The influence of severe hypoalbuminemia on the half-life of vancomycin in elderly patients with methicillin-resistant Staphylococcus aureus hospital-acquired pneumonia

Tomohiro Mizuno,^1,* Fumihiro Mizokami,^2,* Kazuhiro Fukami,² Kazuhiro Ito,² Masataka Shibasaki,³ Tadashi Nagamatsu,¹ Katsunori Furuta,^4
1Department of Analytical Pharmacology, Meijo University Graduate School of Pharmacy, Nagoya, Japan; ²Department of Pharmacy, National Center for Geriatrics and Gerontology, ³Department of Respiratory Medicine, National Center for Geriatrics and Gerontology, ⁴Department of Clinical Research and Development, National Center for Geriatrics and Gerontology, Obu, Japan

*These authors contributed equally to this work

Background: Vancomycin (VCM) treatment outcomes depend on the characteristics of the patient, and it is well known that hypoalbuminemia is a risk factor for poor treatment outcomes, as reported in a previous study. However, the reason that severe hypoalbuminemia has an influence on the treatment outcome of VCM remains unknown.
Objective: To elucidate the association between severe hypoalbuminemia and VCM treatment outcomes, we examined pharmacokinetic/pharmacodynamic (PK/PD) parameters in elderly patients with severe hypoalbuminemia.
Methods: We conducted a retrospective observational study of 94 patients with methicillin-resistant Staphylococcus aureus (MRSA) hospital-acquired pneumonia who had been treated with VCM between January 2006 and December 2012. The 94 patients were divided into severe hypoalbuminemia and non-severe hypoalbuminemia groups. The PK/PD parameters and treatment outcomes of VCM were compared between the two groups.
Results: The half-life of VCM in the severe hypoalbuminemia group was significantly longer than in the non-severe hypoalbuminemia group (33.2 ± 5.4 vs 24.9 ± 1.6; P = 0.049). Area under the concentration curve (AUC)/minimum inhibitory concentration (MIC) values of 250–450 and >450 µg × h/mL were significantly associated with 28-day mortality in the severe hypoalbuminemia group (P < 0.001), whereas AUC/MIC values of <250 µg × h/mL were not associated. We also detected a significant difference in the increased percentage of nephrotoxicity in the severe hypoalbuminemia group (6 of 23 patients [26%]) compared with the non-severe hypoalbuminemia group (6 of 71 patients [8%]; P < 0.001).
Conclusion: These findings indicate that severe hypoalbuminemia influences the half-life of VCM and treatment outcomes in elderly patients (≥75 years of age). To establish a more effective and safer treatment protocol, the issue of malnutrition in elderly patients needs to be addressed and improved.

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