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Open, controlled, randomized study on the efficacy and safety of cefodizime single daily dose versus two daily doses and versus ceftriaxone single daily dose in patients with acute purulent bronchitis and acute purulent exacerbation of chronic bronchitis.

Two hundred and thirty-eight in-patients with signs and symptoms of acute purulent bronchitis or purulent exacerbation of chronic bronchitis at stage 1 and 2 of Anthonisen's classification were enrolled in 11 Centers and randomly assigned to one of the following 3 treatment groups: group A, cefodizime 1 g i.m. qD; group B, cefodizime 1 g i.m. BID; group C, ceftriaxone 1 g i.m. qD. Bacteriological results after treatment were satisfactory in 64 patients (91.4%) of group A, 64 (92.8%) of group B and 74 (94.9%) of group C. Global clinical results after treatment showed satisfactory efficacy in 57 patients (79.2%) of group A, 59 (85.5%) of group B and 63 (80.8%) of group C. There was no statistically significant difference in improvement in single symptoms, global bacteriological or clinical results between the 3 groups. Mild adverse events occurred in only 3 patients (one per group).

Acute Disease↗

Protective immunity to infectious bronchitis in broilers vaccinated against Marek's disease either in ovo or at hatch and against infectious bronchitis at hatch.

Two experiments were conducted using commercial broiler chickens to determine if Marek's disease (MD) vaccines HVT/SB-1 and HVT plus CVI-988 given either in ovo or at hatch adversely affected the efficacy of infectious bronchitis (IB) vaccines (Ark and Mass serotypes) given by eyedrop on the day of hatch. Nonvaccinated negative controls and controls that received only IB vaccines were included in each study. Birds were challenged with either infectious bronchitis virus (IBV) Mass-41 or IBV Ark-99 on either day 26 or 27 of age. Protection was assessed 5 days post-IBV challenged by virus isolation from the trachea. The day of hatch mean antibody titer to IBV was 12,668 +/- 4704 and 2503 +/- 3243 by enzyme-linked immunosorbent assay in experiments 1 and 2, respectively. In each study, nonvaccinated controls had a significantly higher (P < or = 0.05) incidence (88%-100%) of IBV challenge virus isolation than did controls vaccinated for IB but not for MD. Analysis of data from both studies showed that protection to IB in groups that received only IB vaccines at hatch ranged from 55.0% to 77.3%, whereas protection to IB in groups receiving both MD and IB vaccines ranged from 50.0% to 95.5%. In both experiments and within IBV challenge serotype, broilers given MD vaccines (in ovo or at hatch) and IB vaccines at hatch had protection rates to IBV challenges that were not significantly less (P < or = 0.05) than IB protection rates of groups that received only IB vaccines at hatch. Analysis of these data shows that administration of high-titered MD vaccines either in ovo or at hatch did not affect the efficacy of an IB vaccination (serotypes Ark and Mass) given by eyedrop at hatch.

Animals↗

Evaluation of efficacy and safety of erdosteine in patients affected by chronic bronchitis during an infective exacerbation phase and receiving amoxycillin as basic treatment (ECOBES, European Chronic Obstructive Bronchitis Erdosteine Study).

