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논문 기본 정보

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학술저널
저자정보
Wichai Santimaleeworagun (Department of Pharmacy Faculty of Pharmacy Silpakorn University Nakhon Pathom Thailand.Antibiotic O) Changpradub Dhitiwat (Division of Infectious Diseases Department of Medicine Phramongkutklao Hospital Bangkok Thailand.) Jatapat Hemapanpairoa (Antibiotic Optimization and Patient Care Project by Pharmaceutical Initiative for Resistant Bacteri) Sudaluck Thunyaharn (Faculty of Medical Technology Nakhonratchasima College Nakhon Ratchasima Thailand.)
저널정보
대한감염학회 Infection and Chemotherapy Infection and Chemotherapy 제53권 제3호
발행연도
2021.9
수록면
503 - 511 (9page)
DOI
10.3947/ic.2021.0034

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Background: Linezolid, an oxazolidinone antibiotic, is recommended for vancomycinresistant enterococci (VRE). However, 100% free-drug concentration above the minimum inhibitory concentration (fT>MIC) and an area under the curve of free drug to MIC ratio (fAUC24/MIC) >100 were associated with favorable clinical outcome with less emerging resistance. A plasma trough concentration (Ctrough) of linezolid ≥9 μg/mL was also related to hematologic toxicity. Thus, linezolid dose optimization is needed for VRE treatment. The study aimed to determine the in vitro linezolid activity against clinical VRE isolates and linezolid dosing regimens in critically ill patients who met the target pharmacokinetics/ pharmacodynamics (PK/PD) for VRE treatment. Materials and Methods: Enterococcal isolates from enterococcal-infected patients were obtained between 2014 and 2018 at Phramongkutklao Hospital. We used Monte Carlo simulation to calculate the probability of target attainment, and the cumulative fraction of response (CFR) of the free area under the curve to MIC ratio (fAUIC24) was used to calculate the fAUC24/MIC 80 - 100 and fT/MIC >85 - 100% of the interval time of administration for clinical response and microbiological eradication as well as the Ctrough ≥9 μg/mL for the probability of hematologic toxicity. Results: For linezolid MIC determination, the MIC median (MIC50), MIC for 90% growth (MIC90), and range for linezolid were 1.5 μg/mL, 2 μg/mL, and 0.72 - 2 μg/mL, respectively. A dosing regimen of 1,200 mg either once daily or as a divided dose every 12 h gave target attainments of fAUC24/MICs >80 and >100, which exceeded 90% for MICs ≤1 and ≤1 μg/mL, respectively, with a rate of hematologic toxicity <15%. If the expected fT>MICs were >85% and 100%, a 1,200-mg divided dose every 12 h could cover VRE isolates having linezolid MICs ≤1 μg/mL and ≤0.75 μg/mL. Even 600 mg every 8 h and 1,200 mg as a continuous infusion gave a higher target attainment of fAUC24/MIC and a fT>MIC and the target CFR, but those regimens gave Ctrough ≥9 μg/mL rates of 40.7% and 99.6%. Conclusion: The current dosing of 1,200 mg/day might be optimal treatment for infection by VRE isolates with documented MICs ≤1 μg/mL. For treatment of VRE with a MIC of 2 μg/mL or to achieve the target CFR, the use of linezolid with other antibiotic combinations might help achieve the PK/PD target, provide better clinical outcome, and prevent resistance.
#Enterococcus faecium #Minimum inhibitory concentration #Monte Carlo simulation #Thrombocytopenia

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참고문헌 (34)

참고문헌 신청
Reyes K / 2016 / Vancomycin-resistant enterococci: epidemiology, infection prevention, and control / Infect Dis Clin North Am 30:953~965 google schola Ahmed MO / 2018 / Vancomycin-resistant enterococci: a review of antimicrobial resistance mechanisms and perspectives of human and animal health / Microb Drug Resist 24:590~606 google schola World Health Organization (WHO) / WHO publishes list of bacteria for which new antibiotics are urgently needed google schola National Antimicrobial Resistant Surveillance Center / Thailand google schola Rice LB / 2001 / Emergence of vancomycin-resistant enterococci / Emerg Infect Dis 7:183~187 google schola

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