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Vancomycin tolerance, a potential mechanism for refractory gram-positive bacteremia observational study in patients
Amar Safdar1, Kenneth V I Rolston
1Department of Infectious Diseases, Infection Control, and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. asafdar@mdanderson.org
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.
Insights
Vancomycin-tolerant gram-positive infections in cancer patients are challenging. Combination therapy with gentamicin, often with rifampin, effectively treated these infections, preventing recurrence.
Area of Science:
- Infectious Diseases
- Oncology
- Microbiology
Background:
- Clinical significance of vancomycin-tolerant (Vt) gram-positive infections in cancer patients is unclear.
- Vancomycin tolerance is defined as a minimum bactericidal concentration (MBC) > 32 times the minimum inhibitory concentration (MIC).
Observation:
- Eight cancer patients with persistent fever and bacteremia (>72 hours) despite vancomycin therapy were analyzed.
- Causative organisms included Staphylococcus aureus, group G streptococci, and other gram-positive species, all exhibiting vancomycin tolerance.
- Most patients (75%) were neutropenic, including those who underwent stem cell transplantation.
Findings:
- Addition of gentamicin or gentamicin plus rifampin led to rapid defervescence (<24 hours) and resolved bacteremia in all patients.
- No infections recurred after completion of the alternative bactericidal therapy.
Implications:
- Suspect vancomycin-tolerant gram-positive infections when vancomycin therapy fails in cancer patients.
- Early initiation of alternative bactericidal therapy is crucial, particularly for immunocompromised individuals.
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