Multiclinic comparative study of norfloxacin and trimethoprim-sulfamethoxazole for treatment of urinary tract infections

Three hundred seventy patients with upper or lower urinary tract infections were entered into a multicenter, open comparative study. A total of 190 patients were treated with norfloxacin, and 180 patients were treated with trimethoprim-sulfamethoxazole. The percentage of strains susceptible to norfloxacin (99%) was significantly greater (P less than 0.001) than the percentage of strains susceptible to trimethoprim-sulfamethoxazole (90%). The percentages of patients with bacteriological outcomes of eradication were greater in the norfloxacin group (97%) than in the trimethoprim-sulfamethoxazole group (90%). The difference was significant (P less than 0.05). Seven patients (three treated with norfloxacin, four treated with trimethoprim-sulfamethoxazole) experienced early reinfection. Of 370 patients entered into the study, 20 patients experienced clinical adverse effects that were probably or definitely related to the study drug; 6 patients were in the group that received norfloxacin, and 14 were in the group that received trimethoprim-sulfamethoxazole. Study antimicrobial agents were discontinued because of clinical adverse effects in eight patients (norfloxacin, one patient; trimethoprim-sulfamethoxazole, seven patients). Three patients receiving norfloxacin and four patients receiving trimethoprim-sulfamethoxazole had laboratory adverse effects which were classified as probably or definitely drug related. None of the clinical or laboratory adverse effects was serious.     

Randomized, double-blind comparison of ciprofloxacin and trimethoprim-sulfamethoxazole for complicated urinary tract infections.

In a prospective, randomized, double-blind study, the effect of ciprofloxacin (250 mg orally, twice daily) was compared with that of trimethoprim-sulfamethoxazole (160 mg of trimethoprim and 800 mg of sulfamethoxazole orally, twice daily) on 45 patients with complicated urinary tract infections. Pretherapy isolates were all members of the family Enterobacteriaceae. Isolates were eradicated from 18 (82%) of 22 patients treated with ciprofloxacin and 12 (52%) of 23 patients treated with trimethoprim-sulfamethoxazole during and 5 to 9 days after therapy (P = 0.035). Both groups had similar relapse and reinfection rates at 4 to 6 weeks posttherapy. Adverse effects were mild and reversible, occurring in 1 of 22 in the ciprofloxacin group and 6 of 23 in the trimethoprim-sulfamethoxazole group. Disk diffusion susceptibility tests correlated better with broth macrodilution for ciprofloxacin than for trimethoprim-sulfamethoxazole. Ciprofloxacin is a safe, effective alternative to trimethoprim-sulfamethoxazole for the treatment of complicated urinary tract infections.     

Norfloxacin versus trimethoprim-sulfamethoxazole in the therapy of uncomplicated, community-acquired urinary tract infections.

In a prospective, randomized trial, norfloxacin (400 mg perorally, twice a day) was compared with trimethoprim-sulfamethoxazole (160-800 mg perorally, twice a day) in 45 patients with uncomplicated urinary tract infections. Escherichia coli was the most common isolate. Infections due to Enterobacter spp., Proteus mirabilis, Pseudomonas spp., and Staphylococcus spp. were also treated. Norfloxacin was equivalent in effectiveness and safety to trimethoprim-sulfamethoxazole, with a cure rate of 91% at the 5- to 9-day posttherapy visit and 88% at the 4- to 6-week posttherapy visit. It was well tolerated and had a low incidence of side effects.     

Treatment of complicated urinary tract infections with lomefloxacin compared with that with trimethoprim-sulfamethoxazole.

The efficacy of lomefloxacin given at 400 mg once daily for 14 days compared with that of trimethoprim-sulfamethoxazole at 160 and 800 mg, respectively, given twice daily for 14 days in the treatment of symptomatic complicated urinary tract infections was studied in a prospective, randomized, single-blind multicenter study. A total of 133 subjects presenting with signs and symptoms of urinary tract infection and an underlying abnormality consistent with complicated urinary tract infection were enrolled in the study. Bacteriologic cure was significantly better in 68 subjects randomized to lomefloxacin than in 65 subjects randomized to trimethoprim-sulfamethoxazole at short-term follow-up (88 versus 52%; 95% confidence intervals [CIs] 77 and 94% and 39 and 65%, respectively) this difference was no longer significant at long-term follow-up (64 versus 47%; CIs, 52 and 75% and 32 and 57%, respectively). Clinical outcomes were similar for both therapeutic regimens at short- and long-term follow-ups. The organisms that infected the subjects pretherapy were more frequently resistant to trimethoprim-sulfamethoxazole, and drug therapy was discontinued more frequently in subjects treated with trimethoprim-sulfamethoxazole because of adverse antimicrobial effects. In secondary analyses, outcomes did not differ with age or underlying genitourinary abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)     

