A satisfactorily high H. pylori eradication rate was obtained in Japanese ulcer patients with the triple therapy regimen consisting of LPZ 30 mg, AMPC 750 mg, and CAM 200 mg b.i.d.

Arbekacin is widely used in Japan for the treatment of patients infected with methicillin-resistant Staphylococcus aureus (MRSA). In this study, we have determined the optimal concentration targets of arbekacin for both efficacy and safety. A pharmacokinetic-pharmacodynamic analysis was performed to relate exposure to the drug and clinical cure/improvement or nephrotoxicity. Since we have reported the population pharmacokinetic parameters for arbekacin in the preceding paper (Y. Tanigawara, R. Sato, K. Morita, M. Kaku, N. Aikawa, and K. Shimizu, Antimicrob. Agents Chemother. 50:3754-3762, 2006), individual exposure parameters, such as area under the concentration-time curve (AUC), peak concentration (C max ), AUC/MIC, C max / MIC, and trough concentration (C min ) were estimated by the Bayesian method. Logistic regression was used to describe the relationship between exposure to the drug and the probability of clinical cure/improvement or nephrotoxicity. For the clinical efficacy analysis, 174 patients confirmed to have an MRSA infection were evaluated. The C max , C min , and AUC of arbekacin were associated with the probability of clinical cure/ improvement during monotherapy. It was shown that the probability of cure/improvement rose when the C max of arbekacin was increased, with an odds ratio of 6.7 for a change in C max from 7.9 to 12.5 g/ml (P ‫؍‬ 0.037). For the nephrotoxic risk analysis, 333 patients were included, regardless of whether a pathogen was identified. Logistic regression analysis revealed C min and AUC as risk factors of nephrotoxicity (P < 0.005). The estimated probabilities of arbekacin-induced nephrotoxicity were 2.5, 5.2, and 13.1% when the C min values were 1, 2, and 5 g/ml, respectively. The present findings are useful for optimizing the individual dose of arbekacin for the treatment of MRSA-infected patients.

The metabolism and pharmacokinetics of pivalic acid, a major metabolite of S-1108, were studied with three healthy volunteers. Concentrations of S-1006 (the active compound), pivalic acid, and pivaloylcarnitine in plasma and urine were measured after administration of S-1108. Recoveries in urine at the doses of S-1108 given (100 and 200 mg) were 33 to 41% for S-1006, 93% for total pivalic acid, and 89 to 94% for pivaloylcarnitine in 24 h, and maximum concentrations in plasma were 2 ,ug of S-1006 per ml, 1 ,ug of total pivalic acid per ml, and 2 ,ug of pivaloylcarnitine per ml after a 200-mg oral administration of S-1108. More than 90% of the pivalic acid was excreted as pivaloylcarnitine, and no measurable amount of free pivalic acid was present in urine samples, indicating that the pivalic acid liberated from S-1108 was almost quantitatively conjugated with carnitine in the human body. The level of free carnitine in plasma was unaffected by a single 200-mg administration of S-1108, whereas urinary excretion of free carnitine decreased as levels of acylcarnitine increased. The acylcarnitines were excreted primarily in the form of pivaloylcarnitine. This study clearly showed how the pivalic acid was metabolized and excreted in humans. The importance of monitoring carnitine, an essential cofactor in fatty acid metabolism, was also discussed in terms of its utilization by pivalic acid.S-1108, an oral cephem antibiotic, is a prodrug of S-1006 (4a). S-1108 is hydrolyzed by an esterase in the intestinal tracts of humans to produce S-1006, pivalic acid (PA), and formaldehyde in a manner similar to that of other prodrugs having a pivaloyloxymethyl (POM) ester (3,6,18). The metabolic and pharmacokinetic profiles of S-1108 have been intensively studied, including clinical evaluations (12a, 18a). Furthermore, an investigation of the metabolism of PA was needed to confirm the biological profile of the POM ester type of prodrug. The metabolism of PA has been studied by Vickers et al. (19), who found that pivaloylcarnitine (PC) was its major urinary metabolite when the POM ester derivative of methyldopa was given to humans. Since then, PC has been found to be the common metabolite of prodrugs that possess the POM ester group in their chemical structures (5,9,10). Carnitine is an essential cofactor in fatty acid

No abstract

The rapid ID 32 Strep system (bioMérieux, Marcy l'Etoile, France) was evaluated for its ability to identify 21 species of viridans group streptococci; results were compared with DNA-DNA hybridization results and results of conventional physiological tests. A total of 171 strains of the 21 species including 147 clinical strains was analyzed. Of the 156 strains of species included in the database of this system, 136 strains (87%) were correctly identified. Incorrect identification occurred for 13 strains (8%), and no identification was given for 7 strains (5%). It was difficult to differentiate S. mitis and S. oralis accurately with this system. Of the 17 strains identified as S. mitis by the rapid ID 32 Strep system, the results of DNA-DNA hybridization were in agreement for only 3 strains. S. crista and S. parasanguis, which are not included in the database, were identified as S. mitis or S. sanguis or were not identified, but S. parasanguis could probably be identified by using the rapid ID 32 Strep system because the biochemical profile is well characterized for this species. The rapid ID 32 Strep system can be used to differentiate most species for which phenotypic characteristics have been described if the database is revised according to recently reported amended criteria for the identification of viridans group streptococci. However, identification of a few species such as S. mitis and S. oralis is problematic with this system.