Comparative efficacy of once daily, 5-day short-course therapy with clarithromycin extended-release versus twice daily, 7-day therapy with clarithromycin immediate-release in acute bacterial exacerbation of chronic bronchitis

OBJECTIVE: The objective of this study was to compare the efficacy, tolerability, and safety of two clarithromycin regimens, extended-release (ER) 1000 mg once daily for 5 days and immediate-release (IR) 500 mg twice daily for 7 days, in the treatment of acute bacterial exacerbation of chronic bronchitis (ABECB). PATIENTS AND METHODS: This was a double-blind, randomized, parallel-group, multicenter study of ambulatory patients at least 40 years old with a presumptive diagnosis of ABECB, purulent sputum, and documented evidence of chronic obstructive pulmonary disease (COPD), including forced expiratory volume in one second (FEV(1)) < 70% of predicted value. Clinical cure, bacteriological cure, and target pathogen eradication rates were determined at a test-of-cure visit (study days 14-40). Safety was assessed based on the incidence of study drug-related adverse events. RESULTS: A total of 485 patients were randomized (240 to ER and 245 to IR). Clinical cure rates were similar for evaluable patients treated with ER (84%, 157/187) and those treated with IR (84%, 172/204) (95% CI -7.9, 7.2). The bacteriological cure rates were 87% (82/94) and 89% (91/102), and the overall target pathogen eradication rates were 88% (107/122) and 89% (117/131) for the respective treatment groups. The incidence of adverse events was 13% (31/240) in the ER group and 18% (45/245) in the IR group. The rate of gastrointestinal adverse events was lower with ER (8%, 19/240) compared to IR (11%, 26/245). Clarithromycin ER-treated patients reported statistically significantly fewer adverse events due to abnormal taste than did clarithromycin IR-treated patients (3% and 8%, respectively, p = 0.012). CONCLUSION: Both once-daily, 5-day, short-course therapy with clarithromycin ER and 7-day, twice-daily therapy with clarithromycin IR were effective in resolving clinical signs/symptoms of ABECB and eradicating the causative pathogens, with no statistically significant difference in clinical cure rate between the treatment groups. Clarithromycin ER was better tolerated, causing fewer gastrointestinal adverse events and statistically significantly fewer reports of abnormal taste as compared with clarithromycin IR.     

Short-course therapy of acute bacterial exacerbation of chronic bronchitis: a double-blind,randomized, multicenter comparison of extended-release versus immediate-release clarithromycin

OBJECTIVE: The objective of this study was to compare the efficacy and safety of two clarithromycin formulations given for 5 days to patients with acute bacterial exacerbation of chronic bronchitis (ABECB). PATIENTS AND METHODS: This was a double-blind, randomized, multicenter study of ambulatory patients between 40 and 75 years of age with a medical history of chronic bronchitis, chronic obstructive pulmonary disease and a presumptive diagnosis of ABECB who met Anthonisen Type 1 criteria (increased dyspnea, increased sputum volume and increased sputum purulence). Eligible patients received a 5-day course of clarithromycin extended-release (ER) 500 mg once daily or clarithromycin immediate-release (IR) 250 mg twice daily. Clinical cure, bacteriological cure and pathogen eradication rates were determined at the end of therapy and at a follow-up visit. RESULTS: Clinical cure rates were similar at the test-of-cure visit for evaluable patients in the clarithromycin ER group (97%, 298/307) and clarithromycin IR group (98%, 300/307) (95% CI (-3.2, 1.9)). The bacteriological cure rate was 89% and the pathogen eradication rate was 90% in both treatment groups. Resolution or improvement in cough, sputum production, sputum volume and sputum appearance was observed in > 90% of evaluable patients in each treatment group. The incidence of study drug-related adverse events was 6.6% (23/351) in the clarithromycin ER group and 5.4% (19/352) in the clarithromycin IR group. The most frequently occurring study drug-related adverse events were abdominal pain, diarrhea and taste perversion. CONCLUSION: Clarithromycin ER 500 mg once daily for 5 days is equivalent to clarithromycin IR 250 mg twice daily for 5 days in treating adults with ABECB. Both regimens were effective in resolving clinical signs and symptoms of ABECB and eradicating the target pathogens, and were well tolerated.     