Single-dose ceftriaxone versus multiple-dose trimethoprim-sulfamethoxazole in the treatment of acute urinary tract infections.

Fifty-four college women with symptoms of lower urinary tract infections were randomly treated, 25 with 500 mg of ceftriaxone in a single intramuscular dose and 29 with 160 mg of trimethoprim-800 mg of sulfamethoxazole orally twice daily for 7 days. At 1 week after treatment, 23 patients (92%) in the ceftriaxone group and 28 patients (96%) in the trimethoprim-sulfamethoxazole group were cured. Responses of the patients with positive or negative antibody-coated bacteria tests were not significantly different. Four patients (16%) in the ceftriaxone group developed diarrhea and malaise. One patient (4%) in the trimethoprim-sulfamethoxazole group had medication discontinued because of headaches. Leukopenia was found in one patient (4%) in the ceftriaxone group and four patients (14%) in the trimethoprim-sulfamethoxazole group.     

Microflora changes with norfloxacin and pivmecillinam in women with recurrent urinary tract infection

Similar changes in the periurethral and vaginal microflora were observed in 19 women with recurrent urinary tract infection following treatment with norfloxacin (NOR) or pivmecillinam (PIV). Escherichia coli strains were suppressed by both treatments. Staphylococcus spp. and enterococci colony counts increased following PIV treatment in the periurethral flora but remained stable with NOR.     

Ciprofloxacin versus trimethoprim-sulfamethoxazole: treatment of community-acquired urinary tract infections in a prospective, controlled, double-blind comparison.

In this study, we determined the safety and efficacy of the treatment of adults with urinary tract infection with ciprofloxacin hydrochloride (250 mg twice daily for 10 days) in comparison with trimethoprim-sulfamethoxazole (160 mg of trimethoprim and 800 mg of sulfamethoxazole twice daily for 10 days). Patients with signs and symptoms of urinary tract infection were randomized to receive ciprofloxacin (98 women and 5 men) or trimethoprim-sulfamethoxazole (92 women and 8 men). The success rate of therapy was 91% for both treatment arms of the study. Among seven failures after ciprofloxacin therapy, three were due to relapse of infection and two to side effects that necessitated a change in medication; in addition, two patients had persistent symptoms and required hospitalization. Among the six failures associated with trimethoprim-sulfamethoxazole therapy, four were due to relapse, one to persistence of infection, and one to a side effect that necessitated a change in medication. Among the patients treated with trimethoprim-sulfamethoxazole, 32% had mild or moderate adverse reactions; in comparison, 17% of the ciprofloxacin-treated patients had adverse reactions (P = 0.026). For the treatment of urinary tract infection in adult patients in this study, ciprofloxacin and trimethoprim-sulfamethoxazole were equally effective, but ciprofloxacin was associated with fewer adverse reactions.     

Comparison of short-term treatment regimen of ciprofloxacin versus long-term treatment regimens of trimethoprim/sulfamethoxazole or norfloxacin for uncomplicated lower urinary tract infections: a randomized, multicentre, open-label, prospective study

