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
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Purpose: 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)]. 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 ≥ 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.
Abstract
Purpose: 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)]. 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 ≥ 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.
참고문헌 (29)
- Fridkin SK, "Methicillin-resistant Staphylococcus aureus disease in three communities", N Engl J Med, 352, pp.1436~1444 (2005)
- Zetola N, "Communityacquired methicillin-resistant Staphylococcus aureus: an emerging threat", Lancet Infect Dis, 5, pp.275~286 (2005)
- Moreillon P, "Infective endocarditis", Lancet, 363, pp.139~149 (2004)
- Lee DG, "Efficacies of vancomycin, arbekacin, and gentamicin alone or in combination against methicillin-resistant Staphylococcus aureus in an in vitro infective endocarditis model", Antimicrob Agents Chemother, 47, pp.3768~3773 (2003)
- Shelburne SA, "In vitro killing of community-associated methcillin-resistant Staphylococcus aureus with drug combinations", Antimicrob Agents Chemother, 48, pp.4016~4019 (2004)
- Munckhof WJ, "Resistance development in community-acquired strains of methicillin-resistant Staphylococcus aureus: an in vitro study", Int J Antimicrob Agents, 24, pp.605~608 (2004)
- Rybak MJ, "Community-associated methicillinresistant Staphylococcus aureus: a review", Pharmacotherapy, 25, pp.74~85 (2005)
- Tsuji BT, "Community- and health care-associated methicillin-resistant Staphylococcus aureus: a comparison of molecular epidemiology and antimicrobial activities of various agents", Diagn Microbiol Infect Dis, 58, pp.41~47 (2007)
- Rybak MJ, "Prospective evaluation of the effect of an aminoglycoside dosing regimen on rates of observed nephrotoxicity and ototoxicity", Antimicrob Agents Chemother, 43, pp.1549~1555 (1999)
- Proctor RA, "Small colony variants: a pathogenic form of bacteria that facilitates persistent and recurrent infections", Nat Rev Microbiol, 4, pp.295~305 (2006)
- Schaaff F, "Mutations are involved in emergence of aminoglycoside-induced small colony variants of Staphylococcus aureus", Int J Med Microbiol, 293, pp.427~435 (2003)
- Sendi P, "Staphylococcus aureus small colony variants in prosthetic joint infection", Clin Infect Dis, 43, pp.961~967 (2006)
- Turnidge M, "Pharmacodynamics and dosing of aminoglycosides", Infect Dis Clin North Am, 17, pp.503~528 (2003)
- Kim M, "Antimicrobial pharmacodynamics in theory and clinical practice, 2nd ed.", pp.147~175 (2007), Informa Healthcare
- Park C, "Predominance of community-associated methicillin-resistant Staphylococcus aureus strains carrying staphylococcal chromosome cassette mec type IVA in South Korea", J Clin Microbiol, 45, pp.4021~4026 (2007)
- 박철민, "Panton-Valentine Leukocidin 양성 지역사회관련 메티실린 내성 황색포도알균에 의한 항문주위 농양 1예: 국내 보고 및 동아시아 증례 문헌고찰", Infection and Chemotherapy, 40(2), pp.121~126 (2008), 대한감염학회
- Clinical Laboratory Standards Institute, "CLSI performance standards for antimicrobial susceptibility testing; sixteenth informational supplement", ~ (2006)
- Bonapace CR, "Determination of antibiotic effect in an in vitro pharmacodynamic model: com-parison with an established animal model of infection", Antimicrob Agents Chemother, 46, pp.3574~3579 (2002)
- 박윤희, "시험관내 약역학 감염모델을 이용한 Methicillin 내성 포도알균 실험 중 출현한 Small Colony Variants 생성억제를 위한 Arbekacin의 효과", Infection and Chemotherapy, 38(3), pp.154~163 (2006), 대한감염학회
- Houlihan HH, "Pharmacodynamics of vancomycin alone and in combination with gentamicin at various dosing intervals against methcillin-resistant Staphylococcus aureus-infected fibrin-platelet clots in an in vitro infection model", Antimicrob Agents Chemother, 41, pp.2497~2501 (1997)
- von Eiff C, "The small colony variant (SCV) concept -- the role of staphylococcal SCVs in persistent infections", Injury, 37, pp.S26~33 (2006)
- McGrath BJ, "Pharmacodynamic effects of extended dosing intervals of imipenem alone and in combination with amikacin against Pseudomonas aeruginosa in an in vitro model", Antimicrob Agents Chemother, 37, pp.1931~1937 (1993)
- Barclay ML, "Adaptive resistance following single doses of gentamicin in a dynamic in vitro model", Antimicrob Agents Chemother, 36, pp.1951~1957 (1992)
- Domínguez MC, "Application of a spectrophotometric method for the determination of post-antibiotic effect and comparison with viable counts in agar", J Antimicrob Chemother, 47, pp.391~398 (2001)
- Schafer JA, "Consistent rates of kill of Staphylococcus arueus by gentamicin over a 6-fold clinical concentration range in an in vitro pharmacodynamic model (IVPDM)", J Antimicrob Chemother, 58, pp.108~111 (2006)
- Tam VH, "Comparative pharmacodynamics of gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa", Antimicrob Agents Chemother, 50, pp.2626~2631 (2006)
- Blaser J, "Comparative study with enoxacin and netilmicin in a pharmacodynamic model to determine importance of ratio of antibiotic peak concentration to MIC for bactericidal activity and emergence of resistance", Antimicrob Agents Chemother, 31, pp.1054~1060 (1987)
- Baumert N, "Physiology and antibiotic susceptibility of Staphylococcus aureus small colony variants", Microb Drug Resist, 8, pp.253~260 (2002)
- Gavaldà J, "Efficacy of ceftriaxone and gentamicin given once a day by using human-like pharmacokinetics in treatment of experimental staphylococcal endocarditis", Antimicrob Agents Chemother, 46, pp.378~384 (2002)