Pharmacokinetic-pharmacodynamic relationship of arbekacin for treatment of patients infected with methicillin-resistant Staphylococcus aureus.

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 microg/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 microg/ml, respectively. The present findings are useful for optimizing the individual dose of arbekacin for the treatment of MRSA-infected patients.

Efficacy and safety of arbekacin for staphylococcal infection in the NICU.

BACKGROUND: This is a retrospective study on the efficacy and safety of arbekacin (ABK), an aminoglycoside antibiotic, for acquired staphylococcal infection in the neonatal intensive care nursery. PATIENTS AND METHODS: Subjects were 29 infants treated with ABK in a tertiary care neonatal center. They were 23-39 (median 28) weeks' gestation, 530-3334 (median 930) grams at birth, and 3-157 (median 17) days of age. Diagnosis of staphylococcal infection was made by clinical signs and laboratory findings. Sensitivity of the isolated organisms to ABK was tested by the microliquid dilution method. Serum ABK level was monitored to achieve the therapeutic range during the treatment. Effectiveness was defined by improving clinical signs and laboratory findings within 3 days. Effectiveness was studied in relation to type of infection and other antibiotics administered. Auditory brainstem response and serum creatinine changes were studied for ototoxicity and nephrotoxicity assessment, respectively. RESULTS: Twenty-seven (93.1%) cases of infection were attributed to methicillin-resistant Staphylococcus aureus (MRSA) and two (6.9%) were attributed to coagulase-negative staphylococci (CNS). The rate of in vitro sensitivity to ABK was 85.2% for MRSA and 100.0% for CNS. The overall clinical effeciveness rate was 79.3% (23/29) with no difference associated with types of infection. Combination of ABK with sulbactam/ampicillin showed greater effectiveness (100.0%) than with other antibiotics (64.3%) (P < 0.05). There was no abnormal auditory brainstem response or serum creatinine change associated with ABK treatment. CONCLUSION: ABK is an effective and safe antibiotic for the treatment of acquired staphylococcal infection in the neonatal intensive care nursery.

[Dibekacin in the treatment of urinary infections in the elderly]. / La dibékacine dans le traitement de l'infection urinaire du sujet âgé.

Urinary tract infections in the elderly are severe and intractable, often justifying the use of aminoglycosides. We studied the effects of dibekacin in 28 patients, with no vesical catheter, whose average age was 78 +/- 6.1 years. The drug was given for ten days, in an average dose of 2.1 mg/kg/day divided into two injections. Serum concentration was measured after one hour on day 1 and after eight hours on days 1 and 10. Causative pathogens, all susceptible to dibekacin, were: 18 E. coli, 3 Proteus mirabilis, 3 Klebsiella, 1 Enterobacter cloacae, 1 Citrobacter and 2 Staphylococci. MIC and MBC of dibekacin were determined for each microorganism. Dibekacin was discontinued in four cases on day three because of persistent bacteriuria. Ten days after treatment end, 19 patients were cured, 4 had a relapse and 1 was reinfected. Average serum concentration of dibekacin, measured after eight hours, increased from 0.77 +/- 0.48 micrograms/ml on day 1 to 1.78 +/- 1.22 microgram/ml on day 10 (t = 4.42; p less than 0.0005), while, over the same period, there was no significant change in serum creatinine.