Yonsei Med J.  2010 Sep;51(5):722-727. 10.3349/ymj.2010.51.5.722.

Once-Daily Gentamicin Administration for Community-Associated Methicillin Resistant Staphylococcus aureus in an in vitro Pharmacodynamic Model: Preliminary Reports for the Advantages for Optimizing Pharmacodynamic Index

• Kim SW
• Lee DG
• Choi SM
• Park C
• Kwon JC
• Kim SH
• Park SH
• Choi JH
• Yoo JH
• Shin WS

• KMID: 1071424
• DOI: http://doi.org/10.3349/ymj.2010.51.5.722

Abstract

PURPOSE
Community-associated methicillin resistant Staphylococcus aureus (CA-MRSA) infections are increasing. Although gentamicin (GEN) is usually susceptible against CA-MRSA, GEN is rarely considered for treatment as monotherapy. We employed an in vitro pharmacodynamic model (IVPDM) to compare efficacies of GEN against CA-MRSA with two dosing regimens [thrice-daily (TD), once-daily (OD)].
MATERIALS AND METHODS
Using two strains of CA-MRSA, we adopted IVPDM comprised of two-compartments with a surface-to-volume ratio of 5.34 cm-1. GEN regimens were simulated with human pharmacokinetic data of TD and OD. Experiments were performed over 48 hours in triplicate for each strain and dosing regimen.
RESULTS
MICs of GEN for YSSA1 and YSSA15 were 1 and 2 mg/L, respectively. In OD, indices of peak/MIC were > 8.6 at least, in contrast to < 6.4 in TD. A > or = 3-log10 reduction in CFU/mL was demonstrated prior to 4 hours in TD and OD, and continued until 8 hours for both strains. However, reductions in the colony counts at 24 and 48 hours were significantly larger for OD compared to TD in both strains (p < 0.001). During TD, resistance developed in YSSA1 and small colony variants (SCVs) were documented in YSSA15. No resistance or SCVs were observed during OD in both strains.
CONCLUSION
TD and OD showed the same killing slopes until 8 hours. After the 24 hours of experiments, OD of GEN would be advantageous not only in having more reductions in colony counts, but also suppressing the development of resistance or SCVs for 48 hours.

Keyword

Methicillin-Resistant Staphylococcus aureus; gentamicin; pharmacodynamics; once-daily treatment

MeSH Terms

Anti-Bacterial Agents/*administration & dosage/pharmacokinetics/*pharmacology
Drug Administration Schedule
Gentamicins/*administration & dosage/pharmacokinetics/*pharmacology
Humans
Methicillin-Resistant Staphylococcus aureus/*drug effects
Microbial Sensitivity Tests

Figure

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  Fig. 1 Schematic presentation of in vitro pharmacodynamic model.

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  Fig. 2 Time-kill curves of gentamicin against YSSA1 (A) and YSSA15 (B). The results are presented as means ± standard deviations (error bar) of colony counts (log10 CFU/mL) for measurements done in triplicate. GEN, gentamicin; q8h, every 8 hours; q24, every 24 hours; SCVs, small colony variants.

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