Abstract:
:A number of compounds, as exemplified by verapamil and desipramine, have been shown to enhance the susceptibility of resistant malaria parasites to chloroquine. The mechanism by which these agents reverse resistance is still controversial but is though to involve alterations in drug transport causing an increase in steady-state drug concentrations. We have proposed that an alternative resistance mechanism may involve the metabolic deactivation of the drug in some resistant parasites via cytochrome P-450 mixed-function oxidases. If the hypothesis is true, it should be possible to alter drug susceptibility in malaria parasites by the use of agents known to inhibit or induce cytochrome P-450 activities. We have assessed the ability of known inhibitors of cytochrome P-450 enzymes (cimetidine, metyrapone, and alpha-naphthoflavone) to enhance chloroquine susceptibility in Plasmodium falciparum culture-adapted and wild-type isolates in vitro and P. berghei in vivo. In all three systems, the inhibitor cimetidine enhanced parasite susceptibility to chloroquine, and this increase in susceptibility was unrelated to changes in chloroquine steady-state concentrations in vitro or to alterations in host pharmacokinetics in vivo. Additionally, the cytochrome P-450 inducer phenobarbital produced slight decreases in P. falciparum drug susceptibility in vitro. We have compared the ability of the cytochrome P-450 inhibitors cimetidine and metyrapone to enhance drug susceptibility with that of verapamil by using wild-type malaria isolates obtained from Cameroon. Verapamil completely reversed resistance, i.e., to below the cutoff point of 70 nM, in all the resistant isolates. Cimetidine enhanced chloroquine susceptibility in 60% of the isolates and reduced 50% inhibitory concentrations by at least 43% in all the resistant isolates. The compounds tested had little or no effect on the 50% inhibitory concentrations for the susceptible isolates. The data support a possible role for detoxification in chloroquine resistance, and even in the absence of such a process we have observed apparent chemosensitization by agents whose common biological feature is the inhibition of cytochrome P-450 enzymes. Additionally, sensitization has been observed in wild-type isolates of P. falciparum obtained form immune residents of an area of endemicity as well as culture-adapted parasites.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Ndifor AM,Howells RE,Bray PG,Ngu JL,Ward SAdoi
10.1128/aac.37.6.1318subject
Has Abstractpub_date
1993-06-01 00:00:00pages
1318-23issue
6eissn
0066-4804issn
1098-6596journal_volume
37pub_type
杂志文章abstract::Optimal treatment options remain unknown for infective endocarditis (IE) caused by penicillin-resistant (PEN-R) viridans group streptococcal (VGS) strains. The aims of this study were to report two cases of highly PEN-R VGS IE, perform a literature review, and evaluate various antibiotic combinations in vitro and in v...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00516-19
更新日期:2019-07-25 00:00:00
abstract::Amoxicillin and ampicillin were compared at a dose of 250 mg twice daily for 4 weeks to treat Salmonella typhi or Salmonella paratyphi A chronic bacteriuria with intermittent bacteremia. Eleven patients received amoxicillin, and 15 received ampicillin. Concentrations of the two drugs were measured in the urine and ser...
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.20.5.630
更新日期:1981-11-01 00:00:00
abstract::The in vitro activity of cefazolin was assessed by continuous turbidimetric monitoring of cultures of gram-negative bacilli and the results were compared with those previously obtained with other beta-lactam agents using the same strains and methods. Cefazolin was found to induce rapid lysis of ampicillin-susceptible ...
journal_title:Antimicrobial agents and chemotherapy
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doi:10.1128/aac.7.2.191
更新日期:1975-02-01 00:00:00
abstract::Parasitic diseases are of enormous public health significance in developing countries-a situation compounded by the toxicity of and resistance to many current chemotherapeutics. We investigated a focused library of 18 structurally diverse bis-acridine compounds for in vitro bioactivity against seven protozoan and one ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01418-06
更新日期:2007-06-01 00:00:00
abstract::Butylated hydroxytoluene (BHT) is a potent inactivator of the enveloped bacterial virus ø6 at concentrations as low as 3 x 10(-5) M. The viral envelope is not removed by BHT treatment, in contrast to the effects of exposure to the detergent Triton X-100. BHT-treated viruses are morphologically indistinguishable from c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.10.1.96
更新日期:1976-07-01 00:00:00
abstract::Colistin is increasingly used as a salvage therapy for nosocomial infections caused by multidrug-resistant Gram-negative bacteria such as Pseudomonas aeruginosa and Acinetobacter baumannii. However, the available pharmacokinetic (PK) data for colistin are limited to guide dosing. The aim of this study was to develop a...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00271-13
更新日期:2013-05-01 00:00:00
abstract::A series of [(aryl)arylsufanylmethyl]pyridines (AASMP) have been synthesized. These compounds inhibited hemozoin formation, formed complexes (K(D) = 12 to 20 muM) with free heme (ferriprotoporphyrin IX) at a pH close to the pH of the parasite food vacuole, and exhibited antimalarial activity in vitro. The inhibition o...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00898-07
更新日期:2008-02-01 00:00:00
abstract::To study the antimalarial action of chloroquine, normal mouse erythrocytes were used as surrogates for erythrocytoid bodies. These bodies form in the endosomes of intraerythrocytic malaria parasites as they feed on their host and consist of erythrocyte cytoplasm enclosed in a vestige of the erythrocyte membrane. In su...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01652-05
更新日期:2006-07-01 00:00:00
abstract::The activity of cephradine and the influence of pH on its activity against 70 Gardnerella vaginalis strains were determined. Serial dilutions of cephradine (0.062 to 256 micrograms/ml) were incorporated into Dunkelberg agar, inoculated with a Steers replicator, incubated in 5% CO2 for 48 h, and examined. The minimal i...
