Effectiveness of oral moxifloxacin in standard first-line therapy in community-acquired pneumonia.

Based on recent guidelines for the management of community-acquired pneumonia, this study was designed to evaluate the effectiveness of a new fluoroquinolone compared with standard antimicrobial regimens, in conditions relating as closely as possible to the real world setting. In this study, 564 patients were randomised to either oral moxifloxacin (400 mg o.d.) or to standard oral therapy (amoxicillin 1 g t.i.d. or clarithromycin 500 mg b.i.d. alone or in combination) for up to 14 days using a double-blind procedure. The choice between the three standard regimens was made by the clinician prior to randomisation. Clinical response, quality of life, symptoms, healthcare resources and safety were assessed. In the per-protocol population, clinical success was reported for 201 of 215 (93.5%) and 217 of 231 (93.9%) in the moxifloxacin and standard groups, respectively, at 7-10 days post-therapy. At 28-35 days follow-up, continued clinical cure was observed in 183 of 192 (95.3%) moxifloxacin and 207 of 221 (93.7%) standard groups. Drug-related adverse events were reported in 55 of 274 (20%) moxifloxacin and 86 of 279 (31%) standard patients with diarrhoea >5%. Oral moxifloxacin monotherapy was as effective as, and better tolerated than, optimal antibiotic strategy represented either by mono- or combination therapy (amoxicillin and/or clarithromycin) in community-acquired pneumonia management.

Randomized controlled trial of sequential intravenous (i.v.) and oral moxifloxacin compared with sequential i.v. and oral co-amoxiclav with or without clarithromycin in patients with community-acquired pneumonia requiring initial parenteral treatment.

The objective of the present trial was to compare the efficacy, safety, and tolerability of moxifloxacin (400 mg) given intravenously (i.v.) once daily followed by oral moxifloxacin (400 mg) for 7 to 14 days with the efficacy, safety, and tolerability of co-amoxiclav (1.2 g) administered by i.v. infusion three times a day followed by oral co-amoxiclav (625 mg) three times a day, with or without clarithromycin (500 mg) twice daily (i.v. or orally), for 7 to 14 days in adult patients with community-acquired pneumonia requiring initial parenteral therapy. A total of 628 patients were enrolled and assessed by evaluation of their clinical and bacteriological responses 5 to 7 days and 21 to 28 days after administration of the last dose of study medication. Although the trial was designed, on the basis of predefined outcomes, to demonstrate the equivalence of the two regimens, the results showed statistically significant higher clinical success rates (for moxifloxacin, 93.4%, and for comparator regimen, 85.4%; difference [Delta], 8.05%; 95% confidence interval [CI], 2.91 to 13.19%; P = 0.004) and bacteriological success rates (for moxifloxacin, 93.7%, and for comparator regimen, 81.7%; Delta, 12.06%; 95% CI, 1.21 to 22.91%) for patients treated with moxifloxacin. This superiority was seen irrespective of the severity of the pneumonia and whether or not the combination therapy included a macrolide. The time to resolution of fever was also statistically significantly faster for patients who received moxifloxacin (median time, 2 versus 3 days), and the duration of hospital admission was approximately 1 day less for patients who received moxifloxacin. The treatment was converted to oral therapy immediately after the initial mandatory 3-day period of i.v. administration for a larger proportion of patients in the moxifloxacin group than patients in the comparator group (151 [50.2%] versus 57 [17.8%] patients). There were fewer deaths (9 [3.0%] versus 17 [5.3%]) and fewer serious adverse events (38 [12.6%] versus 53 [16.5%]) in the moxifloxacin group than in the comparator group. The rates of drug-related adverse events were comparable in both groups (38.9% in each treatment group). The overall incidence of laboratory abnormalities was similar in both groups. Thus, it is concluded that monotherapy with moxifloxacin is superior to that with a standard combination regimen of a beta-lactam and a beta-lactamase inhibitor, co-amoxiclav, with or without a macrolide, clarithromycin, in the treatment of patients with community-acquired pneumonia admitted to a hospital.

