Comparison of sparfloxacin and ciprofloxacin in the treatment of community-acquired acute uncomplicated urinary tract infection in women. Sparfloxacin Multicenter Uncomplicated Urinary Tract Infection Study Group.

Urinary tract infection (UTI) is a common illness, with > or =30% of all women experiencing a UTI during their lifetime. Less than a decade ago, the standard therapy for acute uncomplicated UTIs involved treatment with > or =7 days of an antibacterial agent, but recent studies using a variety of newly introduced antibiotics, including the fluoroquinolones, have demonstrated that a 1- to 5-day treatment regimen can be equally effective. This randomized, double-masked, multicenter study was conducted to compare the efficacy and tolerability of a single dose of sparfloxacin with those of a 3-day regimen of sparfloxacin and a 7-day regimen of ciprofloxacin in the treatment of women with community-acquired acute uncomplicated urinary tract infection. A total of 1175 women were enrolled; 395 received sparfloxacin as a single 400-mg dose on day 1, 394 received sparfloxacin as a 400-mg loading dose on day 1 followed by 200 mg once daily for 2 additional days, and 386 received ciprofloxacin 250 mg twice daily for 7 days. Patients were comparable with respect to demographic characteristics and underlying conditions. A total of 954 patients were clinically assessable; 490 of these were also bacteriologically assessable. All patients treated were included in the tolerability analysis. Escherichia coli (75.4%), Klebsiella pneumoniae (4.9%), Enterococcus faecalis (4.6%), and Staphylococcus saprophyticus (4.1%) were the most commonly isolated organisms. In the all-treated population, clinical success was achieved 5 to 9 days after therapy in 91.8%, 92.2%, and 91.6% of patients in the single-dose sparfloxacin, 3-day sparfloxacin, and 7-day ciprofloxacin groups, respectively; bacteriologic success was observed in 91.7%, 92.6%, and 96.6% of those in the 3 groups. Sustained clinical success rates 4 to 6 weeks after therapy were 76.6%, 80.2%, and 79.5% in the single-dose sparfloxacin, 3-day sparfloxacin, and 7-day ciprofloxacin groups, respectively; sustained bacteriologic success rates were 80.7%, 90.1%, and 92.6%. The most common adverse events were nausea, headache, vaginal thrush, dizziness, and diarrhea; >92% of adverse events were mild or moderate in severity. The 2 drugs had comparable frequencies of adverse events, except for photosensitivity, which occurred in 3.3% of the 3-day sparfloxacin group, 1.3% of the single-dose sparfloxacin group, and 0.3% of the ciprofloxacin group (P = 0.005). The 3-day sparfloxacin regimen was effective and well tolerated. The initial response to single-dose sparfloxacin treatment was comparable to the response to the other 2 regimens, but the single-dose regimen proved less effective over time, with higher rates of clinical recurrence and bacteriologic relapse. Sparfloxacin provides an alternative to ciprofloxacin for patients with acute uncomplicated urinary tract infection who are not at risk for photosensitivity reactions or adverse events associated with a prolonged corrected QT interval.

Sparfloxacin versus ciprofloxacin for the treatment of community-acquired, complicated skin and skin-structure infections.

