Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: pooled analysis of two phase II studies.

BACKGROUND: Ezetimibe (SCH 58235) is a novel cholesterol absorption inhibitor that selectively and potently blocks intestinal absorption of dietary and biliary cholesterol. OBJECTIVE: Data from 2 multicenter, placebo-controlled, double-blind, randomized, parallel-group, 12-week studies of ezetimibe were pooled to evaluate the drug's effect on lipid parameters in patients with primary hypercholesterolemia. METHODS: After dietary stabilization (National Cholesterol Education Program Step I diet or a stricter diet), washout of lipid-altering drugs, and a 6-week placebo lead-in period, patients with baseline plasma low-density lipoprotein cholesterol (LDL-C) levels > or = 130 and < or = 250 mg/dL and plasma triglyceride (TG) levels < or = 300 mg/dL were randomized to receive either ezetimibe 0.25, 1, 5, or 10 mg, or placebo administered once daily before the morning meal in study A (dose-response study) or ezetimibe 5 or 10 mg or placebo administered once daily before the morning meal or at bedtime in study B (dose-regimen study). RESULTS: A total of 432 patients were included in this pooled analysis, 243 in study A and 189 in study B. The 5- and 10-mg doses of ezetimibe significantly reduced LDL-C levels by 15.7% and 18.5%, respectively (P < 0.01 vs placebo) and significantly increased high-density lipoprotein cholesterol (hDL-C) levels by 2.9% and 3.5%, respectively (P < 0.05 vs placebo). A reduction in plasma TG levels was observed (P = NS). With the 10-mg dose of ezetimibe, 67.8% of patients achieved > or = 15% reduction in plasma LDL-C levels, and 22.0% achieved > or = 25% reduction. With the 5-mg dose, 54.0% of patients achieved > or = 15% reduction in plasma LDL-C levels, and 15.3% achieved > or = 25% reduction. The decrease in plasma LDL-C levels was significantly greater with ezetimibe 10 mg compared with ezetimibe 5 mg (P < 0.05). Ezetimibe was well tolerated, with an adverse event profile similar to that of placebo. CONCLUSIONS: In these two 12-week studies, ezetimibe significantly decreased plasma LDL-C levels and increased plasma HDL-C levels, with a tolerability profile similar to that of placebo.

Treating to meet NCEP-recommended LDL cholesterol concentrations with atorvastatin, fluvastatin, lovastatin, or simvastatin in patients with risk factors for coronary heart disease.

BACKGROUND: Our study compared use of atorvastatin, fluvastatin, lovastatin, and simvastatin for lowering low-density lipoprotein (LDL) cholesterol concentration in patients at risk for coronary heart disease (CHD). The goal was to reach the LDL cholesterol levels recommended by the National Cholesterol Education Program (NCEP). METHODS: A combined total of 344 men and women took part in this 54-week, multicenter, open-label, randomized, parallel-group, active-controlled, treat-to-target study. Patients were selected on the basis of their LDL cholesterol concentration and their risk for CHD. During treatment, doses were titrated at 12-week intervals to a maximum of 80 mg per day of atorvastatin and lovastatin, or 40 mg per day of fluvastatin and simvastatin, with colestipol added if necessary to attain the NCEP-recommended LDL cholesterol concentration. RESULTS: At the starting dose, atorvastatin decreased plasma LDL cholesterol significantly (P < .05) compared with the other reductase inhibitors, and the percentage of patients reaching target LDL cholesterol concentration at the starting dose was significantly greater in the atorvastatin group (P < .05). Overall, a significantly (P < .05) greater percentage (95%) of atorvastatin-treated patients achieved target LDL cholesterol concentration. The safety profile was similar among all reductase inhibitors tested. CONCLUSIONS: At the starting dose, a significantly (P < .05) greater percentage of atorvastatin-treated patients at risk for CHD reached the target LDL cholesterol concentration than patients with treated with other reductase inhibitors.

Mupirocin cream is as effective as oral cephalexin in the treatment of secondarily infected wounds.

