Abstract:
:Concomitant treatment of tuberculosis (TB) and HIV is recommended and improves outcomes. Bedaquiline is a novel drug for the treatment of multidrug-resistant (MDR) TB; combined use with antiretroviral drugs, nevirapine, or ritonavir-boosted lopinavir (LPV/r) is anticipated, but no clinical data from coinfected patients are available. Plasma concentrations of bedaquiline and its M2 metabolite after single doses were obtained from interaction studies with nevirapine or LPV/r in healthy volunteers. The antiretrovirals' effects on bedaquiline and M2 pharmacokinetics were assessed by nonlinear mixed-effects modeling. Potential dose adjustments were evaluated with simulations. No significant effects of nevirapine on bedaquiline pharmacokinetics were identified. LPV/r decreased bedaquiline and M2 clearances to 35% (relative standard error [RSE], 9.2%) and 58% (RSE, 8.4%), respectively, of those without comedication. As almost 3-fold (bedaquiline) and 2-fold (M2) increases in exposures during chronic treatment with LPV/r are expected, dose adjustments are suggested for evaluation. Efficacious, safe bedaquiline dosing for MDR-TB patients receiving antiretrovirals is important. Modeling results suggest that bedaquiline can be coadministered with nevirapine without dose adjustments. The predicted elevation of bedaquiline and M2 levels during LPV/r coadministration may be a safety concern, and careful monitoring is recommended. Further data are being collected in coinfected patients to determine whether dose adjustments are needed. (These studies have been registered at ClinicalTrials.gov under registration numbers NCT00828529 [study C110] and NCT00910806 [study C117].).
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Svensson EM,Dooley KE,Karlsson MOdoi
10.1128/AAC.03246-14subject
Has Abstractpub_date
2014-11-01 00:00:00pages
6406-12issue
11eissn
0066-4804issn
1098-6596pii
AAC.03246-14journal_volume
58pub_type
临床试验,杂志文章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::The recent escalation of occurrences of carbapenem-resistant Pseudomonas aeruginosa has been recognized globally and threatens to erode the widespread clinical utility of the carbapenem class of compounds for this prevalent health care-associated pathogen. Here, we compared the in vitro inhibitory activity of ceftazid...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究
doi:10.1128/AAC.00875-17
更新日期:2017-09-22 00:00:00
abstract::The role of Acinetobacter baumannii ATCC 17978 UmuDC homologs A1S_0636-A1S_0637, A1S_1174-A1S_1173, and A1S_1389 (UmuDAb) in antibiotic resistance acquired through UV-induced mutagenesis was evaluated. Neither the growth rate nor the UV-related survival of any of the three mutants was significantly different from that...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02346-13
更新日期:2014-01-01 00:00:00
abstract::Delafloxacin, an investigational anionic fluoroquinolone, is active against a broad range of Gram-positive and Gram-negative bacteria. In this study, 200 Streptococcus pneumoniae (plus 30 levofloxacin-resistant isolates), 200 Haemophilus influenzae, and 100 Moraxella catarrhalis isolates selected primarily from the Un...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00941-16
更新日期:2016-09-23 00:00:00
abstract::Acanthamoeba keratitis is a severe ocular infection secondary to accidental macro- or microscopic trauma of the cornea. Starting in 1985, a dramatic increase of this infection was recorded along with the spread of contact lens use. This protozoal disease is difficult to treat because of the scarcity of efficacious top...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.9.2232
更新日期:1998-09-01 00:00:00
abstract::The antibiotic bleomycin stimulates deoxyribonucleic acid (DNA) synthesis in toluene-treated Escherichia coli cells. The increase in synthesis is linear with bleomycin concentration. Bleomycin-stimulated DNA synthesis is independent of replication and dependent on DNA polymerase I. Replication is spared as the DNA pol...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.2.239
更新日期:1976-02-01 00:00:00
abstract::The most appropriate vancomycin dosing strategy in pediatric patients weighing ≥70 kg (weight based versus non-weight based) to achieve an area under the concentration-time curve (AUC) of ≥400 mg·liter/h and a trough concentration of <20 mg/liter is not known. Population pharmacokinetic analysis determined that dosing...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02359-18
更新日期:2019-03-27 00:00:00
abstract::Against 307 pneumococci of various resistotypes, dalbavancin MICs were 0.008 to 0.125 microg/ml. All strains were susceptible to vancomycin, teicoplanin, linezolid, and quinupristin-dalfopristin. Dalbavancin at 2x MIC was bactericidal against all 10 pneumococci tested after 24 h. Vancomycin and teicoplanin killed 10 a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.12.5182-5184.2005
更新日期:2005-12-01 00:00:00
