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7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK, Background Switch to unboosted atazanavir (ATV 400 mg qd), although not licensed in Europe, is an attractive off‐label option due to convenience and tolerability. However there is a substantial lack [...]

Background: Unboosted atazanavir with raltegravir has been investigated at 300mg twice daily showing frequent hyperbilirubinemia and selection of resistance-associated mutations., Objectives: Atazanavir 200mg twice daily could increase tolerability and plasma exposure., Study Design: Patients on atazanavir/raltegravir (200/400 twice daily), with self-reported adherence >95% and no concomitant interacting drugs were retrospectively evaluated., Results: 102 patients [72.5% male, age 46.4 years (42-54), BMI 24kg/m 2 (22-26)] were included. CD4+ T lymphocytes were 417 cell/μL (302-704) and 76 patients (74.5%) had HIV-RNA <50 copies/ml. After 123 weeks 18.6% patients showed virological failure and 3.9% discontinued for intolerance. Available genotypes showed selection of major integrase (7/10 patients) and protease resistance-associated mutations (5/13 patients). In patients switching with dyslipidemia (n=67) total, LDL cholesterol and triglycerides significantly decreased. Patients switching with eCRCL<60ml/min (n=27) had no significant changes while patients with eCRCL >60ml/min showed significant decrease (-9.8ml/min, p=0.003) at 96-weeks. Atazanavir and raltegravir trough concentrations were 321ng/mL (147-720) and 412ng/mL (225-695). Self-reported non-adherence (n=4) was significantly associated with virological failure (p=0.02); patients with virological success had borderline longer previous virological control (33 vs. 18 months, p=0.07)., Discussion: Switch to atazanavir/raltegravir was safe and well tolerated allowing optimal drugs' plasma exposure. However, a concerning rate (18.6%) failed with newly selected mutations and stopped ATV/RAL because of DDI and intolerance issues or were lost to follow-up. This regimen might be considered in selected patients, without history of protease inhibitors failure or HBV infection, showing optimal adherence and prolonged suppression., (Copyright © 2016 Elsevier B.V. All rights reserved.)

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.

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.

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.

The results of a pharmacokinetic and clinical study of cephamandol naphate indicated that the drug quickly reaches high plasma concentration after both i.m. and i.v. bolus administration. Urinary excretion of the biologically active form is as much as 84--90% of the total dose and mostly takes place in the first 6 hr. The therapeutic response was good: clinical cure in 90%, marked improvement in 6.6%, no change in 3.3%.

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.

A mean plasma concentration curve, with peaks within the first hour and moderate individual variations, was obtained after a single administration of 800 mg of bacampicillin to 5 healthy volunteers. An adequate antibiotic transfer from the circulation to the bronchial apparatus was demonstrated. Treatment of 34 patients suffering from ampicillin-sensitive bacterial diseases permitted clinical cure of all patients, without onset of side-effects. It is concluded that bacampicillin is preferable to oral ampicillin because of its kinetic and tolerance features.

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.

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.

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.

An investigation conducted on healthy volunteers showed that cefoxitin quickly reaches high plasma concentrations, and is almost completely excreted via the urine within 6 hours. In a series of 21 cases treated with 2 g i.v. in 100 ml of a 5% glucose solution two or three times a day, a clinical cure was achieved in 20, and marked improvement in the remaining patient.

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.

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.

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.

Following a short review of the viruses underlying viral hepatitis and those which, as a secondary factory in the clinical picture, may cause fleeting liver damge, the subdivision of chronic hepatitis conditions on histopathological bases is described. Particular attention is paid to pathogenesis, with a study of the elimination of B virus, correlated to particular histopathological types. A series of 27 PCH and 49 ACH cases is reported. Of special significance was the observation of 14 ACH out of 17 biopsied drug addicts. The therapeutic problem of chronic hepatitis is then tackled.

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.

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.

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.

Following a review of the latest methods of treating infections of the urinary ways, the pharmacokinetic and clinical results of a new antibiotic, Carfecillin, are reported. The examination was carried out on a total of 10 volunteers. The substance showed good serum levels and fair renal excretion with both the 250 mg and the 500 mg p.o. doses. The clinical study was carried out on a double blind basis versus a standard reference (indanyl ester of carbenicillin) in 26 patients and showed the electivity of the antibiotic in the oral treatment of urinary infections under well tolerated conditions.

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%.

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.

The pharmacokinetics of kanendomycin, a new aminoglycoside derived from kanamycin, has been assessed in 15 volunteers after i.m. administration of 100 and 300 mg and i.v. administration of 100 mg. Analysis of the tricompartmental model adopted for the pharmacokinetic study showed that kanendomycin half-life is similar and perhaps superior to that of gentamycin. The antibiotic's bioavailability is of the order of 70-80% of the dose used.