Study of Prevalence, Risk Factors and Outcomes of Vancomycin Minimum Inhibitory Concentration Creep in Methicillin Resistant Staphylococcus Aureus Isolates at a Community Hospital

Background: Vancomycin remains the drug of choice for serious infections caused by methicillin resistant Staphylococcus Aureus (MRSA).The overall prevalence of MRSA infection in our hospital is 56%. Isolates with reduced susceptibility to vancomycin are emerging due to widespread use of vancomycin causing minimum inhibitory concentration (MIC) to increase over time known as MIC creep. Recently there is more evidence to show that patients with vancomycin MIC higher than 1.5 µg/ml are at a risk of treatment failure with vancomycin.

Objective: The objective of our study is to evaluate the prevalence, risk factors and outcomes in patients with MRSA bacteremia and vancomycin MIC creep(defined as vancomycin MIC greater than 2 µg/ml) who received vancomycin (group 1) in comparison to those who were switched to daptomycin or linezolid(Group 2).

 Methods: We reviewed the demographics, risk factors, treatment and outcomes of 18 MRSA isolates with vancomycin MIC of 2 µg/ml or higher who were admitted to our institution(a community teaching hospital) between january 2008-september 2010. MIC was obtained from vitek^® 2 system(Durham,NC). E test was done on 4 isolates. Descriptive analysis was performed.

Results: A total of 475 episodes of MRSA bacteremia were identified during the three year period of which 18(3.8%) had vancomycin MIC of 2 µg/ml or higher. MIC was 4 µg/ml in 1/18 and 2 µg/ml in 17/18 patients. There was an increase in occurrence of the isolates over a three year period- 22 %( 4/18) in 2008, 50% (9/18) in 2009 and 28 %( 5/18) in 2010(january-september 2010 only). Patients in group 2 received vancomycin for an average of 6 days prior to receiving daptomycin/linezolid. The source of infection was catheter related in 13/18, joint infection in 3/18, pneumonia in 1/18 and urinary tract in 1/18 patients. The results are summarized in table 1.

Results	Group 1 (vancomycin) n=8	Group 2 (daptomycin/linezolid) n=10
Mean age (in years)	56	60
Renal disease on hemodialysis	5(62%)	8(80%)
Prior vancomycin  use	6(75%)	8(80%)
Prior MRSA bacteremia  with MIC of 1	2(25%)	4(40%)
Infectious disease(ID) consults (p=0.020)	2(25%)	9(90%)
1.Infective endocarditis  2.Osteomyelitis	1(12%) 2(25%)	0 2(20%)
Mean time to negative blood culture in days	7	5
Mortality-30 day	2(25%)	3(30%)
Mean ventilator days	37	7
Mean hospital length of stay (LOS) in days	40	25
Mean intensive care unit (ICU) LOS in days	40	10
Mean APACHE II Score	22	24

Conclusions: 1.The prevalence of vancomycin MIC creep in our institution over a three year period was 3.8%. This strain could predispose to poor outcomes (increase in ICU and hospital LOS and ventilator days). 

2. Prompt recognition of these isolates along with timely ID consultation may improve outcomes.