Evidence of Linezolid MIC Creep and Resistance among Methicillin-resistant Staphylococcus aureus at a Community Teaching Hospital

Background: Documented linezolid resistance (MIC of >8 mcg/mL) is uncommon, and only a few cases have been reported for Staphylococcus species worldwide.   Recent surveillance studies reported <0.9% of S. aureus having linezolid MIC of 4 mcg/mL, suggesting no evidence of MIC creep.  However, the prevalence of S. aureus with linezolid of MIC of >4 mcg/mL at our institution has increased dramatically from 0.58% to 6.90% in 2007 and 2010, respectively.  

Objective: The objectives were to describe the characteristics of the patients infected/colonized with methicillin-resistant S. aureus (MRSA) with elevated linezolid MICs and to evaluate the risk factors among these patients for the linezolid MIC creep.

Methods: Electronic medical records were used to identify patients with positive MRSA cultures between January 1, 2007 and September 30, 2010.  Only those patients with linezolid MICs of 4mg/L or greater were included in the data collection which included demographics, co-morbid conditions, hospitalization within 3 months, prior linezolid and vancomycin exposure within past 30 days and prior isolation of MRSA within 60 days .  Multivariate analysis was performed to identify independent predictors.

Results: Of the 1,778 MRSA isolates, 73 isolates (4.11%) exhibited elevated linezolid MICs.  During the study period, one MRSA isolate was reported to be resistant to linezolid (MIC > 8 mcg/mL) in 2010 from tracheal aspirate.  The average age was 64.8 years (3 months-97) and there were slightly more male than female patients (55% and 45%, respectively).  Co-morbidities were found in most patients (82.2%) and half of the isolates originated from the community. 

Parameters	MRSA (n=73)
Age > 75 years	32 (43.8%)
BMI, kg/m2 (range)	28.7 (14.8-60.0)
Severe obesity (BMI>30kg/m2)	16 (21.9%)
Chronic renal impairment	20 (33.3%)
Dialysis	14 (23.3%)
Community acquired	36 (49.3%)
History of recent hospitalization	44 (60.3%)
Prior linezolid exposure	3 (4.1%)
Prior vancomycin exposure	18 (24.7%)
Prior MRSA isolation	41 (56.2%)
Critical care unit	16 (21.9%)

Conclusions: Elevated MICs of linezolid and resistance were clearly documented among MRSA infections/colonization during 2007-10.  Recent use of linezolid was rare in our patient population, but prior vancomycin use was more common.  Advanced age, chronic renal impairment, recent hospitalization, and prior MRSA isolation were strong predictors of MRSA isolates with elevated linezolid MIC.