Comparison of norfloxacin and pefloxacin in the prophylaxis of bacterial infection in neutropenic cancer patients.

In this study the efficacy of norfloxacin and pefloxacin for the antibacterial prophylaxis of granulocytopenia was compared in cancer patients following cytostatic treatment. A total of 136 patients was randomly selected to receive either norfloxacin or pefloxacin. Nineteen patients remained afebrile in the norfloxacin group compared with thirty one in the pefloxacin group (p = 0.045). Twenty four microbiologically documented infections (twelve with and twelve without bacteraemia) occurred in sixty seven patients taking norfloxacin, and twelve in sixty nine patients taking pefloxacin (five with and seven without bacteraemia) (p = 0.015). Only one infection caused by Gram-negative bacilli was observed in the pefloxacin group compared with seven in the norfloxacin group (p = 0.019). In conclusion, both microbiological and clinical results showed pefloxacin to be a better antibacterial agent than norfloxacin for these patients.     

Efficacy and safety of gemifloxacin 320 mg once-daily for 7 days in the treatment of adult lower respiratory tract infections.

An open-label, non-comparative study assessed the clinical and bacteriological efficacy of gemifloxacin (320 mg, once-daily for 7 days) in lower respiratory tract infections (LRTI). Patients with acute exacerbation of chronic bronchitis (AECB, n=261) or community-acquired pneumonia (CAP, n=216) were enrolled into the study. Clinical success rates at follow-up (days 21-28) in the intent-to-treat (ITT) population were high, 83.1% in AECB patients (95% CI: 77.9, 87.4) and 82.9% in CAP patients (95% CI: 77.0, 87.5). High bacteriological success rates were achieved (bacteriological ITT population), 91.2% (52/57) in AECB patients (95% CI: 80.0, 96.7) and 77.9% (60/77) in CAP patients (95% CI: 66.8, 86.3). Gemifloxacin was well tolerated with a low incidence of adverse events. Gemifloxacin treatment resulted in high clinical and bacteriological success rates and is a well-tolerated therapy for the treatment of LRTIs.     

Meta-analysis: efficacy of bovine lactoferrin in Helicobacter pylori eradication

Background  Several randomized-controlled trials (RCTs) have sought to determine the efficacy of bovine lactoferrin in Helicobacter pylori eradication with equivocal results.
Aim  To evaluate the effect of bovine lactoferrin supplementation in H. pylori eradication.
Methods  Electronic databases, reviews, bibliographies, abstracts and conference proceedings were searched. Included trials had to be randomized or quasi-randomized and controlled, using bovine lactoferrin in the intervention group, treating Helicobacter -infected subjects and evaluating eradication of H. pylori as an outcome.
Results  The search identified five eligible RCTs (of 169). Data were available for 682 subjects (bovine lactoferrin group- n  = 316; control group- n  = 366). The pooled odds ratio (five studies) for eradication by intention-to-treat analysis was 2.22 (95% CI 1.44–3.44; P  = 0.0003) using the fixed effects model (FEM) and 2.24 (95% CI 1.15–4.35; P  = 0.0003) using the random effects model (REM) (Cochran's Q  = 6.83; P  = 0.145). The pooled risk difference was 0.11 (95% CI 0.05–0.16; P  = 0.0001) by FEM (Cochran's Q  = 6.67; P  = 0.154) and 0.10 (95% CI 0.04–0.17; P  = 0.0023) by REM. There was no significant difference in incidence of adverse effects.
Conclusion  Bovine lactoferrin potentially improves H. pylori eradication rates without any impact on adverse effects, but available evidence is limited and further research is necessary to confirm the findings.     

Short-course therapy of acute bacterial exacerbation of chronic bronchitis: a double-blind,randomized, multicenter comparison of extended-release versus immediate-release clarithromycin

SUMMARY

Objective: The objective of this study was to compare the efficacy and safety of two clarithromycin formulations given for 5 days to patients with acute bacterial exacerbation of chronic bronchitis (ABECB).

