Relationship between vancomycin tolerance and clinical outcomes in Staphylococcus aureus bacteraemia.

BACKGROUND: Previous data have demonstrated the clinical importance of vancomycin MIC values in Staphylococcus aureus bacteraemia (SAB); however, the impact of vancomycin tolerance (VT) is unknown. OBJECTIVES: To compare the frequency of clinical failure between patients with VT and non-VT isolates in SAB. METHODS: This was a retrospective cohort study of patients with SAB, excluding treatment <48 h or polymicrobial bacteraemia. The primary outcome was clinical failure (composite of 30 day mortality, non-resolving signs and symptoms, and 60 day recurrence). Vancomycin MIC and MBC were determined by broth microdilution. The association between VT (MBC/MIC ≥32) and clinical failure was evaluated by multivariable Poisson regression. RESULTS: Of the 225 patients, 26.7% had VT isolates. VT was associated with clinical failure (48.0% overall) in unadjusted analysis [68.3% (n = 41/60) versus 40.6% (n = 67/165); P < 0.001] and this relationship persisted in multivariable analysis (adjusted risk ratio, 1.74; 95% CI, 1.36-2.24; P < 0.001). The association between VT and clinical failure was also consistent within strata of methicillin susceptibility [methicillin susceptible (n = 125, risk ratio, 1.67; 95% CI, 1.20-2.32; P = 0.002); methicillin resistant (n = 100, risk ratio, 1.69; 95% CI, 1.14-2.51; P = 0.010)]. Among methicillin-susceptible SAB cases treated with ß-lactam therapy, VT remained associated with clinical failure (risk ratio, 1.77; 95% CI, 1.19-2.61; P = 0.004). CONCLUSIONS: VT was associated with clinical failure in SAB, irrespective of methicillin susceptibility or definitive treatment. VT may decrease the effectiveness of cell-wall-active therapy or be a surrogate marker of some other pathogen-specific factor associated with poor outcomes. Future research should evaluate if bactericidal non-cell-wall-active agents improve outcomes in VT SAB.

Temporal trends in the incidence of Staphylococcus aureus bacteremia in Olmsted County, Minnesota, 1998 to 2005: a population-based study.

BACKGROUND: There is a paucity of population-based studies on Staphylococcus aureus bacteremia (SAB) in the United States. We determined the incidence of and trends in SAB in Olmsted County, Minnesota, over an 8-year period. METHODS: A retrospective, population-based, cohort study was done to evaluate the initial episodes of SAB occurring in adult residents of Olmsted County, Minnesota, from 1 January 1998 through 31 December 2005, using the microbiology databases at Mayo Clinic and Olmsted Medical Center in Rochester, Minnesota. RESULTS: Of 247 evaluable adult patients with SAB who were included in the incidence calculation, 143 (57.9%) were males, and the median age was 72.1 years (range, 19.5-98.5 years). Episodes of bacteremia were classified according to acquisition type: 58 (23.5%) were nosocomial (N-SAB), 145 (58.7%) were healthcare-associated (HCA-SAB), and 44 (17.8%) were community-acquired (CA-SAB). Methicillin-resistant S. aureus (MRSA) constituted 31.6% of the cases. No community-acquired MRSA bacteremia was noted. The age-adjusted incidence of SAB was 28.3 episodes/100,000 person-years for females and 53.5 episodes/100,000 person-years for males, with an age- and sex-adjusted rate of 38.2 episodes/100,000 person-years. The age- and sex-adjusted incidence of N-SAB, HCA-SAB, and CA-SAB was 9.0, 22.6, and 6.6 episodes/100,000 person-years, respectively. The age- and sex-adjusted incidence of methicillin-susceptible S. aureus was 25.4 episodes/100,000 person-years, and that of MRSA was 12.4 episodes/100,000 person-years. Overall, the incidence rate increased with age but not over the calendar year. The exception was MRSA bacteremia, which increased at a rate of 19.8% (standard error, +/-5.5%) per year during the study. CONCLUSIONS: The incidence of SAB in adults remained stable in Olmsted County, Minnesota, from 1998 to 2005, but the proportion of episodes due to MRSA significantly increased over the 8-year period.

Outcome of enterococcal prosthetic joint infection: is combination systemic therapy superior to monotherapy?

BACKGROUND: The optimal medical or surgical therapy and outcome of enterococcal prosthetic joint infection are unknown. METHOD: We performed a retrospective cohort study involving all patients with enterococcal total hip or knee arthroplasty infection treated at our institution from 1969 through 1999. The outcome for patients treated with combination systemic antimicrobial therapy (a cell wall-active agent and an aminoglycoside) versus monotherapy with a cell wall-active agent was analyzed. RESULTS: Fifty episodes of prosthetic joint infection due to enterococci occurred in 47 patients. The median duration of follow-up was 1253 days (range, 29-4610 days). The median age at the time of diagnosis was 70 years (range, 32-89 years). Fifty percent of episodes (25 of 50 episodes) occurred in male patients; 48% (24 of 50 episodes) involved total hip or knee arthroplasty. The estimate of 2-year survival free of treatment failure was 94% (95% confidence interval [CI], 83%-100%) for patients treated with 2-stage exchange, 76% (95% CI, 58%-100%) for patients treated with resection arthroplasty, and 80% (95% CI, 51.6%-100%) for patients treated with debridement and retention of the components (P=.9). The overall rate of 2-year survival free of treatment failure was 88% (95% CI, 77%-100%) for patients treated with monotherapy and 72% (95% CI, 54%-96%) for patients treated with combination therapy (P=.1). The development of cranial nerve VIII toxicity was significantly more common among patients receiving combination therapy (P=.002). Nephrotoxicity was more frequent in the combination therapy group (occurring in 26% of episodes; P=.09). CONCLUSIONS: Enterococcal prosthetic joint infection is uncommon at our institution. Patients receiving combination therapy and those receiving monotherapy did not differ with respect to outcome. There were more cases of ototoxicity in the combination therapy group than there were in the monotherapy group.

Darunavir.

Darunavir is a nonpeptidic protease inhibitor recently approved for the treatment of antiretroviral therapy-experienced patients. It has potent in vitro activity against viral isolates that are resistant to currently licensed protease inhibitors. In randomized clinical trials with optimized background regimens, it has shown virologic and immunologic responses superior to comparator-based regimens.