Characterization of Vancomycin-Heteroresistant Staphylococcus aureus from the Metropolitan Area of Detroit, Michigan, over a 22-Year Period (1986 to 2007)

Abstract

The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has continued to increase at a dramatic rate in recent years (20,21). This organism is associated with higher rates of morbidity and mortality than methicillin-susceptible strains (16). Vancomycin is the primary treatment for this pathogen; however, the increasing use of this agent for a variety of gram-positive organisms, including MRSA, contributes to the growing burden of nonsusceptible strains in both the community and hospital settings (17). Unfortunately, vancomycin-intermediate S. aureus (VISA) and heteroresistant VISA (hVISA) strains have now been reported and are associated with vancomycin treatment failures (7,10,27). Although the presence of VISA is routinely screened for on the basis of the vancomycin MIC exceeding the breakpoint for susceptibility (27, 33), screening for hVISA is not routinely performed (15,33,37). The reasons for this discrepancy include the fact that the vancomycin MIC for these strains determined by routine testing is reported to be in the susceptible range. Screening for hVISA requires additional testing to reveal its heterovariant phenotype, and these methods are more labor-intensive and costly then routine susceptibility testing. In addition, the methods used for evaluating hVISA are not standardized. Despite these shortcomings, there is a growing need to begin screening for this organism on the basis of an increasing number of reports of vancomycin treatment failure for patients (2,4,12,13,19,24).The objectives of the present study were to screen and characterize clinical isolates of MRSA demonstrating heteroresistance to vancomycin from a collection of isolates spanning a 22-year period.(This report was presented in part at the 17th European Congress of Clinical Microbiology and Infectious Diseases, Munich, Germany, March 2007 [abstr. 302].) MATERIALS AND METHODSBacterial isolates. MRSA isolates from 1986 to 2007 in the Detroit metropolitan area were collected from Detroit Receiving Hospital and Henry Ford Hospital, Detroit, MI, and William Beaumont Hospital, Royal Oak, MI, and from the SENTRY Antimicrobial Surveillance Database on the basis of oxacillin resistance and year (as available). These isolates were part of collections that had been previously used for surveillance studies by investigators in the area or by the SENTRY Surveillance Program. Mu3 (archetype hVISA) (11) was used as the control strain for population analysis profile (PAP)-area under the concentration-time curve (AUC) ratio determination. The infection source of the derived organisms was identified when available. All susceptibility testing and hVISA, VISA, and molecular testing were completed by the Anti-Infective Research Laboratory for the purpose of this investigation during a 1-year time period.Antimicrobial agents and susceptibility testing. Vancomycin analytical powder was obtained from Sigma Chemical Company, St. Louis, MO. Teicoplanin analytical powder was provided by Sanofi-Aventis. Stock solutions of each antibiotic were prep...

Screening for Intermediately Vancomycin-Susceptible and Vancomycin-Heteroresistant Staphylococcus aureus by Use of Vancomycin-Supplemented Brain Heart Infusion Agar Biplates: Defining Growth Interpretation Criteria Based on Gold Standard Confirmation

“…It is cumbersome and not practical for routine use. Several screening methods have been proposed, but their sensitivity and specificity vary, and often confirmation with PAP-AUC is considered necessary (2,4,7,12,15,17). In previous PAP-AUC studies, we noted that the growth on agar plates supplemented with vancomycin concentrations of 4 and 3 mg/liter correlated well with the VISA and hVISA phenotype, respectively (11).…”

“…everal methods of screening for vancomycin intermediately susceptible Staphylococcus aureus (VISA) and heteroresistant (hVISA) strains among clinical isolates exist, but the optimal method has not been clearly defined (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Etest methods, including the Macromethod and glycopeptide resistance detection (GRD), have been suggested, but their sensitivity and specificity are variable and confirmation with the gold standard population analysis profile is considered necessary (2,4,7,10,12,15,17).…”

“…Etest methods, including the Macromethod and glycopeptide resistance detection (GRD), have been suggested, but their sensitivity and specificity are variable and confirmation with the gold standard population analysis profile is considered necessary (2,4,7,10,12,15,17). Several agar screening methods that utilize brain heart infusion (BHI) agar or Mueller-Hinton (MH) agar supplemented with vancomycin or teicoplanin at various concentrations have been proposed (1,4,6,11,13,14,16).…”

Pneumonia Caused by Methicillin-Resistant Staphylococcus aureus: Does Vancomycin Heteroresistance Matter?

“…The area under the population curve was computed using the trapezoidal method in SigmaPlot (version 10; Systat Software, Inc., San Jose, CA, USA) and compared to the AUC of the reference strain Mu3 (ATCC 700698). Isolates tested were considered to be hVISA if the PAP-AUC ratio of the test isolate to Mu3 was Ն0.9 (18,31). The staphylococcal cassette chromosome mec (SCCmec), USA300 or USA400, and accessory gene regulator (agr) type as well as the presence of Panton-Valentine leukocidin (PVL) were determined through multiplex PCR as described previously (32,33).…”

“…Of particular clinical concern is heterogeneous vancomycin-intermediate S. aureus (hVISA) as it often goes undetected by traditional clinical microbiology testing methods, such as automated MIC testing, and, at present, there is no suitable method for realtime identification in the clinical microbiology laboratory (12,13). The prevalence of hVISA in many geographic regions remains unknown; however, reports of its occurrence range from 1.2% to 29.2% of MRSA isolates (14)(15)(16)(17)(18).…”