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KMID : 0984720060380030154
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Infection and Chemotherapy
2006 Volume.38 No. 3 p.154 ~ p.163
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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
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Park Yun-Hee
Lee Dong-Gun
Chun Hye-Sun
Park Chul-Min
Park Sun-Hee
Choi Su-Mi
Lee Hye-Kyung
Park Yeon-Joon
Kim Seong-Yun
Hur Ji-An
Choi Jung-Hyun
Yoo Jin-Hong
Kang Jin-Han
Shin Wan-Shik
Kim Chun-Choo
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Abstract
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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 & 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, Cmax/MIC were less than 9.0 except for ABK 400 mg q24h regimen. In MRSA123, Cmax/MIC were 8.9 on average at ABK 100 mg q12h regimen. But, other regimen showed Cmax/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 Cmax/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.
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KEYWORD
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Staphylococcus aureus, Methicillin resistant, Small colony variants(SCVs), Arbekacin
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