BACKGROUND: Topical antimicrobials have been considered for treatment of secondarily infected wounds because of the potential for reduced risk of adverse effects and greater patient convenience. We compared mupirocin cream with oral cephalexin in the treatment of wounds such as small lacerations, abrasions, or sutured wounds. METHODS: In 2 identical randomized double-blind studies, 706 patients with secondarily infected wounds (small lacerations, abrasions, or sutured wounds) received either mupirocin cream topically 3 times daily or cephalexin orally 4 times daily for 10 days. RESULTS: Clinical success at follow-up was equivalent in the two groups: 95.1% and 95.3% in the mupirocin cream and the cephalexin groups, respectively (95% confidence interval [CI], -4.0% to 3.6%; P = .89). The intention-to-treat success rate was 83% in both groups. Bacteriologic success at follow-up was also comparable: 96.9% in the mupirocin cream and 98.9% in the cephalexin groups (95% CI, -6.0% to 2.0%; P = .22). The occurrence of adverse experiences related to study treatment was similar for the 2 groups, with fewer patients in the mupirocin cream group reporting diarrhea (1.1% vs 2.3% for cephalexin). CONCLUSIONS: Mupirocin cream applied topically 3 times daily is as effective as oral cephalexin given 4 times daily for the treatment of secondarily infected wounds and was well tolerated.

Randomized, double-blind study of ciprofloxacin and cefuroxime axetil for treatment of acute bacterial exacerbations of chronic bronchitis. The Bronchitis Study Group.

In a prospective, multicenter, double-blind study, the interval to clinical relapse in patients with acute bacterial exacerbations of chronic bronchitis from whom a pretherapy pathogen was isolated was compared following treatment with ciprofloxacin or cefuroxime axetil. Clinical and microbiological responses at the end of therapy were secondary efficacy variables. Outpatients randomly received either ciprofloxacin or cefuroxime axetil (500 mg twice a day for 14 days). Three hundred seven patients with acute exacerbations of chronic bronchitis were enrolled, of whom 208 had an exacerbation due to a bacterial pathogen. Clinical resolution at the end of ciprofloxacin and cefuroxime axetil therapy for patients for whom efficacy could be evaluated was 93% and 90%, respectively. Bacteriologic eradication rates were statistically higher for ciprofloxacin recipients (96% [89 of 93]) than for cefuroxime axetil recipients (82% [80 of 97]) (P < .01). The median infection-free interval was 146 days for ciprofloxacin recipients vs. 178 days for cefuroxime axetil recipients (P = .37). In conclusion, ciprofloxacin was associated with an infection-free interval and clinical response that were similar to those associated with cefuroxime axetil, but the bacteriologic eradication rate associated with ciprofloxacin was statistically significantly higher than that associated with cefuroxime axetil.

Fleroxacin 400 mg once daily versus ofloxacin 400 mg twice daily in skin and soft tissue infections.

The efficacy and safety of 10 days' oral treatment with fleroxacin 400 mg once daily were compared with those of ofloxacin 400 mg twice daily in adults with skin and soft tissue infections. The most common diagnoses were skin abscess, cellulitis and wound infection. The most commonly-isolated pathogens were Staphylococcus aureus, Staphylococcus epidermidis and other coagulase-negative staphylococci. Overall bacteriological cure rates in patients with susceptible pathogens were 89% for 158 fleroxacin-treated patients and 97% for 157 ofloxacin-treated patients (treatment difference 8%; 95% confidence intervals 2-14%; p < 0.05). Clinical cure rates were 78% for fleroxacin and 83% for ofloxacin (treatment difference 5%; 95% confidence intervals-5-14%, not statistically significant). The overall safety profiles were similar and the most frequently reported events were insomnia, headache, dizziness, and digestive system disorders. More fleroxacin-treated patients experienced phototoxicity and treatment-limiting adverse events. In conclusion, compared to twice-daily ofloxacin, fleroxacin had similar clinical efficacy and the advantage of once-a-day dosing, but with slightly lower bacteriological cure rate and a higher rate of treatment-limiting adverse events.

Comparison of cefdinir and cefaclor in treatment of community-acquired pneumonia.

