RESUMEN
An SAR study of a screening lead has led to the identification of 2,9-disubstituted 1,2,3,4-tetrahydropyrido[3,4-b]indoles as inhibitors of Staphylococcus aureus enoyl acyl carrier protein reductase (FabI).
Asunto(s)
Antibacterianos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Oxidorreductasas/antagonistas & inhibidores , Antibacterianos/química , Enoil-ACP Reductasa (NADH) , Escherichia coli/efectos de los fármacos , Proteínas de Escherichia coli , Acido Graso Sintasa Tipo II , Concentración 50 Inhibidora , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad , Triclosán/farmacologíaRESUMEN
1,4-Disubstituted imidazole inhibitors of Staphylococcus aureus and Escherichia coli enoyl acyl carrier protein reductase (FabI) have been identified. Crystal structure data shows the inhibitor 1 bound in the enzyme active site of E. coli FabI.
Asunto(s)
Antibacterianos/farmacología , Imidazoles/farmacología , Oxidorreductasas/antagonistas & inhibidores , Antibacterianos/síntesis química , Antibacterianos/química , Enoil-ACP Reductasa (NADH) , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Escherichia coli/efectos de los fármacos , Proteínas de Escherichia coli , Acido Graso Sintasa Tipo II , Imidazoles/síntesis química , Imidazoles/química , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacosRESUMEN
Although the Vitek and MicroScan Walkaway are two of the most commonly used automated antimicrobial susceptibility test systems, few studies have been performed comparing discrepancies between these systems. In this study, 500 Gram negative clinical isolates were tested against ampicillin, ampicillin/sulbactam, ticarcillin, ticarcillin/clavulanate, imipenem, ciprofloxacin, norfloxacin, mezlocillin, and piperacillin to determine the number of major interpretation discrepancies between the two systems. The 500 isolates consisted of 100 isolates each of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis and Enterobacter species. Each isolate was tested simultaneously in both systems using the same standardized inoculum. Eighty-four major discrepancies occurred, of which 48 were reproducible. The reproducible discrepancy rate, for the 4,500 isolate/antimicrobic combinations tested, was 48 of 4500 (1.06%). The rate for individual antimicrobics varied from 17 of 500 (3.4%) for ampicillin to no discrepancies for ticarcillin or ciprofloxacin. Of the 48 reproducible discrepancies, 44 (92%) were Vitek resistant, MicroScan susceptible. Fifteen (31%) of the Vitek and 21 (44%) of the MicroScan results were confirmed by broth microdilution. Disk diffusion results were in agreement with 15 (31%) of the Vitek and 21 (44%) of the MicroScan results. Twelve (25%) of the broth microdilution and 12 (25%) of the disk diffusion results were intermediate. The broth microdilution and disk diffusion results for the 48 isolates with reproducible discrepancies were in agreement more often with MicroScan. However, there was less very major error comparing the Vitek results for these isolates to the broth microdilution and disk diffusion. Overall, the result of this evaluation indicate that the number of major interpretation discrepancies between the two systems is minimal for the isolate/antimicrobic combinations tested.
Asunto(s)
Pruebas de Sensibilidad Microbiana/métodos , Ampicilina/farmacología , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Ciprofloxacina/farmacología , Ácido Clavulánico , Ácidos Clavulánicos/farmacología , Enterobacter/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Imipenem/farmacología , Klebsiella pneumoniae/efectos de los fármacos , Mezlocilina/farmacología , Norfloxacino/farmacología , Penicilinas/farmacología , Piperacilina/farmacología , Proteus mirabilis/efectos de los fármacos , Pseudomonas aeruginosa/efectos de los fármacos , Control de Calidad , Reproducibilidad de los Resultados , Sulbactam , Tienamicinas/farmacología , Ticarcilina/farmacologíaRESUMEN
Previous studies have reported that 15%-34% of Haemophilus influenzae produce beta-lactamase. A surveillance program was developed by SmithKline Beecham Clinical Laboratories to determine the current percentage of beta-lactamase-producing H. influenzae from five selected geographic locations in the United States. In 1993, results of 5750 isolates from specimens submitted to five reference clinical laboratories were evaluated. Data were collected from 29 states and the District of Columbia. The percentages of beta-lactamase-producing H. influenzae was 33% and ranged from 22%-40% for the individual states.
Asunto(s)
Infecciones por Haemophilus/microbiología , Haemophilus influenzae/enzimología , beta-Lactamasas/biosíntesis , Adolescente , Adulto , Anciano , Niño , Preescolar , Intervalos de Confianza , Infecciones por Haemophilus/epidemiología , Humanos , Lactante , Persona de Mediana Edad , Epidemiología Molecular , Estados Unidos/epidemiologíaRESUMEN
Susceptibilities of 414 nasal and 586 nonnasal Staphylococcus aureus isolates, both methicillin resistant and methicillin susceptible, to the topical antimicrobial agent mupirocin were compared. A susceptibility of 99.1% was observed for the 1000 isolates. Nasal and nonnasal isolates showed a similar 90% minimum inhibitory concentration (MIC90) and statistically equivalent percent susceptibilities.
Asunto(s)
Mupirocina/farmacología , Nariz/microbiología , Staphylococcus aureus/efectos de los fármacos , Humanos , Resistencia a la Meticilina , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
This study evaluated the susceptibility of 123 Xanthomonas maltophilia strains to ticarcillin, ticarcillin-clavulanate, ampicillin, amoxicillin-clavulanate, ampicillin-sulbactam, piperacillin, piperacillin-tazobactam, imipenem, and ciprofloxacin by Kirby-Bauer disk, E test, and Sensititre dehydrated microdilution MIC and conventional agar dilution MIC methodology. Intermediate susceptibility breakpoints for members of the family Enterobacteriaceae were used. When results were analyzed as MICs for 50 and 90% of the strains tested and percentages of strains susceptible at the breakpoint, good correlation between the methods was observed, with ticarcillin-clavulanate clearly the most active beta-lactam by all four methods. However, when the various methods were compared with the agar dilution methodology by regression analysis, poor r2 values (0.3 to 0.7) were obtained for compounds with sufficient on-scale values to permit analysis. When the number of strains with log2 ratios of reference agar dilution MICs to test MICs of +3 to -3 were analyzed, correlation was also poor, with many major and very major discrepancies for all methods tested. Results obtained with time-kill studies of nine strains with discrepant ticarcillin-clavulanate MICs appeared to correlate best when compared at 24 h with agar dilution MICs. The concentration of ticarcillin-clavulanate required to reduce the colony count by > or = 2 log10 reduction values for eight of nine strains compared with that for growth controls was < or = 16.0/2.0 micrograms/ml at 6 h and ranged from 16.0/2.0 micrograms/ml to 128.0/2.0 micrograms/ml at 24 h. The susceptibility method of choice for X. maltophilia has not yet been standardized, but time-kill studies correlated best with agar dilution MICs.
Asunto(s)
Antibacterianos/farmacología , Ciprofloxacina/farmacología , Pruebas de Sensibilidad Microbiana/métodos , Xanthomonas/efectos de los fármacos , Inhibidores de beta-Lactamasas , Farmacorresistencia Microbiana , beta-LactamasRESUMEN
Determining a single MIC of an antimicrobial agent that is not included on a routine susceptibility panel can be significantly time-consuming and costly. The UniScept MICRO-MIC, the JustOne, and the E test are single-MIC systems. These systems as well as disk diffusion were compared on the bases of time, cost, and ease of use.