Patients and methods:This was a double-blind, randomized, multicenter study of ambulatory patients between 40 and 75 years of age with a medical history of chronic bronchitis, chronic obstructive pulmonary disease and a presumptive diagnosis of ABECB who met Anthonisen Type 1 criteria (increased dyspnea, increased sputum volume and increased sputum purulence). Eligible patients received a 5-day course of clarithromycin extended-release (ER) 500?mg once daily or clarithromycin immediate-release (IR) 250?mg twice daily. Clinical cure, bacteriological cure and pathogen eradication rates were determined at the end of therapy and at a follow-up visit.

Results: Clinical cure rates were similar at the test-of-cure visit for evaluable patients in the clarithromycin ER group (97%, 298/307) and clarithromycin IR group (98%, 300/307) (95% CI (?3.2,1.9)). The bacteriological cure rate was 89% and the pathogen eradication rate was 90% in both treatment groups. Resolution or improvement in cough, sputum production, sputum volume and sputum appearance was observed in >90% of evaluable patients in each treatment group. The incidence of study drug-related adverse events was 6.6% (23/351) in the clarithromycin ER group and 5.4% (19/352) in the clarithromycin IR group. The most frequently occurring study drug-related adverse events were abdominal pain, diarrhea and taste perversion.

Conclusion: Clarithromycin ER 500?mg once daily for 5 days is equivalent to clarithromycin IR 250?mg twice daily for 5 days in treating adults with ABECB. Both regimens were effective in resolving clinical signs and symptoms of ABECB and eradicating the target pathogens, and were well tolerated.     

Do mucosal defensive agents improve the cure rate when used with dual or triple therapy regimens for eradicating Helicobacter pylori infection?

BACKGROUND: Some of mucosal defensive agents have anti-Helicobacter pylori activities. However, their effectiveness in eradicating H. pylori infection has not been evaluated. AIM: To assess the additive effect of mucosal defensive agents in eradication regimens using statistical analysis. METHODS: Pertinent studies were retrieved using the Medline and the Igaku-chuo-zasshi databases in Japan, reference and congress abstract lists. Studies in which regimens consisted of dual or triple therapy with mucosal defensive agents and without them, were selected from the retrieved studies. Eradication rates were extracted from studies according to intention-to-treat analysis. We evaluated the efficacies of mucosal defensive agents by pooled relative risk of eradication rates and its 95% confidence intervals (95% CI), which were calculated by Mantel-Haenszel method. Heterogeneity among the studies in treatment effect was evaluated by a chi2-test. RESULTS: In dual therapy regimens, mucosal defensive agents demonstrated significant additive effects (pooled relative risk 1.41; 95% CI: 1.24-1.61). In triple therapy regimens, these agents did not provide significant additive effect. The clinical usefulness of specific agents could not be established, when each agent was analysed independently. CONCLUSIONS: Mucosal defensive agents improve the cure rate when used with existing dual therapy regimens for eradicating H. pylori infection.     

Acute exacerbation of chronic bronchitis: expanding short-course therapy

Recent management guidelines for acute exacerbation of chronic bronchitis (AECB) have provided antimicrobial options for different classes of patients according to varying disease severity or risk of treatment failure. In a pivotal, double-blind, double-dummy study comparing azithromycin microspheres (2 g single dose) with the respiratory quinolone levofloxacin (500 mg once daily x 7 days) for the treatment of AECB, the two regimens were equally effective and well tolerated in patients with mild-to-moderate disease (clinical cure rate 93.6% vs. 92.7%, respectively [95% confidence interval (CI) for difference, -3.4, 5.5] and overall bacteriological eradication rate 91.9% vs. 94.4%, respectively (95% CI for difference, -8.8, 3.8). Interestingly, additional post hoc analyses suggest that a single dose of azithromycin also provides comparable clinical efficacy to levofloxacin in patients with a forced expiratory volume in 1 s (FEV1) of less than 70% of the predicted value, a risk factor that would place them in a more severe stratum. These data support azithromycin microspheres as an appropriate option in patients with mild-to-moderate AECB. The potential role of this preparation and other macrolides in patients at higher risk of therapeutic failure requires additional prospective data.     

