Clinical Interventions in Aging (Sep 2013)
The influence of severe hypoalbuminemia on the half-life of vancomycin in elderly patients with methicillin-resistant Staphylococcus aureus hospital-acquired pneumonia
Abstract
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
