High-dose versus low-dose esomeprazole-based triple therapy for Helicobacter pylori infection.

BACKGROUND: This prospective, randomized, controlled study was conducted to compare the efficacies of high-dose and low-dose esomeprazole-based triple therapies for Helicobacter pylori eradication in Taiwan. MATERIALS AND METHODS: From January 2004 to June 2006, 240 H. pylori-infected patients were randomly assigned to undergo high-dose (40 mg b.d.) or low-dose (40 mg o.d.) esomeprazole combined with clarithromycin (500 mg b.d.) and amoxicillin (1 g b.d.) for one week. Follow-up endoscopy was performed at eight weeks after the end of treatment to evaluate the response to therapy. RESULTS: Intention-to-treat analysis demonstrated no differences between eradication rates of high-dose and low-dose groups (92% vs. 90%, respectively, P > 0.05). Per-protocol analysis yielded comparable results (95% vs. 93%). Both groups exhibited similar frequencies of adverse events (13% vs. 11%) and drug compliance (96% vs. 93%). Multivariate analysis indicated that only good compliance (odds ratio: 10.3, 95% CI, 3.0-35.7) was an independent predictor of treatment success. CONCLUSIONS: This work demonstrates that low-dose esomeprazole-based triple therapy yields a similar eradication rate as high-dose esomeprazole-based therapy in Taiwan. Since the cost of the low-dose regime is lower than that of the high-dose regime, low-dose esomeprazole-based triple therapy can reasonably be recommended for the first-line eradication of H. pylori for Taiwanese and probably most Asians.

Efficacy of telithromycin in the treatment of experimental Bacteroides fragilis intraabdominal abscess in the senescent mice.

The efficacy of telithromycin (HMR 3647), a new ketolide, in the treatment of experimental Bacteroides fragilis intraabdominal abscess in young and senescent mice was evaluated. Two different age groups of mice, young (2-3 months) and senescent (18-24 months) were used in this study. Telithromycin (50mg/kg/bid) was compared with clindamycin and metronidazole, both administered in 100 mg/kg/bid doses. Telithromycin cured the infection in 74% of the young and 67% of the old mice but this difference was not significant. Telithromycin efficacy was comparable to that of clindamycin which cured 82% of the young and 75% of the old, but was superior to the efficacy of metronidazole, which cured 61% of the young and 50% of the senescent mice. Young animals that were not cured by any of the three antibiotics showed decrease in the viable bacterial cell counts by two logs while the senescent mice had a one log difference. Serum, pus and tissue concentrations of telithromycin were five-fold higher in the old mice than in the young. Age by itself had no adverse effect on therapeutic outcome of any of the three antibiotics used.

Evaluation of trovafloxacin in the treatment of Klebsiella pneumoniae lung infection in tumour-bearing mice.

Trovafloxacin, a new trifluoroquinolone, was evaluated for its therapeutic efficacy against Klebsiella pneumoniae lung infection in tumour (P388 murine leukaemia cells)-bearing mice, treated with or without a chemotherapeutic agent, daunorubicin (DNR) and in mice without tumour. Its activity was compared with ciprofloxacin and cephazolin. The effect on therapeutic efficacy of the addition of recombinant granulocyte colony stimulating factor (rGCSF) was also examined. Our study showed that both quinolones successfully cured pneumonia owing to infection with K. pneumoniae in mice without tumours but that all antibiotics failed in tumour-bearing mice if DNR was withheld. Substantial differences were noted in DNR-treated tumour-bearing mice with infection-the cure rate with trovafloxacin was 91% whereas the cure rate with ciprofloxacin or cephazolin was 57%. Addition of rGCSF to ciprofloxacin did not substantially improve its efficacy (when assessed by protection against death owing to infection; the survival rate was 41%). Trovafloxacin cure rates ranged from 80 to 90% whether or not rGCSF was added to the treatment regimen. Our results suggest that prior cancer chemotherapy had no adverse effect on the therapeutic efficacy of trovafloxacin, and that trovafloxacin may be a promising therapeutic agent for treatment of bacterial infections in the presence of leucopenia.

In vivo efficacy of trovafloxacin (CP-99,217), a new quinolone, in experimental intra-abdominal abscesses caused by Bacteroides fragilis and Escherichia coli.

