Steady-state pharmacokinetics of ciprofloxacin in plasma from patients with nosocomial pneumonia: penetration of the bronchial mucosa.

A 30-min intravenous (i.v.) infusion of 200 mg of ciprofloxacin was administered twice daily to 12 patients with nosocomial pneumonia scheduled to undergo diagnostic fiberoptic bronchoscopy. The pharmacokinetics of ciprofloxacin were examined at the presumed steady state after 5 days of treatment. Eleven successive plasma samples were collected in the interval from 0 to 12 h after administration, and bronchial mucosa samples were taken 2 h after administration. Concentrations of drug in all samples were assayed by high-performance liquid chromatography with fluorimetric detection. The results showed that the kinetics in plasma did not differ from those determined previously in healthy volunteers. The mean concentrations in plasma peaked at 4.94 +/- 2.90 mg/liter at the end of infusion. The terminal half-life was 4.95 +/- 2.81 h, and the mean residence time 6.13 +/- 3.17 h. A large volume of distribution was calculated: 2.59 +/- 1.43 liters/kg. Mean total body clearance was 23.3 +/- 10.1 liters/h. The concentrations in bronchial mucosa reached 21.6 +/- 5.63 micrograms/g 2 h after drug intake. The tissue-versus-plasma concentration ratios ranged from 10.1 to 26.3 (mean value, 16.9 +/- 5.43). After 6 to 12 days of i.v. treatment, four patients were switched to oral ciprofloxacin. We propose a model for the simultaneous fit of the concentration-time curves obtained after i.v. infusion and oral dosing. The concentrations in tissue observed in this study were in excess of the MICs for bacteria considered to be susceptible to ciprofloxacin.

[In vitro bactericidal effect of a piperacillin-pefloxacin combination against isolated strains of nosocomial pneumopathies in intensive care]. / Activité bactéricide in vitro de l'association pipéracilline-péfloxacine sur des souches isolées de pneumopathies nosocomiales en réanimation.

Combinations of piperacillin and pefloxacin are evaluated in vitro using checkerboard and killing-curves methods against 19 clinical isolates: S. aureus, K. pneumoniae, K. oxytoca, C. freundii, P. stuartii, Ps. aeruginosa, Ps. maltophilia and Ac. anitratum. The static checkerboard method showed more synergistic antibacterial effects than the killing curves method. The best synergistic effects appeared against S. aureus, K. oxytoca, P. stuartii, Ps. aeruginosa Ac. anitratum, including a notable increase of the rapidity of bactericidal activity. The combination PIP 64 micrograms - PEF 4 micrograms prevents the frequent secondary regrowth seen after 6 hours with the antibiotics used alone. No activity is obtained against S. aureus meti-R and Ps. maltophilia.

[Effects of rifampicin on the pharmacokinetics of doxycycline]. / Effet de la rifampicine sur la pharmacocinétique de la doxycycline.

Because of the potential of doxycycline-rifampicin for oral therapy of infectious diseases with intracellular bacteria, specially brucellosis and the well known cytochrome P450 enzyme system inductive activity of rifampicin, we may speculate that this antibiotic can altered the serum concentration-time profile of doxycycline when given in combination. So, the main pharmacokinetic parameters of doxycycline (200 mg/day orally) in seven patients before and after rifampicin association (10 mg/kg/day). According to the results two groups may be individualized: the first (n = 3) showed no variation in the doxycycline++ pharmacokinetic; the second (n = 4) had significant differences (p less than 0.05) for all pharmacokinetic parameters (AUC, T1/2, Cl, Cmax) after association with rifampicin (AUC were half reduced). Moreover, as regard doxycycline half-life, a difference was observed between these two groups before rifampicin treatment: in one case T1/2 was of 17.9 + 6.6 hours, while in the other it was of 9.2 + 2.3 hours. The group with obvious enzyme induction had the longer half life. This suggests that the inductive rifampicin effect would be essentially observed in patients considered as "poor metabolizers". The pharmacokinetic modifications observed are likely of clinical significance on account of the doxycycline serum concentrations decrease under the MIC of most agents of intracellular infections.

[Significance and evaluation of theophyllinemia in clinical medicine]. / Intérêt et valeur en clinique de la théophyllinémie.

The theophyllinemia variations depend upon some factors: -observance of treatment, time of blood swab posology, laboratory technic, concomitant drugs, method of adaptation selected and the mean of administration. The theophylline title is a very important biologic parameter, necessary to the asthma treatment survey through such drug. Daily posology may be adapted to this titrate.