An open clinical study of arbekacin 200 mg q.d. in patients infected with methicillin-resistant Staphylococcus aureus (MRSA) - A clinical pharmacology study

A multi-center collaborative open clinical study was conducted in patients infected with methicillin-resistant Staphylococcus aureus(MRSA) to determine the efficacy and safety of arbekacin(ABK) administered at a dosage regimen of 200 mg q.d. and the relationship between efficacy/ safety and blood ABK concentration (PK/PD). Among 19 patients administered ABK, 14 with pneumonia were included in efficacy evaluation and all 19 in safety evaluation. 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 16.2 μ g/mL and 1.1 μ g/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 12 μ g/mL, regarded as a safety benchmark, the incidence of adverse drug reactions was not higher in patients with a Cmax of ≥ 12 μ g/mL than in those with a Cmax of <12 μ g/mL. This was also the case when the trough concentration of 2 μ g/ mL was used as another safety benchmark. As mentioned above, high Cmax and excellent efficacy of ABK were achieved by the 200 mg q.d. regimen, and the trough concentration was controlled at <2 μ g/mL in many patients. The incidence of adverse drug reactions did not increase with this regimen. The usefulness of ABK 200 mg q.d. was thus confirmed.