Prevalence and clinical implications of heteroresistant vancomycin intermediate Staphylococcus aureus in isolates from bone and joint tissue infections over a 3 year period

Background:

Heteroresistant vancomycin intermediate susceptible Staphylococcus aureus (hVISA) has some subpopulations of organisms that exhibit reduced susceptibility to vancomycin, yet overall MIC of the isolate is within the susceptible range (MIC ≤2 mg/L).  Automated susceptibility test methods may fail to detect hVISA.  Macro Etest has higher sensitivity/specificity for detecting the hVISA strains.  MSSA isolates may also exhibit heteroresistance.  Heteroresistant intermediate susceptible Staphylococcus aureus is associated with agr dysfunction that enhances biofilm formation; hence bone and joint tissue infections may have higher prevalence of heteroresistance.

Objective:

We studied the prevalence of hVISA in all bone and joint tissue Staphylococcus aureus isolates using macro E test.  Clinical implications of these isolates in terms of relapses and bacteremia were assessed.

Methods:

100 Staphylococcus aureus bone and joint tissue isolates stored at -70 C from 2007 to 2009 were used.  Macro-Etest using vancomycin and teicoplanin and a 2.0 McFarland inoculum was done.  Plates were read after 24 and 48 hours of incubation at 35 C.  Heteroresistance was defined as vancomycin and teicoplanin MICs ≥ 8 μg/ml or teicoplanin MIC of ≥ 12 μg/ml.   Review of medical records was also done.

Results:

83/100 isolates grew, 53/83 (63%) were MRSA, 30/ 83 (36%) were MSSA. 12/53 (22%)  MRSA isolates were hVISA.   7/30 (23%)  MSSA isolates were heteroresistant intermediate susceptible S. aureus. Only 3/19 (15%) were hVISA by both vancomycin and teicoplanin definition.  13/19 (68%) were heteroresistant only after 48 hrs.  Only 3/19 (15%) were detected by Vitek (automated method) with vancomycin MIC of 2 μg/ml .  16/19 (84%) MRSA and MSSA isolates had history of exposure to either vancomycin or nafcillin in the past.  17/83 (20%) Staphylococcus aureus isolates relapsed.   4/19 (21%) relapses were associated with hVISA isolates

Conclusions:

We found approximately about 22% heteroresistant intermediate vancomycin susceptible Staphylococcus aureus in bone and joint isolates.  Prevalence of heteroresitant strains was similar for both the MSSA and MRSA isolates. Vancomycin resistance should be considered in recurrent MSSA infections.  68% of the hVISA were detected only at 48 hrs, so cultures should be held for longer duration to detect hVISA .  In our study Vitek detected only 15% of the heteroresistant vancomycin intermediate susceptible Staphylococcus aureus; alternate methods may be needed to detect them.  84% of the hVISA strains had prior exposure to antibiotics raising the concern for increasing MIC’s in the general population.  Clinical implications with respect to relapses and bacteremia from hVISA are uncertain.  Further studies are needed to understand this phenomenon.