Gunnar Englund

Empiric Treatment of Acute Diarrheal Disease with Norfloxacin: A Randomized, Placebo-Controlled Study

OBJECTIVE To evaluate the clinical and microbiologic efficacy and safety of norfloxacin for acute diarrhea. DESIGN Double-blind, placebo-controlled, randomized clinical multicenter trial. SETTING Six departments of infectious disease. PARTICIPANTS Patients 12 years of age or older with a history of acute diarrhea lasting 5 or fewer days. Eighty-five percent of patients (511/598) were evaluable for efficacy. Of these evaluable patients, 70% had traveled abroad within the previous 6 weeks. INTERVENTIONS Patients received either norfloxacin, 400 mg, or placebo twice daily for 5 days. MEASUREMENTS Enteric pathogens were isolated in 51% of the evaluable patients: Campylobacter species in 29%, Salmonella species in 16%, Shigella species in 3.5%, and other pathogens in 2.6%. RESULTS Norfloxacin had a favorable overall effect compared with placebo (cure rate, 63% compared with 51%; P = 0.003). There were statistically favorable effects in culture-positive patients, patients with salmonellosis, and severely ill patients but not in culture-negative patients or patients with campylobacteriosis or shigellosis. A significant difference was noted between norfloxacin and placebo in median time to cure among all evaluable patients (3 compared with 4 days, P = 0.02) and in patients with campylobacteriosis (3 compared with 5 days, P = 0.05) but not in patients. Culture-positive, but not culture-negative patients, in the norfloxacin group had significantly fewer loose stools per day compared with patients in the placebo group from day 2 onward (P less than or equal to 0.01). Norfloxacin was significantly less effective than placebo in eliminating Salmonella species on days 12 to 17 (18% compared with 49%, P = 0.006), whereas the opposite was true for Campylobacter species (70% compared with 50%, P = 0.03). In six of nine patients tested, norfloxacin-resistant Campylobacter species (MIC, greater than or equal to 32 micrograms/mL) appeared after norfloxacin treatment. CONCLUSION Empiric treatment reduced the intensity and, to some extent, the duration of symptoms of acute diarrhea. The effect was restricted to patients who had bacterial enteropathogens or who were severely ill. The clinical usefulness of this treatment is limited by the fact that norfloxacin seems to delay the elimination of salmonella and to induce resistance in campylobacter.

Randomised double-blind study of norfloxacin and cefadroxil in the treatment of acute pyelonephritis

In a coordinated, double-blind multi-centre trial, adults with symptoms of acute pyelonephritis were randomly assigned to receive a two-week course of oral treatment with either 400 mg norfloxacin twice daily or 1 g cefadroxil twice daily. Of 197 patients enrolled in the study, 140 could be evaluated for drug efficacy and 193 for drug safety. Norfloxacin gave a significantly higher bacteriological cure rate than cefadroxil, both at 3 to 10 days (98 % versus 65 %; p<0.0001; 95 % confidence interval (CI) for difference in proportions 21–46 %) and up to eight weeks (87 % versus 48 %; p<0.0001; 95 % CI 25–54 %) after cessation of treatment. The differences between the two regimens were most pronounced in men and in patients with complicating factors such as diabetes mellitus and urinary tract abnormalities. The clinical response during treatment did not differ between the two groups, but symptomatic recurrences at follow-up were more common in the cefadroxil group (28 % versus 3 %; p<0.0001; 95 % CI 14–36 %). Adverse events were more often reported by patients receiving cefadroxil (39 % versus 22 %; p=0.011; 95 % CI 4–30 %) and consisted mainly of gastrointestinal disturbances and vulvo-vaginitis. In terms of bacteriological and clinical efficacy and safety, a two-week course of norfloxacin was superior to a two-week course of cefadroxil for oral treatment of community-acquired acute pyelonephritis.

Optimizing the therapeutic approach of transurethral alprostadil

Objective To investigate the efficacy and safety of two different starting doses of transurethral alprostadil (250 µg and 500 µg, MUSE®, Vivus Inc., Menlo Park, CA, USA, and Astra Läkemedel AB, Södertälje, Sweden) and the need for dose titration in a general population with erectile dysfunction.

Norfloxacin vs. Pivmecillinam in the Treatment of Uncomplicated Lower Urinary Tract Infections in Hospitalized Elderly Patients

In a single-blind, randomized study of multicentre trial design 343 hospitalized geriatric patients (median age 83 years) suffering from symptomatic urinary tract infections (UTI) were treated with either norfloxacin 200 mg twice daily or pivmecillinam 200 mg 3 times daily orally for 7 days to compare the clinical efficacy and safety of the antibiotics in the elderly. The pathogen was Escherichia coli in 56.7%, other gram-negative rods in 37.2% and gram-positive cocci in 6.1%. Up to 18 days after cessation of treatment the original pathogen was eradicated in 60.5% of the 114 who were assessable for the effect of norfloxacin therapy and in 36.5% of the 96 patients in the pivmecillinam group (p less than 0.001). Adverse drug reactions, mostly gastrointestinal disturbances, were noticed in single cases.

REMAINDER TERM ESTIMATE FOR THE ASYMPTOTIC NORMALITY OF THE NUMBER OF RENEWALS

It is well known that the number of renewals in the time interval [0, t] for an ordinary renewal process is approximately normally distributed under general conditions. We give a remainder term estimate for this normal distribution approximation. RENEWAL PROCESS; NORMAL APPROXIMATION; REMAINDER TERM

NXY-059 Does Not Affect Bleeding Time in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled, 3-Period Crossover Phase I Study

NXY‐059 is a novel free radical–trapping neuroprotectant that reduces infarct size and preserves brain function in animal models of acute ischemic stroke. It is the first neuroprotectant to demonstrate a reduction in global disability in a phase III clinical trial, as measured by the modified Rankin Scale. Any effect of NXY‐059 on hemostasis may be important when treating stroke patients. This phase I randomized, double‐blind, placebo‐controlled, 3‐period crossover study compared the effect of NXY‐059, desmopressin, and placebo on bleeding time, platelet aggregation, and adhesion in 30 healthy volunteers. NXY‐059 did not prolong bleeding time compared with placebo: mean (SD) time for NXY‐059, 369.5 seconds (125.0 seconds) versus placebo, 369.1 seconds (136.0 seconds). There were no significant effects on platelet aggregation or adhesion. At a mean unbound plasma concentration (Cuss) of 335 μmol/L, NXY‐059 was well tolerated, with no major safety concerns identified. In conclusion, NXY‐059 does not appear to affect primary hemostasis.

On the coupon collector's remainder term

SummaryEach element in a finite population π is assigned a “bonus value”, i.e. a real number. Elements are selected from π by simple random sampling with replacement and with equal draw probabilities. Each time we receive a “new” element, i.e. an element which has not been previously selected, we receive the corresponding bonus. Let Wn denote the bonus sum after n selections. It is well known that Wn is approximately normally distributed under mild conditions. We give a remainder term estimate of the Berry-Esseen type for this normal distribution approximation.