An international multicentric study was conducted with the aim of demonstrating that erdosteine improves the efficacy of amoxycillin in the treatment of infective exacerbation of chronic bronchitis mainly on the clinical symptomatology (primary objective), on spirometric tests and body temperature, without negatively influencing the tolerance (secondary objectives). The study was conducted as a prospective evaluation, with 2 comparative groups treated with erdosteine (300 mg x 2/day) or placebo in association with amoxycillin (1500 mg/day) for a maximum of 10 days. The design of the trial was double-blind and parallel group with 2 subgroups. The treatments have been assigned randomly to a population of chronic bronchitic patients in exacerbation phase of n = 237 subjects. The study was conducted according to the principles of the Declaration of Helsinki and its amendments (Hong Kong, September 1989). The primary end-point used to determine effectiveness in this study was the global clinical assessment (GCA) which was choosen as a general indication of activity with objective/subjective evaluation of the clinical picture. Secondary endpoints of efficacy are sputum parameters, functional signs of chronic obstructive bronchitis, spirometric tests and overall judgement of efficacy. Safety was evaluated with adverse drug reactions reporting, arterial blood pressure, heart rate and laboratory tests monitoring. The obtained values have been analyzed with two-way and factorial ANOVA, Least Squares Catmod-SAS, Wilcoxon and Chi-square tests. The number of patients included in the effectiveness analysis is of n = 226 subjects, due to the fact that 11 patients were lost due to different reasons. In term of results as far as the primary objective of the study was concerned, erdosteine resulted more active than placebo. The analysis evidenced a very significant difference for treatment, time and interaction time x treatment. No difference on the contrary was observed for center and the interaction center x treatment. Sputum volume, body temperature and spirometric parameters were not significantly influenced by both treatments. Viscosity, appearance as well as functional signs evidenced a modification over time in favour of erdosteine. As safety is concerned the majority of adverse events, both in the erdosteine and in the placebo group, were related to the gastrointestinal area. For erdosteine, of 9/17 side-effects, 3 were epigastralgias, 3 nauseas, 1 diarrhoea, 1 taste loss, 1 hemorrhoids. For placebo of 13/17 related events 3 were epigastralgias, 4 nauseas, 4 diarrhoeas, 1 pyrosis, 1 dry mouth. In terms of severity they have been all defined as mild or moderate degree. Also from a qualitative perspective it is clear that there are no relevant differences between the 2 treatments under evaluation, concerning safety. In conclusion of particular interest is the datum arising from the efficacy/safety evaluation, which indicates that the clinical picture is modified earlier and at deeper degree by the synergistic activity of erdosteine and of the antibiotic without the risk of an augmentation of side-effects incidence.

Aged↗

Efficacy of ciprofloxacin and clarithromycin in acute bacterial exacerbations of complicated chronic bronchitis: interim analysis. Bronchitis Study Group.

In a multicenter, community-based study involving more than 300 primary care physicians in the United States, the efficacy and safety of ciprofloxacin and clarithromycin were compared in the treatment of patients with complicated or severe acute bacterial exacerbations of chronic bronchitis (i.e., those who had failed previous antibiotic treatment within the prior 2 to 4 weeks; those with susceptibility data suggestive of a resistant pathogen; those having three or more acute exacerbations of chronic bronchitis [AECB] within the past year; and those having three or more comorbid conditions). Patients were randomized to either ciprofloxacin (CIP) 750 mg BID or clarithromycin (CLR) 500 mg BID, both administered for 10 days; all patients were treated on an outpatient basis. Clinical response at the end of therapy was the primary efficacy variable. An interim analysis was performed on the results from 743 patients (369 CIP, 374 CLR) with clinical and bacteriologic evidence of a bronchopulmonary infection who had completed an ongoing study as of the end of May 1997. Three hundred nine pathogens were isolated before therapy, including Haemophilus spp (75 isolates), Moraxella catarrhalis (67 isolates), Staphylococcus aureus (55 isolates), and Streptococcus pneumoniae (23 isolates). Seven hundred eighteen patients (97%) were included in the efficacy-valid population. Clinical success at the end of therapy was observed in 90% (272 of 302) and 88% (274 of 313) of efficacy-valid patients treated with CIP and CLR, respectively (95% confidence interval [CI] = -2.4 to 7.6). Corresponding rates for the intent-to-treat population were also 90% (283 of 314) and 88% (281 of 321), respectively (95% CI = -2.3 to 7.5). The bacteriologic response for efficacy-valid patients at the end of therapy was 98% (119 of 122) for CIP-treated and 93% (103 of 111) for CLR-treated patients (95% CI = -0.8 to 10.2). The eradication rates for the three most commonly isolated gram-negative pathogens were 100% for CIP-treated and 95% for CLR-treated patients and 96% each for the two most commonly isolated gram-positive organisms. Superinfections due to respiratory tract pathogens were more common in the CLR group (10 organisms) than in the CIP group (4 organisms). Seventy-four (20%) CIP-treated and 62 (17%) CLR-treated patients reported 118 and 103 respective study-emergent adverse events. Headache, abdominal pain, diarrhea, nausea, and vomiting in CIP-treated patients and diarrhea, nausea, vomiting, and taste perversion in CLR-treated patients were the most commonly reported adverse events. Treatment of patients with complicated or severe AECB with CIP 750 mg BID was associated with rates of clinical success and bacteriologic eradication similar to those with CLR.