OBJECTIVE: To compare the bacteriological and clinical efficacy of three treatments for uncomplicated cystitis in ambulatory pre-menopausal women: ciprofloxacin 250 mg orally twice daily for 3 days, trimethoprim/sulfamethoxazole 160/800 mg orally twice daily for 7 days, and norfloxacin 400 mg orally twice daily for 7 days. MATERIALS AND METHODS: A total of 455 women were randomly assigned to three treatment groups: 151 received ciprofloxacin, 150 received trimethoprim/sulfamethoxazole, and 154 received norfloxacin. Bacteriological cure and clinical resolution were evaluated 5-9 days and 4-6 weeks after completion of treatment. RESULTS: There was no significant difference among the three treatment groups: overall efficacy ranged from 78.5% for the trimethoprim/sulfamethoxazole group, to 84.5% for the ciprofloxacin group. The highest overall incidence of drug-related adverse effects occurred in the trimethoprim/sulfamethoxazole patients. CONCLUSIONS: These data indicate that a 3 day treatment with ciprofloxacin is at least as clinically and bacteriologically effective as 7 day treatments with trimethoprim/sulfamethoxazole and norfloxacin for uncomplicated lower urinary tract infections.     

Single-dose and three-day regimens of ofloxacin versus trimethoprim-sulfamethoxazole for acute cystitis in women.

We compared the safety and efficacy of a single 400-mg dose of ofloxacin, ofloxacin (200 mg) once daily for 3 days, and trimethoprim-sulfamethoxazole (160:800 mg) twice daily for 7 days for the treatment of acute uncomplicated cystitis (urinary tract infection [UTI]) in women. At 5 weeks posttreatment, 35 (81%) of 43 patients treated with single-dose ofloxacin, 40 (89%) of 45 treated with 3 days of ofloxacin, and 41 (98%) of 42 treated with trimethoprim-sulfamethoxazole were cured (P = 0.03, single-dose ofloxacin group versus trimethoprim-sulfamethoxazole group). Retreatment for symptomatic recurrent UTI was given to 7 (16%) of 43 patients initially treated with single-dose ofloxacin, 3 (7%) of 45 patients treated with 3 days of ofloxacin, and 0 of 42 patients treated with trimethoprim-sulfamethoxazole (P = 0.01, single-dose ofloxacin group versus trimethoprim-sulfamethoxazole group). There was a trend in each of the three treatment groups toward an association between persistent or recurrent episodes of significant bacteriuria and a history of UTI in the past year and with diaphragm use. Ofloxacin was more effective than trimethoprim-sulfamethoxazole in eradicating Escherichia coli from rectal cultures during or soon after therapy, but there were no differences at later follow-up visits. Adverse effects were equally common among the three treatment groups. We conclude that single-dose ofloxacin was less effective than 7 days of trimethoprim-sulfamethoxazole for treatment of uncomplicated cystitis in women, while the 3-day ofloxacin regimen and the trimethoprim-sulfamethoxazole regimen were not significantly different in efficacy.     

Comparative trial of norfloxacin and macrocrystalline nitrofurantoin (Macrodantin) in the prophylaxis of recurrent urinary tract infection in women.

Eighty-eight women with a history of recurrent urinary tract infection (at least four attacks in the preceding 12 months) were randomized to take either norfloxacin 200 mg at night (45 patients) or macrocrystalline nitrofurantoin 100 mg at night (43 patients) for 12 months. A decrease in the number of symptomatic attacks while taking this prophylaxis was observed in 94 per cent of the patients and this improvement was maintained during the 6 months following the end of prophylaxis in 69 per cent. The mean interval between symptomatic episodes while taking prophylaxis was 7.2-fold and 6.9-fold greater, respectively, than in the 12 months before starting prophylaxis. There were only nine breakthrough infections during 74 patient-years of prophylaxis, four in patients taking norfloxacin (two enterococci, one Staphylococcus epidermidis, one Escherichia coli), and five in those taking macrocrystalline nitrofurantoin (four E. coli, one Klebsiella pneumoniae). Adverse events caused four patients taking norfloxacin (8 per cent) and seven taking macrocrystalline nitrofurantoin (14 per cent) to stop prophylaxis. Norfloxacin had a marked suppressive effect on the coliform part of the faecal flora, with no emergence of resistance. Thus, norfloxacin appears to be an excellent alternative agent to macrocrystalline nitrofurantoin for the prevention of recurrent urinary infections.     