Once daily clarithromycin extended-release vs twice-daily amoxicillin/clavulanate in patients with acute bacterial sinusitis: a randomized, investigator-blinded study

OBJECTIVE: To compare the efficacy and tolerability of clarithromycin extended-release (ER) to amoxicillin/ clavulanate in patients diagnosed with acute bacterial sinusitis. RESEARCH DESIGN AND METHODS: In a controlled, multicenter, investigator-blinded study, 437 ambulatory patients at least 12 years old with signs/symptoms and radiographic findings of acute sinusitis were randomized to receive clarithromycin ER 1000 mg once daily or amoxicillin/ clavulanate 875 mg/l25 mg twice daily for 14 days. MAIN OUTCOME MEASURES: Clinical and bacteriological response rates were determined at a test-of-cure visit, which was conducted up to 10 days following the completion of treatment. Radiological response was assessed at a follow-up visit. RESULTS: The clinical cure rate in clinically evaluable patients was 98% (184/188) in the clarithromycin ER group and 97% (179/185) in the amoxicillin/clavulanate group (95% CI for the difference in rates [-2.4%, 4.7%]). Clinical cure was sustained at the follow-up visit (96% for each treatment group). The pathogen eradication rates were 94% (61/65) in the clarithromycin ER group and 98% (61/62) in the amoxicillin/clavulanate group (95% CI for difference in rates [-12.0%, 2.9%]). The radiological success rate was 94% (172/183) in both the clarithromycin ER and amoxicillin/clavulanate groups (95% CI for difference in rates [-4.9%, 4.9%]). Symptomatic improvement or relief was observed as early as 2 days-5 days after the initiation of study drug, with a statistically significantly higher resolution rate of sinus pressure (p = 0.027) and improvement/resolution rate of nasal congestion (p = 0.035) during treatment with clarithromycin ER. The resolution/improvement rate at the test-of-cure visit for each treatment group was > or = 94% for the primary acute sinusitis signs/symptoms, with a statistically significantly higher resolution/improvement rate of purulent nasal discharge with clarithromycin ER (p = 0.010). Both study drugs had a positive and rapid impact on quality of life. Patients reported a high level of satisfaction and probability of using either study antibiotic again, and health care resource use was low, with slightly fewer sinusitis-related physician and outpatient visits required by patients in the clarithromycin ER group (p = 0.055). The treatment groups were comparable with respect to incidence of drug-related adverse events. CONCLUSION: In this multinational population of patients with acute bacterial sinusitis, clarithromycin ER was comparable, and for selected measures superior, to amoxicillin/clavulanate based on clinical, bacteriological, and radiological responses as well as quality of life measures, satisfaction with antibiotic therapy, and health care resource utilization.     

甲磺酸培氟沙星注射液治疗40例细菌感染疗效评价

本开放试验中培氟沙星对各系统感染治疗总痊愈率为50％,总有效率为80％。以治疗泌尿系统感染的痊愈率和有效率最高(分别为69.2％和100％),以治疗呼吸系统感染的痊愈率和有效率最低(分别为20％和60％)。本组入选病例中各种需氧细菌对培氟沙星的高敏率和敏感率分别为87.9％和100％。不良反应发生率为7.32％(3/41),主要不良反应为胃肠道不适。     

Failure to eradicate Group A beta-haemolytic streptococci (GABHS) from the upper respiratory tract after antibiotic treatment

The clinical efficacy, safety and bacteriological eradication of Group A beta-haemolytic streptococci (GABHS) from the throat was studied after treatment of streptococcal tonsillopharyngitis with three commonly used oral antibiotics in a prospective, open labelled, comparative, randomised trial of 265 evaluable patients seen in one centre. All three antibiotics were administered in the recommended doses; penicillin V q8 hourly and clarithromycin q12 hourly were given for 10 days and cefprozil q12 hourly for 5 days. Clinical results and adverse events were similar for all three antibiotics used, with a prompt clinical outcome of >95%. Cefprozil had the best bacteriological eradication rate (failed to eradicate: 13.2, 15.1, 2.3; relapses: 13.2, 11.4, 5.7%, for penicillin, clarithromycin and cefprozil, respectively). Oral penicillin remains a clinically effective and safe antibiotic for the treatment of streptococcal pharyngitis. However, compliance and convenience for parents and children when they are asked to follow a 10 days course, especially when the patient has improved from the second or third day, together with the high incidence of bacteriological eradication failures, is an issue.     

