Abstract:
:Implicated as a major mechanism of ethambutol (EMB) resistance in clinical studies of Mycobacterium tuberculosis, mutations in codon 306 of the embB gene (embB306) have also been detected in EMB-susceptible clinical isolates. Other studies have found strong associations between embB306 mutations and multidrug resistance, but not EMB resistance. We performed allelic exchange studies in EMB-susceptible and EMB-resistant clinical M. tuberculosis isolates to identify the role of embB306 mutations in any type of drug resistance. Replacing wild-type embB306 ATG from EMB-susceptible clinical M. tuberculosis strain 210 with embB306 ATA, ATC, CTG, or GTG increased the EMB MIC from 2 microg/ml to 7, 7, 8.5, and 14 microg/ml, respectively. Replacing embB306 ATC or GTG from two high-level EMB-resistant clinical strains with wild-type ATG lowered EMB MICs from 20 microg/ml or 28 microg/ml, respectively, to 3 microg/ml. All parental and isogenic mutant strains had identical isoniazid (INH) and rifampin (RIF) MICs. However, embB306 CTG mutants had growth advantages compared to strain 210 at sub-MICs of INH or RIF in monocultures and at sub-MICs of INH in competition assays. CTG mutants were also more resistant to the additive or synergistic activities of INH, RIF, or EMB used in different combinations. These results demonstrate that embB306 mutations cause an increase in the EMB MIC, a variable degree of EMB resistance, and are necessary but not sufficient for high-level EMB resistance. The unusual growth property of embB306 mutants in other antibiotics suggests that they may be amplified during treatment in humans and that a single mutation may affect antibiotic susceptibility against multiple first-line antibiotics.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Safi H,Sayers B,Hazbón MH,Alland Ddoi
10.1128/AAC.01486-07subject
Has Abstractpub_date
2008-06-01 00:00:00pages
2027-34issue
6eissn
0066-4804issn
1098-6596pii
AAC.01486-07journal_volume
52pub_type
杂志文章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::For six clinical isolates of Chlamydia trachomatis, in vitro susceptibility to erythromycin, azithromycin, and josamycin has been determined. Four isolates were resistant to all the antibiotics and had the mutations A2058C and T2611C (Escherichia coli numbering) in the 23S rRNA gene. All the isolates had mixed populat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.4.1347-1349.2004
更新日期:2004-04-01 00:00:00
abstract::In order to study the mechanism of insusceptibility of Spiroplasma citri to rifampin, we have cloned and sequenced its rpoB gene, which encodes the beta subunit of RNA polymerase. By comparison of the deduced amino acid sequence with sequences of beta subunits from susceptible and resistant bacteria, it was possible t...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.4.858
更新日期:1996-04-01 00:00:00
abstract::In a retrospective review of 24 patients with histoplasmosis, blastomycosis, or coccidioidomycosis treated with voriconazole (most for salvage therapy), the outcome was favorable (improved or stable) for 22 (95.8%) within 2 months of starting voriconazole and for 20 (83.3%) at the last follow-up. Prospective studies a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01148-07
更新日期:2009-04-01 00:00:00
abstract::An ampicillin-sulbactam combination was compared with ampicillin alone, chloramphenicol, clindamycin, and metronidazole against 272 strains of anaerobic bacteria. Chloramphenicol and ampicillin-sulbactam were the most effective, inhibiting 98 to 99% of strains tested at breakpoint (16 micrograms/ml). The combination o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.27.5.876
更新日期:1985-05-01 00:00:00
abstract::The purpose of this study was to assess the effect of voriconazole on the blood tacrolimus concentration in a liver transplant recipient and to examine the interaction between voriconazole and tacrolimus by using human liver microsomes. Two subjects were enrolled in the clinical study: one received voriconazole, and 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.46.9.3091-3093.2002
更新日期:2002-09-01 00:00:00
abstract::The influence of a mission hospital on the evolution of antibiotic resistance in coliform bacteria from a remote antibiotic-free Xhosa community and environment is described. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.10.3.567
更新日期:1976-09-01 00:00:00
abstract::Different mechanisms of erythromycin resistance predominate in group C and G streptococcus (GCS and GGS, respectively) isolates collected from 1992 to 1995 in Finland. Of the 21 erythromycin-resistant GCS and 32 erythromycin-resistant GGS isolates, 95% had the mefA or mefE drug efflux gene and 94% had the ermTR methyl...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.42.6.1493