The efficacy of moxifloxacin in acute exacerbations of chronic bronchitis: a Spanish physician and patient experience.

Chronic bronchitis is a debilitating disease affecting many millions of patients globally. They suffer multiple acute exacerbations each year, often requiring many courses of antimicrobials to enable them to return to normal. The impact of the condition on both the individual patient and society as a whole is considerable and growing; thus antimicrobial therapy should induce rapid and effective outcomes as soon as possible. This open, community-based study of 5737 patients enrolled by over 2000 primary care physicians from across Spain examined the clinical effect of oral moxifloxacin on patients' signs and symptoms of acute exacerbations of chronic bronchitis (AECB) over a 45-day period. The symptoms were assessed using daily diary cards in addition to physician evaluations. Clinical assessment at day 7 showed 93.0% of patients were cured. The patient diary card showed that two-thirds of patients felt better by day 3 or 4. Adverse events were reported in 3.5% of patients in this study, the most common being diarrhoea, nausea and dizziness, and epigastric pain. These reactions were mild to moderate in intensity. There were no patient deaths due to infection during the study. Physicians and patients reported that once-daily moxifloxacin gave fast relief of symptoms of acute exacerbations of chronic bronchitis.

Clinical experience in Germany of treating community-acquired respiratory infections with the new 8-methoxyfluoroquinolone, moxifloxacin.

Moxifloxacin, a new 8-methoxyfluoroquinolone, was evaluated in a large community-based study involving 16,007 patients over a 9-month period. This study was designed as a large post-marketing observational study of the speed, efficacy and tolerability of moxifloxacin when used in clinical practice for the treatment of community-acquired bacterial pneumonia, or acute exacerbations of chronic bronchitis. Physicians and patients were specifically questioned about overall efficacy and safety as well as symptom relief. According to physicians' assessments 96.3% of patients were cured or improved after moxifloxacin treatment. Symptom relief ('feeling better') occurred in almost 70% of patients by day 3 and only 2.3% reported an adverse drug reaction. No individual adverse drug reaction was reported at a frequency above 1%. Among the 209 events considered as serious, only 34 were regarded as possibly or probably related to therapy. There were no moxifloxacin-related clinically relevant cases of phototoxicity, hepatotoxicity or cardiotoxicity. Overall, 92.1% of patients considered moxifloxacin to have been beneficial.

Treatment outcomes in acute exacerbations of chronic bronchitis: comparison of macrolides and moxifloxacin from the patient perspective.

Moxifloxacin, a new respiratory quinolone, was compared with the macrolides azithromycin, clarithromycin and roxithromycin in a cohort study to assess clinical, safety and health-related outcomes of these antimicrobials in general practice settings. In total 332 patients with acute exacerbations of chronic bronchitis (AECB) each received one of the antimicrobial agents for a standard short course of therapy. Random allocation of therapeutic agents occurred by centre, not individuals, and the drugs were prescribed in an open manner. In addition to clinical evaluation by their physicians, all patients kept daily diaries to assess AECB symptoms over the study period, therapy received and quality of life. The overall clinical response rate was 96% and all four regimens were well tolerated. After 14 days there were no significant differences between the study groups, but analyses of patients' daily evaluations of certain AECB specific symptoms showed a faster response rate in the moxifloxacin group.

Five day moxifloxacin therapy compared with 7 day clarithromycin therapy for the treatment of acute exacerbations of chronic bronchitis.