A comparison of observational studies and controlled trials of heparin in ulcerative colitis

OBJECTIVES: To compare the efficacy of heparin in ulcerative colitis (UC) as demonstrated in observational studies and controlled clinical trials. INTRODUCTION: Ulcerative colitis (UC) is a chronic condition with a relapsing and remitting course. Several studies have been conducted (observational and controlled clinical trials) to test the usefulness of heparin in this condition but the results of these studies are variable. Some studies demonstrate efficacy while others do not. METHODS: We pooled the results of observational studies and clinical trials separately in order to compare the results of observational studies and clinical trials using meta-analysis. With the aid of Medline and a manual search in Index Medicus and cross-references of articles published up to July 2003, we identified studies designed to evaluate the effects of heparin on UC. The pooled cure rate in observational studies was calculated. RESULTS: The results of controlled clinical trials evaluated using meta-analysis showed that the pooled cure rate for observational studies was 87.7% (range 80 - 100). The odds ratio for the controlled trial was 0.34 (95% CI 0.08 - 1.49) using a random effects model and 0.21 (95% CI 0.06 - 1.38) using a fixed effects model. The results of meta-analysis demonstrate a non-significant effect of heparin in controlled clinical trials. CONCLUSION: The findings of the clinical trials differ markedly from observational studies and indicate a lack of efficacy of heparin in patients with ulcerative colitis.     

Helicobacter pylori eradication: proton pump inhibitor vs. ranitidine bismuth citrate plus two antibiotics for 1 week-a meta-analysis of efficacy

OBJECTIVE: To compare the efficacy of proton pump inhibitor vs. ranitidine bismuth citrate (RBC) with two antibiotics for 1 week in Helicobacter pylori eradication. METHODS: Randomized trials comparing 1-week regimens with (i) proton pump inhibitor plus two antibiotics [clarithromycin (C) and amoxycillin (A) or a nitroimidazole (N)]; or (ii) RBC plus the same antibiotics. Eradication was confirmed by histology or 13C-urea breath test at least 4 weeks after therapy. Data sources included PubMed database and abstracts from congresses until October 1999. Statistical analysis was by meta-analysis combining the odds ratios (OR) of the individual studies in a global OR (Peto method). RESULTS: Twelve studies met the selection criteria. Nine compared proton pump inhibitor vs. RBC plus C and A, and five compared proton pump inhibitor vs. RBC plus C and N. With RBC, C and A, mean H. pylori eradication efficacy by intention-to-treat analysis (pooled data) was 76.6% (95% CI: 72-81%) and 73.7% (95% CI: 69-78%) with proton pump inhibitor, C and A. The OR for the effect of RBC vs. proton pump inhibitor (plus C and A) on H. pylori eradication was 1.15 (95% CI: 0.8-1.64%). Mean H. pylori eradication with RBC, C and N was 87. 2% (95% CI: 83-91%), and 74.9% (95% CI: 74-84%) with proton pump inhibitor plus these two antibiotics. The OR for the effect of RBC vs. proton pump inhibitor (plus C and N) on H. pylori eradication was 1.76 (95% CI: 1.08-2.85%). CONCLUSION: RBC and proton pump inhibitor have similar efficacy for H. pylori eradication when given with C and A for 1 week, but RBC seems to have a higher efficacy than proton pump inhibitor when C and N are the co-prescribed antibiotics.     

Systematic review and meta-analysis: importance of CagA status for successful eradication of Helicobacter pylori infection

BACKGROUND: Some, but not all studies have provided evidence that the CagA status of Helicobacter pylori strains is a predictive factor for the outcome of eradication therapy. AIM: To clarify the association between CagA status and eradication outcome. METHODS: We included studies reporting the numbers of successful and failed cases in H. pylori-eradication therapy according to the CagA status. Fourteen studies (1529 patients) were included of 325 articles identified in the search. The pooled risk ratio for H. pylori-eradication failure in CagA-negative relative to CagA-positive strains and the pooled risk difference in eradication success between the two groups were used as summary statistics. Meta-regression was used for examining the source of heterogeneity. RESULTS: The summary risk ratio for eradication failure in CagA-negative relative to CagA-positive was 2.0 (95% CI: 1.6-2.4, P < 0.001), corresponding with the summary risk difference for eradication success between the groups of 11% (95% CI: 3-19%, P = 0.011). Meta-regression analysis demonstrated that usage of polymerase chain reaction examination for CagA status and a high proportion of non-ulcer dyspepsia patients were factors for heterogeneity among studies. CONCLUSIONS: Our meta-analysis confirmed the importance of the presence of CagA as a predictor for successful eradication of H. pylori.     

