Abstract:
:Standard antituberculosis (anti-TB) therapy requires the use of multiple drugs for a minimum of 6 months, with variable outcomes that are influenced by a number of microbiological, pathological, and clinical factors. This is despite the availability of antibiotics that have good activity against Mycobacterium tuberculosis in vitro and favorable pharmacokinetic profiles in plasma. However, little is known about the distribution of widely used antituberculous agents in the pulmonary lesions where the pathogen resides. The rabbit model of TB infection was used to explore the hypothesis that standard drugs have various abilities to penetrate lung tissue and lesions and that adequate drug levels are not consistently reached at the site of infection. Using noncompartmental and population pharmacokinetic approaches, we modeled the rate and extent of distribution of isoniazid, rifampin, pyrazinamide, and moxifloxacin in rabbit lung and lesions. Moxifloxacin reproducibly showed favorable partitioning into lung and granulomas, while the exposure of isoniazid, rifampin, and pyrazinamide in lesions was markedly lower than in plasma. The extent of penetration in lung and lesions followed different trends for each drug. All four agents distributed rapidly from plasma to tissue with equilibration half-lives of less than 1 min to an hour. The models adequately described the plasma concentrations and reasonably captured actual lesion concentrations. Though further refinement is needed to accurately predict the behavior of these drugs in human subjects, our results enable the integration of lesion-specific pharmacokinetic-pharmacodynamic (PK-PD) indices in clinical trial simulations and in in vitro PK-PD studies with M. tuberculosis.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Kjellsson MC,Via LE,Goh A,Weiner D,Low KM,Kern S,Pillai G,Barry CE 3rd,Dartois Vdoi
10.1128/AAC.05208-11subject
Has Abstractpub_date
2012-01-01 00:00:00pages
446-57issue
1eissn
0066-4804issn
1098-6596pii
AAC.05208-11journal_volume
56pub_type
杂志文章abstract::A mutant (TX5127) of Enterococcus faecalis OG1RF was generated by disruption mutagenesis of a previously described autolysin gene. TX5127 formed longer chains (2 to 10 cells per chain) than wild-type OG1RF (mainly single cells) during growth in broth even though it had a growth rate similar to that of the parental str...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.11.2883
更新日期:1998-11-01 00:00:00
abstract::Staphylococcus epidermidis is one of the most frequent causes of device-associated infections, because it is known to cause biofilms that grow on catheters or other surgical implants. The persistent increasing resistance of S. epidermidis and other coagulase-negative staphylococci (CoNS) has driven the need for newer ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00504-13
更新日期:2013-10-01 00:00:00
abstract::The objective of this study was to develop a population pharmacokinetic model and to determine a dosing regimen for caspofungin in critically ill patients. Nine blood samples were drawn per dosing occasion. Fifteen patients with (suspected) invasive candidiasis had one dosing occasion and five had two dosing occasions...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00905-20
更新日期:2020-08-20 00:00:00
abstract::Miloxacin, a synthetic antibacterial agent structurally related to oxolinic acid, has a broad spectrum of activity in vitro against gram-negative bacteria and considerable activity in vivo against infections with these bacteria. These observations led to studies on the absorption and excretion of miloxacin in mice, ra...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.18.1.41
更新日期:1980-07-01 00:00:00
abstract::The macrolide-aminoglycoside-streptothricin (MAS) element, an ∼4.2-kb insertion containing erm(B) and aphA3 resistance determinants, distinguishes Streptococcus pneumoniae transposon Tn1545/Tn6003 from Tn6002. Here, it is shown to be an unstable genetic element that, although it lacks recombinase genes, can exploit lo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01487-12
更新日期:2012-11-01 00:00:00
abstract::Microsporidians of the genus Encephalitozoon are an important cause of disease in immunocompromised patients, and there are currently no completely effective treatments. The present study investigated the viability and infectivity of spores of Encephalitozoon cuniculi that had been exposed to resveratrol (RESV), a nat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.7.2497-2501.2004
更新日期:2004-07-01 00:00:00