Anti-Bacterial Agents↗

Treatment of acute exacerbations of chronic bronchitis: comparison of trovafloxacin and amoxicillin in a multicentre, double-blind, double-dummy study. Trovafloxacin Bronchitis Study Group.

The efficacy and safety of trovafloxacin and amoxicillin were compared in a double-blind, double-dummy multicentre trial involving 412 patients (> or = 40 years of age) with acute exacerbations of chronic bronchitis (AECBs). Patients were randomized to 5 days' oral treatment with 200 or 100 mg trovafloxacin administered once daily, or 500 mg amoxicillin given three times daily. Overall clinical efficacy at the end of therapy was similar in each treatment group, with clinical success (cure+improvement) achieved in 88% and 91% of clinically evaluable patients receiving trovafloxacin 200 mg and 100 mg, respectively, and in 89% of amoxicillin-treated patients. Corresponding rates at follow-up were 77%, 85% and 79%, respectively. Similar responses were noted at the end of treatment and end of study in the intent-to-treat patients. Although all three treatments produced similar bacteriological efficacy, there was a trend towards higher eradication rates for Haemophilus influenzae among patients (both clinically evaluable and intent-to-treat populations) treated with trovafloxacin 200 mg compared with those treated with amoxicillin. Both drugs were well tolerated, with treatment-related adverse events, of which headache and gastrointestinal disturbances were the most common, occurring in 12% and 6% of patients in the trovafloxacin 200 mg and 100 mg groups, respectively, and in 9% of amoxicillin-treated patients.

Acute Disease↗

Etiology, susceptibility, and treatment of acute bacterial exacerbations of complicated chronic bronchitis in the primary care setting: ciprofloxacin 750 mg b.i.d. versus clarithromycin 500 mg b.i.d. Bronchitis Study Group.

Although controversial, antimicrobial therapy for the treatment of acute exacerbations of chronic bronchitis (AECB) appears beneficial in patients with a history of repeated infections, those who have comorbid illnesses, and those with marked airway obstruction. In a community-based, open, randomized trial, the efficacy and safety of ciprofloxacin (CIP) 750 mg and clarithromycin (CLA) 500 mg, each given twice daily for 10 days, were compared in 2180 patients with AECB (1083 CIP, 1097 CLA). Patients were >40 years of age and had complicated/severe AECB episodes defined as at least three episodes within the past year, at least three comorbid conditions, previous failed antibiotic treatment for AECB within the previous 2 to 4 weeks, or community susceptibility data indicating a high number of resistant pathogens. Significant bacterial isolates (>10(5) colony-forming units per milliliter) from homogenized sputa were identified. Susceptibility to a range of antimicrobials was determined by the microbroth dilution technique. The majority of patients were white (83%) and were current or previous smokers (81%). Mean patient age was 62 years. A history of at least three AECB episodes in the previous year was reported by 54% of CIP-treated patients and 53% of CLA-treated patients. Of 777 primary isolates positively identified and cultured from 673 patients, the bacterial pathogens isolated and their incidence included Haemophilus species, 28%; Moraxella catarrhalis, 18%; Enterobacteriaceae, 18%; Staphylococcus aureus, 17%; Streptococcus pneumoniae, 7%; and Pseudomonas aeruginosa, 4%. Beta-lactamase production was found in 38% of Haemophilus influenzae, 10% of Haemophilus parainfluenzae, and 85% of M catarrhalis isolates. Thirty-four percent of S pneumoniae isolates were resistant to penicillin (minimum inhibitory concentration > or =0.12 mg/L). Among the 673 patients who were valid for clinical assessment and had a pretherapy pathogen isolated, clinical success and overall bacteriologic eradication rates at the end of therapy were 93% and 98% for CIP versus 90% and 96% for CLA. The differences between CIP and CLA did not reach statistical significance. Superinfections were reported significantly more frequently in CLA-treated (3%) versus CIP-treated patients (1%). Eradication rates for specific organisms for CIP and CLA, respectively, were Haemophilus species, 99% and 93%; M catarrhalis, 99% and 100%; S pneumoniae, 91% and 92%; and Enterobacteriaceae, 100% and 95%. Drug-related adverse events occurred in 12% of CIP-treated patients and 10% of CLA-treated patients. CIP 750 mg b.i.d. had a higher (but not statistically significant) clinical and bacteriologic cure rate than CLA 500 mg b.i.d. in the treatment of patients with bacteriologically proven complicated/severe AECB. The causative bacterial pathogens of AECB appear to be evolving, with a predominance of gram-negative and other resistant organisms observed. Thus antibiotic therapy for at-risk patients with AECB should include agents that have activity against gram-negative pathogens.

