Infect Chemother.  2006 Jun;38(3):154-163.

Once-daily Dosing of Arbekacin Can Suppress the Formation of Small Colony Variants of Methicillin Resistant Staphylococcus aureus in an in vitro Pharmacodynamic Infection Model

Affiliations
  • 1Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. symonlee@catholic.ac.kr
  • 2Catholic Research Institutes of Medical Sciences, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 3Department of Department of Laboratory Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 4Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
  • 5Department of Pediatrics, College of Medicine, The Catholic University of Korea, Seoul, Korea.

Abstract

BACKGROUND: Small colony variants (SCVs) of Staphylococcus aureus have emerged to be commonly associated with persistent and relapsing infections. Arbekacin (ABK) is one of a few alternatives to vancomycin in intractable case of methicillin resistant S. aureus (MRSA) infection. However, it has not yet been defined whethter ABK tends to be efficacious to the MRSA SCVs. In this study, we employed an in vitro pharmacodynamic infection model (IVPDIM) to define efficacies of ABK against MRSA SCVs.
MATERIALS AND METHODS
Using four strains of clinically isolated MRSA (MRSA122, MRSA160, MRSA18, MRSA123), we adopted IVPDIM comprised of two-compartment in which effective surface-to-volume ratio of 5.34 cm(-1). Human pharmacokinetic regimen simulations of ABK were as follows: 100 mg every 12 h (q12h), 200 mg q24h, 200 mg q12h, and 400 mg q24h. Samples were taken from each model at 0, 1, 2, 4, 6, 12, 24, and 30 h, and the bacterial colony counts were determined. The experiments were repeated twice with ABK-administered groups and control group.
RESULTS
MICs of ABK for MRSA122, MRSA160, MRSA18, and MRSA123 were 2, 2, 2, and 1 microgram/mL, respectively. In case of MRSA122, MRSA160, MRSA18, C(max)/MIC were less than 9.0 except for ABK 400 mg q24h regimen. In MRSA123, C(max)/MIC were 8.9 on average at ABK 100 mg q12h regimen. But, other regimen showed C(max)/MIC >9. Four regimens for 4 strains showed statistically different colony counts at 30 h (P=0.000). The more dosage or less frequent dosing interval, the more colonies tended to reduce in all strains. In 100 mg q12h groups, SCVs were observed in all strains within 24 h. With increment of dosage or changing dosing interval from q12h to 24h, SCVs were reduced (P=0.000). Regimen of 400 mg q24h did not let SCVs appear in all strains of MIC 2 microgram/mL during the experiments.
CONCLUSION
SCVs were observed when MIC of ABK against MRSA were 1-2 microgram/mL, especially in most cases of C(max)/MIC <9. Those findings were also associated with re-growth of colony during the experiments. Once-daily dosing of ABK could reduce or eliminate the appearance of SCV.

Keyword

Staphylococcus aureus; Methicillin resistance; Small colony variants (SCVs); Arbekacin

MeSH Terms

Humans
Linear Energy Transfer
Methicillin Resistance*
Methicillin*
Methicillin-Resistant Staphylococcus aureus
Staphylococcus aureus*
Staphylococcus*
Vancomycin
Methicillin
Vancomycin
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