Fluoroquinolones have been shown to be effective in the treatment of complicated skin and skin-structure infections, in part because of their broad-spectrum antibacterial activity against causative pathogens that are resistant to older antimicrobial agents. We enrolled 603 adult patients (>58% male, >85% white) in a double-masked, double-dummy, randomized, multicenter trial to compare the efficacy and tolerability of sparfloxacin (400-mg loading dose followed by 200 mg once daily) with those of ciprofloxacin (750 mg twice daily) for 10 days in the treatment of community-acquired, complicated skin and skin-structure infections. The primary efficacy variable was clinical response, based on assessment of signs and symptoms, in the clinically assessable population. Patients in the sparfloxacin and ciprofloxacin groups were comparable with respect to demographic characteristics, underlying diseases, medical history, and laboratory test results. Wound infection was the most common diagnosis, and Staphylococcus aureus was the most frequently isolated pathogen. For the 475 clinically assessable patients, the clinical success rate (percentage of patients cured or improved) was 90.1% (210/233) with sparfloxacin and 87.2% (211/242) with ciprofloxacin. In this analysis (95% confidence interval [CI], -2.8 to 8.6) and the intent-to-treat analyses (95% CI, -4.2 to 6.2), results with sparfloxacin were statistically equivalent to those with ciprofloxacin (95% CI, -1 to 15.3). For bacteriologically assessable patients, eradication rates were 87.0% (141/162) with sparfloxacin and 79.9% (123/154) with ciprofloxacin (95% CI, -1 to 15.3). Eradication rates of S. aureus and coagulase-negative staphylococcal infections were 90.2% (101/112) with sparfloxacin and 77.9% (88/113) with ciprofloxacin. For patients with 2 or more pathogens at baseline (mixed infections), bacteriologic success was 87.6% for sparfloxacin and 77.9% for ciprofloxacin. Pseudomonas aeruginosa infections were eradicated or presumed eradicated in 71.4% (10/14) of sparfloxacin-treated patients and 87.5% (7/8) of ciprofloxacin-treated patients. Overall success rates in the bacteriologically assessable patients for sparfloxacin (84.6% [137/162]) and ciprofloxacin (78.6% [121/154]) were statistically equivalent (95% CI, -2.5 to 14.5). Tolerability was assessed in all patients who received study medication. The overall frequency of treatment-related adverse events was comparable in the 2 treatment groups (26.5% sparfloxacin, 23.3% ciprofloxacin). Drug-related adverse events involving the digestive system occurred in 7.1% of sparfloxacin-treated patients and 19.0% of ciprofloxacin-treated patients; photosensitivity reactions were reported in 11.1% of patients in the sparfloxacin group and 0.7% of patients in the ciprofloxacin group (P < 0.001). The mean change in QTc interval from baseline to the maximum on-treatment value was greater in the sparfloxacin group (9 milliseconds) than in the ciprofloxacin group (3 milliseconds) (P = 0.005; 95% CI, 0.002 to 0.010). The efficacy of sparfloxacin was comparable to that of ciprofloxacin in the treatment of community-acquired, complicated skin and skin-structure infections, including those caused by staphylococci, the most common pathogens. Sparfloxacin's once-daily regimen, high skin-tissue penetration, and improved activity against gram-positive cocci make it a therapeutic alternative to ciprofloxacin for patients who are not at risk for photosensitivity reactions or adverse events associated with prolongation of the QTc interval.

Safety profile of sparfloxacin, a new fluoroquinolone antibiotic.

The safety profile of sparfloxacin, a newer fluoroquinolone antibiotic, was examined through an integrated analysis of safety data from 6 multicenter phase III trials. These consisted of 5 double-masked, randomized, comparative trials of sparfloxacin (a 400-mg oral loading dose followed by 200 mg/d for 10 days) versus standard therapies (erythromycin, cefaclor, ofloxacin, clarithromycin, and ciprofloxacin) and I open-label trial (noncomparative) in patients with: community-acquired pneumonia (2 trials); acute bacterial exacerbations of chronic bronchitis (1 trial); acute maxillary sinusitis (2 trials, one of which was the noncomparative trial); and complicated skin and skin-structure infections (1 trial). Overall, 401 (25.3%) of 1585 patients treated with sparfloxacin and 374 (28.1%) of 1331 receiving a comparator regimen experienced at least 1 adverse event considered to be related to the study medication. Photosensitivity reactions, usually of mild-to-moderate severity, were seen more frequently with sparfloxacin (7.4%) than with comparator agents (0.5%), whereas gastrointestinal reactions (diarrhea, nausea, dyspepsia, abdominal pain, vomiting, and flatulence), insomnia, and taste perversion were more common in patients taking comparator drugs (22.3% vs 12.1%, 4.3% vs 1.5%, and 2.9% vs 1.2%, respectively). Analysis of electrocardiographic findings showed that the mean change from baseline in QT interval corrected for heart rate (QTc) was significantly greater in sparfloxacin-treated patients (10 msec) than in patients given comparator drugs (3 msec), but no associated ventricular arrhythmias were detected. Adverse events led to discontinuation of study medication in 104 (6.6%) patients receiving sparfloxacin and 118 (8.9%) given com parator drugs. Sparfloxacin may be considered an appropriate choice for the treatment of certain community-acquired infections for patients who are not at risk for photosensitivity reactions or adverse events associated with prolongation of the QTc interval.

