Clinical impact and cost-consequence analysis of ePlex® blood culture identification panels for the rapid diagnosis of bloodstream infections: a single-center randomized controlled trial.

To assess clinical impact and perform cost-consequence analysis of the broadest multiplex PCR panels available for the rapid diagnosis of bloodstream infections (BSI). Single-center, randomized controlled trial conducted from June 2019 to February 2021 at a French University hospital with an institutional antimicrobial stewardship program. Primary endpoint was the percentage of patients with optimized antimicrobial treatment 12 h after transmission of positivity and Gram stain results from the first positive BC. This percentage was significantly higher in the multiplex PCR (mPCR) group (90/105 = 85.7% %, CI95% [77.5 ; 91.8] vs. 68/107 = 63.6%, CI95% [53.7 ; 72.6]; p < 10- 3) at interim analysis, resulting in the early termination of the study after the inclusion of 309 patients. For patients not optimized at baseline, the median time to obtain an optimized therapy was much shorter in the mPCR group than in the control group (6.9 h, IQR [2.9; 17.8] vs. 26.4 h, IQR [3.4; 47.5]; p = 0.001). Early optimization of antibiotic therapy resulted in a non-statistically significant decrease in mortality from 12.4 to 8.8% (p = 0.306), with a trend towards a shorter median length of stay (18 vs. 20 days; p = 0.064) and a non-significant reduction in the average cost per patient of €3,065 (p = 0.15). mPCR identified all the bacteria present in 88% of the samples. Despite its higher laboratory cost, the use of multiplex PCR for BSI diagnosis leads to early-optimised therapy, seems cost-effective and could reduce mortality and length of stay. Their impact could probably be improved if implemented 24/7.

Protective effect of taurine against free radicals damage in the rat myocardium.

Free radicals are highly cytotoxic to the heart and are involved in ischemia/reperfusion injury. In this study, we tested the ability of taurine to neutralize the deleterious effects of free radicals generated ex vivo and in vitro. Taurine was added at a concentration of 0.1 mM to the drinking water of experimental rats during 6 months. The animal hearts were then isolated and submitted to regional ischemia and reperfusion; ventricular fibrillation was significantly reduced as compared to a control group of non-treated animals. Moreover, at a concentration of 1 mM, taurine provided significant cardio-protection against the deleterious effect of free radicals generated by the electrolysis of Krebs-Henseleit buffer. When isolated hearts were perfused with electrolysed buffer, extensive fiber necrosis occurred, as observed by staining with nitro blue tertrazolium, a soluble dye which yields a dark blue formazan stain in the presence of reducing agents This stain was barely detectable when taurine was added to the perfusing electrolysed buffer. To further understand the protecting mechanism of taurine, we used xanthine-xanthine-oxidase as a superoxide (O2-) generating system and monitored the O2- through yield O2--dependent cytochrome c reduction. We demonstrated that taurine did not affect this system, which indicated that it did not scavenge O2- directly. On the other hand, taurine inhibited the auto-oxidation of adrenaline to adrenochrome at pH 7.8 where this auto-oxidation is O2--independent and superoxide dismutase insensitive. We thus conclude that taurine acts as a potent, but non-specific, scavenger of free radicals that cause heart damage and protects against reperfusion-induced ventricular

Taurine and myocardial noradrenaline.

Taurine (CAS 107-35-17) is an anticonvulsant used also as an adjunct in the treatment of cardiovascular disorders. Therefore, we studied its effects noradrenergic transmission in the isolated rabbit heart prelabelled with 3H-noradrenaline. At the concentrations of 1 and 10 mmol/l taurine treatment was without effect on the neuronal and extraneuronal uptake of noradrenaline by the myocardial tissue. At the highest concentration, it decreased the spontaneous release of the transmitter and enhanced its catabolism. Without any significant effect on tyramine-induced noradrenaline release, taurine decreased the release of the amine induced by dimethylphenylpiperazinium and nerve stimulation. These results suggested that taurine may reduce the peripheral sympathetic activity by accelerating noradrenaline catabolism and decreasing its release probably via its ability to prevent a rise of intracellular calcium ion.

[Pharmalogic effects of benzonitrile on the central nervous system]. / Effets pharmacologiques du benzonitrile sur le système nerveux central.

The present experiments intended to explore the psychopharmacological properties of benzonitrile on mice. Benzonitrile decreased motility, muscular force and inquisitiveness. The hypnotic effects of chloral and pentobarbital were increased by benzonitrile. The drug antagonized reserpine-induced palpebral ptosis and apomorphine-induced stereotypy. That benzonitrile was more effective against convulsions induced by pentetrazol and electric shock than those induced by strychnine suggested a central site of action. Perhaps benzonitrile interfers with the release or the action of central amines.

[Pharmacologic effects of glycerolformal on the central nervous system]. / Effets pharmacologiques du glycérolformal sur le système nerveux central.

Glycerolformal is not devoid of action on mice psychomotor behaviour. Administered through the digestive tract with infralethal doses, it can exercice depressing effects on muscular strength and sensitivity to pain without affecting inquisitiveness. It opposes the stimulating effects specific to pentetrazol, amphetamine and apomorphine and is a protection against electric convulsions but tends to increase the toxicity of tryptamine.