Administration of lipid emulsion reduced the hypnotic potency of propofol more than that of thiamylal in mice.

Administration in a lipid emulsion can modify the pharmacodynamics of drugs via a process known as lipid resuscitation. However, the detailed mechanism remains unclear. We studied the volume and another pharmacodynamic effect, the lipid sink, using propofol and thiamylal. Male adult mice (ddY) were intravenously administered 10 ml/kg propofol or thiamylal diluted with physiological saline, 10% soybean oil, or 20% soybean oil. The 50% effective dose (ED50) for achieving hypnosis was calculated using probit analysis. To investigate the volume effect, 0, 10, or 20 ml/kg of saline or soybean oil was administered, either simultaneously or beforehand. Next, a two- or three-fold dose of the anesthetics was administered and the durations of anesthesia were measured. Finally, at 30 s after the first injection, supplemental soybean oil was administered. The mean (± SE) ED50 values of propofol and thiamylal were 5.79 mg/kg (0.61) and 8.83 mg/kg (0.84), respectively. Lipid dilution increased the ED50 values of both anesthetics. After injection of a dose two-fold the ED50 value, the respective mean (± SD) durations of anesthesia were 125 ± 35 s and 102 ± 38 s. Supplemental administration of soybean oil significantly shortened the duration of anesthesia of propofol, but not that of thiamylal. The results indicate that administration of a lipid emulsion vitiated the anesthetic effect of propofol by reducing the non-emulsified free fraction in the aqueous phase, which may elucidate the lipid resuscitation likely caused by the lipid sink mechanism.

In vitro reduction of antibacterial activity of tigecycline against multidrug-resistant Acinetobacter baumannii with host stress hormone norepinephrine.

The host stress hormone norepinephrine (NE), also called noradrenaline, is reported to augment bacterial growth and pathogenicity, but few studies have focused on the effect of NE on the activity of antimicrobials. The aim of this study was to clarify whether NE affects antimicrobial activity against multidrug-resistant Acinetobacter baumannii (MDR-AB). Time-kill studies of tigecycline (TIG) and colistin (COL) against MDR-AB as well as assays for factors contributing to antibiotic resistance were performed using MDR-AB clinical strains both in the presence and absence of 10 µM NE. In addition, expression of three efflux pump genes (adeB, adeJ and adeG) in the presence and absence of NE was analysed by quantitative reverse transcription PCR. Viable bacterial cell counts in TIG-supplemented medium containing NE were significantly increased compared with those in medium without NE. In contrast, NE had little influence on viable bacterial cell counts in the presence of COL. NE-supplemented medium resulted in an ca. 2 log increase in growth and in bacterial cell numbers adhering on polyurethane, silicone and polyvinylchloride surfaces. Amounts of biofilm in the presence of NE were ca. 3-fold higher than without NE. Expression of the adeG gene was upregulated 4-6-fold in the presence of NE. In conclusion, NE augmented factors contributing to antibiotic resistance and markedly reduced the in vitro antibacterial activity of TIG against MDR-AB. These findings suggest that NE treatment may contribute to the failure of TIG therapy in patients with MDR-AB infections.