abstract::Bisbenzamidines, such as pentamidine isethionate, are aromatic dicationic compounds that are active against Pneumocystis and other microbes but are oftentimes toxic to the host. To identify potential anti-Pneumocystis agents, we synthesized bisbenzamidine derivatives in which the parent compound pentamidine was modifi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00126-06
更新日期:2006-07-01 00:00:00
abstract::The purpose of this work was to evaluate the in vitro possibilities of ampicillin-ceftriaxone combinations for 10 Enterococcus faecalis strains with high-level resistance to aminoglycosides (HLRAg) and to assess the efficacy of ampicillin plus ceftriaxone, both administered with humanlike pharmacokinetics, for the tre...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.3.639
更新日期:1999-03-01 00:00:00
abstract::Viridin B, a bacteriocin produced by Streptococcus mitis, copurified with the alpha-hemolysin after ammonium sulfate precipitation and gel filtration on Sephadex G-200. The bacteriocin and hemolysin were separated in some instances by ion-exchange chromatography on diethylaminoethyl-Sephadex A-50, but the two substanc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.15.3.436
更新日期:1979-03-01 00:00:00
abstract::Therapy with nucleoside reverse transcriptase inhibitors (NRTIs) can be associated with mitochondrial toxicity. In vitro studies have been used to predict the predisposition for and characterize the mechanisms causing mitochondrial toxicity. Entecavir (ETV) is an approved deoxyguanosine nucleoside for the treatment of...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01122-07
更新日期:2008-02-01 00:00:00
abstract::Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor with negligible urinary excretion. We assessed the pharmacokinetics and safety of a single oral dose of faldaprevir (480 mg) in 32 HCV-negative subjects with renal impairment or normal renal function. Compared with subjects with normal renal fun...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.03359-14
更新日期:2015-01-01 00:00:00
abstract::Aminoglycoside acetyltransferase was detected in Mycobacterium kansasii and M. fortuitum but not in M. avium-M. intracellulare when they were screened by a radioassay. Aminoglycoside phosphotransferase and nucleotidyltransferase activities were absent from all three species tested. Acetyltransferases from both M. kans...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.1.39-42.2000
更新日期:2000-01-01 00:00:00
abstract::The vesicular stomatitis virus cytopathic effect reduction assay is suitable to quantify polyethylene glycol-alpha interferon 2a (PEG-IFN-alpha 2a) and PEG-IFN-alpha 2b. Human serum and ribavirin did not interfere with the assay. This bioassay was successfully used for assaying PEG-IFN-alpha 2a and PEG-IFN-alpha 2b in...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.9.3610-3612.2004
更新日期:2004-09-01 00:00:00
abstract::Doravirine is a novel nonnucleoside reverse transcriptase inhibitor in development for use with other antiretroviral therapies to treat human immunodeficiency virus type 1 (HIV-1) infection. Doravirine metabolism predominantly occurs via cytochrome P450 3A with <10% of elimination occurring via the renal pathway. As s...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.00326-18
更新日期:2018-07-27 00:00:00
abstract::We have studied the interference of roxithromycin with NADPH oxidase, the key enzymatic system for oxidant production by human neutrophils. Roxithromycin alters the reconstitution of an active enzyme and impairs the translocation to the outer membrane of the cytosolic components p47-phox and p67-phox. Interestingly, i...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.7.2986-2989.2005
更新日期:2005-07-01 00:00:00
abstract::Enterococci are intrinsically resistant to low levels of aminoglycosides. We previously selected in vitro and in vivo Enterococcus faecalis with intermediate-level resistance to gentamicin that did not abolish synergism with a cell-wall-active agent (E. Aslangul et al., Antimicrob. Agents Chemother. 49:4144-4148, 2005...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00390-06
更新日期:2006-11-01 00:00:00
abstract::Four species of members of the family Enterobacteriaceae harboring extended-spectrum beta-lactamase (ESBL) were recovered in a single patient hospitalized in an intensive care unit. Among these isolates, we describe for the first time an ESBL-producing Providencia rettgeri strain. Bacteria from the same species were s...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.8.2069
更新日期:1999-08-01 00:00:00
abstract::Nosocomial pneumonia and sepsis, as well as severe diffuse peritonitis, must be treated early in order to prevent complications such as septic shock and organ dysfunctions. With the availability of new broad-spectrum and highly bactericidal antibiotics, the need of combining beta-lactams with aminoglycosides for the t...
