Renal toxicity of long-term therapy with tenofovir in HIV-infected patients.

Data are sparse on long-term renal toxicity of tenofovir as measured by estimated glomerular filtration rate (eGFR) and progression to advanced stages of chronic kidney disease (CKD). The objective of the study is to determine the incidence of renal impairment associated with the use of tenofovir in HIV-infected patients, using abacavir as a control. In a single tertiary care center, all HIV-infected patients with baseline CKD stage 0 or 1 (CKD-1), who were started on either tenofovir or abacavir from 1998 to 2008 and had at least 1 follow-up eGFR measure on therapy, were included in this retrospective analysis. Progression to CKD stages 2 to 5 was compared using Kaplan-Meier analysis. Progression to CKD-2 and CKD-3 occurred more frequently in patients who received tenofovir than those receiving abacavir (CKD-2, 2-year actuarial frequency, 48.8% vs 23.7%; P < .001, log rank; CKD-3, 5.8% vs 0.0%; P = .028). Only 1 patient in the tenofovir group progressed to CKD-4 and none to CKD-5. Treatment with tenofovir was the only independent factor associated with progression to CKD-2 (hazard ratio [HR], 2.12; 95% confidence interval [CI]: 1.41-3.18; P < .001) and to CKD-3 (HR, 4.91; 95% CI, 1.02-23.7; P = .048). In HIV-infected patients, long-term therapy with tenofovir is associated with mild-to-moderate nephrotoxicity which is significantly higher than in abacavir-treated patients.

Community-acquired pneumonia in the elderly.

BACKGROUND: Community-acquired pneumonia (CAP) is a frequent cause of hospitalization and death among the elderly. OBJECTIVE: This article reviews information on CAP among the elderly, including age-related changes, predisposing risk factors, causes, treatment strategies, and prevention. METHODS: Searches of MEDLINE (January 1990-November 2009), International Pharmaceutical Abstracts (January 1990-November 2009), and Google Scholar were conducted using the terms community-acquired pneumonia, pneumonia, treatment guidelines, and elderly. Additional publications were found by searching the reference lists of the identified articles. Studies that reported diagnostic criteria as well as the treatment outcomes achieved in adult patients with CAP were selected for this review. RESULTS: Three practice guidelines, 5 reviews, and 43 studies on CAP in the elderly were identified in the literature search. Based on those publications, risk factors that predispose the elderly to pneumonia include comorbid conditions, poor functional and nutritional status, consumption of alcohol, and smoking. The clinical presentation of pneumonia in the elderly (>/=65 years of age) may be subtle, lacking the typical acute symptoms (fever, cough, dyspnea, and purulent sputum) observed in younger adults. Pneumonia should be suspected in all elderly patients who have fever, altered mental status, or a sudden decline in functional status, with or without lower respiratory tract symptoms such as cough, purulent sputum, and dyspnea. Treatment of CAP in the elderly should be guided by the latest recommendations of the Infectious Diseases Society of America and the American Thoracic Society (IDSA/ATS), along with consideration of local rates and patterns of antimicrobial resistance, as well as individual patient risk factors for acquiring less common or more resistant pathogens. Recommended empiric antimicrobial regimens generally consist of either a beta-lactam plus a macrolide or a respiratory fluoroquinolone alone. Adherence to the IDSA/ATS guidelines has been found to improve in-hospital mortality (adherence vs nonadherence, 8%; 95% CI, 7%-10% vs 17%; 95% CI, 14%-20%; P< 0.01), length of hospital stay (8 days; interquartile range [IQR], 5-15 vs 10 days; IQR, 6-24 days, respectively; P < 0.01), and time to clinical stability in elderly patients with CAP (percentage of stable patients by day 7, 71%; 95% CI, 68%-74% vs 57%; 95% CI, 53%-61%, respectively; P < 0.01). All elderly patients should be vaccinated against pneumococcal disease and influenza based on recommendations from the Centers for Disease Control and Prevention. Lifestyle modifications and nutritional support are also important elements in the prevention of pneumonia in the elderly. CONCLUSION: Adherence to established guidelines, along with customization of antimicrobial therapy based on local rates and patterns of resistance and patient-specific risk factors, likely will improve the treatment outcome of elderly patients with CAP.