更新日期:1998-06-01 00:00:00
abstract::Ceftizoxime was evaluated in the treatment of 18 patients (6 adults and 12 children) with bacterial meningitis. In seven patients Haemophilus influenzae was the causative agent, in three Neisseria meningitidis, in five Streptococcus pneumoniae, and in one each alpha-streptococcus and Escherichia coli; one case was cul...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.25.2.258
更新日期:1984-02-01 00:00:00
abstract::[14C]aztreonam was administered intramuscularly (50 mg/kg) to male and female rats. Groups of 10 rats (five male and five female) were sacrificed at 0.25, 2, 6, and 24 h after dosing. Blood and various tissues were removed from six rats (three male and three female) in each group for determination of total radioactivi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.2.127
更新日期:1984-08-01 00:00:00
abstract::Therapeutic treatment for systemic mycoses is severely hampered by the extremely limited number of antifungals. The difficulty of treatment of fungal infections in the central nervous system is further compounded by the poor central nervous system (CNS) penetration of most antifungals due to the blood-brain barrier. O...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00212-12
更新日期:2012-07-01 00:00:00
abstract::Viral entry inhibitors represent an emerging mode of therapy for human immunodeficiency virus type 1 (HIV-1) infection. PRO 542 (CD4-immunoglobulin G2) is a tetravalent CD4-immunoglobulin fusion protein that broadly neutralizes primary HIV-1 isolates. PRO 542 binds to the viral surface glycoprotein gp120 and blocks at...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.48.2.423-429.2004
更新日期:2004-02-01 00:00:00
abstract::Hepatitis C virus (HCV)-infected patients undergoing liver transplantation universally experience rapid reinfection of their new liver graft. Current treatment protocols do not prevent graft reinfection and, in addition, an accelerated disease progression is observed. In the present study, we have evaluated a novel st...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00633-11
更新日期:2011-11-01 00:00:00
abstract::The CcrA beta-lactamase from Bacteroides fragilis TAL3636 was cloned into Escherichia coli and purified from inclusion bodies. This group 3 metalloenzyme hydrolyzed most beta-lactam antibiotics, including cephamycins and carbapenems. Following inhibition by chelators, enzyme activity was recovered with the cations Zn2...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.5.1155
更新日期:1992-05-01 00:00:00
abstract::The efficacy of a new liposomal formulation of amphotericin B was compared to that of amphotericin B deoxycholate (Fungizone) in a murine model of visceral leishmaniasis induced by Leishmania infantum. Median effective doses (ED50) were determined with two different strains: strain 1 was obtained from an untreated pat...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.8.1731
更新日期:1997-08-01 00:00:00
abstract::Platelet-activating factor (PAF) is a potent endogenous proinflammatory mediator implicated in the pathogenesis of septic shock. A double-blind randomized placebo-controlled trial of an intravenous PAF receptor antagonist (lexipafant) was conducted with 131 adult Thai patients with suspected severe sepsis (66 of whom ...
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.44.3.693-696.2000
更新日期:2000-03-01 00:00:00
abstract::We evaluated the diffusion of pefloxacin into the cerebrospinal fluid (CSF) in 15 patients with bacterial meningitis or ventriculitis, 14 of whom were treated with other antibiotics. Three doses of pefloxacin were administered at 12-h intervals to 11 patients intravenously and to 4 patients orally. Individual doses we...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.3.289
更新日期:1984-09-01 00:00:00
abstract::In Escherichia coli the frequency of spontaneous single-step mutation to high levels of resistance to the newer 4-quinolone agent norfloxacin was confirmed to be over 300-fold lower than that to the older agent nalidixic acid. Serial passage on incremental concentrations of drug was necessary to produce mutants highly...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.29.4.639
更新日期:1986-04-01 00:00:00
abstract::Sixteen healthy male volunteers participated in a randomized, balanced, three-way crossover study comparing the pharmacokinetics of cefmetazole, cefoxitin, and cefmetazole with probenecid pretreatment. Single 2-g doses of cefmetazole sodium and cefoxitin sodium were given intravenously as a 5-min infusion. Concentrati...
