Proposed Pharmacokinetic-Pharmacodynamic Breakpoint of Garenoxacin and Other Quinolones.

The pharmacokinetic-pharmacodynamic (PK-PD) breakpoints (BPs) of garenoxacin (GRNX) and other oral quinolones were calculated using Monte Carlo simulation (MCS) based on the distribution of changes in their plasma concentrations. PK-PD BPs of 400 mg once a day (QD) of GRNX for the free area under the curve/minimum inhibitory concentration (fAUC/MIC) for 30 strains of Streptococcus pneumoniae and 100 strains of gram-negative bacteria (G [－]) were 0.5 and 0.125 µg/mL, respectively. PK-PD BPs of other quinolones for S. pneumoniae/G (－) were 1/0.25 µg/mL for levofloxacin (LVFX) 500 mg QD, 0.5/0.125 µg/mL for moxifloxacin (MFLX) 400 mg QD, 0.0625/0.0156 µg/mL for sitafloxacin (STFX) 50 mg twice a day (BID) (100 mg QD), and 0.125/0.0313 µg/mL for STFX 100 mg BID. We also investigated the hypothetical probability of target attainments (PTAs) of fAUC/MIC for community-acquired pneumonia (CAP) using MCS, in consideration of the isolation frequencies of the three main causative pathogens of CAP: S. pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. For hypothetical CAP in adults, PTA of fAUC/MIC was 100% with GRNX and MFLX, 96%-97% with STFX at 100 mg BID, 45%-46% with LVFX, and 53%-58% with STFX at 100 mg QD and 50 mg BID. Based on the PK-PD BP, GRNX showed higher fAUC/MIC than the other quinolones tested against the three main pathogens of respiratory infections.

[Antibiotic susceptibility of blood-borne Streptococcus pneumoniae and efficacy assessment of respiratory quinolones using Monte Carlo simulation].

We analyzed Streptococcus pneumoniae isolates from the bloodstream between April 2005 and February 2007. We analyzed isolates of 28 strains from medical facilities in Gifu prefecture to determine antibiotic susceptibility, genotype of penicillin-binding protein (PBP) genes and macrolide resistant genes. We also assessed the efficacy of respiratory quinolones using Monte Carlo simulation. Garenoxacin (GRNX) and moxifloxacin (MFLX) showed the lowest MIC90 value of 0.125 microg/mL, followed by MIC90 of imipenem (IPM) of 0.25 microg/mL and tosufloxacin (TFLX), MIC90 of meropenem (MEPM) and vancomycin (VCM) of 0.5 microg/mL. Twenty-two strains possessed at least one mutation in PBP-encoding genes pbp1a, pbp2x or pbp2b and seven strains possessed all three mutant alleles. Twenty-two strains possessed either of macrolide resistant genes ermB or mefA, and one strain possessed both. On efficacy assessment, we calculated the probability of target attainment for free-drug area under the curve (fAUC)/MIC ratio (fAUC/MIC). GRNX and MFLX showed a probability of 90% or more at fAUC/MIC of 30 and 125, each considered effective against Gram-positive bacteria and suppression of resistance development, furthermore, GRNX showed a probability of 89.7% at fAUC/MIC of 250.

Diversity and similarity of microbial communities in petroleum crude oils produced in Asia.

To understand microbial communities in petroleum crude oils, we precipitated DNA using high concentrations of 2,2,4-trimethylpentane (isooctane) and purified. Samples of DNA from five crude oils, (Middle East, 3; China, 1; and Japan, 1) were characterized based upon their 16S rRNA gene sequences after PCR amplification and the construction of clone libraries. We detected 48 eubacterial species, one cyanobacterium, and one archaeon in total. The microbial constituents were diverse in the DNA samples. Most of the bacteria affiliated with the sequences of the three oils from the Middle East comprised similar mesophilic species. Acinetobacter, Propionibacterium, Sphingobium and a Bacillales were common. In contrast, the bacterial communities in Japanese and Chinese samples were unique. Thermophilic Petrotoga-like bacteria (11%) and several anaerobic-thermophilic Clostridia- and Synergistetes-like bacteria (20%) were detected in the Chinese sample. Different thermophiles (12%) and Clostridia (2%) were detected in the Japanese sample.

Development of a novel biofilm continuous culture method for simultaneous assessment of architecture and gaseous metabolite production.

The way that gaseous metabolite production changes along with biofilm architecture development is poorly understood. To address this question, we developed a novel flow reactor biofilm culture method that allows for simultaneous assessment of gaseous metabolite production and architecture visualization. In this report, we establish the utility of this method using denitrification by Pseudomonas aeruginosa biofilms as a model system. Using this method, we were able to collect and analyze gaseous metabolites produced by denitrification and also visualize biofilm architecture in a nondestructive manner. Thus, we propose that this novel method is a powerful tool to investigate potential relationships between biofilm architecture and the gas-producing metabolic activity of biofilms, providing new insights into biofilm ecology.