In this multinational, randomized, double-blind study, the efficacy and safety of a 5 day course of moxifloxacin 400 mg orally od was compared with that of a 7 day course of clarithromycin 500 mg orally bd. in 750 patients with acute exacerbations of chronic bronchitis, characterized by at least two of the symptoms: sputum purulence, increased sputum volume or increased dyspnoea. Seven days after the end of therapy, clinical cure was achieved for 89% (287 of 322) of efficacy-evaluable patients in the moxifloxacin group and 88% (289 of 327) of patients in the clarithromycin group (95% CI, -3.9%, 5.8%). At follow-up (21-28 days post-treatment), the continued clinical cure rates were 89% (256 of 287) for moxifloxacin and 89% (257 of 289) for clarithromycin. A total of 342 pathogenic bacteria were isolated from the sputum of 287 patients. The most common pathogens were Haemophilus influenzae (37%), Streptococcus pneumoniae (31%) and Moraxella catarrhalis (18%). Seven days post-treatment, a successful bacteriological response was obtained for 77% (89 of 115) of patients in the moxifloxacin group and 62% (71 of 114) of patients in the clarithromycin group, indicating superiority of moxifloxacin (95% CI, 3.6%, 26.9%). Both treatments were well tolerated with few adverse events. This study demonstrated that for the treatment of acute exacerbations of chronic bronchitis a 5 day course of moxifloxacin 400 mg od was clinically equivalent and bacteriologically superior to a 7 day course of clarithromycin 500 mg bd.

The efficacy and safety of a new ciprofloxacin suspension compared with co-amoxiclav tablets in the treatment of acute exacerbations of chronic bronchitis.

A multinational, multicentre, randomized, prospective, parallel-group study compared treatment with ciprofloxacin administered as an oral suspension (500 mg twice daily for 7 days) with co-amoxiclav tablets (625 mg three times daily for 7 days) in patients suffering from acute exacerbations of chronic bronchitis (AECB). A total of 147 of 165 cases treated with ciprofloxacin (89.1%) and 146 of 162 cases treated with co-amoxiclav (90.1%) were classified as being clinical successes at the primary efficacy assessment 7 days after the end of therapy (assessed as reduced cough, improvement in dyspnoea, reduction in 24-h sputum volume or reduced purulence of sputum). Treatment equivalence was statistically confirmed; treatment difference:--1.0%, 95% CI--6.6% and 4.5%. Before treatment, 128 bacterial strains were isolated from 103 patients (60 ciprofloxacin and 68 co-amoxiclav). The most commonly isolated organism was Haemophilus influenzae (60 isolates), followed by Moraxella catarrhalis (12 isolates), Streptococcus pneumoniae (11 isolates) and Staphylococcus aureus (10 isolates). At day 14, 40 of 46 ciprofloxacin-treated patients (87.0%) and 46 of 55 co-amoxiclav-treated patients (83.6%) who were valid for bacteriological analysis were classified as being bacteriological success (classed as eradication, eradication with colonization or presumed eradication; treatment difference: 3.3%, 95% CI--8.3% and 14.9%). The adverse event profile was comparable between treatment groups. Most adverse events considered possibly or probably related to study drug were related to the gastrointestinal system and were of mild or moderate severity: nausea (13% ciprofloxacin, 10.6% co-amoxiclav), flatulence (10.3% ciprofloxacin, 3.9% co-amoxiclav), abdominal pain (7.6% ciprofloxacin, 7.3% co-amoxiclav) and diarrhoea (4.3% ciprofloxacin, 6.7% co-amoxiclav). We concluded that a 7-day course of ciprofloxacin suspension is equivalent to a 7-day course of co-amoxiclav tablets in terms of clinical and bacteriological efficacy and tolerability for the treatment of AECB. Thus, ciprofloxacin suspension may offer a suitable alternative treatment for AECB patients who have difficulty in swallowing, or who prefer liquid medications to tablets.

Oral ciprofloxacin in the treatment of pseudomonas exacerbations of paediatric cystic fibrosis: clinical efficacy and safety evaluation using magnetic resonance image scanning.

