Colistin- and polymyxin-induced nephrotoxicity: focus on literature utilizing the RIFLE classification scheme of acute kidney injury.

With the reintroduction of colistimethate and polymyxin B into clinical practice, a review of their individual and comparative nephrotoxicity attributes as reported in contemporary literature was undertaken. Given variability in definitions used for acute kidney injury, a particular focus was placed on studies utilizing the Risk-Injury-Failure-Loss-End Stage Kidney Disease (RIFLE) criteria of assessment to provide for standardized comparison. Primary risk factors examined included the influence of dosing and the receipt of concomitant nephrotoxins. The typical severity and time course of renal injury that develops were also analyzed. Nephrotoxicity rates with colistimethate appear to approach 50%, and could be of lower frequency and severity with polymyxin B based on limited literature. Acute kidney injury generally appears to be mild to moderate in magnitude and reversible in nature, though as many as 20% of patients experiencing it may require renal replacement therapy of some duration. The majority of studies showed some relationship with dosing- variably reported as being associated with daily dose or cumulative exposure. Traditional nephrotoxic agents did not appear to confer additional risk individually in the majority of investigations, though receipt of multiple concurrent nephrotoxins did yield a relationship in several. Further studies will be required to better characterize the renal adverse effect profile of these agents, particularly in the case of polymyxin B.

Physician-pharmacist comanagement of hypertension: a randomized, comparative trial.

OBJECTIVE: To compare the effectiveness of an evidence-based, systematic approach to hypertension care involving comanagement of patients by primary care physicians and clinical pharmacists versus usual care in reducing blood pressure in patients with uncontrolled hypertension. METHODS: Patients in a staff model medical group with uncontrolled hypertension were randomized to either a usual care (UC) or a physician-pharmacist comanagement (PPCM) group. All physicians in the study received both group and individual education and participated in the development of an evidence-based hypertension treatment algorithm. Physicians were then given the names of their patients whose medical records documented elevated blood pressures (defined as systolic > or = 140 mm Hg and/or diastolic > or = 90 mm Hg for patients aged < 65 yrs, and systolic > or = 160 mm Hg and/or diastolic > or = 90 mm Hg for those aged > or = 65 yrs). Patients randomized to the UC group were managed by primary care physicians alone. Those randomized to the PPCM group were comanaged by their primary care physician and a clinical pharmacist, who provided patient education, made treatment recommendations, and provided follow-up. Blood pressure measurements, antihypertensive drugs, and visit costs/patient were obtained from medical records. RESULTS: One hundred ninety-seven patients with uncontrolled hypertension participated in the study. Both PPCM and UC groups experienced significant reductions in blood pressure (systolic -22 and -11 mm Hg, respectively, p < 0.01; diastolic -7 and -8 mm Hg, respectively, p < 0.01). The reduction in systolic blood pressure was greater in the PPCM group after adjusting for differences in baseline blood pressure between the groups (p < 0.01). More patients achieved blood pressure control in the PPCM than in the UC group (60% vs 43%, p = 0.02). Average provider visit costs/patient were higher in the UC than the PPCM group ($195 vs $160, p = 0.02). CONCLUSIONS: An evidence-based, systematic approach using physician-pharmacist comanagement for patients with uncontrolled hypertension resulted in improved blood pressure control and reduced average visit costs/patient.