abstract::Group B beta-hemolytic streptococci (GB-BHS) frequently cause severe infection in newborns. Previous in vitro studies showed accelerated killing of GB-BHS by ampicillin plus gentamicin as compared with ampicillin alone. To extend the in vitro observations, mice were infected experimentally with GB-BHS and treated with...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.11.5.817
更新日期:1977-05-01 00:00:00
abstract::(S)-9-(3-Hydroxy-2-phosphonylmethoxypropyl)adenine [(S)-HPMPA], (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)-2,6-diaminopurine [(S)-HPMPDAP], cyclic (S)-HPMPA [(S)-cHPMPA], 9-(2-phosphonylmethoxyethoxyethyl)-2,6-diaminopurine (PMEDAP), and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [(S)-HPMPC] were examined fo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.11.2440
更新日期:1991-11-01 00:00:00
abstract::The gene coding for aminoglycoside 2'-N-acetyltransferase Ia [AAC(2')-Ia] from Providencia stuartii was amplified by PCR and cloned. The resulting construct, pACKF2, was transferred into Escherichia coli for overexpression of AAC(2')-Ia as a fusion protein with an N-terminal hexa-His tag. The fusion protein was isolat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.8.2238-2244.2001
更新日期:2001-08-01 00:00:00
abstract::Development of anthrax countermeasures that may be used concomitantly in a postexposure setting requires an understanding of the interaction between these products. Anthrax immune globulin intravenous (AIGIV) is a candidate immunotherapeutic that contains neutralizing antibodies against protective antigen (PA), a comp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00460-13
更新日期:2013-11-01 00:00:00
abstract::Himastatin, a cyclohexadepsipeptide antibiotic, had in vivo antitumor activity against localized P388 leukemia and B16 melanoma but had no distal site antitumor activity. An in vitro Bacillus subtilis well-agar diffusion assay was employed to test the hypothesis that himastatin was enzymatically inactivated. The activ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.11.2633
更新日期:1994-11-01 00:00:00
abstract::The post-β-lactamase-inhibitor effect (PBLIE) of tazobactam combined with ceftolozane was evaluated by time-kill assays on two clinical Escherichia coli strains producing CTX-M-15 with or without TEM-1. The organisms were exposed (2 h) to 4 μg/ml/4 μg/ml of ceftolozane-tazobactam (4× MIC), 4 μg/ml of ceftolozane, and ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02398-13
更新日期:2014-01-01 00:00:00
abstract::The physicochemical constants and some structural parameters (topological, steric, and electronic) of eight third-generation monofluorate quinolones (six uncommercialized and two used clinically [ciprofloxacin and enrofloxacin]) were determined: pKa, intrinsic solubility (S0), chromatographic capacity factor, partitio...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.9.1996
更新日期:1997-09-01 00:00:00
abstract::Vancomycin has been associated with acute kidney injury in preclinical and clinical settings; however, the precise exposure profiles associated with vancomycin-induced acute kidney injury have not been defined. We sought to determine pharmacokinetic/pharmacodynamics indices associated with the development of acute kid...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00416-17
更新日期:2017-10-24 00:00:00
abstract::An in vitro investigation of the structure-activity profiles for a range of 9-anilinoacridines on drug-resistant Plasmodium falciparum is reported. C-3, 6-diamino substitution, low lipophilicity, and high pKa values substantially increased the activities of the 9-anilinoacridines tested. There appeared to be no correl...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.3.403
更新日期:1993-03-01 00:00:00
abstract::Enterobacteriaceae producing the OXA-48 carbapenemase are emerging worldwide, leaving few treatment options. Efficacy has been demonstrated in vivo with ceftazidime against a ceftazidime-susceptible OXA-48 isolate but not with imipenem despite maintaining susceptibility. The relationship between phenotype and in vivo ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01947-13
更新日期:2014-01-01 00:00:00
abstract::The in vitro activity of OPC-17116, a new C-5 methyl fluoroquinolone, was compared with the activities of other fluoroquinolones. OPC-17116 inhibited 50% of the members of the family Enterobacteriaceae tested and 90% of Haemophilus influenzae, Neisseria species, and Moraxella catarrhalis isolates at less than or equal...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.6.1310
更新日期:1992-06-01 00:00:00
abstract::We examined the effect of antibiotic treatment on establishment of intestinal colonization by Candida glabrata in adult mice. Subcutaneous ceftriaxone, piperacillin-tazobactam, clindamycin, and metronidazole promoted increased density of stool colonization, whereas cefepime, levofloxacin, and aztreonam did not. These ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.1.438-440.2005
