Abstract:
:The creation of new chemotherapeutic regimens that permit shortening the duration of treatment is a major priority for antituberculosis drug development. In this study, we used the murine model of experimental tuberculosis therapy to determine whether incorporation of the investigational new nitroimidazopyran PA-824 into the standard first-line regimen has the potential to shorten the 6-month duration of treatment. As demonstrated previously, PA-824 alone had significant bactericidal activity over the first 2 months of treatment. Moreover, the substitution of PA-824 for isoniazid led to significantly lower lung CFU counts after 2 months of treatment and to more rapid culture-negative conversion compared to the standard regimen of rifampin, isoniazid, and pyrazinamide. Despite this, there was no difference in the proportion of mice relapsing after completing 6 months of therapy (2 of 19 mice treated with PA-824 in place of isoniazid relapsed versus 0 of 46 mice treated with the standard regimen). Meanwhile, no other PA-824-containing regimen tested was superior to the standard regimen on any assessment. Thus, we were unable to establish a clear role for PA-824 in a treatment-shortening regimen that includes two or more of the current first-line drugs. Future preclinical studies should include the evaluation of novel combinations of PA-824 with new drug candidates in addition to existing antituberculosis drugs for their potential to substantially improve the treatment of both drug-susceptible and multidrug-resistant tuberculosis.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Nuermberger E,Rosenthal I,Tyagi S,Williams KN,Almeida D,Peloquin CA,Bishai WR,Grosset JHdoi
10.1128/AAC.00451-06subject
Has Abstractpub_date
2006-08-01 00:00:00pages
2621-5issue
8eissn
0066-4804issn
1098-6596pii
50/8/2621journal_volume
50pub_type
杂志文章abstract::Hypocrellins A and B were evaluated for in vitro antimicrobial and antileishmanial activities. Hypocrellin A exhibited promising activity against Candida albicans and moderate activity against Staphylococcus aureus, methicillin-resistant S. aureus, Pseudomonas aeruginosa, and Mycobacterium intracellulare. Hypocrellin ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.11.4450-4452.2004
更新日期:2004-11-01 00:00:00
abstract::Mycobacterium tuberculosis and the fast-growing species Mycobacterium abscessus are two important human pathogens causing persistent pulmonary infections that are difficult to cure and require long treatment times. The emergence of drug-resistant M. tuberculosis strains and the high level of intrinsic resistance of M....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01696-17
更新日期:2018-04-26 00:00:00
abstract::Primaquine is currently the only drug available for radical cure of Plasmodium vivax and P. ovale liver infection stages, but limited safety data exist for children <10 years of age. Detailed daily assessments of side effects in glucose-6-phosphate dehydrogenase (G6PD)-normal children treated with 14 days of primaquin...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05566-11
更新日期:2012-04-01 00:00:00
abstract::Daptomycin is a lipopeptide antibiotic with activity against gram-positive bacteria, including Staphylococcus aureus. We defined the pharmacodynamic parameters that determine the activity of daptomycin for S. aureus using in vitro methods and the Craig (W. A. Craig, J. Redington, and S. C. Ebert, J. Antimicrob. Chemot...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.3.845-851.2001
更新日期:2001-03-01 00:00:00
abstract::A total of 521 unique clinical isolates from cancer patients with primarily (>90%) bloodstream infections were tested for susceptibility to ceftazidime-avibactam and comparators using broth microdilution methods. Ceftazidime-avibactam inhibited 97.8% of all Enterobacteriaceae (n = 321) at the susceptibility breakpoint...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02106-16
更新日期:2017-03-24 00:00:00
abstract::A dipeptide lantibiotic, named Smb, in Streptococcus mutans GS5 was characterized by molecular genetic approaches. The Smb biosynthesis gene locus is encoded by a 9.5-kb region of chromosomal DNA and consists of seven genes in the order smbM1, -T, -F, -M2, -G, -A, -B. This operon is not present in some other strains o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.2.541-548.2005
更新日期:2005-02-01 00:00:00
