title: [Antibacterial activities and PK/PD parameters of aminoglycosides against recent clinical isolates of gram-negative rods].
abstract: We examined antibacterial activities and PK/PD parameters of six kinds of aminoglycosides against seven bacterial species of clinical isolates in 2001. Aminoglycoseides examined were gentamicin (GM), dibekacin (DKB), tobramycin (TOB), amikacin (AMK), netilmicin (NTL), and isepamicin (ISP), and bacterial isolates used were each 50 strains of Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Proteus spp., Serratia marcescens and Pseudomonas aeruginosa. All aminoglycosides showed good activities with low MICs against 6 species of Enterobacteriacea except S. marcescens. Eight strains (3.2%) among them were resistant to one or more aminoglycosides. Resistance to multiple aminoglycosides were detected in 16 strains (32%) of S. marcescens, among which 13 strains were resistant to AMK but susceptible to ISP. Three (6%) strains of P. aeruginosa were resistant to multiple drugs, one of which was resistant to all six aminoglycosides, and others were moderately susceptible to AMK and ISP, and susceptible to GM, AMK and ISP. Using a ratio of peak serum concentration to MIC90 (Cmax/MIC90) or a ratio of area under the curve to MIC90 (AUC/MIC90) as a pharmacokinetic and pharmacodynamic (PK/PD) parameter, we estimated the efficacy of the drug. An excellent effect of ISP, which was injected intramuscularly or intravenously at a dose of 400 mg, was expected for strains of Enterobacteriacea except S. marcescens. The Cmax/MIC90 ratios for S. marcescens were comparably higher in GM and ISP and that for P. aeruginosa were rather high in TOB when compared to other aminoglycosides. Another PK/PD parameter, AUC/MIC90 ratio, was high enough in NTL and ISP for Enterobacteriacea, suggesting good efficacy of these drugs. The (AUC/MIC90) ratios for S. marcescens were comparably high in GM and ISP, and that for P. aeruginosa were high in TOB, DKB, and ISP.
authors.affiliation: Laboratory of Drug Resistance in Bacteria, Gunma University School of Medicine.
authors.forename: Toyoji
authors.initials: T
authors.lastname: Okubo
authors.forename: Shizuko
authors.initials: S
authors.lastname: Iyobe
mesh_terms: D000583:Amikacin / Q000493:pharmacokinetics / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000494:pharmacology*; D003982:Dibekacin / Q000493:pharmacokinetics / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D005839:Gentamicins / Q000493:pharmacokinetics / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D009428:Netilmicin / Q000493:pharmacokinetics / Q000494:pharmacology; D014031:Tobramycin / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins; D003982:Dibekacin; D009428:Netilmicin; D000583:Amikacin; C016927:isepamicin; D014031:Tobramycin