A multi-center collaborative open clinical study was conducted in patients infected with methicillinresistant Staphylococcus aureus (MRSA) to determine the efficacy and safety of arbekacin (ABK) administered at a dosage regimen of 200mg q. d. and the relationship between efficacy/safety and blood ABK concentration (PIVPD).
Effectiveness (clinical efficacy) against MRSA-caused pneumonia was 71.4% and eradication/decrease (bacteriological efficacy) was 46.2%, showing favorable results. We thus confirmed that the 200 mg q.d.regimen of ABK would be effective against MRSA-caused pneumonia. Evaluating pharmacokinetic parameters, mean Cmax and Ctrough values were 16.2μg/mL and 1.1μg/mL, respectively, and the elimination half-life was prolonged in patients with moderate to severe renal dysfunction. As a result of PK/PD analysis, it was estimated that the expected clinical effect could be obtained when the ratio of Cmax/MIC exceeded 7 or 8, but it was difficult to clarify the target value due to the small sample size.In safety evaluation, the incidence of adverse drug reactions related to subjective/objective findings was 15.8% and the incidence of adverse reactions related to abnormal laboratory findings was 36.8%, and no unknown adverse drug reactions were observed. As a serious adverse event, shock was noted in one patient, but the causal relationship to ABK was ruled out. When patients were categorized with Cmax by whether or not reaching 12μg/mL, regarded as a safety benchmark, the incidence of adverse drug reactions was not higher in patients with a Cmax of≥12μg/mL than in those with a Cmax of<12μg/mL. This was also the case when the trough concentration of 2μg/mL, was used as another safety benchmark.
As mentioned above, high Cmax and excellent efficacy of ABK were achieved by the 200mg q. d. regimen, and the trough concentration was controlled at<2μg/mL., in many patients. The incidence of adverse drug reactions did not increase with this regimen.The usefulness of ABK 200mg q. d. was thus confirmed.

View full abstract

The use of antibiotics to Pseudomonas aeruginosa was studied in relation to the antimicrobial susceptibility using 3, 002 clinical isolates of P. aeruginosa obtained from patients of Public Fujioka General Hospital between 2002 and 2006. The high proportion of isolates showed susceptibility to piperacillin (PIPC), amikacin (AMK) and levofloxacin (LVFX), and the number of strains with resistance to the tree antibiotics did not change during this period. Use of carbapenems, especially imipenem (IPM) was decreased year by year. However, the number of resistance strains did not change.Use of carbapenems was not associated with the drug susceptibility of the isolates. The patterns of the susceptibility to IPM were different from that to meropenem (MEPM). IPM-resistant strains were susceptible to other antibiotics, while MEPM-resistant strains were resistant to other antibiotics.Especially, all of 20 isolates which were resistant to IPM and susceptible to MEPM were susceptible to PIPC, ceftazidime (CAZ), aztreonam (AZT) and AMK. Since the permeabilitychannels of P. aeruginosa are different for IPM and MEPM and the efflux systems are associated only with MEPM, the cross-resistance of P. aeruginosa to MEPM and other antibiotics should be carefully considered in treatment of infectious disease caused P. aeruginosa.

View full abstract

Prulifloxacin (PUFX, Sword^®Tablets 100), an oral quinolone antibiotic, was approved for marketing on October 8, 2002.In the 3 years from January 2004 to 2007, we studied practical use in compliance with new Good Postmarketing Surveillance Practices (GPMSP).
Of 4, 034 cases collected from 539 medical institutes nationwide, we evaluated 3, 076 for safety and 2, 881 for clinical efficacy, with the following results:
1) The incidence of adverse drug reactions, 1.01% (31 cases/3, 076 cases), was lower than that in clinical studies before marketing approval, 9.20% (270 cases/2, 936 cases). The most frequently observed adverse drug reaction was diarrhea, at 0.33% (10 cases/3, 076 cases). No serious adverse reaction was observed.
2) Clinical efficacy in each infection was from 932-100%, in each disease 90% or more excluding pneumonia, and results were equivalent to those in studies before marketing approval.