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.33.3.356
更新日期:1989-03-01 00:00:00
abstract::Beta-l-2',3'-didehydro-2',3'-dideoxy-N(4)-hydroxycytidine (l-Hyd4C) was demonstrated to be an effective and highly selective inhibitor of hepatitis B virus (HBV) replication in HepG2.2.15 cells (50% effective dose [ED(50)] = 0.03 microM; 50% cytotoxic dose [CD(50)] = 2,500 microM). In the present study, we investigate...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01176-09
更新日期:2010-01-01 00:00:00
abstract::As drug resistance continues to grow, treatment strategies that turn resistance into a disadvantage for the organism will be increasingly relied upon to treat infections and to lower the rate of multidrug resistance. The majority of work in this area has investigated how resistance evolution toward a single antibiotic...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01273-20
更新日期:2020-12-16 00:00:00
abstract::Weak T-cell reactivity to hepatitis B virus (HBV) is thought to be the dominant cause for chronic HBV infection. Treatment with adefovir dipivoxil (ADV) increases the rate of HBV e antigen (HBeAg) loss; however, the immune mechanisms associated with this treatment response are not understood. Serial analysis of HBV-sp...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00467-07
更新日期:2008-01-01 00:00:00
abstract::The Michaelis-Menten inhibitory constants (Kis) and the concentrations required for 50% inhibition of the Plasmodium falciparum dihydropteroate synthetase were determined for six sulfa drugs. These drugs inhibited the in vitro growth of P. falciparum (50% lethal concentration) at concentrations of 30 to 500 nM; these ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.2.267
更新日期:1991-02-01 00:00:00
abstract::Clofazimine (CFZ) is a poorly soluble antibiotic and anti-inflammatory drug indicated for the treatment of leprosy. In spite of its therapeutic value, CFZ therapy is accompanied by the formation of drug biocrystals that accumulate within resident tissue macrophages, without obvious toxicological manifestations. Theref...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00265-16
更新日期:2016-05-23 00:00:00
abstract::Twenty-four children with cancer and localized herpes zoster were randomized to receive either topical polyinosinic acid-polycytidylic acid [poly(I:C)] or a saline placebo. Solutions containing 1.0 or 2.5 mg of drug per ml were applied to the lesions every 3 h, seven times a day for 7 consecutive days. Serial, standar...
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.8.3.289
更新日期:1975-09-01 00:00:00
abstract::The cytochrome P450 enzyme-encoding genes rosC and rosD were cloned from the rosamicin biosynthetic gene cluster of Micromonospora rosaria IFO13697. The functions of RosC and RosD were demonstrated by gene disruption and complementation with M. rosaria and bioconversion of rosamicin biosynthetic intermediates with Esc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02092-12
更新日期:2013-03-01 00:00:00
abstract::Rabbits with nutritionally variant viridans group streptococcal experimental endocarditis were treated three times daily for 3 days with procaine penicillin (1.2 X 10(6) U) alone or together with low-dose streptomycin (2 mg/kg), high-dose streptomycin (8 mg/kg), low-dose gentamicin (0.32 mg/kg), or high-dose gentamici...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.30.3.465
更新日期:1986-09-01 00:00:00
abstract::MUC7 12-mer-L exhibits potent in vitro antifungal activity in low-ionic-strength buffers. In this study, we investigated the anticandidal activity and stability of MUC7 12-mer-L and its all-D-amino-acid isomer, along with Hsn5 12-mer (P113) and magainin-II, in human clarified and unclarified saliva in the absence or p...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.6.2336-2342.2005
更新日期:2005-06-01 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::Susceptibilities of 121 clinical Helicobacter pylori strains to metronidazole were determined by both a 5-micrograms metronidazole disk diffusion test and a plate dilution method in duplicate and after different periods of incubation. The distribution of MICs of metronidazole against H. pylori among the strains was fo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.38.10.2357
更新日期:1994-10-01 00:00:00