The efficacy of trovafloxacin in treating Bacteroides fragilis and Escherichia coli infections was investigated and compared to the efficacy of combined clindamycin and gentamicin therapy in an experimental model of intra-abdominal abscesses in rats. Rats were treated with different doses of CP-116,517-27, a parenteral prodrug of trovafloxacin. Response to treatment was evaluated by mortality rate and elimination of infection (cure rate). Mortality in the control group was 85.4%, whereas in rats treated with trovafloxacin, it was close to 0%. The highest cure rate (89.3%) resulted from the administration of 40 mg of CP-116,517-27 per kg of body weight three times a day (TID) for 10 days (equivalent to 18.15 mg of active drug trovafloxacin per rat per day). The therapeutic response with trovafloxacin was comparable to that of a combination therapy of clindamycin (75 mg/kg) plus gentamicin (20 mg/kg) TID (cure rate, 74%; mortality rate, 5%). The measured peak levels of trovafloxacin in serum and abscess pus were 2.6 +/- 0.3 and 5.2 micrograms/ml, respectively. The tumor necrosis factor alpha levels in the untreated animals were high compared to those for rats treated with trovafloxacin or clindamycin plus gentamicin. These results demonstrate that trovafloxacin as a single agent appears to be as successful as clindamycin plus gentamicin in the treatment of experimental intra-abdominal abscesses in rats.

Ciprofloxacin versus ceftazidime in skin and soft tissue infections.

Intravenous ciprofloxacin therapy was evaluated in comparison with i.v. ceftazidime in the treatment of skin and soft tissue infections and were found to be comparable. Intravenous or peroral forms of ciprofloxacin may be used instead of intravenously given third generation cephalosporins or aminoglycosides in the treatment of even severe infections of the skin and soft tissue.

Therapeutic evaluation of difloxacin (A-56619) and A-56620 for experimentally induced Bacteroides fragilis-associated intra-abdominal abscess.

Difloxacin (A-56619) and A-56620, two novel fluoroquinolones, were tested in comparison with ciprofloxacin, cefoxitin, and combined clindamycin and gentamicin in the treatment of experimentally induced intraabdominal abscess associated with Bacteroides fragilis. Difloxacin was found to be as effective as clindamycin-gentamicin. A-56620, despite achieving subtherapeutic levels in serum, was found to be as effective as cefoxitin. Both difloxacin and A-56620 were effective in vivo against experimentally induced intra-abdominal abscess in rats.

Cefmenoxime therapy for gynecologic and obstetric infections.

Cefmenoxime, a new third-generation cephalosporin, was used as a single drug in the therapy for female genital tract infections. Therapeutic response was considered satisfactory in 21 of 22 cases of pelvic inflammatory disease, six of nine tuboovarian abscesses, two of three severe wound infections, and all five cases of endometritis. Overall, 34 of 39 patients responded. The peak serum antibiotic levels in this study ranged from 15.8 to 64 (average 48.7) micrograms/mL, and the trough level ranged from 0.9 to 4 (average 3.1) micrograms/mL. Cefmenoxime was tested in vitro against 424 isolates of anaerobes including 208 strains of bacteroides of which 80 were Bacteroides fragilis. Cefmenoxime inhibited the growth of 90% or greater of the organisms (minimal inhibitory concentration 90) at less than or equal to 64 micrograms/mL. The minimal inhibitory concentration for 75% of B fragilis was 32 micrograms/mL. This study suggests that cefmenoxime as a single-drug therapy is effective in the treatment of female genital tract infections caused by aerobic (including the gonococcus) and anaerobic bacteria.

Newer beta-lactam antibiotics in the treatment of experimental Staphylococcus aureus endocarditis.

Antistaphylococcal activity of three beta-lactam antibiotics, i.e. cefmenoxime, cefotaxime and latamoxef (moxalactam) was compared with that of nafcillin by studying cure rates of aortic valvular endocarditis caused by one of three clinical isolates of Staphylococcus aureus in New Zealand white male rabbits. The animals were randomly allocated to a control and four antibiotic treatment groups. Each animal except the controls received 60 mg/kg of one antibiotic intramuscularly twice daily for two weeks, beginning 24 h after induction of endocarditis. The aortic valve was sterilized in 11 of 15 (73%) animals treated with cefmenoxime, nine of 13 (69%) treated with cefotaxime, 11 of 13 (85%) treated with latamoxef and 12 of 15 (80%) treated with nafcillin. All nine animals in the control group developed aortic valvular vegetations with an average of 2.4 X 10(9) cfu/g. The differences in sterility rates resulting from treatment with the four antibiotics were not statistically significant (P greater than 0.70).