Ciprofloxacin is effective for treating pulmonary infection in adult cystic fibrosis patients, and demonstrates excellent efficacy against Pseudomonas aeruginosa, but its use in paediatric cystic fibrosis patients has been limited because quinolone-induced cartilage toxicity has been observed in juvenile animals and has been considered a potential risk for children. Children with cystic fibrosis (n = 26; aged 6-16 years), with proven P. aeruginosa colonization of their sputum, were enrolled into a 14-day, open, non-comparative study. Patients were assigned to twice-daily treatment with oral ciprofloxacin 250 mg, 500 mg or 750 mg, depending on their body weight. None of the patients exhibited any signs or symptoms of arthropathy, as assessed by magnetic resonance imaging of the right knee, during or immediately after treatment, or at the 3-month post-therapy assessment. Cough, sputum production and sputum purulence were improved in more than 70% of patients. Patients showed a mean weight increase of 0.4 kg (95% confidence interval 0.1 to 0.7 kg) over the study period. Only one patient required a repeat chest radiograph, which showed no resolution of the abnormal radiographic appearances. Three patients reported adverse events during the trial, none of which were considered to be related to the study treatment.

Safety and efficacy of ciprofloxacin in paediatric patients--review.

Like all fluoroquinolones, ciprofloxacin causes articular damage in juvenile animals. Consequently, this drug was not recommended for children or pregnant women. However, due to its antibacterial effectiveness and convenience of oral administration, ciprofloxacin is now increasingly used for the treatment of certain infectious conditions in children and adolescents aged less than 18 years. In this paper the published literature on this subject is reviewed. Up to now, data are available on more than 1,500 paediatric patients who were given ciprofloxacin, two-thirds of whom were suffering from acute infectious bronchopulmonary exacerbations of cystic fibrosis, mainly due to Pseudomonas aeruginosa. The effectiveness of oral ciprofloxacin for this indication compared well to that of standard intravenous combination regimens. The majority of the remaining published trials was conducted in children with multiresistant typhoid fever; the administration of ciprofloxacin was successful in up to 100% of the cases. The safety profile of ciprofloxacin in children and adolescents was very similar to that observed in adult patients. Adverse events were noted in 5-15%, with gastrointestinal, skin and central nervous system reactions being the most common. Reversible arthralgia occurred in 36 out of 1,113 patients with cystic fibrosis, and in no case could cartilage damage be demonstrated by radiographic procedures. Thus, publication data clearly suggest that the administration of ciprofloxacin to children is effective and safe, but there is a need for further prospective, well-controlled clinical trials.

Intratracheal application of Sephadex in rats leads to massive pulmonary eosinophilia without bronchial hyperreactivity to acetylcholine.

Fourteen Brown-Norway rats were pretreated with physiological saline (n = 7) or 500 micrograms Sephadex (n = 7) intratracheally. 24 h later, a bronchial provocation test was performed under pentobarbital anaesthesia using increasing doses of acetylcholine aerosol and the degree of bronchospasm was measured using a modified Konzett-Rössler method. Subsequently, leucocyte counts were determined in the bronchoalveolar lavage fluid (BALF), BALF cells were differentiated, and the chemiluminescence of the BALF leucocytes were measured. Finally, the lungs were removed and histologically examined. The cell count in the BALF was significantly (p less than 0.05) increased in the animals pretreated with Sephadex compared to those in the saline group (mean value +/- SEM: 0.38 +/- 0.07 vs. 0.15 +/- 0.02 x 10(6)/ml). This difference was also reflected in the chemiluminescence measurements (2.51 +/- 0.53 vs. 0.20 +/- 0.03 x 10(6) counts/0.5 ml). In the Sephadex-treated animals there was also a significant increase in the absolute number of neutrophil (0.040 +/- 0.010 vs. 0.011 +/- 0.002 x 10(6)/ml) and, in particular, eosinophil granulocytes (0.188 +/- 0.055 vs. 0.003 +/- 0.001 x 10(6)/ml) in the total leucocytes of the BALF. Lung histology showed massive perialveolar and peribronchial oedema and granulomatous infiltrates, primarily with eosinophils, after intratracheal application of Sephadex; these findings were not observed in the saline group. None of these changes in the rats pretreated with Sephadex manifested themselves in increased bronchial reactivity to acetylcholine aerosol. It is uncertain if the Sephadex-induced increase in the eosinophil count is accompanied by an activation of this cell population, which appears to be of importance for the occurrence of bronchial hyperreactivity.(ABSTRACT TRUNCATED AT 250 WORDS)