Acute Disease↗

A recombinant fowl adenovirus expressing the S1 gene of infectious bronchitis virus protects against challenge with infectious bronchitis virus.

The spike peplomer S1 subunit sequence from avian infectious bronchitis virus (IBV) Vic S strain was expressed in a plasmid under the control of the fowl adenovirus (FAV) major late promoter (MLP). Two recombinants were constructed in FAV serotype 8 (FAV 8) by inserting the expression cassette between the SnaBI and XbaI restriction enzyme sites (clone DA3) or between the SpeI sites (clone CA6-20). Expression of the S1 gene in the recombinants was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) by 20h post-infection. Commercial broiler chickens were orally vaccinated at day 0 or day 6 post-hatch and challenged at day 35 post-hatch. FAV antibody ELISA confirmed that maternal antibody directed against inclusion body hepatitis (serotype 8) had decayed in control birds and that FAV specific serum IgG responses were produced in vaccinated birds at the time of challenge. Further, an S1 specific antibody response was detected prior to challenge. Birds were challenged with either Vic S (serotype B) or N1/62 (serotype C) strains of IBV. The tracheas of challenged birds were analyzed by RT-PCR and re-isolation of virus. In birds vaccinated at day 6, 90-100% protection at the trachea was induced against either homologous or heterologous challenge. The construction of a recombinant FAV expressing S1 of IBV demonstrates the potential of an alternative vaccination strategy against IBV.

Administration, Oral↗

Infectious bronchitis immunity: its study in chickens experimentally infected with mixtures of infectious bronchitis virus and Escherichia coli.

The live infectious bronchitis (IB) vaccine, H120, protected chickens against intranasal challenge with a mixture of Escherichia coli strains (E. coli Pool) and IB virus (IBV) strains of the same (Massachusetts) serotype as H120; it usually also protected against challenge with the E. coli Pool and IBV strains of other serological types. When these challenge strains were themselves used as vaccines they usually protected against challenge with a mixture of the E. coli Pool and an IBV strain of the Massachusetts serotype (VF69-149) or an IBV strain not of the Massachusetts serotype (HVI-116). Poor protection, when observed, was most common in those experiments involving a minority of the IBV strains that had been incriminated in recent outbreaks of disease in vaccinated flocks of chickens. Much lower concentrations of IBV strain VF69-149 and E. coli O18 were found in the nose, trachea and spleen of H120-vaccinated chickens killed at different times after they were given a mixture of these organisms than were found in these sites in similarly challenged unvaccinated chickens. Some protection against challenge with IBV and the E. coli Pool was also observed in chickens vaccinated with an inactivated IBV strain; it was much less effective than that obtained following vaccination with the corresponding live IBV strain.

Administration, Intranasal↗

[Incidence of bronchitis in Vienna. Studies on the detection of the incidence of chronic bronchitis in Vienna].

Exact epidemiological studies about the frequency of respiratory tract disease are difficult to perform. Vague definitions and inhomogeneous examination modalities render a comparison of results difficult. Some statements can be made. Chronic bronchitis occurs more often in males. The significance increases with advancing age. Smoking habits are of utmost importance. Indoor and outdoor air pollution is without doubt a significant agent in the etiology of chronic respiratory disease.

Adult↗

[Organisation of bronchitis dispensaries-problems and present situation in the north-eastern region of the GDR (a pilot study of the bronchitis dispensary of the Pediatric Clinic, University of Greifswald) (author's transl)].

The dator on the care of children with CNSLD obtained from pediatricians working at out-patient departments in 15 districts of the Rostock and Neubrandenburg counties (in the north-eastern region of the GDR) are analyzed in a pilot study. This survey shows that there are 6 standard bronchitis dispensaries and on additional dispensary with highly specialized diagnostic equipment (Pediatric Clinic of the University of Greifswald) in 7 of the districts. In the remaining districts care of these children is provided within the framework of general medical outpatient care. 2% of the children having CNSLD only 36% receive medical treatment, which is a rather low percentage. This situation will be improved on the basis of better cooperation with the family doctors and the out-patient departments for lung diseases.

Adolescent↗