Dosage regimen of arbekacin for methicillin-resistant Staphylococcus aureus infection in newborns and infants.
BACKGROUND
Arbekacin (ABK) is an aminoglycoside antibiotic that has a dose-dependent bactericidal action. Because it inhibits the production of toxic shock syndrome toxin-1 (TSST-1) by methicillin-resistant Staphylococcus aureus (MRSA), it has attracted attention as a therapeutic drug for MRSA infection. In this study, the authors investigated the pharmacokinetics of ABK based on therapeutic drug monitoring (TDM), in order to establish an effective dosage regimen with minimal adverse reactions in MRSA infected newborns and infants.


METHODS
Arbekacin was administered to nine MRSA infected newborns and infants between October 2000 and March 2002. Following the initial ABK administration, blood was collected and the blood concentration of ABK was measured. The blood concentrations of ABK were analyzed by the two-compartment model or by a model-independent method in order to elucidate the pharmacokinetics of ABK. Pharmacokinetic analysis was performed using WinNonlin Professional V3.1.


RESULTS
The mean age at initial ABK administration was 24.0 +/- 26.0 days (postconceptional age: 39.2 +/- 3.9 weeks). The increase in the peak blood concentration of ABK was 2.40 +/- 0.20 microg/mL per mg ABK per kg bodyweight, showing great consistency among cases. The elimination half-life of ABK was 0.22-3.52 h in the alpha phase (T(1/2alpha)) and 2.42-33.44 h in the beta phase (T(1/2beta)), showing great variation among cases. The distribution volume was 0.75 +/- 0.13 L/kg, and systemic clearance was 0.054 +/- 0.012 L/h/kg. ABK alleviated clinical symptoms and inflammations in all cases.


CONCLUSIONS
Nine newborns and infants with MRSA infection and various underlying diseases were successfully treated with TDM-based administration of ABK with no severe adverse reactions.
Yoshida
Koichi
K
Department of Pediatrics, Nara Hospital, Kinki University School of Medicine, Nara, Japan. koichi21yoshida@yahoo.co.jp
Minowa
Hideki
H
Ebisu
Reiko
R
Uchida
Yumiko
Y
Takahashi
Yukihiro
Y
Yoshioka
Akira
A
D000617:Aminoglycosides / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001682:Biological Availability; D001724:Birth Weight; D003982:Dibekacin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007363:Intensive Care Units, Neonatal; D008297:Male; D020714:Maximum Tolerated Dose; D016106:Methicillin Resistance; D011446:Prospective Studies; D012720:Severity of Illness Index; D013203:Staphylococcal Infections / Q000175:diagnosis / Q000188:drug therapy*; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000302:isolation & purification; D016896:Treatment Outcome
D000617:Aminoglycosides; D003982:Dibekacin; C031986:arbekacin