Effectiveness of short-course therapy (5 days) with grepafloxacin in the treatment of acute bacterial exacerbations of chronic bronchitis.

Three hundred eighty-nine patients were enrolled in a double-masked, multicenter, randomized clinical trial comparing the clinical and bacteriologic efficacies and safety of a 5-day course (n = 195) versus a 10-day course (n = 194) of grepafloxacin 400 mg once daily in the treatment of acute bacterial exacerbations of chronic bronchitis (ABECB). Patients in the 5-day treatment group received placebo on days 6 through 10. Bacteriologic assessments were based on cultures of sputum specimens obtained before and, when possible, during and after treatment. Organisms were isolated from the pretreatment sputum specimens of 332 of 388 (86%) patients, the primary pathogens being Haemophilus parainfluenzae, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Staphylococcus aureus (29%, 19%, 4%, 5%, and 5% of isolates, respectively). Among isolates tested for beta-lactamase production, results were positive in 25% of H influenzae isolates and 90% of M catarrhalis isolates. Forty-two percent of S pneumoniae isolates demonstrated reduced susceptibility (intermediate or high-level resistance) to penicillin. A satisfactory clinical outcome (cure or improvement) was achieved in 83% (128 of 155) and 81% (122 of 150) of clinically evaluable patients treated with grepafloxacin for 5 or 10 days, respectively. Pathogens were eradicated or presumed eradicated in 77% (106 of 138) and 80% (98 of 123) of bacteriologically evaluable patients treated with grepafloxacin for 5 or 10 days, respectively. The 2 treatment groups were equivalent with respect to both clinical and bacteriologic efficacy, and no statistically significant differences in the incidence of drug-related adverse events were seen between the 2 groups. Substantial symptom relief was evident with both treatment regimens by the first during-treatment measurement, which occurred between days 3 through 5. These results indicate that treatment with 400 mg grepafloxacin once daily for 5 days is as well tolerated and effective as treatment for 10 days in patients with ABECB. The lower cost compared with a 10-day regimen and the increased likelihood that patients will complete the entire shorter, once-daily regimen make the 5-day grepafloxacin regimen a useful therapeutic option in the treatment of ABECB.

Comparison of single-dose cefuroxime axetil with ciprofloxacin in treatment of uncomplicated gonorrhea caused by penicillinase-producing and non-penicillinase-producing Neisseria gonorrhoeae strains.

A randomized, multicenter, investigator-blind trial was conducted to compare the efficacies of cefuroxime axetil and ciprofloxacin for treatment of patients with uncomplicated gonorrhea caused by penicillinase-producing Neisseria gonorrhoeae (PPNG). A total of 832 patients (434 females and 398 males) received a single oral dose of cefuroxime axetil (1,000 mg [417 patients]) or ciprofloxacin (500 mg [415 patients]). N. gonorrhoeae was eradicated from the cervix in 114 of 118 (97%) and 118 of 119 (99%) bacteriologically evaluable females treated with cefuroxime axetil and ciprofloxacin, respectively (P = 0.213; difference, -2%; 95% confidence interval, -6 to 1%), and from the urethra in 154 of 166 (93%) and 171 of 171 (100%) bacteriologically evaluable male patients treated with cefuroxime axetil and ciprofloxacin, respectively (P < 0.001; difference, -7%; 95% confidence interval, -11 to -3%). Both treatments were effective in eradicating N. gonorrhoeae in females with rectal infections (cefuroxime axetil, 29 of 30 [97%]; ciprofloxacin, 25 of 25 [100%]; P = 1.00). In small numbers of patients, cefuroxime axetil was less effective than ciprofloxacin in treating males with pharyngeal infections (eradication in 4 of 10 and in 8 of 8 patients, respectively; P = 0.013). PPNG was eradicated from the cervix in 22 of 23 (96%) and 32 of 32 (100%) bacteriologically evaluable female patients treated with cefuroxime axetil and ciprofloxacin, respectively (P = 0.418; difference, -4%; 95% confidence interval, -13 to 4%), and from the urethra in 35 of 36 (97%) and 34 of 34 (100%) bacteriologically evaluable male patients treated with cefuroxime axetil and ciprofloxacin, respectively (P = 1.00; difference, -3%; 95% confidence interval, -8 to 3%). The incidences of drug-related adverse events were similar for the two study drugs. In summary, treatment with a single oral dose of cefuroxime axetil is as effective as treatment with a single oral dose of ciprofloxacin in eradicating PPNG from males and females with uncomplicated gonorrhea (urethral and endocervical), and both regimens are well-tolerated. However, in the present study, cefuroxime axetil was less effective than ciprofloxacin in treating urethral gonococcal infections in male patients, although both study drugs were highly effective in treating cervical gonococcal infections in female patients.

