Safety and efficacy of HMG-CoA reductase inhibitors for treatment of hyperlipidemia in patients with HIV infection.

STUDY OBJECTIVE: To assess the efficacy and safety of HMG-CoA reductase inhibitors (statins) in patients with human immunodeficiency virus (HIV) infection and hyperlipidemia. DESIGN: Retrospective analysis. SETTING: HIV clinic. PATIENTS: Twenty-six HIV-infected patients with hyperlipidemia. INTERVENTION: Five patients received pravastatin, 13 lovastatin, 10 simvastatin, and 2 atorvastatin (total 30 courses). MEASUREMENTS AND MAIN RESULTS: Reductions in cholesterol and triglycetides were used to assess efficacy; creatine kinase (CK), liver enzymes, and myalgia were markers of statin toxicity. After a median of 8.2 and 7.2 months of treatment, the agents collectively reduced median baseline total cholesterol 27% (354 to 263 mg/dl) and triglycerides 15% (513 to 438 mg/dl), respectively. Two patients, one with marked CK elevations, experienced myalgias with lovastatin, and two experienced transaminase elevations 3 or more times the upper limit of normal. CONCLUSION: Statins are effective in reducing total cholesterol and triglycerides in HIV-infected patients, although lipid levels infrequently return to normal. Lovastatin should be avoided in patients receiving concomitant drugs that may potentiate skeletal muscle toxicity with this agent.

Hyperlipidemia associated with HIV protease inhibitor use: pathophysiology, prevalence, risk factors and treatment.

Despite potent antiretroviral activity, the HIV-1 protease inhibitors have recently been associated with abnormal serum lipoprotein concentrations. The purpose of this review is to describe serum lipid abnormalities related to protease inhibitor use. A MEDLINE search up to June 1, 1999, and abstracts from recent scientific meetings were primary data sources. Lipid disturbances in HIV-infected patients receiving protease inhibitors generally consist of elevated triglycerides and total cholesterol levels; HDL cholesterol is often reduced. The pathophysiological mechanism by which the protease inhibitors induce these lipid abnormalities has been hypothesized, but is unknown. Cases of pancreatitis and coronary heart disease have been described in hyperlipidemic patients receiving protease inhibitors. Treatment of protease inhibitor-related hyperlipidemia is unknown. Exchanging the offending protease inhibitor for nevirapine may be helpful in certain patients. Atorvastatin in combination with gemfibrozil has been used with limited success in a small number of individuals.

National survey of extended-interval aminoglycoside dosing.

A random sample survey of 500 acute care hospitals in the United States was conducted to evaluate the adoption of extended-interval aminoglycoside dosing (EIAD). The survey revealed that EIAD has been adopted in 3 of every 4 acute care hospitals, a 4-fold increase since 1993. Of the 74.7% of hospitals reporting EIAD, 64% had written guidelines. Equal or less toxicity (87.1%), equal efficacy (76.9%), and cost-savings (65.6%) were common rationales. There has been a trend toward higher adult dosages of gentamicin (e.g., >5 mg/kg/dose) and an increase in the adoption of EIAD across all age groups (neonatal, 11%, and pediatric, 23%). Monitoring of aminoglycoside concentrations has shifted to a single determination of concentration, at 6-18 h after drug administration. The most common methods of dosage adjustment for declining renal function were an interval extension with the same dose (47%) or use of the Hartford nomogram (32%).

Levofloxacin and sparfloxacin: new quinolone antibiotics.

OBJECTIVE: To discuss the pharmacology, pharmacokinetics, spectrum of activity, clinical trials, and adverse effects of levofloxacin and sparfloxacin, two new fluoroquinolone antibiotics. DATA SOURCES: Literature was identified by a MEDLINE search from January 1985 to September 1997. Abstracts and presentations were identified by review of program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy from 1988 to 1996. STUDY SELECTION: Randomized, controlled clinical studies were selected for evaluation; however, uncontrolled studies were included when data were limited for indications approved by the Food and Drug Administration (FDA). In vitro data were selected from comparison trials whenever available. Only in vitro trials that provided data on the minimum inhibitory concentrations required to inhibit 90% of isolates were used. Data from North American studies were selected whenever available. DATA EXTRACTION: Data were evaluated with respect to in vitro activity, study design, clinical and microbiologic outcomes, and adverse drug reactions. DATA SYNTHESIS: Levofloxacin and sparfloxacin are active against pathogens frequently involved in community-acquired upper and lower respiratory tract infections, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Mycoplasma pneumoniae, Legionella pneumophila, and Chlamydia pneumoniae. Both compounds have enhanced activity compared with ciprofloxacin against most gram-positive bacteria, including enterococci, streptococci, and staphylococci, and retain good activity against most Enterobacteriaceae and Pseudomonas aeruginosa. Sparfloxacin has greater anaerobic activity than levofloxacin, which is more active than ciprofloxacin or ofloxacin. Although many clinical studies are available only in abstract form, the clinical data demonstrate that these new quinolones are effective for most community-acquired upper and lower respiratory tract infections, urinary tract infections, gonococcal and nongonococcal urethritis, and skin and skin structure infections. FDA-approved indications are limited for both compounds to date. CONCLUSIONS: Levofloxacin and sparfloxacin have improved gram-positive activity compared with that of older fluoroquinolones, and are administered once daily. Sparfloxacin-associated photosensitivity may limit its therapeutic usefulness. Clinical trials confirm that these agents are as effective as traditional therapies for the management of community-acquired pneumonia, acute exacerbations of chronic bronchitis, sinusitis, urinary tract infections, acute gonococcal and nongonococcal urethritis, and skin and skin structure infections.