title: Pharmacodynamics of vancomycin in elderly patients aged 75 years or older with methicillin-resistant Staphylococcus aureus hospital-acquired pneumonia.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors: Department of Pharmacy, National Center for Geriatrics and Gerontology, Obu, Aichi, Japan. mizokami@ncgg.go.jp
authors: Fumihiro
authors: F
authors: Mizokami
authors: Masataka
authors: M
authors: Shibasaki
authors: Yasunori
authors: Y
authors: Yoshizue
authors: Takeshi
authors: T
authors: Noro
authors: Tomohiro
authors: T
authors: Mizuno
authors: Katsunori
authors: K
authors: Furuta
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003428:Cross Infection / Q000188:drug therapy / Q000378:metabolism*; D005260:Female; D006801:Humans; D007564:Japan; D008297:Male; D055624:Methicillin-Resistant Staphylococcus aureus; D012189:Retrospective Studies; D013203:Staphylococcal Infections / Q000188:drug therapy / Q000378:metabolism*; D014640:Vancomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*
chemical_list: D000900:Anti-Bacterial Agents; D014640:Vancomycin
keywords: elderly patients; methicillin-resistant Staphylococcus aureus; pharmacodynamics; pharmacokinetics; vancomycin
references: Arch Gerontol Geriatr. 2012 Jul-Aug;55(1):152-6
references: 21820190
references: J Clin Microbiol. 2004 Jun;42(6):2398-402
references: 15184410
references: Curr Opin Pulm Med. 2009 May;15(3):218-22
references: 19373090
references: Am J Respir Crit Care Med. 2005 Feb 15;171(4):388-416
references: 15699079
references: Clin Infect Dis. 2007 Jun 15;44(12):1536-42
references: 17516395
references: Antimicrob Agents Chemother. 2008 Sep;52(9):3315-20
references: 18591266
references: Am J Respir Crit Care Med. 2011 Dec 15;184(12):1409-17
references: 21920919
references: Am J Respir Crit Care Med. 2002 Apr 1;165(7):867-903
references: 11934711
references: Clin Biochem Rev. 2010 Feb;31(1):21-4
references: 20179794
references: Chest. 2004 Feb;125(2):607-16
references: 14769745
references: J Am Geriatr Soc. 1997 Aug;45(8):945-8
references: 9256846
references: J Am Pharm Assoc (Wash). 2002 Nov-Dec;42(6):847-57
references: 12482007
references: Clin Pharmacokinet. 2004;43(13):925-42
references: 15509186
references: Curr Med Chem. 2010;17(6):571-84
references: 20015034
references: Clin Infect Dis. 2001 May 15;32 Suppl 2:S114-32
references: 11320452
references: Arch Intern Med. 2006 Oct 23;166(19):2138-44
references: 17060545
references: Chest. 2006 Oct;130(4):947-55
references: 17035423
references: Chest. 2005 Dec;128(6):3854-62
references: 16354854
references: Clin Microbiol Infect. 2008 Feb;14(2):116-23
references: 18076672
references: Mikrobiyol Bul. 2013 Apr;47(2):199-210
references: 23621720
references: Rev Panam Salud Publica. 2012 Nov;32(5):343-50
references: 23338691
references: Respirology. 2008 Nov;13(6):880-5
references: 18657061
references: Eur Rev Med Pharmacol Sci. 2013 Feb;17 Suppl 1:2-8
references: 23436659
references: Clin Geriatr Med. 1990 May;6(2):269-83
references: 2184923
references: Am J Infect Control. 2003 Dec;31(8):481-98
references: 14647111
references: Clin Infect Dis. 2006 Jan 1;42 Suppl 1:S35-9
references: 16323118