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Pharmacodynamics of vancomycin in elderly patients aged 75 years or older with methicillin-resistant Staphylococcus aureus hospital-acquired pneumonia

Authors Mizokami F , Shibasaki M, Yoshizue Y, Noro T, Mizuno T, Furuta K, Noguchi A

Received 20 June 2013

Accepted for publication 10 July 2013

Published 7 August 2013 Volume 2013:8 Pages 1015—1021


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 3

Fumihiro Mizokami,1 Masataka Shibasaki,2 Yasunori Yoshizue,1 Takeshi Noro,1 Tomohiro Mizuno,3 Katsunori Furuta4

1Department of Pharmacy, 2Department of Respiratory Medicine, National Center for Geriatrics and Gerontology, Obu, 3Department of Analytical Pharmacology, Meijo University Graduate School of Pharmacy, Nagoya, 4Department of Clinical Research and Development, National Center for Geriatrics and Gerontology, Obu, Japan

Background: Methicillin-resistant Staphylococcus aureus (MRSA) infections are associated with significant mortality and health care costs. To improve treatment outcomes for MRSA, a better understanding of the pharmacokinetic/pharmacodynamic parameters of vancomycin is required to develop optimal dosing strategies, particularly in elderly patients (≥75 years of age) with limited renal function. The purpose of this study was to determine whether pharmacokinetic indices for vancomycin are associated with mortality from MRSA hospital-acquired pneumonia in elderly patients.
Methods: We conducted a retrospective observational study with 28-day mortality as the primary outcome for 94 patients with MRSA hospital-acquired pneumonia who had been treated with vancomycin from January 2006 through December 2012. Our most recent sampling of MRSA isolates had a minimum inhibitory concentration (MIC) for vancomycin of 1 µg/mL (86%), indicating that the area under the curve (AUC) was equal to the AUC/MIC in these isolates. The primary data from 28-day survivors and nonsurvivors were compared.
Results: Among 94 elderly patients, the mean age was 82 (75–99) years. Multivariate analyses revealed that, among the factors examined, only the nonoptimal AUC (<250, >450 µg*h/mL) was an independent predictor of 28-day mortality in elderly patients (odds ratio 23.156, 95% confidence interval 6.814–78.687, P < 0.001). We detected a significant difference for increasing nephrotoxicity in nonsurvivors (nine of 32 patients [28%]) compared with survivors (three of 62 patients [4.8%], P = 0.003).
Conclusion: This finding indicates that patients with potentially poor renal function are likely to have increased AUC values and a poor prognosis. Consideration of the pharmacokinetics/pharmacodynamics of vancomycin and targeting an AUC/MIC value of 250–450 µg*h/mL may result in improved treatment outcomes for elderly patients with MRSA hospital-acquired pneumonia.

Keywords: methicillin-resistant Staphylococcus aureus, elderly patients, vancomycin, pharmacokinetics, pharmacodynamics

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