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 conflicting results. We performed population PK modeling using data from one of these studies to identify optimal dosage ranges. Ghanaian children with tuberculosis on recommended therapy with rifampin (RIF), isoniazid (INH), pyrazinamide (PZA), and ethambutol (EMB) for at least 4 weeks had blood samples collected predose and at 1, 2, 4, and 8 hours postdose. Drug concentrations were determined by validated liquid chromatography-mass spectrometry methods. Nonlinear mixed-effects models were applied to describe the population PK of those drugs using MonolixSuite2016R1 (Lixoft, France). Bayesian estimation was performed, the correlation coefficient, bias, and precision between the observed and predicted areas under the concentration-time curve (AUCs) were calculated, and Bland-Altman plots were analyzed. The population PK of RIF and PZA was described by a one-compartment model and that for INH and EMB by a two-compartment model. Plasma maximum concentration (Cmax) and AUC targets were based on published results for children from India. The lowest target values for pediatric TB patients were attainable at the WHO-recommended dosage schedule for RIF and INH, except for N-acetyltransferase 2 non-slow acetylators (rapid and intermediate acetylators) in the lower-weight bands. However, higher published adult targets were not attainable for RIF and INH. The targets were not achieved for PZA and EMB. (This study has been registered at ClinicalTrials.gov under identifier NCT01687504.).
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Horita Y,Alsultan A,Kwara A,Antwi S,Enimil A,Ortsin A,Dompreh A,Yang H,Wiesner L,Peloquin CAdoi
10.1128/AAC.00008-18subject
Has Abstractpub_date
2018-08-27 00:00:00issue
9eissn
0066-4804issn
1098-6596pii
AAC.00008-18journal_volume
62pub_type
临床试验,杂志文章abstract::The minimal inhibiting concentrations (MIC) of ampicillin, trisulfapyrimidines, and various combinations of these drugs were determined for four clinical isolates of Nocardia asteroides on Mueller-Hinton agar. The combination of ampicillin and sulfonamides was found to be synergistic for three of the four isolates whe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.1.3.215
更新日期:1972-03-01 00:00:00
abstract::High dosages of ceftriaxone are used to treat central nervous system (CNS) infections. Dosage adaptation according to the glomerular filtration rate is currently not recommended. Ceftriaxone pharmacokinetics (PK) was investigated by a population approach in patients enrolled in a French multicenter prospective cohort ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1128/AAC.00634-19
更新日期:2019-08-23 00:00:00
abstract::Borrelia burgdorferi, a spirochete and the causative agent of Lyme disease, has been reported to be susceptible to a variety of antimicrobial agents. In this investigation, the action of vancomycin, a glycopeptide antibiotic not previously known to have activity against spirochetes, against borrelias was examined. The...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.5.1115
更新日期:1993-05-01 00:00:00
abstract::A 7.7-kilobase BamHI fragment was cloned from the transconjugant of a clinical isolate of Escherichia coli containing a 120-kilobase multiresistance IncC plasmid. The recombinant plasmid conferred resistance to kanamycin, gentamicin, tobramycin, sulfamethoxazole, and trimethoprim. This clone was used to generate a ser...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.1.96
更新日期:1985-07-01 00:00:00
abstract::Fluoroquinolones are antibiotics with central excitatory side effects. These adverse effects presumably result from inhibition of gamma-aminobutyric acid (GABA) binding to GABA(A) receptors. This GABA antagonistic effect is greatly potentiated by the active metabolite of fenbufen, biphenylacetic acid (BPAA). Neverthel...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.46.2.471-477.2002
更新日期:2002-02-01 00:00:00
abstract::Tetracycline-resistant isolates of Pasteurella multocida and Pasteurella haemolytica obtained from various locations in the United States and Canada were studied to determine the distribution of the tet(H) gene. Of the 31 isolates examined, 25 were found to contain the tet(H) gene. Chromosomal or plasmid DNA obtained ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.6.1558
更新日期:1996-06-01 00:00:00
abstract::Management of treatment-experienced human immunodeficiency virus patients has become complex, and therapy may need to include two protease inhibitors at therapeutic doses. The objective of this study was to characterize the pharmacokinetics in serum of saquinavir (1,000 mg twice daily [b.i.d.]), lopinavir (400 mg b.i....