The clinical efficacy and safety of bacampicillin twice daily in comparative studies

In 16 controlled, randomized, comparative studies a total of 953 patients were treated for urinary tract infection, sinusitis, otitis media or chronic bronchitis. The aim was to evaluate the efficacy and safety of bacampicillin in a twice daily dosage, compared with three times daily dosages of bacampicillin, ampicillin, amoxycillin and a twice daily dosage of co-trimoxazole. Bacampicillin was given in amounts of either 400 or 800 mg to 422 of the patients in these studies. The twice daily dosage of bacampicillin eradicated 89% of the causative bacteria of urinary tract infections compared to 86% with the other regimens. In acute sinusitis 92% and 96% of the patients were either cured or improved when treated with 400 and 800 mg bacampicillin twice daily respectively. Similar percentages occurred in the groups given the three times daily dosages. In exacerbation of chronic bronchitis, 800 mg bacampicillin twice daily was the minimum effective dosage and 84% of the patients were either cured or improved with this regimen. Adverse drug reactions due to bacampicillin at all dose levels were less frequent than those of other anti-microbials. The lowest frequency of diarrhoea, 2.4%, was seen in the group given 400 mg bacampicillin twice daily. Dosages of 400 or 800 mg bacampicillin twice daily had a reliable efficacy combined with a low frequency of adverse reactions in respiratory and urinary tract infections.     

In vitro susceptibility testing procedures for fosfomycin tromethamine.

Fosfomycin tromethamine (previously fosfomycin trometamol) is an orally administered fosfomycin which may be used for single-dose therapy of uncomplicated urinary tract infections. Fosfomycin tromethamine, norfloxacin, and trimethoprim-sulfamethoxazole inhibited greater than 90% of 352 bacterial isolates representing 25 different species; trimethoprim and nalidixic acid had narrower spectrums of activity. Strains of Escherichia, Citrobacter, Enterobacter, and Klebsiella species were much more susceptible when glucose-6-phosphate was added to the test medium, but isolates belonging to other genera were not affected.     

Ofloxacin versus trimethoprim-sulfamethoxazole for treatment of acute cystitis.

We compared the safety and efficacies of ofloxacin and trimethoprim-sulfamethoxazole for the treatment of acute uncomplicated cystitis in women enrolled in a multicenter study. Data from three centers were combined for this report because the study design and study populations were identical, and patients were enrolled within an 18-month period. Cure rates for evaluable patients 4 weeks after treatment were high for all regimens: ofloxacin (200 mg) twice daily for 3 days, 22 of 25 (88%) cured; ofloxacin (200 mg) twice daily for 7 days, 42 of 49 (86%) cured; ofloxacin (300 mg) twice daily for 7 days, 25 of 25 (100%) cured; and trimethoprim-sulfamethoxazole (160/800 mg) twice daily for 7 days, 46 of 52 (88%) cured. Ofloxacin was more effective than trimethoprim-sulfamethoxazole in eradicating Escherichia coli from rectal cultures during and 1 week after treatment. Both ofloxacin and trimethoprim-sulfamethoxazole markedly reduced vaginal colonization with E. coli during and 4 weeks after therapy. Emergence of resistant coliforms in rectal flora was found in 5 (19%) of 27 patients treated with trimethoprim-sulfamethoxazole but none of 50 ofloxacin-treated patients who were studied (P = 0.004). Adverse effects were equally common among the four treatment groups. We conclude that 3 to 7 days of ofloxacin is as safe and effective as trimethoprim-sulfamethoxazole for treatment of uncomplicated cystitis in women and that ofloxacin effectively reduces the fecal and vaginal reservoirs of coliforms in such patients.     

Trimethoprim-rifampin, a new combination agent: efficacy in localized urinary infection and influence on microflora.

Twenty women with recurrent or persistent urinary tract infections were treated with a fixed combination of trimethoprim-rifampin (TMP-RAM). The site of infection was established by the antibody-coated bacteria test. Sixteen women had upper tract infections (antibody-coated bacteria tests positive); eight were cured, three failed, and five relapsed. All four women with lower tract infections (antibody-coated bacteria tests negative) were cured. Three of five patients with structural abnormalities failed. The 12 cures and 5 relapses were associated with organisms susceptible to either TMP (minimal inhibitory concentration, less than or = to 7 micrograms/ml) or RAM (minimal inhibitory concentration, less than or = to 32 micrograms/ml). In contrast, two of the three failures were associated with organisms resistant to both TMP and RAM. In one patient, RAM resistance emerged during treatment. During therapy, urinary strains were eradicated from the periurethral and anal-canal areas in all but 3 fo 16 patients. Adverse reactions, noted in 16 women, included nausea (10), dizziness (6), headaches (2), rash (1), an blurred vision (1). Antimicrobial susceptibility data on 246 isolated from urinary, periurethral, and anal-canal specimens are included. Our findings suggest that TMP-RAM is effective in urinary infections and may prevent the emergence of RAM-resistant strains.     