Six hundred ninety patients were enrolled in a multicenter, randomized, double-blind trial comparing the efficacy and safety of cefdinir with those of cefaclor in the treatment of community-acquired pneumonia. Patients received either 10 days of treatment with cefdinir (n = 347) at 300 mg twice daily or 10 days of treatment with cefaclor (n = 343) at 500 mg three times daily. Microbiological assessments were performed on sputum specimens obtained at admission and at the two posttherapy visits, if available. Respiratory tract pathogens were isolated from 538 (78%) of 690 patient admission sputum specimens, with the predominant pathogens being Haemophilus parainfluenzae, Haemophilus influenzae, Streptococcus pneumoniae, and Staphylococcus aureus. The microbiological eradication rates at the test-of-cure visit were 92% (238 of 260 pathogens) and 93% (245 of 264 pathogens) for the evaluable patients treated with cefdinir and cefaclor, respectively. A satisfactory clinical response (cure plus improvement) was achieved in 89% (166 of 187) and 86% (160 of 186) of the evaluable patients treated with cefdinir and cefaclor, respectively. Except for the incidence of diarrhea, adverse event rates while on treatment were equivalent between the two treatment groups. Diarrhea incidence during therapy was higher for patients treated with cefdinir (13.7%) than for patients treated with cefaclor (5.3%). These results indicate that cefdinir is effective and safe in the treatment of patients with pneumonia.

Equivalent efficacy and reduced occurrence of diarrhea from a new formulation of amoxicillin/clavulanate potassium (Augmentin) for treatment of acute otitis media in children.

OBJECTIVE: To compare the safety and efficacy, in treating acute otitis media (AOM) in children, of a new formulation of amoxicillin/clavulanate potassium (Augmentin) oral suspension providing 45/6.4 mg/kg/day and administered twice daily (bid) for 5 and 10 days, respectively, with the safety and efficacy of the original formulation providing 40/10 mg/kg/day and administered three times daily (tid) for 10 days. STUDY DESIGN: Eight hundred sixty-eight children ages 2 months to 12 years with AOM were randomly assigned to one of the three treatment groups. Stringent criteria were used for the diagnosis of AOM and for determinations of "cure" and "improvement." Subjects were reexamined on Days 12 to 14 and 32 to 38. RESULTS: Among subjects whose treatment and follow-up conformed fully to protocol, the proportion of treatment successes (clinically cured or improved) on Days 12 to 14 was 78.8% (149 of 189) in the tid 10-day group, 86.5% (154 of 178) in the bid 10-day group and 71.1% (140 of 197) in the bid 5-day group. Corresponding values on Days 32 to 38 were 64.2% (95 of 148) in the tid 10-day group, 63.1% (94 of 149) in the bid 10-day group and 57.8% (93 of 161) in the bid 5-day group. None of the differences between the tid 10-day regimen and either of the 2 bid regimens were statistically significant, but the bid 10-day regimen was significantly more effective than the bid 5-day regimen in younger subjects. In the study population as a whole, results were similar to those in per protocol subjects. Overall the incidence of protocol-defined diarrhea was 26.7% (74 of 277) in the tid 10-day group, compared with 9.6% (27 of 280) in the bid 10-day group (P < 0.0001) and 8.7% (25 of 286) in the bid 5-day group (P < 0.0001). CONCLUSIONS: In comparison with the original formulation of Augmentin administered tid for 10 days in the treatment of AOM in children, the new formulation administered bid for 10 days provides at least equivalent efficacy and causes substantially less diarrhea. Administration for 5 days appears not to provide equivalent efficacy, but the difference appears limited to younger children and the margin of difference is small.

Effectiveness of short-course therapy (5 days) with cefuroxime axetil in treatment of secondary bacterial infections of acute bronchitis.

