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 (< or = 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.