[In vivo pharmacokinetic of amikacin and its pharmacodynamic in combination with cefepime, cefpirome and meropenem in an in vitro/ex vivo micropig model]. / Pharmacocinétique de l'amikacine in vivo et sa pharmacodynamie en association avec le céfépime, cefpirome et méropénème dans un modèle in vitro/ex vivo de microporc.

Three female Yucatan micropigs were included and received a single dose of amikacin (15 mg/kg) by short infusion (30 min) combined either with a single dose of cefepime or cefpirome (30 mg/kg/12 h) or meropenem (7 mg/kg/8 h). The beta-lactams were administered either by intravenous intermittent injection or by continuous infusion. The mean elimination half-life and clearance value of amikacin were 1.88 h and 2.15 ml/min.kg-1 respectively. These pharmacokinetic parameters were similar to those obtained in man (t1/2 = 2,42 h et Cl = 1,61 ml/min kg-1). Furthermore, they were not affected by coadministration of cefepime, cefpirome and to meropenem. While resistant to cefepime, cefpirome and amikacin, Klebsiella pneumoniae producing ESBL was susceptible to combination of these cephalosporins with amikacin in an in vitro/ex vivo micropig model. For the six dosage regimens used in this study, the killing activities were similar and resulted in at least 4 log decrease at 6 h after drug exposure. For antimicrobial combination consisting of bolus dosing of amikacin plus continuous infusion of cefepime or cefpirome, the 12 h serum bactericidal titers (SBTs) were 1:8 for cefepime and 1:2 for cefpirome dosage regimen. When each drug administered intermittently, the 12 h SBTs were 1:4 for cefepime and 1:2 for cefpirome. The 8 h SBTs for dosing schedule containing meropenem combined with amikacin were 1:4 and 1:16 after 30 min short infusion and continuous infusion respectively. In conclusion, our study showed that the micropig model is a reliable model for pharmacokinetic investigation of amikacin. It was concluded that beta-lactam antibiotics tested with amikacin may be coadministered by using the standard recommended dosing regimen of amikacin. Continuous infusion of beta-lactams combined with once dosing of amikacin seems to be as or more effective than intermittent injection of each drug.

[HPLC, RIA, FPIA. Evaluation of 3 methods for the assay of vancomycin]. / HPLC, RIA, FPIA. Evaluation de trois méthodes de dosage de la vancomycine.

We describe a rapid and accurate high performance liquid chromatographic (HPLC) method for vancomycin quantitation. This method is then compared with two immunoassays, RIA and FPIA. The chemical extraction step needed for HPLC is simple and rapid. Both conventional reversed phase HPLC and high speed reversed phase HPLC were tested. The mobile phase was a mixture of aqueous ammonium acetate and acetonitrile. Specificity of the HPLC assay was good. Serum levels in 112 clinical specimens assayed by HPLC were regressed against the levels obtained for the same samples by both RIA and FPIA. The correlation was good (RIA : r = 0.945; FPIA : r = 0.967). Considering the disadvantages of RIA, HPLC and FPIA emerge as the methods of choice.

Determination of vancomycin in human serum by high-pressure liquid chromatography.

A rapid, accurate, reverse-phase high-pressure liquid chromatographic procedure for vancomycin quantitation in human serum, cerebrospinal fluid, and peritoneal fluid was developed. This procedure involves a simple chemical extraction of the antibiotic and is suitable for each of these body fluids. The column and mobile phase used provided a good resolution of the vancomycin peak with a retention time of 6.1 min. The precision of the assay was within the requirement for a daily routine clinical application. Coefficients of variation for within-day reproducibility were 5.80 and 6.28%, respectively, for samples at 50 and 25 micrograms/ml, and for between-day reproducibility they were 11.4 and 11.1%, respectively. No interference was found with respect to beta-lactam and aminoglycoside antibiotics and many other currently used drugs, indicating a good specificity for the procedure. The detection limit of 100 ng/ml has proven to be sufficient for monitoring drug levels in serum obtained after usual dosages. Drug levels in 112 clinical serum specimens assayed by high-pressure liquid chromatography were regressed against the levels obtained for the same samples by radioimmunoassay and fluorescent polarization immunoassay. Correlation coefficients were 0.945 and 0.967, respectively, and were highly significant (alpha less than 0.001).

[Circulating immune complexes in hospital patient. Results in 3650 tests (author's transl)]. / Les complexes immuns chez les malades hospitalisés. Réflexions après 3650 recherches de complexes immuns.

The presence or absence of circulating immune complexes was investigated by the polyethylene-Clq immunodiffusion test in 3650 sera from 3000 hospital patients. Circulating immune complexes were detected in a large number of various diseases, but they were not always present, even in cases of diseases considered as caused by them. Testing for circulating immune complexes therefore is of limited clinical value and is only justified when there are hopes of finding a responsible antigen.

[Use of serum s-IgA detection in liver pathology (author's transl)]. / Intérêt de la détection des IgA sécrétoires dans le sérum en pathologie hépatique.

Secretory IgA (sIgA) were searched in 60 sera of healthy blood donors and in 1 590 sera of subjects having various diseases. 20 percent of these subjects showed an increased amount of sIgA in their sera. The only subjects presenting a constant increase (sometimes more than 20 fold the normal amount) were people with liver diseases. Quantitation of sIgA, in relation with the determination of the IgA/transferrin ratio (IgA/T) in sera, showed an important difference between Laennec's cirrhosis on one hand and virus hepatitis or post-hepatitic cirrhosis on the other. In Laennec's cirrhosis a moderate increase in sIgA went with a strong elevation of the IgA/T ratio, the latter being proportional to the degree of evolution of the disease. In virus hepatitis, the sIgA amount was largely increased while the IgA/T ratio remained at a normal value.

[Serum IgE Statistical study of 2000 measurements]. / Les IgE sériques. Etude statistique de 2000 dosages

In a statistical analysis of more than 2000 IgE estimations, the authors corroborate the importance of this determination for diagnosis of asthma, eczema and rhinitis. Serum IgE levels are also elevated in parasitic diseases, and may be elevated in some other cases in which there are several disorders, such as cirrhosis and leukemia.

[Immunoglobulins A in the vagina. Assay and study of their specificity]. / Immunoglobulines A dans le vagin. Dosage et étude de leur spécificité

The authors have titrated, by the Laurell technique, immunoglobulin A in vaginal washings ; the quantity of IgA found is higher for women having a pathogenic vaginal flora. Using immunofluorescence technique, and peroxydase-marked antibodies, the authors found specific IgA directed against Lactobacillus, N. gonorrhoeae and Candida albicans.