Abstract:
:We report the ultrastructural alterations induced during the proliferative stages of Trypanosoma (Schizotrypanum) cruzi, the causative agent of Chagas' disease, by two ergosterol biosynthesis inhibitors, ketoconazole and terbinafine, which had previously been shown to be potent growth inhibitors whose effects are potentiated when used in combination (J. A. Urbina, K. Lazardi, T. Aguirre, M. M. Piras, and R. Piras, Antimicrob. Agents Chemother. 32:1237-1242, 1988). Epimastigotes treated with a low concentration of ketoconazole (1 microM), which blocks ergosterol biosynthesis at the level of C-14 demethylation of lanosterol and induces cell lysis coincident with total ergosterol depletion, showed gross alterations of the kinetoplast-mitochondrion complex, which swelled and lost the organization of its inner membrane and the electron-dense bodies of its matrix. Thus, coincident with the beginning of cell lysis, the kinetoplast-mitochondrion complex occupied greater than 80% of the cell volume, while other subcellular structures such as the nucleus and subpellicular microtubules were not affected. Terbinafine, which blocks ergosterol synthesis in these cells at the level of squalene synthetase and thus leads to almost immediate arrest of growth at concentrations greater than 1 microM, produced proliferation of glycosomelike bodies, binucleated cells (arrest at cytokinesis), and eventually massive vacuolization. When the drugs were combined, the predominant effect was mitochondrial swelling, which was more drastic and took place earlier than that observed in cells treated with ketoconazole alone. In amastigotes proliferating in Vero cells, ketoconazole at the concentration required to eradicate the parasites (10 nM) produced mitochondrial swelling, the appearance of autophagic vacuoles containing partially degraded subcellular material, and finally a general breakdown of the subcellular structures. Terbinafine at 3 microM induced more limited ultrastructural damage to the amastigotes consistent with increased vacuolization of the cells and the appearance of occasional autophagic vacuoles. When the drugs were used in combination, just 1 nM was required for the total eradication of parasites, the ultrastructural effects were more extensive, and cell disintegration occurred earlier than when any of the drugs was used alone at a much higher concentration. No effect of the drugs on the ultrastructure of the host cells were observed at any of the concentrations tested.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Lazardi K,Urbina JA,de Souza Wdoi
10.1128/aac.34.11.2097subject
Has Abstractpub_date
1990-11-01 00:00:00pages
2097-105issue
11eissn
0066-4804issn
1098-6596journal_volume
34pub_type
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::KBP-7072 is a novel aminomethylcycline antibiotic in clinical development for community-acquired pneumonia. The goal of present studies was to determine which pharmacokinetic/pharmacodynamic (PK/PD) parameter magnitude correlated with efficacy in the murine pneumonia infection model against Staphylococcus aureus and S...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02404-18
更新日期:2019-02-26 00:00:00
abstract::Leptospirosis and scrub typhus are important causes of acute fever in Southeast Asia. Options for empirical therapy include doxycycline and azithromycin, but it is unclear whether their efficacies are equivalent. We conducted a multicenter, open, randomized controlled trial with adult patients presenting with acute fe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1128/AAC.00508-07
更新日期:2007-09-01 00:00:00
abstract::Anidulafungin concentrations were quantified with high-pressure liquid chromatography (HPLC) and UV detection of the ascites fluid and pleural effusion of 10 adult critically ill patients. Samples were collected from ascites fluid and from pleural drains or during paracentesis and thoracentesis, respectively. Anidulaf...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02326-17
更新日期:2018-03-27 00:00:00
abstract::We studied polymyxin B resistance in 10 pairs of clinical Acinetobacter baumannii isolates, two of which had developed polymyxin B resistance in vivo. All polymyxin B-resistant isolates had lower growth rates than and substitution mutations in the lpx or pmrB gene compared to their parent isolates. There were signific...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/AAC.01884-15
更新日期:2015-12-01 00:00:00