Five hundred thirty-seven patients were enrolled in two independent, investigator-blinded, multicenter, randomized clinical trials comparing the clinical and bacteriologic efficacies and the safety of 5- or 10-day treatment with cefuroxime axetil with those of 10-day treatment with amoxicillin-clavulanate in the treatment of secondary bacterial infections of acute bronchitis. Patients received either 5 or 10 days of treatment (n = 177 in each group) with cefuroxime axetil at 250 mg twice daily or 10 days of treatment (n = 183) with amoxicillin-clavulanate at 500 mg three times daily. Patients in the cefuroxime axetil (5 days) group received placebo on days 6 to 10. Bacteriologic assessments were based on sputum specimen cultures obtained preceding and, when possible, following treatment. Organisms were isolated from the pretreatment sputum specimens of 242 of 537 (45%) patients, with the primary pathogens being Haemophilus influenzae, Haemophilus parainfluenzae, Moraxella catarrhalis, Streptococcus pneumoniae, and Staphylococcus aureus (28, 25, 13, 9, and 8% of isolates, respectively). Pathogens were eradicated or presumed to be eradicated in 87% (52 of 60), 91% (53 of 58), and 86% (60 of 70) of bacteriologically evaluable patients treated with cefuroxime axetil (5 days), cefuroxime axetil (10 days), and amoxicillin-clavulanate, respectively. A satisfactory clinical outcome (cure or improvement) was achieved in 82% (107 of 130), 86% (117 of 136), and 83% (130 of 157) of the clinically evaluable patients treated with cefuroxime axetil (5 days), cefuroxime axetil (10 days), and amoxicillin-clavulanate, respectively. Treatment with amoxicillin-clavulanate was associated with a significantly higher incidence of drug-related adverse events than was treatment with cefuroxime axetil for either 5 or 10 days (P = 0.001), primarily reflecting a higher incidence of drug-related gastrointestinal adverse events (37 versus 19 and 15%, respectively; P < 0.001), particularly diarrhea and nausea. These results indicate that treatment with cefuroxime axetil at 250 mg twice daily for 5 days is as effective as treatment for 10 days with either the same dose of cefuroxime axetil or amoxicillin-clavulanate at 500 mg three times daily in patients with acute bronchitis. In addition, treatment with cefuroxime axetil for either 5 or 10 days is associated with significantly fewer gastrointestinal adverse events, particularly diarrhea and nausea, than is 10-day treatment with amoxicillin-clavulanate.

The superficial femoral vein. A potentially lethal misnomer.

OBJECTIVE: To assess the potential for error in interpretation of venous duplex reports that use the term "superficial femoral vein." DESIGN: Three surveys conducted by mail. SETTING: Three multispecialty medical groups, anatomy departments of all US medical schools, and vascular laboratories. PARTICIPANTS: A total of 46 family practitioners and general internists, 95 chairpersons of departments of anatomy, and 85 laboratory directors. MAIN OUTCOME MEASURES: Proposed treatment of a patient with leg pain and an acute thrombosis of the superficial femoral vein; what nomenclature(s) for the deep thigh veins is (are) felt to be correct, what are acceptable alternatives, what is taught to students and which is preferred; and what terminology is being used in lower limb venous duplex reports. RESULTS: Only 24% (11/46) of the respondents would have administered anticoagulants to the patient as described. Only 3% (3/95) of anatomists felt the term "superficial femoral vein" was correct, 22% (21/95) felt it was an acceptable alternative (though only 9% [9/95] taught it to medical students), and only 7% (7/95) of anatomists felt the term was preferred for everyday use. The term "superficial femoral vein" is used by 93% (79/85) of vascular laboratories in lower limb venous duplex reports. CONCLUSION: Although the overwhelming majority of vascular laboratories use the term "superficial femoral vein" in venous duplex reports, the use of this term is potentially hazardous to patients. Most primary care physicians have not been taught and are not aware that the superficial femoral vein is a deep vein and that acute thrombosis of this vessel is potentially life threatening.

Clinical comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of patients with secondary bacterial infections of acute bronchitis.

