Risk factors for treatment failure in patients receiving vancomycin for hospital-acquired methicillin-resistant Staphylococcus aureus pneumonia.

BACKGROUND: The rate of vancomycin failure in patients with hospital-acquired pneumonia (HAP) caused by methicillin-resistant Staphylococcus aureus (MRSA) has exceeded 40% in several studies. This observation was attributed initially to the lack of weight-based dosing and targeting of lower trough concentrations. However, a subsequent study demonstrated no additional benefit in patients who achieved trough vancomycin concentrations >15 mg/L compared with patients with concentrations between 5 and 15 mg/L. We sought to identify contributors to vancomycin failure in patients with MRSA HAP. METHODS: This was a retrospective study of patients in a surgical intensive care unit with MRSA HAP who received vancomycin between January 1, 2005, and July 31, 2007. Clinical outcomes, microbiological data, prior antibiotic exposure, ventilator days, co-morbidities, and demographics were compared in patients with clinical success and those with treatment failure. Their characteristics were compared using a two-sided Fisher exact test or Mann-Whitney U test, as appropriate for nominal or continuous data. RESULTS: More patients in the treatment failure group had received one or more doses of vancomycin within 90 days leading up to MRSA HAP (84% vs. 47%; p = 0.04). In addition, the duration of prior vancomycin exposure was significantly longer among patients in the treatment failure group (6 vs. 0 days; p < 0.05). There were no statistically significant differences in the percentages of patients who achieved a vancomycin trough concentrations > or =15 mg/dL within the first 48 h (28% vs. 17%; p = 0.69), 72 h (44% vs. 39%; p = 1.0), or 96 h (56% vs. 44%; p = 0.74) after starting treatment. Patients in the failure group had a significantly higher overall mortality rate (32% vs. 0; p = 0.02). CONCLUSIONS: These data suggest that patients who have recent exposure to vancomycin are at high risk for vancomycin failure and may benefit from an appropriate alternative when a diagnosis of MRSA HAP is made.

Predictors of unstable anticoagulation in African Americans.

OBJECTIVE: We sought to identify contributors to unstable anticoagulation in African Americans. PATIENTS AND METHODS: Sixty African Americans on warfarin were enrolled. Cytochrome P450 2C9 and vitamin K epoxide reductase genotypes and vitamin K intake were assessed, and clinical and dietary data during the 12 months prior to enrollment were collected. Data were compared between stable and unstable patients, classified based on the proportion of international normalized ratio (INR) values outside the therapeutic range. RESULTS: The median proportion of out-of-range INRs among study participants was 44%; 28 patients had a higher proportion of INRs out-of-range and were included in the unstable group, with the remaining constituting the stable group. The median (IQR) number of clinic visits/year was higher among unstable versus stable patients [18 (15-22) vs. 16 (13-19); P = 0.03]. Higher warfarin doses, lower adherence, vomiting or diarrhea, and use of antiinfective agents were more common among unstable patients. Genotype was not associated with anticoagulation stability. After regression analysis, only poor adherence and gastrointestinal illness remained predictive of unstable anticoagulation. In a control group of Caucasians of similar age and sex distribution, poor adherence, but not gastrointestinal illness, was associated with unstable anticoagulation. CONCLUSION: We conclude that poor warfarin adherence and gastrointestinal illness are major contributors to unstable anticoagulation in African Americans. Our data suggest that, similar to Caucasians, improving warfarin adherence rates may be an important mean to improve anticoagulation control in African Americans. In addition, close monitoring during acute illness may be particularly important in this population.

Interaction between warfarin and cranberry juice.

Warfarin is extensively used for anticoagulation to a target international normalized ratio of 2.0-3.0 for most indications or 2.5-3.5 for high-risk indications; however, many drugs and dietary supplements induce fluctuations in the international normalized ratio. Such fluctuations may lead to therapeutic failure or bleeding complications. Cranberry juice is increasingly used for the prevention and adjunctive treatment of urinary tract infections. The United Kingdom's Committee on Safety of Medicines has alerted clinicians to a potential interaction between warfarin and cranberry juice and has advised that patients avoid their concurrent use. Review and analysis of the literature revealed that ingestion of large volumes of cranberry juice destabilize warfarin therapy. Small amounts of juice are not expected to cause such an interaction. Clinicians should be aware of this potential interaction and monitor and counsel patients accordingly.