A meta-analysis of clinical trials of paclitaxel- and sirolimus-eluting stents in patients with obstructive coronary artery disease

AIM: This meta-analysis was conducted to compare the effects of drug (paclitaxel and sirolimus)-eluting stents with bare metal stents on major adverse cardiac events, restenosis rates and late loss of arterial lumen diameter in patients with obstructive coronary artery disease. METHODS: Randomized, controlled clinical trials comparing sirolimus- and paclitaxel-eluting stents with bare metal stents were identified through electronic and manual search. Fixed effects method of Mantel-Haenszel and random effects method of DerSimonian and Laird were used for computing the pooled odds ratio (OR) and 95% confidence intervals (CI) for major adverse cardiac events and restenosis rates. Standardized mean difference with 95% CI was calculated for late-loss of arterial lumen diameter. RESULTS: A total of 13 studies were included in the meta-analysis. As compared with bare metal stents, the use of sirolimus- and paclitaxel-eluting stents significantly reduced the major adverse cardiac events (pooled OR 0.35; 95% CI 0.24-0.50), restenosis rates (pooled OR 0.27; 95% CI 0.15-0.47), and late loss of arterial lumen diameter (mean difference 0.57 mm, 95% CI 0.49-0.68). CONCLUSION: Paclitaxel- and sirolimus-eluting stents significantly reduced the incidence of major adverse cardiac events, restenosis rates, and late loss of arterial lumen diameter as compared with bare metal stents.     

Treatment options for Helicobacter pylori infection when proton pump inhibitor-based triple therapy fails in clinical practice

BACKGROUND: The effectiveness of Helicobacter pylori eradication regimens has not been extensively investigated in the clinical practice setting. The optimal treatment choice after an initial failed eradication attempt has not been determined. AIMS: To evaluate proton pump inhibitor-based triple therapies as first-line eradication regimens in clinical practice, and to establish the efficacy of second-line regimens in the context of an initial failed eradication attempt. METHODS: Three hundred and eight patients with dyspepsia and evidence of H. pylori at endoscopy were recruited. As first-line therapy, 116 patients received omeprazole 20 mg b.d. in combination with amoxycillin 1 g b.d. and clarithromycin 500 mg b.d. (OAC) while 192 patients received omeprazole 20 mg b.d. in combination with metronidazole 400 mg b.d. and clarithromycin 250 mg b.d. (OMC). H. pylori status was reassessed at least 4 weeks after therapy (25 patients failed to attend for further testing). Of 52 patients with an initial failed eradication attempt, 20 patients received a 1 week quadruple therapy regimen incorporating omeprazole 20 mg b.d., tripotassium dicitrato bismuthate 120 mg q.d.s., tetracycline 500 mg q.d.s. and metronidazole 400 mg t.d.s., 20 patients received a 2-week proton pump inhibitor-based triple therapy regimen as described, and 12 patients received a further 1-week proton pump inhibitor-based triple therapy regimen. RESULTS: Including 308 patients, the intention-to-treat (ITT) eradication rates for OAC and OMC as first-line regimens were 72% (95% CI: 63-80%) and 73% (95% CI: 67-79%) respectively. A per protocol (PP) analysis on the 283 patients who completed follow-up gives an initial eradication rate of 78% (95% CI: 69-86%) for OAC and 79% (95% CI: 73-85%) for OMC. There were 60 patients (21%; 95% CI: 17-26%) in whom the initial eradication attempt was unsuccessful. With second-line therapy, H. pylori was successfully eradicated in a further 35/52 (67%; 95% CI: 58-73%) patients. The eradication rates with the quadruple regimen and 2-week triple therapy regimens were 75% (95% CI: 56-94%) and 80% (95% CI: 63-98%) respectively (P = 0. 71). The eradication rate with a repeat 1-week regimen was 33% (95% CI: 7-60%). CONCLUSIONS: The eradication rates achieved in this 'in practice' study with recommended first-line 1-week proton pump inhibitor-based triple therapy regimens were lower than the rates achieved with similar regimens in the clinical trial setting. A repeat 1-week proton pump inhibitor-based triple therapy regimen was not successful as a salvage therapy. Both the 2-week proton pump inhibitor-based triple therapy regimen and the 1-week quadruple therapy regimen were successful second-line treatments in >/=75% of patients.     