口服加替沙星与左氧氟沙星治疗下呼吸道和尿路感染的前瞻性多中心随机对照研究

目的：评价加替沙星片治疗下呼吸道感染及尿路感染的疗效与安全性。方法：以左氧氟沙星片为对照药，在248例下呼吸道和尿路感染中进行疗效和安全性的多中心随机对照观察。加替沙星组125例，其中下呼吸道感染50例，尿路感染75例；左氧氟沙星组123例，其中下呼吸道感染54例，尿路感染69例。给药方案分别为治疗下呼吸道感染加替沙星片400mg1次／d口服，左氧氟沙星片200mg2次／d口服，疗程均为7—14d；肾盂肾炎、复杂性尿路感染及反复发作性尿路感染加替沙星片400mg1次／d口服，左氧氟沙星200mg2次／d口服，疗程均为7—14dl急性单纯性下尿路感染加替沙星片200mg1次／d口服，左氧氟沙星片100mg2次／d口服，疗程均为5d。结果：加替沙星组125例和左氧氟沙星组123例的临床有效率分别为95．2％(119／125)和91．9％(113／123)，临床痊愈率分别为68．8％(86／125)和63．4％(78／123)；细菌清除率分别为89．3％(100／112)和89．5％(94／105)；不良反应发生率分别为25．3％(40／158)和18．6％(30／161)，实验室检查异常发生率为14．7％(22／150)和15．8％(24／152)。上述结果经统计学处理，差异均无显性。结论：本研究结果显示加替沙星片治疗下呼吸道及尿路感染的疗效和安全性与左氧氟沙星片相仿。     

Prospective, randomized, placebo-controlled trial of norfloxacin for the prophylaxis of recurrent urinary tract infection in women.

Thirty women were randomized in a double-blind, placebo-controlled study to receive either norfloxacin, 200 mg orally daily at bedtime, or placebo for the prevention of recurrent bladder infection. Subjects were followed monthly to monitor compliance and symptoms, for urine culture and periurethral and anal canal swabs to monitor colonization, and for blood specimens for hematologic and biochemical studies to monitor safety. During 1 year of follow-up, 10 of 15 placebo subjects and none of 15 norfloxacin subjects developed infection (P less than 0.001). Adverse effects occurred with equal frequencies in the two groups. For norfloxacin subjects, only 2 (1.6%) of 129 periurethral and 4 (3.1%) of 129 anal canal swabs showed colonization with aerobic gram-negative organisms, while 16 (22%) of 73 periurethral and 47 (64%) of 73 anal canal swabs from placebo subjects showed colonization. Daily therapy with norfloxacin at bedtime is effective in preventing recurrent cystitis. During 1 year of norfloxacin therapy, colonization was infrequent and superinfection with norfloxacin-resistant organisms did not occur.     

Treatment of urinary tract infections with a combination of amoxicillin and clavulanic acid.

A 10-day course of amoxicillin (250 mg)-potassium clavulanate (125 mg) was administered three times daily to 116 female college students with urinary tract infections. All of the bacterial isolates from these patients were susceptible to amoxicillin-potassium clavulanate in vitro; only 81.0% were susceptible to amoxicillin alone. Evaluations at 1 week after completion of this course showed that clinical and bacteriological cures had been achieved in 96.9% of those who completed therapy. Cures were sustained in 85.6% of the patients examined at 4 weeks after the end of therapy. Therapeutic responses were comparable, irrespective of the results of antibody-coated bacteria tests. All strains of Enterobacteriaceae isolated from the rectal and urogenital sites at 1 week after therapy were susceptible to amoxicillin-potassium clavulanate. The proportion of fecal Escherichia coli resistant to amoxicillin alone increased from 13.3% before therapy to 35.6% at 1 week after therapy. Adverse drug reactions consisted of gastrointestinal symptoms (9.8%) and rashes (4.1%). Sixteen patients (14.2%) developed symptomatic candida vaginitis by 1 week after therapy.     