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.48.11.4256-4262.2004
更新日期:2004-11-01 00:00:00
abstract::In an effort to discover novel, noncarbohydrate inhibitors of influenza virus neuraminidase we hypothesized that compounds which contain positively charged amino groups in an appropriate position to interact with the Asp 152 or Tyr 406 side chains might be bound tightly by the enzyme. Testing of 300 alpha- and beta-am...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.45.9.2563-2570.2001
更新日期:2001-09-01 00:00:00
abstract::Many pathogenic and commensal organisms are multidrug resistant due to exposure to various antibiotics. Often, this antimicrobial resistance is encoded by integrons that occur on plasmids or that are integrated into the bacterial chromosome. Integrons are commonly associated with bacterial genera in the family Enterob...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.45.3.723-726.2001
更新日期:2001-03-01 00:00:00
abstract::Candida parapsilosis has emerged as a common cause of invasive fungal infection, especially in Latin America and in the neonatal setting. C. parapsilosis is part of a closely related group of organisms that includes the species Candida orthopsilosis and Candida metapsilosis. All three species show elevated MICs for th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00262-08
更新日期:2008-07-01 00:00:00
abstract::The kinetics of the lethal action of metronidazole and the formation of acetamide have been studied in a strain of Bacteroides fragilis which is relatively resistant to metronidazole. As with a susceptible strain of B. fragilis, the data are consistent with a model in which a labile intermediate in metronidazole metab...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.21.1.131
更新日期:1982-01-01 00:00:00
abstract::Hepatitis C virus (HCV) inhibitors include direct-acting antivirals (DAAs) such as NS3 serine protease inhibitors, nucleoside and nonnucleoside polymerase inhibitors, and host-targeting antivirals (HTAs) such as cyclophilin inhibitors that have been developed in recent years. Drug-resistant HCV variants have been repo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00294-11
更新日期:2011-09-01 00:00:00
abstract::The in vitro susceptibilities of 151 unique clinical isolates of Mycoplasma pneumoniae, Mycoplasma hominis, Mycoplasma fermentans, Mycoplasma genitalium, and Ureaplasma species to DC-159a, an investigational fluoroquinolone, in comparison with those to other agents were determined. Macrolides were the most active agen...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00849-08
更新日期:2008-10-01 00:00:00
abstract::Conventional therapy for human cytomegalovirus (CMV) relies on inhibition of the viral DNA polymerase. Ganciclovir (GCV) is the first-line therapy, but when GCV-resistant strains emerge, alternative therapies are extremely limited and are associated with significant toxicities. Combination of anti-CMV agents that act ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01972-13
更新日期:2014-01-01 00:00:00
abstract::A new class of pyridine oxide derivatives as inhibitors of human immunodeficiency virus type 1 (HIV-1) and/or HIV-2 replication in cell culture has been identified. The compounds, which specifically inhibit HIV-1, behave as typical nonnucleoside reverse transcriptase inhibitors (NNRTIs). The most active congener of th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.47.9.2951-2957.2003
更新日期:2003-09-01 00:00:00
abstract::The polymorphic fungus Candida albicans is one of the most versatile opportunistic pathogens in humans. Many organs of the human body are potential targets for infection by this pathogen, but infection is commonly localized in the gastrointestinal tract, an environment providing anaerobic growth conditions. We describ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.7.2350-2354.2004
更新日期:2004-07-01 00:00:00
abstract::A randomized, prospective, double-blind, double-dummy, multicenter study investigated the efficacy and safety of 10 days of oral therapy with grepafloxacin at 400 mg once daily, grepafloxacin at 600 mg once daily, or ciprofloxacin at 500 mg twice daily in 624 patients with acute bacterial exacerbations of chronic bron...
