호중구감소 생쥐 감염모델로 평가한 황색포도알균 접종량 차이에 따른 Vancomycin의 효능
Efficacy of Vancomycin against Staphylococcus aureus according to Inoculum Size in a Neutropenic Mouse Infection Model
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with treatment failure, which could be attributable to an inoculum effect (IE). Using a neutropenic mouse thigh infection model, we tried to evaluate the in vivo IE of vancomycin against S. aureus.Background: Staphylococcus aureus is one of the most important gram-positive pathogens in many clinical situations. Use of vancomycin against methicillin resistant S. aureus (MRSA) has been anecdotally associatedMaterials and Methods: Twenty strains of S. aureus were used. Minimum inhibitory concentrations (MICs) were determined by the Clinical and Laboratory Standards Institute guideline. Six-week-old specific-pathogen-free, female CD-1 mice weighing 23-27 grams were used. The neutropenic mice received inoculations of 5.02-5.74 log10 CFU/thigh in one thigh (low inoculum, LI), and 7.22-7.73 log10 CFU/thigh in the other thigh (high inoculum, HI) before therapy. The mice were treated with 6 hourly subcutaneous doses of vancomycin (3.125-100 mg/kg) for 24 h. Single-dose serum pharmacokinetics of vancomycin was determined. Dose-response data were analyzed by an Emax model using non-linear regression. Static doses and area under the curve (AUC)/MIC for bacteriostatic effect at each inoculum were calculated and compared. The ratio of static dose and AUC/MIC between HI and LI (IE index) provided the magnitude of IE for each organism. Results: Five methicillin-susceptible S. aureus (MSSA) strains and 15 MRSA strains were used. Vancomycin MICs of the 20 strains varied by 4-fold (0.5-2 mg/L). The AUC/MIC ratio was the major parameter determining the efficacy of vancomycin against S. aureus . Mean (range) static dose on LI and HI was 20.7 (11.8-35.1) and 136.7 (32.1-314), respectively. The mean IE index of static dose between them was 7.39. Mean (range) of AUC/MIC on LI and HI was 27.0 (6.61-66.6) and 152.3 (46.2-344), respectively, which produced a mean IE index of AUC/MIC of 7.47. The IE indices of the MSSA strains were significantly higher than those of the MRSA strains (11.3 vs. 6.1 on static dose [P=0.018], 11.4 vs. 6.2 on AUC/MIC [P=0.034]). Conclusions: With a 100-fold inoculum increment of S. aureus , at least a 7-fold dose of vancomycin would be required to show the same bacteriostatic effect. Thus, IE as well as MICs is an important parameter in selecting and adjusting a dose and dosage interval along with the resistance profile in the treatment of S. aureus infections. IE to vancomycin observed in the in vivo neutropenic mouse model was more evident for MSSA strains than for MRSA strains.
