Correlation between macrolide lung pharmacokinetics and therapeutic efficacy in a mouse model of pneumococcal pneumonia.

The correlation between the pharmacokinetics of erythromycin, roxithromycin, clarithromycin, spiramycin and azithromycin and their efficacy was investigated in two pneumococcal pneumonia models. Female Swiss and C57B1/6 mice were infected with Streptococcus pneumoniae strain P4241 by the intratracheal per oral route. This virulent strain produces acute pneumonia with death within 3-4 days (Swiss mice), or subacute pneumonia with death within 10 days (C57B1/6 mice) in untreated mice and the outcome of the disease is closely related to progressive weight loss. Swiss mice received three doses of each macrolide 50 mg/kg bd beginning 18 h post-infection. C57B1/6 mice received three doses of each macrolide 25 mg/kg, bd (except azithromycin was 12.5 mg/kg bd) beginning 48 h post-infection. Cure rates were evaluated on the basis of body weight variations recorded daily after the end of treatment. Pharmacokinetic parameters were determined in infected and non-infected mice after a single dose of each macrolide 50 mg/kg sc. The pharmacokinetics of azithromycin was also determined in leucopenic Swiss mice. We observed a hierarchy of in-vivo efficacy as follows: azithromycin > spiramycin = clarithromycin > roxithromycin = erythromycin which did not correlate with in-vitro MIC or MBC. The same hierarchy was found in terms of the lung T1/2. Lung T1/2s of macrolides could thus be predictive of their efficacy in respiratory tract infections. A reduced tissue AUC of azithromycin was seen in leucopenic mice suggesting leucocytes may help transport macrolides to sites of infection.

[Loco-regional anesthesia for surgery of limbs]. / Anesthésie locorégionale pour la chirurgie des membres.

This article is a review of recent data concerning: plexus and peripheral nerve blocks for the upper and lower limbs, intravenous regional anesthesia, and medullary, epidural and spinal anaesthesia. We have focused on the advantages and disadvantages of each technique which should be taken into account for their selection. Regional anaesthesia techniques are not without risks, and advantages are perhaps not as obvious now as was reported in the past, especially in the case of medullary spinal or peridural anaesthesia.

[Block of the superior laryngeal nerve for ORL endoscopy. Description of a simplified technique]. / Le bloc du nerf laryngé supérieur pour les endoscopies ORL. Description d'une technique simplifiée.

The usual anterior and lateral routes used for superior laryngeal (SL) nerve blocks are not often used because too difficult to carry out. A simpler and easier technique is described, which blocks the SL nerve at the level of the greater cornu of the hyoid bone. Because the nerve is not located accurately with this technique, a larger volume of local anaesthetic is required. This technique was tested in 31 patients scheduled for endoscopies with rigid tubes. The mean duration of endoscopy was 30 +/- 10 min. The use of 8 ml 1% lidocaine for the block 30 min surgical anaesthesia. In 2 patients, the SL nerve block alone was sufficient. In 26 others a complement with a benzodiazepine (flunitrazepam, n = 9, mean dose 0.8 mg; midazolam, n = 17, mean dose 5 mg) was required. In 4 of these patients, attempts of oesophagoscopy gave rise to hypertension and tachycardia. General anaesthesia with propofol and tracheal intubation were therefore used. In the last 3 patients, intercricothyroid jet ventilation was used, requiring general anaesthesia (propofol and succinylcholine). The SL nerve block was satisfactory in 24 patients with total vocal cord paralysis and no haemodynamic reaction to painful stimuli in the blocked area. No complication was observed. It is concluded that this technique is useful and easier to carry out than the usual ones.

Pancuronium pharmacokinetics in patients with liver cirrhosis.

The serum and urinary concentrations of pancuronium were measured in 14 surgical patients with cirrhosis and 12 patients free from liver disease undergoing abdominal surgery. A two-compartment open model was used in the pharmacokinetic analysis of the data. A two-fold increase in both the distribution half-life (T 1/2 alpha) from 11 min to 24 min and in the elimination half-life (T 1/2 beta) from 114 min to 208 min was observed in patients with cirrhosis. In these individuals, the total apparent volume of distribution of pancuronium was increased by 50%. Plasma clearance of pancuronium was decreased by 22%. No significant difference was found in the urinary excretion and biotransformation pattern of pancuronium. These results suggest that there is a risk of prolonged duration of action of pancuronium in patients with cirrhosis. In these patients, the initial dose to achieve adequate muscle relaxation is high and simultaneously there is slow disappearance of pancuronium from plasma. These alterations are mainly a consequence of the increase in the distribution volume of pancuronium in patients with cirrhosis.