Two independent, investigator-blinded, multicenter, randomized clinical trials compared the clinical and bacteriologic efficacy and safety of two oral antibiotics, cefuroxime axetil and amoxicillin/clavulanate, in the treatment of patients with secondary bacterial infections of acute bronchitis (hereafter denoted acute bronchitis). Three hundred sixty patients with signs and symptoms of acute bronchitis were enrolled at 22 centers and were randomly assigned to receive 10 days of treatment with either cefuroxime axetil 250 mg twice daily (BID) (n= 177) or amoxicillin/clavulanate 500 mg three times daily (TID) (n = 183). Patients were assessed for both clinical and bacteriologic responses once during treatment (at 3 to 5 days) and twice after treatment (at 1 to 3 days and at 13 to 15 days). Bacteriologic assessments were based on sputum specimen cultures obtained before treatment and, when possible, after treatment. Organisms were isolated from the pretreatment sputum specimens of 162 (45%) of 360 patients, with the primary pathogens being Haemophilus influenzae, Haemophilus parainfluenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus (28%, 25%, 11%, 9%, and 8% of isolates, respectively). Thirty-four percent of the H influenzae isolates and 94% of the M catarrhalis isolates that were tested for beta-lactamase production were positive. A satisfactory clinical outcome (cure or improvement) was achieved in 86% (117 of 136) and 83% (130 of 157) of the clinically assessable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (P = 0.45). With respect to the eradication of bacterial pathogens, a satisfactory outcome (cure, presumed care, or cure with colonization) was obtained in 91% (53 of 58) and 86% (60 of 70) of bacteriologically assessable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (P = 0.32). Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events than was treatment with cefuroxime axetil (39% vs 23%; P = 0.001), primarily reflecting a higher incidence of drug-related gastrointestinal adverse events (37% vs 15%; P < 0.001), particularly diarrhea and nausea. Four patients in the cefuroxime axetil group and eight patients in the amoxicillin/clavulanate group withdrew from the study because of drug-related adverse events. These results indicate that cefuroxime axetil 250 mg BID is as effective as amoxicillin/clavulanate 500 mg TID in the treatment of patients with acute bronchitis but produces fewer gastrointestinal adverse events, particularly diarrhea and nausea.

Comparison of oral cefpodoxime proxetil and cefaclor in the treatment of skin and soft tissue infections.

This multicenter, randomized, double-blind study was designed to compare the safety and efficacy of cefpodoxime proxetil and cefaclor in the treatment of skin and soft tissue infections. Patients were aged > or = 12 years with acute (< or = 7 days duration), single-site skin or skin-structure infections. The 7- to 10-day treatment regimens were cefpodoxime proxetil (400 mg cefpodoxime) orally with food twice a day with cefaclor-matched placebo (orally, fasting, three times a day); or cefaclor (Ceclor; 500 mg anhydrous equivalent) orally, fasting, three times a day, with cefpodoxime-matched placebo (orally with food twice a day). Clinical progress and cultures were evaluated upon admission to the study; on study days 7-10 and 15-18; and 2-3 weeks after treatment. Cefpodoxime had lower minimum inhibitory concentrations against the majority of Staphylococcus species than did cefaclor. Both treatments were highly effective (99% pathogen eradication and 86% cure rate). These high eradication rates were not unexpected in this study of minor infections in which patients with resistant pathogens were excluded. Cefaclor had a higher failure rate [2 (4%) of 57], than did cefpodoxime [2 (1%) of 139; p not significant]. Most patients in both groups completed treatment as planned: 185 (74%) of 249 cefpodoxime-treated patients and 91 (75%) of 122 cefaclor-treated patients. Both treatments were well tolerated and considered safe and effective in the treatment of skin and skin structure infections. However, the twice-a-day dosing regimen for cefpodoxime proxetil compared with the three-times-a-day regimen for cefaclor may result in better patient compliance.

Evaluation of cefuroxime axetil and cefadroxil suspensions for treatment of pediatric skin infections.

A randomized, single-blind, multicenter study was conducted to evaluate the safety and efficacy of cefuroxime axetil and cefadroxil suspensions for the treatment of skin or skin structure infections in 287 children. Each drug was given at a dosage of 30 mg/kg of body weight per day in two divided doses. Staphylococcus aureus and Streptococcus pyogenes, or a combination of the two, were the primary pathogens isolated from infected skin lesions. A satisfactory bacteriological response (cure or presumed cure) was obtained in 97.1 and 94.3% of children in the cefuroxime axetil and cefadroxil groups, respectively (P greater than 0.05). Satisfactory clinical responses (cure or improvement) were more likely to occur in cefuroxime axetil recipients than in cefadroxil recipients (97.8 versus 90.3%; P less than 0.05). Both regimens were equally well tolerated, with adverse events occurring in 7.9 and 6.1% of cefuroxime axetil and cefadroxil recipients, respectively. There were more patients who refused to take cefuroxime axetil (7 of 189) than there were who refused to take cefadroxil (0 of 98), but the difference was not statistically significant (P = 0.1). In this study, cefuroxime axetil was at least as effective as cefadroxil in resolving skin and skin structure infections in children.