Vancomycin tolerance, a potential mechanism for refractory gram-positive bacteremia observational study in patients with cancer

BACKGROUND. The clinical significance of infections caused by vancomycin-tolerant (Vt) Gram-positive organisms in patients with cancer remains unclear. METHODS. Twenty-five patients with nonenterococcal Gram-positive bloodstream infection, which was refractory to vancomycin therapy, were identified by reviewing the Infectious Diseases consultation database at the tertiary care cancer center. Among these, 8 patients in whom vancomycin-tolerance was documented are described. Antibiotic tolerance was defined as a >32 times increase in minimum bactericidal concentration compared with minimum inhibitory concentration. RESULTS. Eight patients with persistent fever and bacteremia of >72 hours' duration after the initiation of vancomycin therapy were treated. The median age of these patients, which included 3 men and 5 women, was 44 years ± 11 years. Solid tumors were more common (6 patients) and 2 patients had acute leukemia. Six patients (75%) were neutropenic (absolute neutrophil count <500/mm³), including 2 breast cancer patients who had undergone autologous stem cell transplantation. The causative organisms were Staphylococcus aureus (n = 3 patients), group G streptococci (n = 2 patients), and Staphylococcus epidermidis, Streptococcus mitis, and Streptococcus sanguis (1 patient each). All isolates demonstrated a minimum bactericidal concentration for vancomycin that was at least 32 times greater than the minimum inhibitory concentration. Rapid defervescence (≤24 h) and resolution of bacteremia occurred with the addition of gentamicin (4 patients) or gentamicin plus rifampin (4 patients). None of these infections recurred after discontinuation of therapy. CONCLUSIONS. Lack of clinical and/or microbiologic response to vancomycin should raise the suspicion of possible infection due to Vt Gram-positive bacteria, and alternative bactericidal therapy should be instituted early, especially in patients with underlying immune suppression.