abstract::Cefamandole has a broader spectrum and greater potency than the other cephalosporins. It includes Haemophilus influenzae, most strains of Enterobacter, and many strains of indole-positive Proteus and Bacteroides, with a lower minimal inhibitory concentration for Escherichia coli, Klebsiella, etc. Concentrations of dru...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/aac.10.5.814
更新日期:1976-11-01 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::Following a veterinary and behavioral survey of chimpanzees from a natural population in Uganda, leaf samples of Trichilia rubescens were collected because of the unusual method of ingestion observed. The methanolic crude extract of T. rubescens leaves exhibited significant antimalarial activity in vitro. Bioassay-dir...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.8.3196-3199.2004
更新日期:2004-08-01 00:00:00
abstract::Despite being genetically monomorphic, the limited genetic diversity within the Mycobacterium tuberculosis complex (MTBC) has practical consequences for molecular methods for drug susceptibility testing and for the use of current antibiotics and those in clinical trials. It renders some representatives of MTBC intrins...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,评审
doi:10.1128/AAC.01641-12
更新日期:2012-12-01 00:00:00
abstract::Aspergillus flavus is the second most significant pathogenic cause of invasive aspergillosis; however, its emergence risks and mechanisms of voriconazole (VRC) resistance have not yet been elucidated in detail. Here, we demonstrate that repeated exposure of A. flavus to subinhibitory concentrations of VRC in vitro cau...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01216-18
更新日期:2018-10-24 00:00:00
abstract::In this study, we investigated the in vitro activity of SCH-56592 (SCH), a new triazole antifungal agent. We compared the activity of SCH with those of itraconazole (ITZ) and amphotericin B (AB) against 60 clinical isolates of Aspergillus spp. by using a microtiter format. Incubation was done at 37 degrees C for 48 h,...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.5.1124
更新日期:1997-05-01 00:00:00
abstract::Novel antibiotics approved by noninferiority trials may become less effective over time in two scenarios: (i) the treatment effect in studies of novel antibiotics may be consistently worse than studies of older antibiotics; (ii) when a decreasingly effective control arm is used in a series of noninferiority trials. Ou...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01597-20
更新日期:2020-10-20 00:00:00
abstract::The pyrazinamide (PZA) analog 5-chloropyrazinamide (5-Cl PZA) is active against mycobacterial species, including PZA-resistant strains of Mycobacterium tuberculosis. In M. smegmatis, overexpression of the type 1 fatty acid synthase (FAS I) confers resistance to 5-Cl PZA, a potent FAS I inhibitor. Since M. tuberculosis...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00529-10
更新日期:2010-12-01 00:00:00
abstract::A nationwide susceptibility survey of the Bacteroides fragilis group was continued at New England Medical Center in 1983. A total of 555 strains were obtained from eight centers in the United States. In addition to the nine antimicrobial agents studied in the two previous years, three other agents were added to the ev...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.5.675
更新日期:1985-11-01 00:00:00
abstract::ABT-492 is a novel quinolone with potent activity against gram-positive, gram-negative, and atypical pathogens, making this compound an ideal candidate for the treatment of community-acquired pneumonia. We therefore compared the in vitro pharmacodynamic activity of ABT-492 to that of levofloxacin, an antibiotic common...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.48.1.203-208.2004
更新日期:2004-01-01 00:00:00
abstract::A sequential therapy of caspofungin (CAS) and fluconazole (FLC) administration for treatment of Candida albicans infection was investigated. Treatment with CAS followed by FLC was as effective as CAS treatment given alone for the same duration. Our data suggest that switching from CAS to FLC is a potentially explorabl...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.10.4056-4058.2004
更新日期:2004-10-01 00:00:00
abstract::The effect of protein binding on the activity of teicoplanin against Staphylococcus aureus was evaluated. Bactericidal rates of teicoplanin in cation-supplemented Mueller-Hinton broth (SMHB) and in a 1:1 mixture of pooled human serum and cation-supplemented Mueller-Hinton broth (PHS-SMHB) were compared with those of v...
