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Sulbactam is a new β-lactamase inhibitor with pharmacokinetic characteristics in humans similar to those of ampicillin. A total of 41 patients hospitalized in the Clinic of Infectious Diseases, University of Naples, for chronic liver diseases, were treated with sulbactam/ampicillin (ratio 1: 2) for urinary, respiratory, biliary tract or soft tissue infections. Sulbactam/ampicillin was administered im or iv at a dosage of 3–9 g/day depending on the site and severity of the infection. All the patients treated with sulbactam/ampicillin had clinical signs and symptoms of infection, and all the organisms isolated were sensitive to sulbactam/ampicillin (MIC less than 16 mg/l). For both Gram-positive and Gram-negative bacteria the sulbactam/ampicillin MICs were much lower than the ampicillin MICs. In agreement with the favourable in-vitro results, we observed good therapeutic efficacy. 85% of the patients recovered or improved within a few days of therapy, with no clinical relapses, and in 81% of the infections the responsible bacteria were completely eradicated. We observed a low number of side effects (3/41 oral candidosis; 3/41 pain at the im injection site) and no change in the blood chemistry tests. [ABSTRACT FROM PUBLISHER]

In this multicenter study the authors evaluated the clinical and microbiological efficacy and the local and general safety of cefoperazone sodium in 1,546 patients (946 males and 600 females, mean age 61.3 years) with lower respiratory tract (1,044) and urinary tract (539) infections. Results were very encouraging with 95.3% of clinical cures or improvement, 91.6% of microbiological eradication, and a local and general safety which was always extremely high, i.e. 96.9% and 98.3% respectively.

The pharmacokinetics of bacampicillin, a prodrug of ampicillin which is absorbed from the gastrointestinal tract, were studied in 10 healthy male volunteers after administration of 1,200 mg in a single oral dose. The pharmacokinetic analysis was carried out by applying a single-compartment kinetic model with zero-order absorption. The apparent duration of absorption (T) was about 1 h for all subjects. The peak plasma concentrations (Cmax) were 17.89 +/- 1.82 micrograms/ml, and the mean plasma half-life during beta-phase was 1.17 +/- 0.14 h. The area under the curve was 41.22 +/- 5.29 micrograms.h/ml. The mean urinary recovery during 24 h amounted to 76.4 +/- 3.65% of the dose.

In an open, randomized clinical study, the safety and efficacy of sulbactam/ampicillin was compared to that of cefotetan in 95 hospital patients with gynecologic or obstetric infections. Sulbactam/ampicillin (1 g:2 g), was administered intravenously every 8 h to 46 patients, and cefotetan (2 g) was administered intravenously every 12 h to 49 patients. All 23 patients with obstetric infections and 18 of the 23 patients with gynecologic infections treated with sulbactam/ampicillin were evaluated as cured. All 21 patients with obstetric infections and 23 of the 28 patients with gynecologic infections treated with cefotetan were evaluated as cured. No side effects requiring discontinuation of therapy or reduction of the dose administered, were observed.

Several in vitro parameters of sulbactam combined with ampicillin (Sbt/Amp) were studied in order to evaluate and compare its microbiological properties with those of beta-lactamase stable beta-lactams (ceftriaxone, cefamandole, cefoxitin). The intrinsic activity of Sbt/Amp was satisfactory and comparable to that of other beta-lactams and no significant difference was observed against beta-lactamase producing or non-producing bacteria. Besides, it was determined that sulbactam, when combined with ampicillin at different ratios (1:2, 5:1), with and without preincubation (60 min) reduces the hydrolysis of ampicillin determined by ten different standard beta-lactamases. The hydrolysis rates of ampicillin become as low as those of cefoxitin, cefamandole and ceftriaxone, which are beta-lactamase stable cephalosporins. In fact, all the antibiotics under examination were slightly hydrolyzed by several beta-lactamases, but such slight hydrolysis did not affect the antibacterial activity against beta-lactamase producing bacteria. About 50% of non-beta-lactamase producing bacteria (18 strains of different bacterial species) produced an inducible beta-lactamase after ten daily subcultures with sub-inhibitory concentrations of each antibiotic, but minimum inhibitory concentrations (MICs) of Sbt/Amp never increased after stimulation in contrast with other drugs whose MICs were much higher in consequence of this procedure. Finally, no spontaneous resistant mutant to Sbt/Amp was detected, but several mutants appeared in response to the other drugs. Sulbactam makes ampicillin as effective as beta-lactamase stable cephalosporins and its use does not determine an increase of resistance or selection of resistant mutants.

The difficulties encountered in the treatment of onychomycosis are primarily related to the necessity of prolonged systemic therapy. Many of these difficulties could, then, be avoided by the use of an effective local treatment. The present study compared the effectiveness and tolerability of two topical ungual preparations: a 28% solution of tioconazole and a 2% tincture of miconazole. The therapeutic results and tolerability of both preparations were found to be satisfactory. The tioconazole preparation proved to be slightly more effective although the difference was not statistically significant.

The pharmacokinetics of cefoperazone was determined following single and multiple intravenous and intramuscular administrations in man. Ten subjects at each dose level were given eleven successive doses, at 12 h intervals of 500 and 1000 mg i.m. and i.v.. Serum concentrations and urinary excretion were determined in all subjects after the first, fifth and eleventh doses. The first i.m. doses yielded mean peak serum levels of 37 micrograms/ml and 76 micrograms/ml at 1.0 h after injection. The first i.v. doses yielded mean serum levels of 93 and 180 micrograms/ml at 5 min after the injection. No tendency toward drug accumulation was observed on multiple dosage. The pharmacokinetics could be described by a linear, open, two-compartment model of drug distribution. The terminal serum half-life (2.1-2.4 h after i.v. doses and 2.6-2.8 h after i.m. doses) remained essentially constant over the period of the study by dose levels. The no-significant differences of areas under the curve between the two routes, at two doses, show the absolute bioavailability of cefoperazone was about 95% following i.m. administration. The high binding to serum proteins (90%) influences favourably the pharmacokinetic parameters of cefoperazone. It yielded high and prolonged serum concentrations and has very useful distribution properties. These favourable properties, together with its good antibacterial activity, suggest that cefoperazone will be effective in treating bacterial infections in human beings.