Treatment of community-acquired acute uncomplicated urinary tract infection with sparfloxacin versus ofloxacin. The Sparfloxacin Multi Center UUTI Study Group.

The efficacy and safety of a 3-day regimen of sparfloxacin were compared with those of a 3-day regimen of ofloxacin for the treatment of community-acquired acute uncomplicated urinary tract infections. Four hundred nineteen women were enrolled in a randomized, open-label, observer-blinded, multicenter study; 204 received sparfloxacin as a 400-mg loading dose on the first day and 200 mg once daily thereafter, and 215 received ofloxacin as 200 mg twice daily. A total of 383 patients met the criteria for clinical evaluability, and 174 were also bacteriologically evaluable; all treated patients were included in the safety analysis. Escherichia coli (86%) and Staphylococcus saprophyticus (4.6%) were the organisms most commonly isolated. Positive clinical responses were obtained 5 to 9 days after therapy in more than 92% of the patients in each group; sustained clinical cure rates 4 to 6 weeks after therapy were 78.3 and 76.9% in the sparfloxacin and ofloxacin groups, respectively. A positive bacteriologic response was observed in 98% of the bacteriologically evaluable patients in each treatment group at 5 to 9 days posttherapy and in 88.2 and 92.6% of the patients in the sparfloxacin and ofloxacin groups, respectively, 4 to 6 weeks after therapy. Almost 90% of all adverse events were of mild or moderate severity; the most frequent events at least possibly related to drug treatment were those common to the fluoroquinolones, namely, nausea, diarrhea, headache, insomnia, and photosensitivity. Photosensitivity was more frequent in the sparfloxacin group (6.9% versus 0.5% in the ofloxacin group); insomnia was more frequent in the ofloxacin group (3.7% versus 1.0% in the sparfloxacin group). These data suggest that a once-daily, 3-day regimen of sparfloxacin is effective and generally well tolerated in the treatment of acute uncomplicated urinary tract infections.

Sustained antihypertensive activity of diltiazem SR: double-blind, placebo-controlled study with 24-hour ambulatory blood pressure monitoring.

A new polymeric matrix technology provides a sustained-release formulation of diltiazem hydrochloride (diltiazem SR) suitable for once-daily therapy. The efficacy and safety of diltiazem SR were evaluated in a multicenter, randomized, double-blind, placebo-controlled, parallel-group study. After a single-blind, placebo lead-in period, 275 patients with mild to moderate essential hypertension were assigned to receive placebo or diltiazem SR 120, 240, 360, or 480 mg once daily for 4 weeks. The efficacy evaluation was based on office and 24-hour ambulatory blood pressure monitoring. Twenty-four hours after the last dose in the 4-week, double-blind treatment period, the mean reduction from baseline in supine diastolic blood pressure ranged from 5.1 to 10.6 mm Hg in the diltiazem SR 120- to 480-mg groups, resulting in a significant linear trend across all treatments (P less than .001). Reductions in systolic blood pressure were similar. Ambulatory blood pressure monitoring, performed in 138 patients, confirmed the dose-response relationship and showed consistent antihypertensive activity throughout the 24-hour dosing interval. The percentage of patients reporting adverse events was similar in the placebo- and active-treated groups. The results of this study indicate that diltiazem SR is well tolerated, lowers blood pressure in a dose-related manner, and provides sustained activity throughout the 24-hour dosing interval.