A Phase 3, multicenter, open-label study was conducted to confirm the clinical efficacy and safety of a single 2.0g dose of a new formulation of the macrolide antibiotic azithromycin, namely, a sustained-release oral suspension formulation (azithromycin SR), in patients with acute pharyngolaryngitis, acute tonsillitis or acute rhinosinusitis.
The clinical efficacy (efficacy rate) on Day 8, which was the primary endpoint, in the “clinical per protocol set” was 88.5%(77/87 subjects) for the entire population. The efficacy rate by disease was 97.1%(34/35 subjects) for acute pharyngolaryngitis, 94.4%(17/18 subjects) for acute tonsillitis, and 76.5%(26/34 subjects) for acute rhinosinusitis. The efficacy rate increased over time in subjects with acute rhinosinusitis (91.2 and 100% on Days 15 and 29, respectively).
The bacteriological response (eradication rate) on Day 8 in the “bacteriologic per protocol set” was 78.1%(25/32 subjects) for the entire population. The eradication rate by disease was 92.3%(12/13 subjects) or acute pharyngolaryngitis, 66.7%(4/6 subjects) for acute tonsillitis, and 69.2%(9/13 subjects) for acute rhinosinusitis. The eradication rate increased over time in subjects with acute rhinosinusitis [100%(13/13 subjects) on Day 15].
As for safety, the incidence of treatment-related adverse events was 54.5%(54/99 subjects). The incidence of diarrhoea and/or abdominal pain (36.4%) was high, but all of these cases recovered. No severe or serious adverse events, deaths or discontinuations due to adverse events were noted in this study.
Based on the abovementioned results, we conclude that azithromycin SR administered as a single 2.0g oral dose is highly effective and well tolerated for the treatment of acute pharyngolaryngitis, acutetonsillitis and acute rhinosinusitis. Azithromycin SR is considered as a very useful antibiotic from various aspects, including drug compliance, for the treatment of otorhinolaryngological infections in clinical practice.

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Suicide gene therapy with the herpes simplex virus thymidine kinase (HSVtk) and ganciclovir (GCV) have shed light on the cancer gene therapy. However, a serious concern arose on account of the expression of HSVtk in normal cells, which can induce cytotoxicity. Here, we propose a novel strategy called D-RECS (drug or gene delivery system responding to cellular signals) for the development of a target cell-specific gene expression system. Polymers carrying the peptide substrate specific for each kinase (IκB kinase, Protein kinase Cα, and Src kinase) were prepared as the gene carriers. The results of the biochemical analyses revealed that the gene carriers enabled regulation of the gene expression in response to extraordinary activated kinase signals. This strategy represents an improvement of the technique of suicide gene therapy.

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The activity of antibacterial agents against aerobic Gram-positive cocci (28 species, 1, 020 strains) and anaerobic bacteria (21 species, 170 strains) isolated from clinical specimens in 2004 at 16 clinical facilities in Japan were studied using either broth microdilution or agar dilution method. The ratio of methicillin-resistant strains among Staphylococcus aureus was 63.1% and Staphylococcus epidermidis 84.2%, suggesting that resistant strains were isolated at high frequency. Vancomycin (VCM), linezolid (LZD), and quinupristin/dalfopristin (QPR/DPR) had good antibacterial activity against methicillin-resistant S.aureus and methicillin-resistant S.epidermidis, with MIC₉₀s of ≤2μg/mL. The ratio of penicillin (PC) intermediate and resistant strains classified by mutations of PC-binding proteins among Streptococcus pneumoniae was 86.5%. Cefpirome, ceftriaxone, carbapenem antibiotics, VCM, and teicoplanin had MIC₉₀s of ≤1μg/mL against PC-intermediate and resistant S.pneumoniae strains. VCM and teicoplanin also showed good antibacterial activity against Enterococcus faecalis and Enterococcus faecium with MIC₉₀s of ≤2μg/mL, and no resistant strains were detected. Of E.faecium strains, 7.8% showed intermediate and 23.4% resistant to LZD or QPR/DPR. Among anaerobes, carbapenems showed good activity against Peptococcaceae, Bacteroides spp., and Prevotella spp. The susceptibility of Bacteroides spp. other than Bacteroides fragilis to these antibiotics, however, appeared to be lowered, necessitating well-focused surveillance studies.

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We determined MICs of antibacterial agents against 1, 248 clinical strains of aerobic Gram-negative bacteria (19 genus or species) isolated at 16 Japanese facilities in 2004. MICs were determined using mostly broth microdilution method and antibacterial activity was assessed. Antibacterial susceptibility of Enterobacteriaceae to most β-lactams was comparable to that described in our previous report on isolates in 2002. Strains producing extended-spectrum β-lactamases (ESBL) accounted for 2.5% of Escherichia coli, 0% of Klebsiella spp., and 92% of Proteus spp. Notably, 16.7% of Proteus mirabilis was found to produce ESBL. Most antibacterial agents showed good activity against Moraxella catarrhalis. Among Haemophilus influenzae, 9.3% produced β-lactamase and 57.7% were β-lactamase-negative ampicillin-resistant strains when classified by penicillinbinding protein 3 mutation. Although few antibacterial agents against Pseudomonas aeruginosa have potent activity, only three agents-tobramycin, doripenem, and amikacin-showed an MIC₉₀ of ≤8μg/mL. Of all P.aeruginosa strains, 8.9% were resistant to seven or more agents of ten antipseudomonal agents, a decrease compared to results reported in 2002. Against other glucose-non-fermentative Gram-negative bacteria, the activity of most antibacterial agents was similar to that in 2002.

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