Tenofovir plasma concentrations according to companion drugs: a cross-sectional study of HIV-positive patients with normal renal function.

As the risk of tenofovir-associated renal toxicity has been found to be proportional to the drug plasma concentration, our aim was to measure the determinants of tenofovir plasma exposure in HIV-positive patients with normal renal function. A cross-sectional analysis was conducted in HIV-positive patients chronically receiving tenofovir-containing highly active antiretroviral therapies (HAARTs). Patients on tenofovir-containing antiretroviral regimens, presenting 22 to 26 h after drug intake, having estimated glomerular filtration rates above 60 ml/min, reporting high adherence to antiretroviral medications (above 95% of the doses), and signing a written informed consent were included. Plasma tenofovir concentrations were measured through a validated high-performance liquid chromatography-mass spectrometry (HPLC/LC-MS) method. The tenofovir trough concentrations in 195 patients (median, 50 ng/ml, and interquartile range, 35 to 77 ng/ml) were significantly associated with the estimated glomerular filtration rate, body mass index, and third-drug class (protease-containing versus protease-sparing regimens) (with the highest exposure in unboosted-atazanavir recipients). The results of multivariate analysis showed that the third-drug class and the weight/creatinine ratio were independent predictors of tenofovir trough concentrations. This cross-sectional study shows that tenofovir trough concentrations are predicted by the weight/creatinine ratio and by the coadministered antiretrovirals, with protease inhibitors (whether boosted or unboosted) being associated with the highest plasma exposure. These data, previously available in healthy subjects or for some drugs only, could be useful for designing strategies to manage tenofovir-associated toxicity, since this toxicity has been reported to be dose dependent.

[Treatment of chronic hepatitis with interferon-beta]. / Osservazioni sul trattamento di epatiti croniche con beta interferone.

Thirty-five patients suffering from chronic viral hepatitis were treated with beta-IFN during two periods: 22 during 1991 and 13 in 1992. Patients in the first group were treated with a dose of 3 MUI beta-IFN three times a week for six months with a follow-up of 1 year; those patients treated during 1992 received the same dose but over a period of 12 months. The results confirm a satisfactory response (33%) and a good drug tolerability in patients enrolled in 1991. Those patients tho commenced treatment in 1992 will be the subject of a subsequent analysis.

[Cefixime. Microbiologic, kinetic and clinical profile]. / Cefixime. Profilo microbiologico, cinetico e clinico.

The microbiological, kinetic and clinical profile of cefixime, a IIIrd generation cephalosporin, administered orally, is presented. Cefixime is highly active versus Gram-negative aerobic bacteria while, with respect to Gram-positive bacteria, it is only active against Str. pneumoniae, Str. pyogenes, Str. agalactiae, and Str. bovis. It has no action against anaerobics. Endowed with good kinetics, cefixime possesses a favourable tissue distribution. Cefixime is highly indicated in infections of the upper and lower airways where the aethiology is prevalently due to Str. pneumoniae, H. influenzae and B. catarrhalis, that are extremely sensitive to the antibiotic. It is concluded that the therapeutic armamentarium has been enriched by a new, highly active antibiotic that, administered in a monodese/die, ca satisfy patient compliance.

[Secretory IgA. Recent progress]. / IgA secretorie. Recenti acquisizioni.

After a brief introduction on the role of the immune system, the paper illustrates the methods of IgA production and their local protective functions. Those pathologies in which the monitoring of IgA levels plays a diagnostic and prognostic role are also described. In conclusion, the current methods used for the correct evaluation of IgA2 titres are discussed: RIA and competitive immunoenzymatic and immunofluorescent tests, although the latter can only be used on biopsy tissue.

[Bacampicillin vs amoxicillin in respiratory pathology]. / Bacampicillina vs amoxicillina in patologia respiratoria.

Clinical research was conducted to evaluate the comparative therapeutic efficacy in respiratory pathology of 800 mg X 2 per diem bacampicillin v. 1000 mg X 2 per diem amoxicillin, both orally administered. The results were more or less identical and are interpreted as indicating the better constant absorption of the precursor, hence its higher concentration gradient that produces a higher antibiotic concentration in the lungs.

[Cephalosporins and enzymuria]. / Cefalosporine ed enzimuria.

Urinary enzyme excretion was studied in 56 patients treated with cephalosporins in order to evaluate their potential nephrotoxicity. Only in 4 out of 56 patients (7%) was increased NAG, gamma-GT, AlP excretion seen. A rapid return to normal values was observed just after the end of the therapy.

[Cefoperazone: microbiological, kinetic and clinical studies]. / Cefoperazone: ricerca microbiologica, cinetica e clinica.

In vitro cefoperazone proved more active against the tested gram-negative bacteria than either piperacillin or mezlocillin. When administered in 1 g venous bolus the antibiotic achieved high plasmatic concentrations that were still adequate after 8 hours. 33.2% was excreted by the kidneys and a considerable amount by the biliary way. Cefoperazone produced a clinical cure in 35/36 patients (97.22%). A disulfiram-like effect was noted in 18.18%.

[Clinico-epidemiologic findings in a group of patients with acute viral hepatitis]. / Rilievi clinico-epidemiologici su una casistica di epatite virale acuta.

Certain clinical and epidemiological findings among 2262 AVH patients are reported. The patients were all admitted to the A. di Savoia Hospital for Infectious Diseases in Turin over a two-year period.

[Piperacillin: microbiological and clinical studies]. / Piperacillina: ricerca microbiologica e clinica.