Abstract
with treatment failure, which could be attributable to an inoculum effect (IE). Using a neutropenic mouse thigh infection model, we tried to evaluate the in vivo IE of vancomycin against S. aureus.Background: Staphylococcus aureus is one of the most important gram-positive pathogens in many clinical situations. Use of vancomycin against methicillin resistant S. aureus (MRSA) has been anecdotally associatedMaterials and Methods: Twenty strains of S. aureus were used. Minimum inhibitory concentrations (MICs) were determined by the Clinical and Laboratory Standards Institute guideline. Six-week-old specific-pathogen-free, female CD-1 mice weighing 23-27 grams were used. The neutropenic mice received inoculations of 5.02-5.74 log10 CFU/thigh in one thigh (low inoculum, LI), and 7.22-7.73 log10 CFU/thigh in the other thigh (high inoculum, HI) before therapy. The mice were treated with 6 hourly subcutaneous doses of vancomycin (3.125-100 mg/kg) for 24 h. Single-dose serum pharmacokinetics of vancomycin was determined. Dose-response data were analyzed by an Emax model using non-linear regression. Static doses and area under the curve (AUC)/MIC for bacteriostatic effect at each inoculum were calculated and compared. The ratio of static dose and AUC/MIC between HI and LI (IE index) provided the magnitude of IE for each organism. Results: Five methicillin-susceptible S. aureus (MSSA) strains and 15 MRSA strains were used. Vancomycin MICs of the 20 strains varied by 4-fold (0.5-2 mg/L). The AUC/MIC ratio was the major parameter determining the efficacy of vancomycin against S. aureus . Mean (range) static dose on LI and HI was 20.7 (11.8-35.1) and 136.7 (32.1-314), respectively. The mean IE index of static dose between them was 7.39. Mean (range) of AUC/MIC on LI and HI was 27.0 (6.61-66.6) and 152.3 (46.2-344), respectively, which produced a mean IE index of AUC/MIC of 7.47. The IE indices of the MSSA strains were significantly higher than those of the MRSA strains (11.3 vs. 6.1 on static dose [P=0.018], 11.4 vs. 6.2 on AUC/MIC [P=0.034]). Conclusions: With a 100-fold inoculum increment of S. aureus , at least a 7-fold dose of vancomycin would be required to show the same bacteriostatic effect. Thus, IE as well as MICs is an important parameter in selecting and adjusting a dose and dosage interval along with the resistance profile in the treatment of S. aureus infections. IE to vancomycin observed in the in vivo neutropenic mouse model was more evident for MSSA strains than for MRSA strains.
참고문헌 (35)
- Wisplinghoff H, "Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study", Clin Infect Dis, 39, pp.309~317 (2004)
- Weber JT, "Community-associated methicillin-resistant Staphylococcus aureus", Clin Infect Dis, 41(4), pp.S269~S272 (2005)
- Levine DP, "Vancomycin: a history", Clin Infect Dis, 42(1), pp.S5~S12 (2006)
- Karchmer AW, "Staphylococcus aureus and vancomycin: the sequel", Ann Intern Med, 115, pp.739~741 (1991)
- Fridkin SK, "Epidemiological and microbiological characterization of infections caused by Staphylococcus aureus with reduced susceptibility to vancomycin, United States, 1997-2001", Clin Infect Dis, 36, pp.429~439 (2003)
- LaPlante KL, "Impact of high-inoculum Staphylococcus aureus on the activities of nafcillin, vancomycin, linezolid, and daptomycin, alone and in combination with gentamicin, in an in vitro pharmacodynamic model", Antimicrob Agents Chemother, 48, pp.4665~4672 (2004)
- 김성한, "Outcome of vancomycin treatment in patients with methicillin-susceptible Staphylococcus aureus bacteremia", ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 52, pp.192~197 (2008), 미국의사협회
- Stryjewski ME, "Use of vancomycin or first-generation cephalosporins for the treatment of hemodialysis-dependent patients with methicillin-susceptible Staphylococcus aureus bacteremia", Clin Infect Dis, 44, pp.190~196 (2007)
- Rybak MJ, "Emergence of methicillin-resistant Staphylococcus aureus with intermediate glycopeptide resistance: clinical significance and treatment options", Drugs, 61, pp.1~7 (2001)