Comparison of oral cefuroxime axetil and oral amoxycillin/clavulanate in the treatment of community-acquired pneumonia.

Cefuroxime axetil has been evaluated previously in the treatment of lower respiratory tract infections, but not specifically in the treatment of community-acquired pneumonia. In a multicentre, investigator-blinded clinical trial, 162 patients with community-acquired pneumonia were randomly assigned to receive orally either cefuroxime axetil 500 mg bid (n = 84) or amoxycillin/clavulanate 500 mg/125 mg tid (n = 78) for 10 days. Organisms were isolated from the pretreatment sputum specimens of 97 of 162 (60%) patients, the commonest isolates being Streptococcus pneumoniae (38%) and Haemophilus influenzae (18%). A satisfactory clinical outcome (cure or improvement) was achieved in 100% (55 of 55) and 96% (49 of 51) of the clinically evaluable patients treated with cefuroxime axetil or amoxycillin/clavulanate, respectively (P = 0.23). With respect to eradication of bacterial pathogens, a satisfactory outcome (cure, presumed cure or cure with colonization) was obtained in 94% (32 of 34) and 93% (37 of 40) of bacteriologically evaluable patients treated with cefuroxime axetil or amoxycillin/clavulanate, respectively (P = 1.00). Both treatment regimens used in this study were well tolerated. The most common drug-related adverse experiences were gastrointestinal events, reported by 8% and 4%, respectively, of the patients in the amoxycillin/clavulanate and cefuroxime axetil groups, a difference which was not statistically significant (P = 0.32). These results indicate that cefuroxime axetil twice a day is as effective as amoxycillin/clavulanate three times a day in the treatment of outpatients with mild to moderate community-acquired pneumonia.

Effectiveness of five days of therapy with cefuroxime axetil suspension for treatment of acute otitis media.

BACKGROUND: In recent years there has been considerable interest in reducing the duration of antibiotic treatment regimens in patients with common bacterial infections. We conducted two independent, investigator-blinded, multicenter, randomized clinical trials, one of which included microbiologic evaluation of middle ear fluid obtained by tympanocentesis, comparing the efficacy and safety of 5 or 10 days of treatment with cefuroxime axetil suspension (CAE) with that of 10 days of treatment with amoxicillin/clavulanate suspension (AMX/CL) in children with acute otitis media. METHODS: A total of 719 pediatric patients from the ages of 3 months to 12 years were enrolled in the 2 studies. Patients received CAE for either 5 or 10 days at 30 mg/kg/day in 2 divided doses (n = 242 and 235, respectively) or AMX/CL for 10 days at 40 mg/kg/day in 3 divided doses (n = 242). Patients in the CAE (5 days) group received placebo on Days 6 through 10. In the study that included tympanocentesis, bacteriologic assessments were based on middle ear fluid cultures obtained pretreatment and, when possible, after treatment in patients with an unsatisfactory clinical outcome. RESULTS: Organisms were isolated from the pretreatment middle ear fluid specimens of 177 of 244 (73%) patients undergoing tympanocentesis, with the primary pathogens being Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis (37, 35 and 12% of isolates, respectively). Pathogens were eradicated or presumed to be eradicated in 92% (24 of 26), 84% (32 of 38) and 95% (36 of 38) of bacteriologically evaluable patients treated with CAE for 5 or 10 days or with AMX/CL, respectively. A satisfactory clinical outcome (cure or improvement) occurred in 69% (101 of 147), 70% (121 of 173) and 74% (131 of 177) of clinically evaluable patients treated with CAE (5 days), CAE (10 days) or AMX/CL, respectively. Treatment with AMX/CL was associated with a significantly higher incidence of drug-related adverse events than was treatment with CAE for either 5 or 10 days (P < 0.001), primarily reflecting a higher incidence of drug-related gastrointestinal adverse events (34% vs. 17 and 12%, respectively; P < 0.001), particularly diarrhea. CONCLUSIONS: Treatment with CAE given twice daily for 5 days is equivalent to treatment for 10 days either with the same regimen of CAE or with AMX/CL given three times daily in pediatric patients with acute otitis media.

