The safety and efficacy of high versus low vancomycin trough levels in the treatment of patients with infections caused by methicillin-resistant Staphylococcus aureus: a meta-analysis.
BACKGROUND
Recent guidelines have recommended vancomycin trough levels of 15-20 mg/L for treatment of serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, high trough levels may increase risk of nephrotoxicity and mortality, and high vancomycin trough levels have not been well studied. This study was designed to combine safety and efficacy results from independent studies and to compare between high and low vancomycin trough levels in the treatment of MRSA-infected patients using meta-analysis.


METHODS
From 19 eligible studies, 9 studies were included in meta-analysis to compare clinical success between high and low vancomycin trough levels, while 10 and 11 studies met criteria for comparing trough levels and nephrotoxicity and trough levels and mortality, respectively. The PubMed/Medline, Web of Science, and Scopus databases, and hand searching were used to identify eligible studies dated up to March 2016. Of 2344 subjects with MRSA infection, 1036 were assigned to trough levels ≥15 mg/L and 1308 to trough levels <15 mg/L.


RESULTS
High vancomycin trough levels were found to be associated with risk of nephrotoxicity (odds ratio [OR] 2.14, 95 % confidence interval [CI] 1.42-3.23 and adjusted OR 3.33, 95 % CI 1.91-5.79). There was no evidence of difference between high and low vancomycin trough levels for mortality (OR; 1.09; 95 % CI 0.75-1.60) or clinical success (OR 1.07; 95 % CI 0.68-1.68).


CONCLUSIONS
In this study, high vancomycin trough levels were identified as an independent factor associated with risk of nephrotoxicity in MRSA-infected patients. Association between vancomycin trough levels and both adverse effects and clinical outcomes requires further study.
Clinical Epidemiology Unit, Office for Research and Development, Faculty of Medicine, Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Siriraj, Bangkoknoi, Bangkok, 10700, Thailand. sasima.ton@mahidol.ac.th.
Sasima
S
Tongsai
Division of Infectious Diseases and Tropical Medicine, Faculty of Medicine, Siriraj Hospital, Mahidol University, 2 Wang Lang Road, Siriraj, Bangkoknoi, Bangkok, 10700, Thailand.
Pornpan
P
Koomanachai
Clinical success; Meta-analysis; Methicillin-resistant Staphylococcus aureus; Mortality; Nephrotoxicity; Vancomycin trough levels
J Intensive Care Med. 2011 Nov-Dec;26(6):385-91
21606058
Int J Infect Dis. 2012 Nov;16(11):e804-10
22917921
Clin Infect Dis. 2012 Mar 1;54(5):621-9
22247123
Pharmacotherapy. 2012 Mar;32(3):195-201
22392452
Int J Antimicrob Agents. 2013 Mar;41(3):255-60
23312606
Int J Antimicrob Agents. 2006 Mar;27(3):259-62
16472993
Pharmacotherapy. 1995 Jan-Feb;15(1):85-91
7739950
Korean J Intern Med. 2013 Nov;28(6):678-86
24307843
Int J Antimicrob Agents. 2010 Dec;36 Suppl 2:S55-7
21129922
Anaesth Intensive Care. 2011 Nov;39(6):1030-7
22165354
J Clin Microbiol. 2004 Jun;42(6):2398-402
15184410
Chest. 2010 Dec;138(6):1356-62
20558550
Biometrics. 1994 Dec;50(4):1088-101
7786990
Int J Infect Dis. 2013 Feb;17(2):e93-e100
23089040
Am J Med. 2010 Dec;123(12):1143-9
21183005
Int J Antimicrob Agents. 2012 Nov;40(5):474-5
22883416
Braz J Infect Dis. 2003 Jun;7(3):224-8
14499046
J Antimicrob Chemother. 2010 Aug;65(8):1784-91
20554570
Antimicrob Agents Chemother. 2008 Sep;52(9):3315-20
18591266
J Burn Care Res. 2013 Jan-Feb;34(1):e1-9
23292591
Am J Health Syst Pharm. 2009 Jan 1;66(1):82-98
19106348
BMC Infect Dis. 2012 Apr 27;12:104
22540223
Control Clin Trials. 1986 Sep;7(3):177-88
3802833
Chest. 2006 Oct;130(4):947-55
17035423
J Infect Dis. 2003 Mar 15;187(6):929-38
12660939
Expert Rev Anti Infect Ther. 2011 Jun;9(6):657-67
21692671
Crit Care Med. 2014 Dec;42(12):2527-36
25083977
Antimicrob Agents Chemother. 2008 Apr;52(4):1330-6
18227177
J Antimicrob Chemother. 2007 Oct;60(4):788-94
17623693
Biometrics. 2000 Jun;56(2):455-63
10877304
Am J Respir Crit Care Med. 2005 Feb 15;171(4):388-416
15699079
Eur J Clin Microbiol Infect Dis. 2009 Jun;28(6):585-90
19067002
Clin Infect Dis. 2011 Apr 15;52(8):975-81
21460309
Clin Infect Dis. 2004 Jun 15;38(12):1700-5
15227615
S Afr Med J. 2012 May 25;102(7):616-9
22748440
Diagn Mol Pathol. 2011 Sep;20(3):184-8
21817905
Nurs Res. 2003 Jul-Aug;52(4):256-61
12867783
BMC Infect Dis. 2011 Dec 05;11:335
22142287
Int J Nurs Stud. 2012 Sep;49(9):1084-90
22521852
Clin Microbiol Infect. 2009 Feb;15(2):125-36
19291144
Expert Opin Drug Saf. 2010 Jan;9(1):9-14
20021290
Antimicrob Agents Chemother. 2013 Jun 24;:null
23796929
Int J Antimicrob Agents. 2008 Oct;32(4):326-32
18617372
Clin Infect Dis. 2008 Jan 15;46(2):193-200
18171250
J Antimicrob Chemother. 2010 May;65(5):1015-8
20200036
J Antimicrob Chemother. 2012 Jul;67(7):1760-8
22556382
Antimicrob Agents Chemother. 2013 Feb;57(2):734-44
23165462
Antimicrob Agents Chemother. 2011 Dec;55(12):5475-9
21947388
J Clin Microbiol. 2009 Jun;47(6):1640-4
19369444
Diagn Microbiol Infect Dis. 2011 Dec;71(4):408-14
21924852
Arch Intern Med. 2006 Oct 23;166(19):2138-44
17060545
BMJ. 1997 Sep 13;315(7109):629-34
9310563
PLoS One. 2013 Sep 17;8(9):e75171
24069391
Clin Microbiol Infect. 2013 Jul;19(7):E291-7
23490021
J Chemother. 1997 Dec;9(6):420-6
9491842
Am J Surg. 2010 Jun;199(6):804-16
20227056
Clin Ther. 2007 Jun;29(6):1107-15
17692725
Ann Clin Microbiol Antimicrob. 2007 Oct 30;6:13
17967199
J Infect Dis. 2010 Jan 15;201(2):311-2; author reply 312-3
20034343