- Brook I, "Inoculum effect", Rev Infect Dis, 11, pp.361~368 (1989)
- Lamp KC, "In vitro pharmacodynamic effects of concentration, pH, and growth phase on serum bactericidal activities of daptomycin and vancomycin", Antimicrob Agents Chemother, 36, pp.2709~2714 (1992)
- Mercier RC, "Pharmacodynamic evaluation of a new glycopeptide, LY333328, and in vitro activity against Staphylococcus aureus and Enterococcus faecium", Antimicrob Agents Chemother, 41, pp.1307~1312 (1997)
- Moise PA, "Susceptibility relationship between vancomycin and daptomycin in Staphylococcus aureus: facts and assumptions", Lancet Infect Dis, 9, pp.617~624 (2009)
- Craig WA, "Pharmacokinetic", pharmacodynamic parameters: rationale for antibacterial dosing of mice and men, 1998, pp.26, 1~12
- Ambrose PG, "Pharmacokinetics-pharmacodynamics of antimicrobial therapy: it's not just for mice anymore", Clin Infect Dis, 44, pp.79~86 (2007)
- Performance standards for antimicrobial susceptibility testing; eighteenth informational supplement, "Clinical and Laboratory Standards Institute", CLSI, ~, pp.CLSI document M100-S18 (2008)
- Craig WA, "In vivo pharmacodynamics of ceftobiprole against multiple bacterial pathogens in murine thigh and lung infection models", Antimicrob Agents Chemother, 52, pp.3492~3496 (2008)
- Craig WA, "In vivo pharmacodynamics of new lipopeptide MX-2401", Antimicrob Agents Chemother, 54, pp.5092~5098 (2010)
- Stratton CW, "In vitro susceptibility testing versus in vivo effectiveness", Med Clin North Am, 90, pp.1077~1088 (2006)
- Woods DD, "The relation of p-aminobenzoic acid to the mechanism of the action of sulphanilamide", Br J Exp Pathol, 21, pp.74~90 (1940)
- Stevens DL, "The role of vancomycin in the treatment paradigm", Clin Infect Dis, 42(1), pp.S51~S57 (2006)
- Nannini EC, "Determination of an inoculum effect with various cephalosporins among clinical isolates of methicillin-susceptible Staphylococcus aureus", Antimicrob Agents Chemother, 54, pp.2206~2208 (2010)
- Gould IM, "Is vancomycin redundant for serious staphylococcal infection", Int J Antimicrob Agents, 36(2), pp.S55~S57 (2010)
- Rybak MJ, "Vancomycin therapeutic guidelines: a summary of consensus recommendations from the infectious diseases Society of America, the American Society of Health-System Pharmacists, and the Society of Infectious Diseases Pharmacists", Clin Infect Dis, 49, pp.325~327 (2009)
- Nettey H, "In vitro antimicrobial effect of encapsulated vancomycin on internalized Staphylococcus aureus within endothelial cells", Drug Dev Ind Pharm, 33, pp.133~139 (2007)
- Carryn S, "Intracellular pharmacodynamics of antibiotics", Infect Dis Clin North Am, 17, pp.615~634 (2003)
- Donlan RM, "Biofilms: survival mechanisms of clinically relevant microorganisms", Clin Microbiol Rev, 15, pp.167~193 (2002)
- Conly JM, "VISA, hetero-VISA and VRSA: The end of the vancomycin era", Can J Infect Dis, 13, pp.282~284 (2002)
- Proctor RA, "Staphylococcal small colony variants have novel mechanisms for antibiotic resistance", Clin Infect Dis, 27(1), pp.S68~S74 (1998)
- 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
- Ekdahl C, "Rapid decrease of free vancomycin in dense staphylococcal cultures", Eur J Clin Microbiol Infect Dis, 24, pp.596~602 (2005)
- Chambers HF, "Parenteral antibiotics for the treatment of bacteremia and other serious staphylococcal infections, in The staphylococci in human disease", pp.583~601 (1997), Churchill Livingstone
- Performance standards for antimicrobial susceptibility testing; sixteenth informational supplement, "Clinical and Laboratory Standards Institute", CLSI, ~, pp.CLSI document M100-S15 (2006)
- 정경태, "Nationwide Surveillance Study of Vancomycin-Intermediate Staphylococcus aureus Strains in Korean Hospitals from 2001 to 2006", Journal of Microbiology and Biotechnology, 20(3), pp.637~642 (2010), 한국미생물·생명공학회
- Howden BP, "Treatment outcomes for serious infections caused by methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility", Clin Infect Dis, 38, pp.521~528 (2004)