Oral toxicity of pefloxacin, norfloxacin, ofloxacin and ciprofloxacin: comparison of biomechanical and histopathological effects on Achilles tendon in rats

Four fluoroquinolones (pefloxacin, norfloxacin, ofloxacin and ciprofloxacin) were compared according to their biomechanical and histopathological effects on rat Achilles tendon. Wistar rats were divided into one untreated control and four treatment groups in parallel. Pefloxacin mesylate dihydrate (40 mg/kg), norfloxacin (40 mg/kg), ofloxacin (20 mg/kg) and ciprofloxacin (50 mg/kg) were administered by gavage twice daily for three consecutive weeks. 6 weeks after treatment, the test animals were euthanised and Achilles tendon specimens were collected. A computer monitored tensile testing machine was utilised for biomechanical testing. The mean elastic modulus of the control group was significantly higher than that of the norfloxacin and pefloxacin groups (p<0.05 and p<0.01, respectively). The mean yield force (YF) of the control group was significantly higher than those of ciprofloxacin, norfloxacin and pefloxacin groups (p<0.001, p<0.05 and p<0.01, respectively). The mean ultimate tensile force (UTF) of the control group was significantly higher than of the ciprofloxacin, norfloxacin, and pefloxacin groups (p<0.001, p<0.05 and p<0.01, respectively). Hyaline degeneration and fibre disarrangement were observed in the tendons of the ciprofloxacin, pefloxacin, and ofloxacin treated-groups, whereas myxomatous degeneration was observed only in the ciprofloxacin and pefloxacin groups. In conclusion, these findings in our rat model reveal significant deterioration of biomechanical parameters following fluoroquinolone exposure, and indicate significantly higher biomechanical toxicity for ciprofloxacin and pefloxacin.     

Evaluation of area under the inhibitory curve (AUIC) and time above the minimum inhibitory concentration (T>MIC) as predictors of outcome for cefepime and ceftazidime in serious bacterial infections

The objective of this study was to evaluate the relationship of the predicted pharmacodynamic parameters 24-h area under the inhibitory curve (AUIC=area under the concentration-time curve for 24h of dosing/minimum inhibitory concentration (AUC0-24/MIC) and time above the minimum inhibitory concentration (T>MIC) with clinical and microbiological outcomes in patients with bacteraemia and sepsis treated with cefepime or ceftazidime. Pharmacokinetic and pharmacodynamic parameters were derived for 76 of 107 patients enrolled in two prospective, randomised, clinical trials comparing cefepime with ceftazidime for the treatment of sepsis with bacteraemia, lower respiratory tract infection or complicated urinary tract infection. The relationships between the pharmacodynamic parameters and outcomes were examined. Whilst no significant differences in clinical outcomes were observed between cefepime and ceftazidime, there were significant differences in the pharmacodynamic analysis. Patients with an AUIC> or =250 had significantly greater clinical cure (79% vs. 33%; P=0.002) and bacteriological eradication (96% vs. 44%; P<0.001) than patients with an AUIC<250. Patients with T>MIC of 100% had significantly greater clinical cure (82% vs. 33%; P=0.002) and bacteriological eradication (97% vs. 44%; P<0.001) than patients with T>MIC of <100%. Both microbiological and clinical cure rates were suboptimal in patients receiving cefepime or ceftazidime for the treatment of serious infections if the AUIC was <250 or T>MIC was <100%.     

Once daily clarithromycin extended-release vs twice-daily amoxicillin/clavulanate in patients with acute bacterial sinusitis: a randomized,investigator-blinded study

ABSTRACT

Objective: To compare the efficacy and tolerability of clarithromycin extended-release (ER) to amoxicillin/clavulanate in patients diagnosed with acute bacterial sinusitis.