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.42.1.114
更新日期:1998-01-01 00:00:00
abstract::The distributions of tet(M) and conjugative transposons related to Tn1545 were studied by hybridization in 47 clinical isolates of Streptococcus pneumoniae resistant to tetracycline. Resistance to tetracycline was always associated with resistance to minocycline and was due to the presence of the tet(M) gene. Associat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.8.1657
更新日期:1991-08-01 00:00:00
abstract::The activity of NXL103 against 108 strains of Haemophilus influenzae was tested using Haemophilus test media (HTM) obtained from various sources. With the exception of those obtained with stored HTM, MICs did not differ significantly, with MIC(50) and MIC(90) values of 0.5 and 0.5 to 1 microg/ml, respectively, in each...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00587-06
更新日期:2006-11-01 00:00:00
abstract::Current antimalarials are under continuous threat due to the relentless development of drug resistance by malaria parasites. We previously reported promising in vitro parasite-killing activity with the histone methyltransferase inhibitor BIX-01294 and its analogue TM2-115. Here, we further characterize these diaminoqu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04419-14
更新日期:2015-02-01 00:00:00
abstract::A clinical trial was designed to evaluate the efficacy and safety of cefotaxime, a new semisynthetic, broad-spectrum cephalosporin, in the therapy of community-and hospital-acquired pneumonias. Thirty-nine males (mean age, 65 years) were treated for 41 episodes of pneumonia. Only five patient did not have a serious un...
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.21.2.327
更新日期:1982-02-01 00:00:00
abstract::The effect of antacid on the bioavailability of cefprozil was investigated in a two-way crossover study. Eight healthy male subjects received a single 500-mg oral dose of cefprozil with and without coadministration of 30 ml of an antacid suspension containing magnesium hydroxide and aluminum hydroxide (Maalox). Cefpro...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.5.962
更新日期:1992-05-01 00:00:00
abstract::The ST5 lineage of methicillin-resistant Staphylococcus aureus (MRSA) is one of the most globally disseminated hospital-associated MRSA (HA-MRSA) lineages. We isolated a new local variant (designated ST764) over at least 5 years that causes invasive infections, including necrotizing fasciitis, and is carried by medica...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01147-12
更新日期:2013-04-01 00:00:00
abstract::The antimicrobial activity of CS-940, a new trifluorinated quinolone drug, was tested against 761 clinical isolates. CS-940 activity against members of the family Enterobacteriaceae was most similar to that of ciprofloxacin and ofloxacin, with a large range of MICs inhibiting 90% of isolates tested (MIC90S) of 0.015 t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.10.2325
更新日期:1995-10-01 00:00:00
abstract::Chromosomally mediated penicillin resistance in Neisseria gonorrhoeae occurs in part through alterations in penicillin-binding proteins (PBPs) and a decrease in outer membrane permeability. However, the genetic and molecular mechanisms of transformation of a penicillin-susceptible strain of N. gonorrhoeae to high-leve...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.46.3.769-777.2002
更新日期:2002-03-01 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::Ceftaroline-avibactam and comparator agents were tested by the broth microdilution method against 20,089 isolates consecutively collected in 2010 and 2011 from 75 U.S. medical centers. Ceftaroline-avibactam was active against Enterobacteriaceae (4,908 strains; MIC90, 0.25 μg/ml; highest MIC, 4 μg/ml), including merope...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02436-12
更新日期:2013-04-01 00:00:00
abstract::The in vitro activity of tosufloxacin (A-61827; T-3262) against 15 clinical isolates of Chlamydia trachomatis and 31 recent clinical isolates of Neisseria gonorrhoeae, including 15 spectinomycin-resistant N. gonorrhoeae and 16 penicillinase-producing N. gonorrhoeae, was determined. Tosufloxacin was compared with doxyc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.34.6.971
更新日期:1990-06-01 00:00:00
abstract::Omadacycline is a first-in-class aminomethylcycline antibiotic with microbiological activity against Gram-positive and Gram-negative aerobes and anaerobes and atypical bacteria that is being developed for the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneu...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.01393-16
更新日期:2016-11-21 00:00:00
abstract::Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the last remaining options for first-line gonorrhea treatment, was isolated in Japan. Here, we confirm and characterize a second strain (F89) with high-level cefix...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05760-11
更新日期:2012-03-01 00:00:00