2018-02-23 00:00:00
abstract::The pharmacokinetics of gentamicin C(1), C(2), and C(1a) were studied in six beagles after administration of gentamicin at 4 mg/kg of body weight as a single intravenous bolus dose. Plasma concentrations of the gentamicin components were analyzed with a novel high-performance liquid chromatography method capable of id...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.6.1443-1447.2000
更新日期:2000-06-01 00:00:00
abstract::Acinetobacter baumannii is a Gram-negative bacterium that causes nosocomial infections worldwide. This microbe's propensity to form biofilms allows it to persist and to survive on clinical abiotic surfaces for long periods. In fact, A. baumannii biofilm formation and its multidrug-resistant nature severely compromise ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01045-15
更新日期:2015-10-12 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::The Pseudomonas R factor RP1 determines an inducible tetracycline resistance similar to that described for Escherichia coli R factors. The level of RP1-determined resistance measured by minimal inhibitory concentration testing is dependent on the host bacteria and corresponds to the magnitude of decrease in tetracycli...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.6.2.183
更新日期:1974-08-01 00:00:00
abstract::Novel antibiotics approved by noninferiority trials may become less effective over time in two scenarios: (i) the treatment effect in studies of novel antibiotics may be consistently worse than studies of older antibiotics; (ii) when a decreasingly effective control arm is used in a series of noninferiority trials. Ou...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01597-20
更新日期:2020-10-20 00:00:00
abstract::The Capnocytophaga sputigena isolate NOR, responsible for septicemia, was resistant to amoxicillin and narrow-spectrum cephalosporins. In a cloning experiment, a new gene, bla(CSP-1), was identified; this gene encodes a novel extended-spectrum beta-lactamase (ESBL) that shares only 52% and 49% identities with the CME-...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00791-09
更新日期:2010-05-01 00:00:00
abstract::Seven hundred twenty-three isolates of Moraxella catarrhalis obtained from outpatients with a variety of infections in 30 medical centers in the United States between 1 November 1994 and 30 April 1995 were characterized in a central laboratory. The overall rate of beta-lactamase production was 95.3%. When the National...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.40.12.2884
更新日期:1996-12-01 00:00:00
abstract::Susceptibility tests using 7 antimicrobial agents (carbenicillin, chloramphenicol, clindamycin, penicillin, cephalothin, metronidazole, and tetracycline) were run against 35 anaerobes including Bacteroides fragilis (17), other gram-negative bacilli (7), clostridia (5), peptococci (4), and eubacteria (2). Results in tr...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.3.351
更新日期:1979-03-01 00:00:00
abstract::The present study examined the efficacy of using multiple mechanisms as part of a topical microbicide to inactivate herpes simplex virus (HSV) by combining theaflavin-3,3'-digallate (TF-3) and lactic acid (LA) over the pH range of 4.0 to 5.7 to mimic conditions in the female reproductive tract. Six clinical isolates o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00659-13
更新日期:2013-08-01 00:00:00
abstract::Accurate assessment of the risk factors for colonization with vancomycin-resistant enterococci (VRE) among high-risk patients is often confounded by nosocomial VRE transmission. We undertook a 15-month prospective cohort study of adults admitted to high-risk units (hematology, renal, transplant, and intensive care) in...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.47.8.2492-2498.2003
更新日期:2003-08-01 00:00:00
abstract::Acyclovir cream has been available for the treatment of herpes labialis in numerous countries outside the United States for over a decade. Evidence for its efficacy comes from a few small clinical trials conducted in the 1980s. To examine more comprehensively the efficacy and safety of this formulation, we conducted t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1128/aac.46.7.2238-2243.2002
更新日期:2002-07-01 00:00:00