Prevalence and Characteristics of Heteroresistant Vancomycin-Intermediate Staphylococcus aureus Bacteremia in a Tertiary Care Center

Abstract

Hashomer, Israel, were assessed for hVISA by using the Etest macromethod. A total of 16 patients (6%) were positive for hVISA. Resistance to teicoplanin alone and to vancomycin alone using the Etest macromethod was found in 14 and 10 patients, respectively. Standard MICs to vancomycin were between 1 to 4 mg/ml. Most of these isolates (12 of 16 [75%]) would have been missed without specific testing. The median number of bacteremic days was 4. Seven patients had positive blood cultures for more than 5 days. Twelve patients died, and for eight of these the deaths were directly related to hVISA sepsis. We found that hVISA bacteremia was prevalent in our institution, and we suggest seeking hVISA in patients with persistent S. aureus bacteremia.Infections due to methicillin-resistant Staphylococcus aureus (MRSA) are responsible for 50% of hospital acquired S. aureus infections with increasing morbidity and mortality (13). A recent meta-analysis demonstrated increased mortality in bacteremia associated with MRSA compared to methicillin-susceptible S. aureus (MSSA) (5). Glycopeptides are considered the drug of choice for treating MRSA bacteremia and sepsis. S. aureus strains with reduced vancomycin susceptibility were first reported in 1997 (9). S. aureus strains with reduced vancomycin susceptibility include vancomycin-resistant S. aureus strains (VRSA; MIC Ն 16 g/ml) and vancomycin-intermediate S. aureus strains (VISA; MIC ϭ 4 to 8 g/ml). Until 2006, the MIC for VISA was defined as 8 to 16 g/ml by the Clinical and Laboratory Standards Institute (CLSI; formerly the National Committee for Clinical Laboratory Standards), and these guidelines are still the ones approved by the U.S. Food and Drug Administration for vancomycin; the MIC for heterogeneous VISA (hVISA) strains was defined by the presence of subpopulations of VISA at a rate of 1 organism per 10 5 to 10 6 organisms (14,15,20,23). Up till April 2006 only four cases with infections due to VRSA have been reported, which exhibit the vanA gene complex found in vancomycin-resistant enterococci (2, 3, 12). A few dozen VISA strains have been reported in recent years, which have slower growth rates, thickened cell walls, and reduced levels of PBP4. The underlying genetic and biochemical mechanism by which this occurred is not known. The majority of these cases with VISA have occurred in patients who were treated with vancomycin for prolonged periods of time (7,11,19). hVISA seems to be the stage that precedes the development of VISA, and it is believed that vancomycin creates a selective pressure for these resistant strains (21).The best method for detecting hVISA is controversial. Methods are not standardized, and no clear guidelines have been issued. Population analysis profiling (PAP) is considered the gold standard, but this approach is labor-intensive and expensive. Thus, it is not realistic to use such a method for a routine service in a busy hospital setup. Various other methods used to detect hVISA were described and compared by Walsh et al. (22). Of the numerou...

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

“…Isolates were screened by the macromethod Etest to detect hVISA, with no confirmation by PAP (194). Sixteen hVISA cases were identified (6%), and although those authors were not able to directly link outcome to MIC, there was a higher mortality rate in this group, and they reported an hVISA-attributable mortality of 50%.…”

“…After the first reports of VISA and hVISA from Japan, it did not take long for this resistance phenotype to be recognized around the world. Strains of S. aureus (predominately MRSA) demonstrating the hVISA or VISA phenotype have now been reported for many countries including the United States, Japan, Australia, France, Scotland, Brazil, South Korea, Hong Kong, South Africa, Thailand, Israel, and others (22,67,69,77,79,82,94,158,167,194,195,206,258,284,300,326,327,331,352,354,366,373). A retrospective analysis of stored isolates detected previously unrecognized hVISA/VISA strains at least back to 1987 in the United States and back to a similar period in France, Spain, and Germany (11,22,39,276,288); however, there has been some concern about the potential loss of resistance during prolonged storage, which could impact results of such retrospective analyses.…”

“…In Israel in 2003 and 2004, 6% of patients with MRSA bacteremia had hVISA when blood culture isolates were screened using the MET, many of which would have been missed with routine testing (194). A study of MRSA isolates from 63 French hospitals found that only 0.7% of isolates were hVISA isolates after screening with BHI agar containing 6 g teicoplanin per ml and confirmation by PAP (37), with similarly low rates found by some other French studies and in Belgium (69,230,271).…”

“…Essentially, an hVISA isolate is an S. d S. aureus with reduced susceptibility (SA-RVS) is defined as follows: (i) MIC of Ն4 g per ml (91,306) or (ii) area under vancomycin concentrationkill curve of Ն0.9 of the AUC of type strain Mu3 (124). hVISA is defined as follows: (i) VSSA strain that upon subculture stably produces subcolonies with MICs in the VISA/VRSA range at a frequency of Ն1 ϫ 10 6 according to the population analysis profile (PAP) (114); (ii) AUC ratio of Ն0.9 of the AUC of type strain Mu3, referred to as PAP/AUC (48,118,155); or (iii) modified high-inoculum Etest read at 48 h (193,194).…”

Molecular characteristic of Staphylococcus aureus isolates in a Chinese teaching hospital

“…In this study, 9 out of 156 MRSA isolates (5.9%) were identified as hVISA by MET. In USA, Italy, Canada, France, Israel, Belgium and Asia, the prevalence of hVISA in MRSA was 7.5, 2.8, 1.3, 0.21, 6, 0.7 and 4.3% (Rybak et al, 2008;Campanile et al, 2010;Adam et al, 2010;Reverdy et al, 2001;Maor et al, 2007;Nonhoff et al, 2005;Song et al, 2004), respectively. The disparity in the prevalence of hVISA in different areas may be due to the different detection methods, geographical differences and variable incidence.…”