Cefpodoxime-proxetil versus trimethoprim-sulfamethoxazole for short-term therapy of uncomplicated acute cystitis in women

One hundred sixty-three women with uncomplicated acute lower urinary tract infections were included in a multicenter randomized study comparing cefpodoxime-proxetil (one 100-mg tablet twice daily) with trimethoprim-sulfamethoxazole (one double-strength tablet [160/800 mg] twice daily) for 3 days. A total of 30 women in both arms were excluded from the study for various reasons. At 4 to 7 days after the discontinuation of therapy, 62 of 63 (98.4%) cefpodoxime-proxetil recipients and 70 of 70 (100%) trimethoprim-sulfamethoxazole patients were clinically cured and demonstrated bacteriological eradication, respectively. At 28 days after treatment, 48 of 55 (87.3%) and 43 of 50 (86%) cefpodoxime-proxetil recipients as well as 51 of 60 (85%) and 42 of 50 (84%) trimethoprim-sulfamethoxazole recipients were clinically cured and demonstrated bacteriological eradication, respectively. Independently of the prescribed regimen, a significant difference (P < 0.001) in failure rates was observed only for patients with a previous history of three or more episodes of acute cystitis per year. With the exception of one patient in the trimethoprim-sulfamethoxazole arm who discontinued therapy because of gastrointestinal pain, both antimicrobials were well tolerated. In conclusion, cefpodoxime-proxetil treatment for 3 days was as safe and effective as trimethoprim-sulfamethoxazole for 3 days for the treatment of uncomplicated acute cystitis in women.     

Lack of emergence of resistant fecal flora during successful prophylaxis of traveler''s diarrhea with norfloxacin.

Norfloxacin, a new quinolone carboxylic acid derivative, was compared with an identical-appearing placebo preparation in a prospective, randomized, double-blind trial for prevention of traveler's diarrhea among 120 U.S. students arriving in Mexico. Prophylaxis was continued for 2 weeks. Diarrhea was defined as four unformed stools in 24 h plus an additional symptom of enteric disease. In the norfloxacin prophylaxis group, 4 of 56 subjects (7%) experienced diarrhea, compared with 36 of 59 subjects (61%) in the placebo group. The difference was significant (P less than 0.0001). In contrast to our previous experience with use of trimethoprim-sulfamethoxazole to prevent traveler's diarrhea, quantitative stool cultures in the norfloxacin-treated group revealed a significant decline of normal aerobic fecal flora during prophylaxis (P less than 0.0005). Among stool samples from norfloxacin-treated subjects, 32 of 38 (84%) cultured on day 7 and 34 of 37 (92%) cultured on day 14 had no gram-negative bacilli. After norfloxacin was discontinued, fecal flora returned to pretreatment levels. No gram-negative aerobic flora resistant to norfloxacin were found during weekly quantitative cultures before, during, or after therapy.     

Randomized comparison of cefepime and ceftazidime for treatment of skin, surgical wound, and complicated urinary tract infections in hospitalized subjects.

We undertook a prospective, randomized open comparison of the broad-spectrum cephalosporins cefepime and ceftazidime in treatment of hospitalized subjects with skin or wound infections and complicated nosocomial urinary tract infections. Cefepime treatment (dosage, 2.0 g intravenously twice daily for 4 to 28 days) was successful in 36 (90%) of 40 infections of the skin and skin structure or wounds and in 16 (84%) of 19 nosocomial urinary tract infections. Ceftazidime treatment, 2.0 g every 8 h, was successful in 34 (96%) of 36 infections of the skin and skin structure and in 15 (88%) of 17 urinary tract infections. Microbiological eradication rates of each agent overall and for Pseudomonas aeruginosa were greater than 90%. In the cefepime group, one death occurred, contributed to by an enterococcal superinfection acquired during study drug therapy, and there were two mild and transient adverse experiences observed. Cefepime was comparable to ceftazidime in treatment of infections of the skin and skin structure requiring hospitalization and of complicated nosocomial urinary tract infections.