Research design and methods: In a controlled, multicenter, investigator-blinded study, 437 ambulatory patients at least 12?years old with signs/symptoms and radiographic findings of acute sinusitis were randomized to receive clarithromycin ER 1000?mg once daily or amoxicillin/clavulanate 875?mg/125?mg twice daily for 14?days.

Main outcome measures: Clinical and bacteriological response rates were determined at a test-of-cure visit, which was conducted up to 10?days following the completion of treatment. Radiological response was assessed at a follow-up visit.

Results: The clinical cure rate in clinically evaluable patients was 98% (184/188) in the clarithromycin ER group and 97% (179/185) in the amoxicillin/clavulanate group (95% CI for the difference in rates [–2.4%, 4.7%]). Clinical cure was sustained at the follow-up visit (96% for each treatment group). The pathogen eradication rates were 94% (61/65) in the clarithromycin ER group and 98% (61/62) in the amoxicillin/clavulanate group (95% CI for difference in rates [–12.0%, 2.9%]). The radiological success rate was 94% (172/183) in both the clarithromycin ER and amoxicillin/clavulanate groups (95% CI for difference in rates [–4.9%, 4.9%]). Symptomatic improvement or relief was observed as early as 2?days–5?days after the initiation of study drug, with a statistically significantly higher resolution rate of sinus pressure (?p = 0.027) and improvement/resolution rate of nasal congestion (?p = 0.035) during treatment with clarithromycin ER. The resolution/improvement rate at the test-of-cure visit for each treatment group was ≥ 94% for the primary acute sinusitis signs/symptoms, with a statistically significantly higher resolution/improvement rate of purulent nasal discharge with clarithromycin ER (?p = 0.010). Both study drugs had a positive and rapid impact on quality of life. Patients reported a high level of satisfaction and probability of using either study antibiotic again, and health care resource use was low, with slightly fewer sinusitis-related physician and outpatient visits required by patients in the clarithromycin ER group (?p = 0.055). The treatment groups were comparable with respect to incidence of drug-related adverse events.

Conclusion: In this multinational population of patients with acute bacterial sinusitis, clarithromycin ER was comparable, and for selected measures superior, to amoxicillin/clavulanate based on clinical, bacteriological, and radiological responses as well as quality of life measures, satisfaction with antibiotic therapy, and health care resource utilization.     

A randomised, double-blind trial comparing ceftobiprole medocaril with ceftriaxone with or without linezolid for the treatment of patients with community-acquired pneumonia requiring hospitalisation

Community-acquired pneumonia (CAP) is a serious infection requiring hospitalisation in 20% of cases. The novel cephalosporin ceftobiprole has microbiological activity against the major bacterial pathogens causing CAP, including Streptococcus pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae, as well as against Staphylococcus aureus, including meticillin-resistant S. aureus (MRSA). This was a multicentre, double-blind study in which 706 patients with CAP severe enough to require hospitalisation were randomised to ceftobiprole or to an expert-recommended course of ceftriaxone ± linezolid (comparator group). Clinical and microbiological outcomes were determined 7-14 days after completion of therapy (test-of-cure visit). For the 469 clinically evaluable patients, cure rates were 86.6% vs. 87.4% for ceftobiprole and comparator, respectively [95% confidence interval (CI) of the difference, -6.9% to 5.3%]; in the intention-to-treat (ITT) analysis of 638 CAP patients, these cure rates were 76.4% vs. 79.3%, respectively (95% CI of the difference, -9.3% to 3.6%). A typical bacterial pathogen was identified in 29% of the ITT population. Microbiological eradication rates in the 144 microbiologically evaluable patients were 88.2% and 90.8% for the respective treatment groups (95% CI of the difference, -12.6% to 7.5%). Both study drugs were well tolerated, with but a minority of patients requiring premature discontinuation due to an adverse event (6% in the ceftobiprole group and 4% in the comparator group). The overall incidence of treatment-related adverse events was higher in the ceftobiprole group, primarily owing to differences in rates of self-limited nausea (7% vs. 2%) and vomiting (5% vs. 2%). In summary, ceftobiprole was non-inferior to the comparator (ceftriaxone ± linezolid) in all clinical and microbiological analyses conducted, suggesting that ceftobiprole has a potential role in treating hospitalised patients with CAP. [ClinicalTrails.gov identifier: NCT00326287].