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.35.6.1089
更新日期:1991-06-01 00:00:00
abstract::The antibacterial activities of K-4619 (3-de-O-methylsporaricin A sulfate) were compared with those of sporaricin A, amikacin, dibekacin, and gentamicin. K-4619 exhibited a high order of activity against gram-positive and gram-negative bacteria, including Pseudomonas aeruginosa. Its activity against Providencia specie...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.2.187
更新日期:1984-08-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04727-14
更新日期:2015-04-01 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::Blastocystis is an enteric parasite with extensive global prevalence. Studies have linked infection with this protist with a variety of gastrointestinal disorders, including irritable bowel syndrome. Due to the polymorphic nature of Blastocystis, studies on the parasite could be complicated, as results can be easily m...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00208-18
更新日期:2018-07-27 00:00:00
abstract::Staphylococci are the leading cause of hospital-acquired infections worldwide. Increasingly, they resist antibiotic treatment owing to the development of multiple antibiotic resistance mechanisms in most strains. Therefore, the activity and efficacy of recombinant lysostaphin as a drug against this pathogen have been ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01422-13
更新日期:2014-01-01 00:00:00
abstract::Mice infected with Plasmodium berghei served as donors of erythrocytes with a high level of parasitemia for the study of ferriprotoporphyrin IX (FP) polymerization. Six hours after treatment of these mice with 3 micromol of chloroquine per 25 g of body weight, there were significant losses of heme polymerase I (HPA I)...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.11.2461
更新日期:1997-11-01 00:00:00
abstract::Chagas disease is a parasitic infection that leads to a significant public health problem in countries where the disease is endemic and where it is nonendemic. Benznidazole is the most commonly used drug for the etiological treatment of Chagas disease. Patients treated with benznidazole suffer frequent adverse drug re...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.04078-14
更新日期:2015-01-01 00:00:00
abstract::This is a substudy of a larger randomized controlled trial on HIV-infected Zambian children, which revealed that cotrimoxazole prophylaxis reduced morbidity and mortality despite a background of high cotrimoxazole resistance. The impact of cotrimoxazole on the carriage and antibiotic resistance of Streptococcus pneumo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,随机对照试验
doi:10.1128/AAC.01409-09
更新日期:2010-09-01 00:00:00
abstract::A penicillin beta-lactamase (PCase) was extracted from Pseudomonas aeruginosa Rms139(+) and purified by means of column chromatography. The isoelectric point of Rms139 PCase was 5.7 and its molecular weight was 22,500 +/- 1,000. The optimal pH for the hydrolysis of benzylpenicillin was 7.0 to 7.5 and the optimal tempe...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.9.1.55
更新日期:1976-01-01 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::We assessed cutaneous ethanol (ETOH) and isopropanol (ISOP) absorption after intensive (30 times per h) use of alcohol-based hand-rub solutions by healthcare workers (HCWs). ETOH was detectable in the breath of 6/20 HCWs (0.001 to 0.0025%) at 1 to 2 min postexposure and in the serum of 2/20 HCWs at 5 to 7 min postexpo...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01320-06
更新日期:2007-03-01 00:00:00
abstract::In concert with the development of novel beta-lactams and broad-spectrum cephalosporins, bacterially encoded beta-lactamases have evolved to accommodate the new agents. This study was designed to identify, at the sequence level, the genes responsible for the extended-spectrum-beta-lactamase (ESBL) phenotypes of Escher...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00883-08
更新日期:2009-02-01 00:00:00
abstract::Pharmacodynamic parameters have become increasingly important for the determination of the optimal dosing schedules of antibiotics. In this study, the postantibiotic effects (PAEs), the postantibiotic sub-MIC effects (PA SMEs), and the sub-MIC effects (SMEs) of roxithromycin, clarithromycin, and azithromycin on refere...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.1.221
更新日期:1995-01-01 00:00:00