Antibiotic prophylaxis during clean neurosurgery: a large, multicenter study using cefuroxime.

Cefuroxime is a second-generation cephalosporin with in vitro activity against the organisms that are commonly associated with neurosurgical wound infections. Other properties of cefuroxime are an elimination half-life of 1.3 hours, which yields prolonged serum concentrations, and its ability to penetrate the blood-brain barrier in proportion to the degree of inflammation. A prospective, multicenter, open-label study was conducted to evaluate the efficacy and safety of cefuroxime for antibiotic prophylaxis in patients undergoing clean neurosurgery. Cefuroxime 1.5 g was given intravenously 25 to 60 minutes before surgery; for procedures lasting more than 3 hours, cefuroxime 750 mg was given intravenously 8 hours after the initial dose. Patients were examined before surgery, daily during hospitalization, and at 8 weeks after surgery. A total of 956 adults were enrolled in the study. The most common procedures in study patients were laminectomy (41.8% of patients) or craniotomy (24.3%), and the mean duration of surgery was 3.2 hours. Infection occurred in 2 (0.3%) of 592 assessable patients by the time of discharge and in 1 additional patient by the 8-week follow-up evaluation for a total of 3 (0.5%) of 560 assessable patients. Drug-related adverse events occurred in 5 (0.5%) of 956 patients. These results indicate that antibiotic prophylaxis with cefuroxime is associated with a low incidence of postoperative wound infection and is well tolerated in patients undergoing clean neurosurgery.

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.

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.

Clinical comparison of cefuroxime axetil suspension and amoxicillin/clavulanate suspension in the treatment of pediatric patients with acute otitis media with effusion.

Two independent, investigator-blinded, multicenter, randomized clinical trials, one of which included microbiologic evaluation of middle-ear fluid obtained by use of tympanocentesis, compared the efficacy and safety of two oral antibiotics, cefuroxime axetil suspension and amoxicillin/clavulanate suspension, in the treatment of children 3 months to 12 years old diagnosed with acute otitis media with effusion (AOME). Four hundred seventy-seven pediatric patients with signs and symptoms of AOME were enrolled at 20 centers and were randomly assigned to receive 10 days of treatment with either cefuroxime axetil suspension 30 mg/kg per day in two divided doses (n = 235) or amoxicillin/clavulanate suspension 40 mg/kg per day in three divided doses (n = 242). Patients were assessed for their response to treatment once during treatment (at 3 to 5 days) and twice after treatment (at 1 to 4 days and at 14 to 18 days). In the study that included tympanocentesis, bacteriologic assessments were based on middle-ear fluid cultures obtained pretreatment, and, when possible, posttreatment in patients with an unsatisfactory clinical outcome. Organisms were isolated from the pretreatment middle-ear fluid specimens of 120 (73%) of 164 patients undergoing tympanocentesis, with the primary pathogens being Streptococcus pneumoniae. Haemophilus influenzae, and Moraxella catarrhalis (27%, 24%, and 6% of isolates, respectively). Forty-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 obtained in 70% of clinically assessable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (P = 0.40). With respect to the eradication of bacterial pathogens, in the study that included tympanocentesis a satisfactory outcome (cure or presumed cure) was obtained in 84% (32 of 38) and 95% (36 of 38) of bacteriologically assessable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (P = 0.26). Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events than was treatment with cefuroxime axetil (37% vs 16%; P < 0.001), primarily reflecting a higher incidence of drug-related gastrointestinal adverse events (34% vs 12%; P < 0.001), particularly diarrhea. Eight patients in the cefuroxime axetil group and 11 patients in the amoxicillin/clavulanate group withdrew from the studies because of drug-related adverse events. These results indicate that cefuroxime axetil suspension 15 mg/kg twice daily is as effective as amoxicillin/clavulanate suspension 13.3 mg/kg three times daily in the treatment of pediatric patients with AOME, but produces fewer gastrointestinal adverse events, particularly diarrhea.

