Vancomycin-Intermediate Staphylococcus epidermidis: Curio or Omen?

In this issue, Garrett and colleagues report a case of bloodstream infection caused by a strain of Staphylococcus epidermidis that exhibited reduced susceptibility to vancomycin.1 Two isolates, collected on different days, were tested against vancomycin in three different laboratories. In disk-diffusion assays, both isolates appeared to be susceptible to vancomycin. However, tests using the Microscan Walk-Away System (MicroScan, West Sacramento, CA) yielded minimum inhibitory concentrations (MICs) of 16 μg/mL. E-tests and broth microdilution assays yielded MICs of 8 μg/mL. Both values fall within the intermediate range for vancomycin. Strains of S epidermidis with MICs 4 μg/mL are considered susceptible, and strains with MICs 32 μg/mL are considered resistant.2 Strains with values in the intermediate range are variably said to have decreased susceptibility, intermediate resistance, or increased resistance. The term vancomycin-intermediate S epidermidis, or VISE, is appealing because of its consistency with the terminology used for the original isolates of Staphylococcus aureus with similar MICs.3,4 Regardless of the terminology, the basic phenomenon is new to the clinical microbiology laboratory. Three features of the reported case suggest that these intermediate MIC values are more than laboratory anomalies. First, the patient had received almost 40 days of vancomycin therapy prior to developing bacteremia caused by the S epidermidis isolate with reduced susceptibility. Prolonged exposure to vancomycin and the presence of an indwelling central venous catheter probably constitute an ideal setting for the development of resistance. Second, the patient was symptomatic at the time of the bacteremia, and the isolate was recovered from specimens obtained through both the Groshong central venous catheter and a peripheral vein. These details unequivocally establish the clinical diagnosis of infection. Lastly, the bacterium was reisolated from both sites 5 days later, despite ongoing therapy with vancomycin. Because the central venous catheter was sterile when it was removed 2 days later, persistence of bacteremia for 5 days seems unusual. This sluggish response suggests that the therapeutic power of vancomycin was impaired or reduced; however, this suggestion requires the caveat that serum concentrations of vancomycin were not reported. What are hospital epidemiologists and others to make of this case report? Is the observation a curio or novelty— just “one of those things” that soon will be forgotten? Or is it an omen, a harbinger of things to come? Although no one can be certain at this point, several lines of evidence suggest that this case is a warning of more to come. Of note, cases of infection caused by S epidermidis with reduced susceptibility or frank resistance to vancomycin have been reported from Europe during the last several years.5-7 In one report from the United Kingdom, a patient developed peritonitis associated with chronic ambulatory peritoneal dialysis (CAPD) after receiving repeated courses of vancomycin.6 Two different strains of S epidermidis isolated from this individual had vancomycin MICs of 8 and 32 μg/mL, respectively. Another report from the Slovak Republic described four cancer patients with catheter-associated bloodstream infections caused by strains of S epidermidis with vancomycin MICs of 16 μg/mL.7 Central venous catheters, neutropenia, prophylaxis with ofloxacin, and prior vancomycin therapy were common antecedents in these four patients. Multiple sightings of S epidermidis isolates with decreased susceptibility suggest the arrival of an important trend. Such a trend is not unexpected in light of the increasing prevalence of nosocomial infections caused by coagulasenegative staphylococci and the corresponding increase in vancomycin use to treat them. Moreover, all of the reported cases have arisen in the logical setting, with prior vancomycin therapy and indwelling prosthetic devices.