A microbiological and clinical study of the action of piperacillin is presented. The drug showed an excellent in vitro antibacterial action on gram positive and gram negative microorganisms. Its in vitro action on Ps. aeruginosa (70.8% of strains inhibited) was also extremely interesting, making it the second most effective of the antibiotics tested after polymyxin B and colistin, polypeptides unsuitable for clinical use. In vivo, the administration of piperacillin achieved a clinical and bacteriological cure in 35 out of 40 patients and a clinical cure in 2 out of 40. It was only therapeutically unsuccessful in 3 cases. It is concluded that its microbiological, kinetic and tolerance features make piperacillin suitable for a wide range of therapeutic purposes.

[Microbiological, kinetic and clinical study on a new cephamycin: cefotetan]. / Ricerca microbiologica, cinetica e clinica su una nuova cefamicina: cefotetan.

Microbiological, kinetic and clinical studies were conducted on a new cephamycin, cephotetan. In vitro the antibiotic was found to be very effective against all strains tested. It had a particularly strong action against Gram negative bacteria too. Kinetically speaking, an intravenous bolus produced a high plasmatic concentration with a half life of about 4 hours. Elimination via the kidneys was fastest in the first 3 hours after administration (49.82%) and the slowed down. 82.76% of the dose administered was excreted within 24 hours. This antibiotics is particularly indicated in cases of urinary, respiratory and biliary infections.

[Kinetic and clinical studies on a new cephalosporin: Cefotiam]. / Ricerca cinetica e clinica su una nuova cefalosporina: Cefotiam.

Kinetic and clinical evaluation of cefotiam, a new cephalosporin, is reported. It was found that the drug is rapidly distributed to the tissues. Equilibrium between tissues and plasma is reached in about an hour. Some 90-91% of the dose administered is excreted in the urine, and accumulation does not occur. A clinical cure was obtained in 27 of a series of 35 patients (77.1%). Improvement was observed in 7 cases (20%). The antibiotic proved ineffective in the remaining cases (2.8%). Tolerance was excellent and there were no side-effects worthy of note.

[The therapeutic activity of stepronin in viral hepatitis]. / Studio sull'attività terapeutica di stepronin in corso di epatite virale.

The therapeutic effect of stepronin in 5% glucosate solution has been evaluated in 55/110 viral hepatitis cases (10/55 of A type, 37/55 of B type and 8/55 of nA type nB type), versus other cases (8/55 of A type, 40/55 of B type of 7/55 of nA nB type), treated with 5% glucose solution only. In 18/110 viral hepatitis case of A type, final results with the two different therapies have not shown statistically significantly changes and were comparable. Particularly favourable, in the patients treated, the results obtained in viral hepatitis of B type and nA nB type, were very significant statistically at the end of therapy. In particular, the 2 transaminasic activities had a beneficial influence. Tolerance was very good: only in there cases nettlerash was observed and therapy interrupted in one patient. Therefore the validity of this sulphydryl pro-drug in the treatment of acute viral hepatitis of B and nA and nB type is confirmed.

[Epidemiologic and clinical studies of 6 cases of leptospirosis from the province of Turin]. / Osservazioni epidemiologiche e cliniche su 6 casi di leptospirosi provenienti dalla provincia torinese.

Six cases of leptospirosis from the outer suburbs of province of Turin are presented. Some epidemiological aspects are considered, and reference is made to the need for early diagnosis, along with prompt antibiotic management to ensure successful resolution. Mention is also made of the need for careful control of renal function, since its impairment is the most serious complication associated with leptospirosis.

[Clinico-epidemiologic study on 1258 cases of viral hepatitis admitted to Piedmont hospitals 1977-1979]. / Indagine clinico-epidemiologica su 1258 casi di epatite virale, ricoverati in Piemonte negli anni 1977-79.

A clinical and epidemiological assessment of 1258 hospital patients in Piedmont in 1977-1979 showed that, at present, the frequency of hepatitis A and B can be regarded as virtually the same, that males are more frequently affected, that AVH A is more frequent in early life, whereas AVH B is significantly more common later, that urban areas are more frequently stricken than rural areas, that AVH A is more common in persons living in groups, whereas AVH B is more frequent among pensioners and the unemployed (the latter being primarily drug-addicts). Patients with AVH A, and hence a minor hepatitic involvement, had shorter hospital stays, while the immune response in both types of hepatitis is characterized by a more frequent increase in gamma-globulins, coupled with arise in IgM levels.

[Clinical study on a new cephalosporin: CGP 9000 (cefroxadine)]. / Ricerca clinica su una nuova cefalosporina: CGP 9000 (cefroxadina).

CGP 9000 (cefroxadine), a new cephalosporine derived from N-acyl-3-alkoxy-7-amino-3-cefem-4-carboxylic acid for exclusively oral use, has been experimented on 67 patients, 41 adults and 20 children. CGP 9000 appeared to possess good therapeutic activity, even in low doses: its rapid absorption and moderate sero-protein bond are a guarantee of an immediate and almost total bioavailability.

[Pharmacokinetics of intravenous rifampicin (RMP) and its clinical evaluation in purulent bacterial meningitis]. / Farmacocinetica della rifampicina (RMP) per via venosa e sua valutazione clinica in corso di menmingite purulenta batterica.

A combined kinetic and clinical study showed that rifampicin displays good tissue diffusibility, though it may have a tendency to accumulate. A liquor transfer sufficient for the bacteria most commonly responsible for meningeal inflammation was observed; 15/18 cases of purulent bacterial meningitis treated were clinically cured without sequelae, while 1 displayed considerable improvement. Two patients died from unforseen, uncontrollable complications that were not related to administration of the drug.