abstract::The in vitro susceptibilities of 112 clinical isolates of Haemophilus ducreyi to six antimicrobial agents were determined. These isolates were obtained in Kigali, Rwanda, during three studies on genital ulcer disease performed in 1986 (18 isolates), 1988 (23 isolates), and 1991 (71 isolates). All H. ducreyi isolates w...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.7.1647
更新日期:1994-07-01 00:00:00
abstract::Bloodstream infection (BSI) due to multidrug-resistant Klebsiella is associated with high rates of morbidity and mortality. The aim of this study was to identify predictors of in-hospital mortality among patients with BSI due to ceftazidime-resistant (CAZ-R) Klebsiella pneumoniae at a tertiary care medical center. Pat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.5.1715-1720.2006
更新日期:2006-05-01 00:00:00
abstract::Omadacycline is an effective therapy for community-acquired bacterial pneumonia (CABP). Given its potent activity against methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA), we sought to determine the pharmacodynamic activity and target pharmacokinetic/pharmacodynamic (PK/P...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02058-19
更新日期:2020-01-27 00:00:00
abstract::Many potent antiviral drugs have been developed against HIV-1, and their combined action is usually successful in achieving durable virus suppression in infected individuals. This success is based on two effects: additive or even synergistic virus inhibition and an increase in the genetic threshold for development of ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01486-17
更新日期:2017-11-22 00:00:00
abstract::We administered 1 g of imipenem along with equal amounts of cilastatin (a dehydropeptidase I inhibitor) or 2 g of moxalactam intravenously over a period of 30 min to six volunteers in a crossover manner 1 week apart. The antibiotic concentrations and pharmacokinetics for each drug were determined and integrated with t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.29.3.412
更新日期:1986-03-01 00:00:00
abstract::The activities of DU-6859a, levofloxacin, ofloxacin, sparfloxacin, and ciprofloxacin against bite wound isolates were determined by the agar dilution method. DU-6859a was the most active compound (MICs, < or = 0.125 microg/ml) against all Pasteurella species, Staphylococcus aureus, and streptococci; anaerobes were sus...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.5.1193
更新日期:1997-05-01 00:00:00
abstract::A total of 6,991 unique patient isolates of Streptococcus pneumoniae were collected from October 1997 to June 2002 from 25 medical centers in 9 of the 10 Canadian provinces. Among these isolates, 20.2% were penicillin nonsusceptible, with 14.6% being penicillin intermediate (MIC, 0.12 to 1 microg/ml) and 5.6% being pe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.6.1867-1874.2003
更新日期:2003-06-01 00:00:00
abstract::We found earlier that deferoxamine (DFO), a drug used for treatment of iron overload, is active against a rat model of Pneumocystis carinii pneumonia (PCP). We had assumed a mode of action by deprivation of nutritional iron; however, data here show that DFO penetrates P. carinii, causing irreversible damage, thus indi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.12.3560-3565.2001
更新日期:2001-12-01 00:00:00
abstract::Study of the antimicrobial spectrum of valinomycin revealed that, in addition to the gram-positive bacteria reported in literature, Streptococcus pyogenes and Clostridium sporogenes are also susceptible to this antibiotic. The minimal inhibitory concentrations (MIC) of the antibiotic for S. pyogenes grown aerobically ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.3.1.63
更新日期:1973-01-01 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::The aims of the study were to investigate the prevalence of azole resistance among Aspergillus fumigatus clinical isolates. A total of 533 clinical isolates that had been collected between 1995 and 2006, from 441 patients, were screened. No resistance was detected in isolates collected between 1995 and 1997. Starting ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02234-15
更新日期:2015-11-09 00:00:00
abstract::Ga(3+) is a semimetal element that competes for the iron-binding sites of transporters and enzymes. We investigated the activity of gallium maltolate (GaM), an organic gallium salt with high solubility, against laboratory and clinical strains of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resista...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00700-09
