Pharmacodynamics of moxifloxacin against a high inoculum of Escherichia coli in an in vitro infection model.

OBJECTIVES: Escherichia coli is the leading bacterial species implicated in intra-abdominal infections. In these infections a high bacterial burden with pre-existing resistant mutants are likely to be encountered and resistance could be amplified with suboptimal dosing. Our objective was to investigate the pharmacodynamics of moxifloxacin against a high inoculum of E. coli using an in vitro hollow fibre infection model (HFIM). METHODS: Three wild-type strains of E. coli (ATCC 25922, MG1655 and EC28044) were studied by exposing approximately 2 x 10(8) cfu/mL (20 mL) to escalating dosing regimens of moxifloxacin (ranging from 30 to 400 mg, once daily). Serial samples were obtained from HFIM over 120 h to enumerate the total and resistant subpopulation. Quinolone resistance-determining regions of gyrA and parC of resistant isolates were sequenced to confirm the mechanism of resistance. RESULTS: The pre-exposure MIC of the three wild-type strains was 0.0625 mg/L. Simulated moxifloxacin concentration profiles in HFIM were satisfactory (r(2) >or= 0.94). Placebo experiments revealed natural mutants, but no resistance amplification. Regrowth and resistance amplification was observed between 30 mg/day (AUC/MIC = 47) and 80 mg/day dose (AUC/MIC = 117). Sustained bacterial suppression was achieved at >or=120 mg/day dose (AUC/MIC = 180). Point mutations in gyrA (D87G or S83L) were detected in resistant isolates. CONCLUSIONS: Our results suggest that suboptimal dosing may facilitate resistance amplification in a high inoculum of E. coli. The clinical dose of moxifloxacin (400 mg/day) was adequate to suppress resistance development in three wild-type strains. Clinical relevance of these findings warrants further in vivo investigation.

Quantitative assessment of combination antimicrobial therapy against multidrug-resistant Acinetobacter baumannii.

Treatment of multidrug-resistant bacterial infections poses a therapeutic challenge to clinicians; combination therapy is often the only viable option for multidrug-resistant infections. A quantitative method was developed to assess the combined killing abilities of antimicrobial agents. Time-kill studies (TKS) were performed using a multidrug-resistant clinical isolate of Acinetobacter baumannii with escalating concentrations of cefepime (0 to 512 mg/liter), amikacin (0 to 256 mg/liter), and levofloxacin (0 to 64 mg/liter). The bacterial burden data in single and combined (two of the three agents with clinically achievable concentrations in serum) TKS at 24 h were mathematically modeled to provide an objective basis for comparing various antimicrobial agent combinations. Synergy and antagonism were defined as interaction indices of <1 and >1, respectively. A hollow-fiber infection model (HFIM) simulating various clinical (fluctuating concentrations over time) dosing exposures was used to selectively validate our quantitative assessment of the combined killing effect. Model fits in all single-agent TKS were satisfactory (r(2) > 0.97). An enhanced combined overall killing effect was seen in the cefepime-amikacin combination (interactive index, 0.698; 95% confidence interval [CI], 0.675 to 0.722) and the cefepime-levofloxacin combination (interactive index, 0.929; 95% CI, 0.903 to 0.956), but no significant difference in the combined overall killing effect for the levofloxacin-amikacin combination was observed (interactive index, 0.994; 95% CI, 0.982 to 1.005). These assessments were consistent with observations in HFIM validation studies. Our method could be used to objectively rank the combined killing activities of two antimicrobial agents when used together against a multidrug-resistant A. baumannii isolate. It may offer better insights into the effectiveness of various antimicrobial combinations and warrants further investigations.

Inorganic/organic mesoporous silica as a novel fiber coating of solid-phase microextraction.

Mesoporous materials were employed as fast, sensitive and efficient fiber coatings of solid-phase microextraction (SPME) for the first time. Three micrometer as-synthesized C(16)-MCM-41 particles were immobilized onto stainless steel wire with 100mum coating thickness. In combination with high performance liquid chromatography (HPLC), extraction efficiency and selectivity of C(16)-MCM-41 were investigated using aromatic hydrocarbons. Effect of extraction and desorption time, extraction temperature, stirring rate and ionic strength on extraction efficiency were examined. Aanalytical merits of SPME with C(16)-MCM-41 coating were evaluated. The chromatographic peak area is proportional to the concentration of anthracene in the range 0.5-150mugl(-1). The limit of detection was 0.05mugl(-1) (S/N=3) and the relative standard deviation (R.S.D.) was 0.033%.

[Comparative study of room-temperature phosphorescence of 1-bromonaphthalene induced by synergetic effect of nonionic surfactants and beta-cyclodextrin].

Room-temperature phosphorescence of 1-BrN induced by a combination of OPE-10 and Triton X-100 with beta-CD was comparatively studied. In terms of molecular size and dimensions of beta-CD, the octyl group and phenyl group of OPE-10 and Triton X-100 were incorporated into the cavity of beta-CD and the complexes with the stoichiometry of 1:1 were formed. The removal of water molecules inside the cavity results in a greater apolar interior. By enhanced hydrophobic interaction, the cavity occupied by OPE-10 and Triton X-100 is able to further capture another 1-BrN and form close packing 1:1:1 ternary inclusion complexes with apparent stability constant of 1.09 x 10(5) and 4.47 x 10(5) L2 x mol(-2), respectively. 1-BrN shows bright phosphorescence at room temperature due to the greater rigidity in the limited space and the favorable microenvironment shielding from external quenchers and quenching effect on the fluorescence of the phenyl group of OPE-10 and Triton X-100 within the same cavity. In the case of Triton X-100, the larger tert-octyl group better shields off external quenchers such as dissolved oxygen and iodide ion. Energy transfer from the excited phenyl group of Triton X-100 to adjacent 1-BrN acceptor was observed.

[Study of the acupuncture effect on monoamine transmitters in rabbit plasma and brain tissue by high performance liquid chromatography with electrochemical detection].

A rapid and simple method for the study of the acupuncture effect on monoamine transmitters and related compounds in rabbit plasma and brain tissue by high performance liquid chromatography with electrochemical detection was developed. An ODS column was selected as the separation column at 25 degrees C, and pH 4.50, 0.02 mol/L of trisodium citrate-0.05 mol/L sodium phosphate dibasic to methanol (95:5, volume ratio) without ion-pair at a flow rate of 1.0 mL/min. Four compounds, epinephrine (E), norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT), were simultaneously separated and determined under the above conditions. Twenty rabbits were investigated after the acupuncture action upon the central neurotransmitters. The sufficient data showed that acupuncture could significantly affect the activities of the neurotransmitters including E, NE, DA and 5-HT, and the changed functions of the neurotransmitter systems induced by acupuncture not only lead to the neurotransmitter content increase both in brain and plasma but also cause the increase of rabbit breed ability. The results show that the method is very simple and fast. The method is valuable not only for clinical diagnosis but also for research work.