Preclinical and clinical studies have indicated that only a very small number of patients with a diminished repolarization reserve in the heart suffer complications in drug-induced long QT syndrome by high-risk drugs. Drug assessment using sensitive, reliable in vivo proarrhythmia models provides important information to predicting the onset of TdP in such patients.

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We tested 690 strains-410 strains of 6 Candida species and 280 strains of 4 Aspergillus species-isolated from patients suspected of having fungal infections in medical institutions in Japan for about 2 years between February 2003 and November 2004 for susceptibility to micafungin and 7 other antifungal agents. MICs of these antifungal agents for Candida species and Aspergillus species were determined by broth microdilution based on NCCLS M27-A and NCCLS M38-P.Antifungal agents tested were micafungin (MCFG), amphotericin B (AMPH-B), fluconazole (FLCZ), itraconazole (ITCZ), miconazole (MCZ), 5-fluorocytosine (5-FC), caspofungin (CAS), and voriconazole (VRCZ).MICs of MCFG for 130 strains of Candida albicans, including FLCZ-resistant strains, and 50 strains each of Candida tropicalis and Candida glabrata were 0.03μg/mL or less and were the lowest in all antifungal agents tested. MICs of MCFG for 50 strains each of Candida parapsilosis and Candida guilliermondii were 2-8μg/mL and some strains exhibited slightly higher MICs.MICs of VRCZ for these strains were 0.25μg/mL or less and were the lowest in all antifungal agents tested. MIC₉₀s of MCFG for 100 strains of Aspergillus fumigatus were 1/16 those of ITCZ and VRCZ and 1/32 those of CAS.A similar trend was seen in the other 180 strains of Aspergillus species, i.e., MICs of MCFG for these strains were the lowest in all antifungal agents tested, and no strains showed more than 0.03μg/mL MICs.
These results suggest that the antifungal activity of MCFG against Candida and Aspergillus species isolated in recent years is the most potent compared to those of antifungal agents currently available in Japan and CAS used in the United States and Europe, and that MCFG is useful in the treatment of mycosis due to these fungi.

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In Japan, the intracutaneous reaction test has been regarded as mandatory, when any antibiotics is administered intravenously. The policy is not based on evidence, but on custom. The value of this test to the detection of anaphylaxis has been questioned, but no evidence suggesting otherwise has been found. In 2003. Japanese Society of Chemotherapy summarized evidence on anaphylaxis associated with the administration of antibiotics and recommended that the intracutaneous reaction test be abolished. We conducted a questionnaire to collect data on how physicians responded to this change. We sent questionnaire to 527 departments and received 274 answers. Fifty-four percent of the departments had discontinued or were preparing to stop using the intracutaneous reaction test, while 18% of them are described still continued to use the test. Among the departments that hesitated to stop using the test, one of the biggest concerns was how to observe patients. In the guideline on measure for anaphylaxis as a result of antibiotics use, which were published by the Japanese Society of Chemotherapy, observation is required during the administration of antibiotics. Practically, such observation can be difficult, because of staff shortage at many Japanese hospitals. Moreover, some physicians misunderstood that it was not necessary to observe patients, if an intracutaneous reaction test was conducted. The reason for the discontinuation of the test dose not appears to be widely known. Adverse events caused by anaphylaxis should be surveyed, the guideline should be reassessed, if necessary.