Clinical comparison of cefuroxime axetil and amoxicillin/clavulanate in the treatment of patients with acute bacterial maxillary sinusitis.

PURPOSE: This multicenter study compared the clinical and bacteriologic efficacy of two oral antibiotics, cefuroxime axetil and amoxicillin/clavulanate, in the treatment of acute bacterial maxillary sinusitis. PATIENTS AND METHODS: Three hundred seventeen patients with clinical and radiographic evidence of acute maxillary sinusitis were enrolled at nine centers and were randomly assigned to receive 10 days of treatment with cefuroxime axetil 250 mg twice daily (n = 157) or amoxicillin/clavulanate 500 mg three times daily (n = 160). Patients were assessed for both clinical and bacteriologic responses once during treatment (5 to 7 days) and twice after treatment (1 to 3 days and 4 weeks). Bacteriologic assessments were based on needle aspirates of the maxillary sinus obtained pretreatment and, when possible, at the first posttreatment visit. RESULTS: Organisms were isolated from the pretreatment sinus aspirates of 198 of 317 (62%) patients, with the primary isolates being Streptococcus pneumoniae (22%), Haemophilus spp. (17%), Staphylococcus aureus (13%), and Haemophilus influenzae (10%). A satisfactory clinical outcome (cure or improvement) was achieved in 85% (98 of 115) and 82% (102 of 124) of the clinically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (P = 0.446). With respect to the eradication of the bacterial pathogens, a satisfactory outcome (cure or presumed cure) was obtained in 84% (31 of 37) and 87% (34 of 39) of bacteriologically evaluable patients treated with cefuroxime axetil or amoxicillin/clavulanate, respectively (p = 0.567). Treatment with amoxicillin/clavulanate was associated with a significantly higher incidence of drug-related adverse events (13% versus 3%, p = 0.001), particularly diarrhea (8% versus 1%, p = 0.001). Two patients in the cefuroxime axetil group and three patients in the amoxicillin/clavulanate group withdrew from the study due to adverse events. CONCLUSIONS: Our results indicate that cefuroxime axetil twice a day is as effective as amoxicillin/clavulanate three times a day in the treatment of acute bacterial maxillary sinusitis but produces fewer adverse effects.

Postmarketing comparison of labetalol and propranolol in hypertensive patients.

A survey was conducted to compare the safety and effectiveness of labetalol and propranolol under routine conditions of clinical use. Patients received either labetalol (n = 805) or propranolol (n = 135) twice daily, according to package insert instructions, for six weeks. Every two weeks the patients were evaluated and weight, heart rate, blood pressure, dose, and adverse symptoms were recorded. Both treatment groups experienced a significant decline in blood pressure at six weeks; blood pressure decreased by 24/15 mmHg in the labetalol patients and by 20/14 mmHg in the propranolol patients. Heart rate decreased significantly in both groups, but the drop in the propranolol group was greater than in the labetalol group. Significantly more propranolol-treated patients reported fatigue (15.2% versus 6.3%), impotence (9.0% versus 3.2%), bad dreams (2.3% versus 0.3%), and cold extremities (2.3% versus 0%). Dizziness was reported more frequently by the labetalol group (9.1% versus 3.8%). Overall, both drugs were safe and effective in treating hypertension, but complaints of beta-blocker-associated side effects were more frequent with propranolol.

Increased lead absorption in children of workers in a lead storage battery plant.

Exposure to toxic materials originating in the workplace has been recognized in families of workers in several industries. However, to date this problem has not been studied in the storage battery production industry. Twenty-seven one- to six-year-old children of 22 workers at a storage battery plant at high risk of exposure to lead oxide were compared with 32 one- to six-year-old children in 22 neighborhood control families for evidence of increased lead absorption. Workers' children had significantly higher blood lead (p less than 0.001) and erythrocyte protoporphyrin (p less than 0.003) values than control children. Household exposures to lead in paint and water were similar for the two groups, but workers' homes had significantly higher concentrations of lead in dust (p less than 0.001). It is postulated that lead is brought home on the skin, hair and clothing of the workers and that their children are ingesting or inhaling the lead in household dust. This is the first report of increased lead absorption in children of workers in this industry.