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

Fumihiro Mizokami,¹ Masataka Shibasaki,² Yasunori Yoshizue,¹ Takeshi Noro,¹ Tomohiro Mizuno,³ Katsunori Furuta<sup>4

1</sup>Department 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