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Of 8, 856 patients enrolled in a special survey on levofloxacin (LVFX) therapy for pharyngitis, tonsillitis, and acute bronchitis associated with fever (≥38°C), 7, 597 free of complications or underlying disease were studied to determine the safety of LVFX used in combination with nonsteroidal anti-inflammatory drugs (NSAIDs). LVFX was coadministered with NSAIDs in 64.4% of patients (4, 890/7, 597). Phenylacetic acid and propionic acid derivatives, which require “coadministration with care”, were used in 37.2% (2, 828/7, 597). The incidence of adverse central nervous system (CNS) effects in the presence or absence of NSAIDs therapy was 0.04% (1/2, 707) in the non-NSAIDs group, 0.07% (2/2, 828) in the group receiving phenylacetic acid or propionic acid derivatives, and 0.10% (2/2, 062) in the group using other NSAIDs. No significant difference was seen between groups. CNS symptoms included dizziness in two patients and wobbling, insomnia, and drowsiness in one patient each, but no convulsions. The incidence of adverse CNS effects related to the daily dose of LVFX was 0% (0/458) in patients given 200mg/day (100mg b.i.d.), 0.07% (4/5, 716) in patients given 300mg/day (100mg t.d.s.), 0.10% (1/1, 031) in patients receiving 400mg/day (200mg b.i.d.), and 0% (0/65) in patients receiving 600mg/day (200mg t.d.s.). No significant difference was seen between groups, nor when patients were stratified by the presence or absence of concomitant NSAIDs therapy. The incidence of adverse CNS effects was 0.06% (4/7, 088) in patients <65 years old, 0.28% (1/358) in those from 65 to 74 years old, and 0% (0/151) in those ≥75 years, showing no significant difference. No significant difference was seen when patients were stratified by the presence or absence of concomitant NSAIDs therapy.
These results suggest that NSAIDs have very little influence on adverse CNS reactions to LVFX in patients without underlying disease.

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The activities of various antibacterial agents against aerobic gram-positive cocci (28 species, 981 strains) and anaerobic bacteria (21 species, 181 strains), which were isolated from various clinical specimens in 2002 at fifteen clinical facilities in Japan, were studied using either the broth-microdilution or agar-dilution method. The percentages of methicillin-resistant strains among Staphylococcus aureus and Staphylococcus epidermidis were 58.7% and 84.5%, respectively; these bacteria were isolated at a high frequency. Arbekacin, vancomycin (VCM), and quinupristin/dalfopristin (QPR/DPR) had good antibacterial activities against methicillin-resistant S. aureus and methicillin-resistant S. epidermidis, with MIC₉₀S of ≤2μg/mL. The percentage of penicillin (PC)-intermediate and PC-resistant strains among Streptococcus pneumonia, was 81.2%. Among the cephems, cefcapene, cefditoren, cefpirome, and ceftriaxone had MIC₉₀S of ≤1μg/mL against PC-intermediate and PC-resistant strains. Among the new quinolones, tosufloxacin, gatifloxacin, and moxifloxacin had MIC₉₀S of ≤1μg/mL against PC-susceptible, PC-intermediate, and PC-resistant strains. VCM and teicoplanin inhibited the growth of all isolates of Entmcoccus faecalis and Enterococus faecium at ≤2μg/mL, and resistant strains were not detected, suggesting that these agents had good activities against these species. On the other hand, E. faecium strains intermediate or resistant to linezolid or QPR/DPR were found in 5.8% or 15.9% of all strains, respectively. Among the anaerobes, carbapenems showed good activities against Bacteroides spp., Prevotella spp. and Peptostreptococcu spp. However, since several Bacteroides strains were resistant to them, the susceptibility of this species should be monitored.

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We determined the MICs of various antibacterial agents against 1, 163 clinical strains of aerobic gramnegative bacteria (19 genus or species) isolated at fifteen Japanese facilities in 2002. The MICs were determined using mostly the broth microdilution method, and the activities of the agents were assessed. The antibacterial susceptibilities of Enterobacteriaceae to most β-lactams were comparable to those described in our previous report on isolates obtained in 2000; however, the percentages of new-quinolones (NQs)-intermediate or NQs-resistant strains increased. Strains producing extended-spectrum β-lactamases accounted for 1.4% of the Escherichia coli, 1.5% of the Klebsiella spp., and 8.1% of the Proteus spp. Most antibacterial agents showed good activities against Moraxella catarrhalis. On the other hand, the percentage of NQs-intermediate or NQs-resistant strains among Neisseria gonorrhoeae was high at 87%, similar to the results reported in 2000. β-lactamase-producing and β-lactamase-negative ampicillin-resistant strains accounted for 6% and 50% of Haemophilus influenzae isolates, respectively. The activities of most antibacterial agents against Pseudomonas aeruginosa were lower than those in 2000, whereas only doripenem showed an MIC₉₀ of 8μg/mL. The strains resistant to seven or more agents among ten anti-pseudomonal agents accounted for 14.4%. Against other glucose-non-fermentative gram-negative bacteria, the activities of most antibacterial agents, including NQs, were lower than those in 2000.

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