View full abstract

The clinical efficacy of micafungin (MCFG), the first echinocandin antifungal agent approved in Japan, in surgery, emergency, and intensive-cue medicine has only been studied in a limited number of cases, with no large-scale reports filed as of this writing. We conducted a postmarketing surveillance study to evaluate MCFG efficacy and safety at 63 medical departments in Japan. MCFG was given to patients with a fever exceeding 375°C, either diagnosed with a proven fungal infection based on mycological or histopathological examination, or diagnosed with a suspected fungal infection with high risk factors, based on surveillance culture or serum β-D glucan testing. Efficacy was evaluated using the AKOTT algorithm created by our group for objectively evaluating antifungal agent efficacy in patients with both fungal and bacterial infections. Of the 180 patients enrolled, 68 were excluded by exclusion criteria or other reasons and 112 patients (58 with proven candidiasis, 1 with proven aspergillosis, and 53 with suspected fungal infection) were evaluated for efficacy. MCFG was administered at a mean maximum daily dose of 104 mg for a mean duration of 142 days. It was effective in 72 patients, ineffective in 28, and of undeterminable efficacy in 12, for overall clinical efficacy of 72.0%. Classified by diagnosis, MCFG was effective in 78.6% of those with proven candidiasis (44/56) and 65.1% with suspected fungal infection (28/43), but ineffective in 1 patient with aspergillosis.MCFG successfully eradicated 77.6% (52/67) of fungi isolated in patients. Some 69 drug-related adverse reactions, mainly abnormal hepatic function, occurred in 37 of 178 patients in safety evaluation (20.8%), but the event incidence was not dose-dependent. One adverse reaction, skin eruption, had a probable causal relationship to drug treatment.In conclusion, MCFG shows high clinical efficacy and safety in the treatment of deep-seated fungal infection in surgery, emergency, and intensive-care medicine, indicating good potential as a first-line drug for both targeted and empirical therapies.

View full abstract

In a postmarketing surveillance study for comparison with previous results, we determined the susceptibility to micafungin (MCFG) and other antifungal drugs-amphotericin B, fluconazole, itraconazole, miconazole, flucytosine, caspofungin, and voriconazole-for 690 strains (410 of 6 Candida species and 280 of 4 Aspergillus species), isolated from patients with suspected fungal infection visiting medical facilities in Japan between January 2005 and December 2006. MIC levels against Candida and Aspergillus species were determined according to the broth microdilution, as specified by Clinical and Laboratory Standards Institute (CLSI) documents M27-A and M38-P. For Candida species, MIC levels for score 2, currently being standardized by the CLSI as criteria for MIC determination of echinocandin antifungal drugs against Candida species, were determined for reference in addition to score O. MIC₉₀ levels of MCFG against 130 Candida albicans isolates, including those fluconazole-resistant were 0.015 μg/mL, and against 50 isolates each of Candida tropicalis 0.03 μg/mL, Candida glabrata 0.015 μg/mL, Candida parapsilosis 2 μg/mL, Candida krusei 025 μg/mL, and Candida guilliermondii 4 μg/mL. MIC₉₀ levels of MCFG against 100 Aspergillus fumigatus isolates were 0.015 μg/mL and against another 180 Aspergillus isolates 0.008 to 0.03 μg/mL. MIC levels of MCFG against Candida and Aspergillus species determined in this study remained unchanged compared to those against isolates sampled in 2001-2002 and 2003-2004. MIC levels of MCFG for score 2 tended to be lower than those for score O, with a markedly significant difference between scores observed in MIC against C. guilliermondii. These findings indicate that MCFG exerts the most potent antifungal activity of antifungal drugs studied and that the susceptibility of target fungi to MCFG remained high compared to previous biennial surveillance conducted from 2001.

View full abstract