更新日期:2010-01-01 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::The pharmacokinetics of meropenem and its ring-opened metabolite (ICI 213,689) were investigated with eight young (20- to 34-year-old) and eight elderly (67- to 80-year-old) healthy male volunteers given single 30-min intravenous infusions of 500 mg of meropenem. All subjects had normal age-correlated glomerular funct...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.7.1437
更新日期:1992-07-01 00:00:00
abstract::The aim of this study was to investigate the influence of hypovolemia on the distribution of imipenem in muscle extracellular fluid determined by microdialysis in awake rats. Microdialysis probes were inserted into the jugular vein and hind leg muscle. Imipenem recoveries in muscle and blood were determined in each ra...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.12.4974-4979.2005
更新日期:2005-12-01 00:00:00
abstract::The effect of 19 antimicrobial agents on human polymorphonuclear leukocyte function was evaluated by chemiluminescence assays, yeast phagocytosis and killing, and lactate dehydrogenase release. Tetracycline and trimethoprim inhibited chemiluminescence and reduced killing at therapeutic concentrations of 2 microgram/ml...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.1.15
更新日期:1981-07-01 00:00:00
abstract::Sordarin and its derivatives are antifungal compounds of potential clinical interest. Despite the highly conserved nature of the fungal and mammalian protein synthesis machineries, sordarin is a selective inhibitor of protein synthesis in fungal organisms. In cells sensitive to sordarin, its mode of action is through ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01603-07
更新日期:2008-05-01 00:00:00
abstract::Three Haemophilus parainfluenzae strains isolated from the urogenital tract harbored a beta-lactamase-coding 3.2-megadalton plasmid identical, by restriction endonuclease digestion and hybridization with radioactive and biotin-labeled probes specific for the TEM-1 beta-lactamase and TnA sequences, to the 3.2-megadalto...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.31.6.966
更新日期:1987-06-01 00:00:00
abstract::There is significant interest in the development of mass spectrometry (MS) methods for antimicrobial resistance protein detection, given the ability of these methods to confirm protein expression. In this work, we studied the performance of a liquid chromatography, tandem MS multiple-reaction monitoring (LC-MS/MS MRM)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00461-19
更新日期:2019-08-23 00:00:00
abstract::The tight packing of six fatty acids in the lipid A constituent of lipopolysaccharide (LPS) has been proposed to contribute to the unusually low permeability of the outer membrane of gram-negative enteric bacteria to hydrophobic antibiotics. Here it is shown that the Escherichia coli msbB mutant, which elaborates defe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.6.1459
更新日期:1999-06-01 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::PER-1 is an extended-spectrum β-lactamase that is encoded by a gene located in composite transposon Tn1213 made by two distinct insertion sequences, namely, ISPa12 and ISPa13. In vitro mobilization performed in Escherichia coli shows that Tn1213 is functional and is able to mobilize the blaPER-1 gene, although at a ve...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02453-17
更新日期:2018-02-23 00:00:00
abstract::Macrolide-resistant mutants of Campylobacter jejuni and Campylobacter coli were selected in vitro using erythromycin and tylosin. These mutants exhibited modifications in the ribosomal proteins L4 (G74D) and L22 (insertions at position 86 or 98). A synergy between the CmeABC efflux pump and these modifications in conf...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00616-06
更新日期:2006-11-01 00:00:00
abstract::An open, randomized comparison of ofloxacin (200 mg, every 12 h) given orally for 5 days and ceftriaxone (3 g, once daily) given intravenously for 3 days in the treatment of uncomplicated enteric fever was conducted in Ho Chi Minh City, Vietnam. Salmonella paratyphi type A was isolated from six patients. Salmonella ty...
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.38.8.1716
更新日期:1994-08-01 00:00:00