[Glycopeptide heteroresistance and tolerance in hospital grampositive isolates: "invisible" phenomena to the clinician with clinical implications?].

This article reviews the concepts of heteroresistance and tolerance to glycopeptides in gram-positive bacteria isolated from hospitalised patients. Heteroresistance (resistant subpopulations among the total bacterial population of the strain, that can be selected by the treatment) and tolerance (capability of survival, but not growth, in the presence of usually lethal antibiotic concentrations) have in common several characteristics: 1) the absence of its determination in laboratory daily practice, 2) they implied a decrease in antimicrobial activity not reflected in MIC values (thus being "invisible" to clinicians in daily routine laboratory reports), 3) the decrease in antimicrobial activity may have clinical implications and 4) they affect a wide spectrum of gram positive bacteria in the hospital (Staphylococcus aureus, coagulase-negative staphylococci, enterococci and different estreptococcal species). The decrease produced in the bactericidal activity (that is critical for the treatment of bacteremias, endocarditis, meningitis and infections in immunocompromised patients) has clinical implications such aspersistance of bacteremia, refractory bacteremia, relapse of infections and increased length of stay. Two strategies are possible to overcome tolerance and heteroresistance: addition of antibiotics to obtain bactericidal activity by synergism (key factor for which it should be taken intoaccount antagonic combinations or high resistance to aminoglycosides when choosing the antibiotic regimen), or the use of bactericidal compounds to which grampositive bacteria show susceptibility and absence of heteroresistance and tolerance (in contrast to glycopeptides), as is the case of lipopeptide daptomycin.