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.
OBJECTIVE
Community-associated methicillin resistant Staphylococcus aureus (CAMRSA) 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)].


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-log(10) 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.


CONCLUSIONS
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.
Kim
Sun Woo
SW
Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Lee
Dong-Gun
DG
Choi
Su-Mi
SM
Park
Chulmin
C
Kwon
Jae-Cheol
JC
Kim
Si-Hyun
SH
Park
Sun Hee
SH
Choi
Jung-Hyun
JH
Yoo
Jin-Hong
JH
Shin
Wan-Shik
WS
D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004334:Drug Administration Schedule; D005839:Gentamicins / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests
D000900:Anti-Bacterial Agents; D005839:Gentamicins