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pub_type: 杂志文章
doi:10.1128/aac.24.3.418
更新日期:1983-09-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.35.6.1235
更新日期:1991-06-01 00:00:00
abstract::Penicillin-binding protein 5 (PBP5) is one of the most abundant PBPs in Pseudomonas aeruginosa. Although its main function is that of a cell wall dd-carboxypeptidase, it possesses sufficient β-lactamase activity to contribute to the ability of P. aeruginosa to resist the antibiotic activity of the β-lactams. The study...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00505-13
更新日期:2013-07-01 00:00:00
abstract::The free ligand, deferroviridomycin A, and its iron(II) complex, viridomycin A, were detected in culture supernatant fluids of Streptomyces viridans 1671 and were structurally characterized as 4-hydroxy-3-nitrosobenzaldehyde and tris(4-hydroxy-3-nitrosobenzaldehydato-N3,O4)ferrate(II), respectively. We investigated th...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.20.4.558
更新日期:1981-10-01 00:00:00
abstract::We tested the hypothesis that the bacterial load at the infection site could impact considerably on the pharmacokinetic/pharmacodynamic (PK/PD) parameters of fluoroquinolones. Using a rat lung infection model, we measured the influence of different marbofloxacin dosage regimens on selection of resistant bacteria after...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00608-09
更新日期:2009-11-01 00:00:00
abstract::Acute otitis media, a polymicrobial disease of the middle ear cavity of children, is a significant public health problem worldwide. It is most frequently caused by encapsulated Streptococcus pneumoniae and nontypeable Haemophilus influenzae, although the widespread use of pneumococcal conjugate vaccines is apparently ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.01992-16
更新日期:2017-01-24 00:00:00
abstract::The influence of vancomycin and flavophospholipol (FPL) on the transfer rate of conjugative plasmids harboring the vancomycin resistance operon vanA was determined in several clinical and animal isolates of Enterococcus faecium. FPL significantly inhibited the frequency of transfer of conjugative VanA plasmids up to 7...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.44.11.3189-3192.2000
更新日期:2000-11-01 00:00:00
abstract::In 1989 and 1990, a large number of ampicillin-resistant strains of Enterococcus faecium were isolated from infected patients treated at intensive care units in Berlin, Germany. Twenty-five clinical isolates, including five different biotypes as classified by acid production from various sugars and a wide range of sus...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.4.783
更新日期:1992-04-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02624-12
更新日期:2013-06-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.4.4.383
更新日期:1973-10-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.4.962
更新日期:1996-04-01 00:00:00
abstract::Analysis of the evolution of drug target genes under changing drug policy is needed to assist monitoring of Plasmodium falciparum drug resistance in the field. Here we genotype Pfcrt and Pfdmr1 of 700 isolates collected in French Guiana from 2000 (5 years after withdrawal of chloroquine) to 2008, i.e., the period when...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.05280-11
更新日期:2012-03-01 00:00:00
abstract::Resistance of Streptococcus pneumoniae to fluoroquinolones is caused predominantly by amino acid substitutions at positions Ser79 of ParC and Ser81 of GyrA to either Phe or Tyr encoded in the quinolone resistance-determining regions of the parC topoisomerase IV and gyrA DNA gyrase genes. Analysis of highly resistant c...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.49.6.2479-2486.2005
更新日期:2005-06-01 00:00:00
abstract::Clinical treatment failures have been reported to occur in early Lyme borreliosis (LB) for many suitable antimicrobial agents. Investigations of possible resistance mechanisms of the Borrelia burgdorferi complex must analyze clinical isolates obtained from LB patients, despite their receiving antibiotic treatment. Her...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
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更新日期:2005-04-01 00:00:00
abstract::This analysis of nearly 10,000 hospital-associated urinary tract infection (UTI) episodes due to Escherichia coli showed that fluoroquinolone and third-generation-cephalosporin resistance rates were 34.5% and 8.6%, respectively; the rate of concurrent resistance to both agents was 7.3%. Fluoroquinolone resistance rate...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.02505-15
更新日期:2016-04-22 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:2017-07-25 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.36.7.1573
更新日期:1992-07-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.39.1.107
更新日期:1995-01-01 00:00:00
abstract::In enterobacteria, the ampG gene encodes a transmembrane protein (permease) that transports 1,6-GlcNAc-anhydro-MurNAc and the 1,6-GlcNAc-anhydro-MurNAc peptide from the periplasm to the cytoplasm, which serve as signal molecules for the induction of ampC β-lactamase. The role of AmpG as a transporter is also essential...
journal_title:Antimicrobial agents and chemotherapy
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更新日期:2010-11-01 00:00:00
abstract::To date, the majority of pharmacokinetic/pharmacodynamic (PK/PD) discussions have focused on PK/PD relationships evaluated at steady-state drug concentrations. However, a concern with reliance upon steady-state drug concentrations is that it ignores events occurring while the pathogen is exposed to intermittent subopt...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,评审
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更新日期:2012-06-01 00:00:00