更新日期:2005-01-01 00:00:00
abstract::The effects of probenecid on the pharmacokinetics and renal clearance of acyclovir were studied in humans. Acyclovir (5 mg/kg) was given as a 1-h infusion to three volunteers with normal renal function both before and after oral administration of probenecid (1 g). The kinetics were well described by a two-compartment ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.5.804
更新日期:1982-05-01 00:00:00
abstract::Occidiofungin is produced by the soil bacterium Burkolderia contaminans MS14 and is structurally similar or identical to the burkholdines, xylocandins, and cepacidines. This study identified the primary cellular target of occidiofungin, which was determined to be actin. The modification of occidiofungin with a functio...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01585-18
更新日期:2018-12-21 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::An in situ method for sensitive detection of differences in the action of chlorhexidine against subpopulations of cells in Candida albicans biofilms is described. Detection relies on monitoring the kinetics of propidium iodide (PI) penetration into the cytoplasm of individual cells during dosing with chlorhexidine. Ac...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.11.3522-3531.2002
更新日期:2002-11-01 00:00:00
abstract::Ceftriaxone in short courses has emerged as an effective alternative to chloramphenicol for the treatment of typhoid fever. To study the pharmacokinetics of ceftriaxone in acute typhoid fever, 10 febrile Nepalese adolescents and young adults with blood culture-positive illness were treated with 3 g of ceftriaxone (int...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.10.2415
更新日期:1994-10-01 00:00:00
abstract::Daptomycin pharmacokinetics were evaluated for burn patients. Burn patients had decreases in the maximum concentration of the drug in serum (44%) and the area under the concentration-time curve (47%) and increases in the volume of distribution (64%) and total clearance (77%) compared to healthy volunteers. In burn pat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.01321-07
更新日期:2008-05-01 00:00:00
abstract::Analysis of two clonally related multiresistant Pseudomonas aeruginosa isolates led to the identification of a novel IMP-type metallo-β-lactamase. IMP-29 was significantly different from the other IMP variants (the closest variant being IMP-5 with 93% amino acid identity). The bla(IMP-29) gene cassette was carried by ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05838-11
更新日期:2012-04-01 00:00:00
abstract::The results of treatment of 10 patients with anaerobic infections with metronidazole are presented. Six patients were cured, three showed initial good response but circumstances required a change to another drug, and one patient did not respond. The unique spectrum of the drug, its pharmacology, and limitations are di...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.7.5.672
更新日期:1975-05-01 00:00:00
abstract::No studies have investigated whether discontinuation of ethambutol (EMB) based on the susceptibility to isoniazid and rifampin as determined by the GenoType MTBDRplus assay would be appropriate. We aimed to determine the feasibility of discontinuing EMB before the end of intensive phase treatment based on the result o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00980-19
更新日期:2019-09-16 00:00:00
abstract::Berberine, a quaternary alkaloid, and several of its derivatives were tested for efficacy against Leishmania donovani and Leishmania braziliensis panamensis in golden hamsters. Tetrahydroberberine was less toxic and more potent than berberine against L. donovani but was not as potent as meglumine antimonate (Glucantim...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.5.918
更新日期:1990-05-01 00:00:00
abstract::A major concern of immunocompromised patients, in particular those with AIDS, is susceptibility to infection caused by opportunistic pathogens such as Pneumocystis jirovecii, which is a leading cause of pneumonia in immunocompromised patients. We report the first kinetic and structural data for 2,4-diamino-6-[(2',5'-d...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00172-13
更新日期:2013-06-01 00:00:00
abstract::Highly drug-resistant Salmonella enterica serovar Indiana became the most common serovar in broilers with diarrhea in China over the course of this study (15% in 2010 to 70% in 2014). While most S. Indiana isolates (87%, 384/440) were resistant to 13 to 16 of the 16 antibiotics tested, 89% of non-S. Indiana isolates (...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03009-15
更新日期:2016-01-11 00:00:00