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.38.6.1309
更新日期:1994-06-01 00:00:00
abstract::In response to the need for rapid, inexpensive, high-throughput assays for antimycobacterial drug screening, a microplate-based assay which uses Alamar blue reagent for determination of growth was evaluated. MICs of 30 antimicrobial agents against Mycobacterium tuberculosis H37Rv, M. tuberculosis H37Ra, and Mycobacter...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.5.1004
更新日期:1997-05-01 00:00:00
abstract::In vitro activity of tebipenem, a new oral carbapenem antibiotic, against clinical Haemophilus influenzae isolates was compared with those of 8 reference agents. Isolates were classified into 6 resistance classes after PCR identification of beta-lactamase genes and ftsI gene mutations. For all isolates, the minimal co...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00054-10
更新日期:2010-09-01 00:00:00
abstract::To test the hypothesis that establishing gastrointestinal colonization with multiresistant Enterococcus faecium (VRE) C68 results from expansion of the enterococcal population in the upper small bowel, we compared VRE quantities recovered from the proximal, middle, and distal segments of the small bowel from mice trea...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00125-06
更新日期:2006-09-01 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::Time-kill studies were used to examine the in vitro activities of penicillin G, RP 59500, erythromycin, ciprofloxacin, sparfloxacin, and vancomycin against 10 pneumococci expressing various degrees of susceptibility to penicillin and erythromycin. RP 59500 MICs for all strains were 0.5 to 2.0 micrograms/ml, while eryt...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.9.2065
更新日期:1994-09-01 00:00:00
abstract::Gentamicin was successfully incorporated into neutral, anionic, and cationic liposomes, and the percentage of gentamicin incorporated was found to be a function of lipid concentration. Gentamicin did not leak out of the liposomes over a 3-week period at 4 degrees C. When liposome-associated gentamicin was administered...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.17.4.544
更新日期:1980-04-01 00:00:00
abstract::The in vitro activity of ketolide HMR 3647 against coryneform bacteria isolated from clinical samples was evaluated. Except against Corynebacterium jeikeium and C. urealyticum, HMR 3647 showed high activity against Corynebacterium spp., being more active than 14- and 16-membered macrolides, azithromycin, or clindamyci...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.12.3290
更新日期:1998-12-01 00:00:00
abstract::A new SHV-derived extended-spectrum beta-lactamase (SHV-24) conferring high-level resistance to ceftazidime but not cefotaxime and cefazolin was identified in Japan. This enzyme was encoded by a transferable 150-kb plasmid from an Escherichia coli clinical isolate. The pI and K(m) for CAZ of this enzyme were 7.5 and 3...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.6.1725-1727.2000
更新日期:2000-06-01 00:00:00
abstract::Recent studies using laboratory clones have demonstrated that several antiretroviral protease inhibitors (PIs) inhibit the growth of Plasmodium falciparum at concentrations that may be of clinical significance, especially during human immunodeficiency virus type 1 (HIV-1) and malaria coinfection. Using clinical isolat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00169-08
更新日期:2008-07-01 00:00:00
abstract::In published studies, cohorts of patients with bacteremia due to vancomycin-resistant Enterococcus (VRE) have predominantly been infected with Enterococcus faecium. Little is known about the epidemiology and outcomes associated with bacteremia due to VR Enterococcus faecalis. A retrospective study of isolates obtained...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.06299-11
更新日期:2012-05-01 00:00:00