Telithromycin is as effective as amoxicillin/clavulanate in acute exacerbations of chronic bronchitis.

This randomized, double-blind study evaluated the efficacy and safety of a short, 5-day course of telithromycin, a new ketolide antibacterial, compared with a standard 10-day course of amoxicillin/clavulanate, in the treatment of acute exacerbations of chronic bronchitis (AECB). The study enrolled 325 adult patients with AECB and a history of chronic obstructive pulmonary disease (COPD). Patients received either telithromycin 800 mg once daily (qd) for 5 days (followed by placebo for 5 days) or amoxicillin/clavulanate 500/125 mg three times daily (tid) for 10 days. Clinical cure rates for telithromycin post-therapy (Days 17-21, test-of-cure) and late post-therapy (Days 31-36) were 86.1 and 78.1%, respectively; 82.1 and 75.0% for amoxicillin/clavulanate. Excellent clinical cure rates were also observed for high-risk patients. Bacteriologic outcome was satisfactory for 69.2% of telithromycin recipients vs 70.0% for amoxicillin/clavulanate recipients. Both treatments were generally well tolerated, although the frequency of drug-related adverse events was almost two-fold higher for amoxicillin/clavulanate (25.0 vs. 13.1%). Thus, a 5-day course of telithromycin 800 mg qd is an effective and well-tolerated alternative to a standard 10-day course of amoxicillin/clavulanate 500/125 mg tid for first-line empiric treatment of AECB in adults with COPD.

Improved tolerability of felodipine compared with amlodipine in elderly hypertensives: a randomised, double-blind study in 535 patients, focusing on vasodilatory adverse events. The International Study Group.

The primary aim of this double-blind, parallel group trial was to compare incidence of newly occurring vasodilatory adverse events in elderly patients treated with recommended once-daily doses of felodipine extended release (ER) or amlodipine. A total of 535 patients over 65 years old with a sitting diastolic blood pressure of 90-115 mmHg and/or systolic blood pressure 160-220 mmHg, were recruited at 46 centres worldwide. Patients were randomised to felodipine ER 2.5 mg or amlodipine 5 mg. If blood pressure was > 160/90 mmHg after three or six weeks, felodipine ER was increased to 5 and 10 mg and amlodipine to 10 mg. After nine weeks, average doses of felodipine ER and amlodipine were 5.5 mg and 7.3 mg, respectively. Newly occurring vasodilatory adverse events were reported by 32% of felodipine ER patients and 43% of amlodipine patients (p = 0.007). Both treatments effectively reduced blood pressure 24 hours post-dose. Using a low starting dose and individual titration, felodipine ER achieves good control of blood pressure with few vasodilatory side-effects.

A comparison of clarithromycin with ampicillin in the treatment of outpatients with acute bacterial exacerbation of chronic bronchitis.

One hundred and twenty-five outpatients with clinical symptoms of an acute bacterial exacerbation of chronic bronchitis were enrolled in a multicentre, double-blind, randomized clinical trial to compare the efficacy and safety of oral clarithromycin and ampicillin. Only those patients presenting with pathogens cultured from pre-treatment specimens susceptible to both study drugs were included in the study; beta-lactamase producing strains were excluded. Sixty patients received clarithromycin 250 mg 12-hourly and 65 had ampicillin 250 mg 6-hourly for 7-14 days. Clinical and bacteriological evaluations were performed pre-treatment, during treatment, and post-treatment within 48 h of cessation of therapy. All adverse events reported were evaluated. Twenty patients from the clarithromycin group and 24 from the ampicillin group were withdrawn from the study when no pathogen was isolated from the pre-treatment specimens. Twenty-eight patients who received clarithromycin and 23 who received ampicillin were evaluable for clinical and bacteriological efficacy. Both treatment groups were similar with respect to clinical and bacteriological response rates. The clinical cure rate for clarithromycin was 96% (27/28) compared with 91% (21/23) for the ampicillin group. Clarithromycin achieved a bacteriological cure rate of 96% (27/28) compared with 100% (23/23) for the ampicillin group. Adverse events, which were generally mild and associated with the digestive system, were reported by 11.7% of patients receiving clarithromycin and 1.5% of patients receiving ampicillin. Adverse events caused two patients in each group to discontinue treatment. Laboratory profiles for both groups were unremarkable throughout treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Felodipine in combination with a beta-adrenoceptor blocker as an effective substitute for triple therapy in severe hypertension. The Australian Felodipine Multicentre Study Group.

We have studied the efficacy and tolerability of felodipine plus a beta-adrenoceptor blocker in 79 patients with essential hypertension previously treated with a combination of three or more anti-hypertensive agents, one of which was a beta-adrenoceptor blocker. After a 4-week run-in period on the same beta-blocker plus placebo (as a substitute for the other agents in the regimen), felodipine was added and its dose titrated to achieve a supine diastolic blood pressure or less than 90 mm Hg. This was followed by a 12-week maintenance phase in all patients, and 47 patients entered an optional long-term follow-up for an additional 9 months. The mean supine blood pressure was 149/88 mm Hg at entry and 174/108 mm Hg after the run-in phase. Felodipine significantly reduced the blood pressure to 142/85 mm Hg after dose titration and to 141/84 mm Hg after 12 weeks, 94% of patients achieving a supine diastolic blood pressure of 90 mm Hg or below. This reduction was maintained in the patients who were followed for 12 months. The adverse events recorded were usually mild, transient, and typical for an effective precapillary vasodilator. Nine of 74 patients (11%) were withdrawn in the first phase of the study because of adverse events and 5 of 47 patients were withdrawn during the long-term follow-up. These results show that the efficacy and tolerability of a combination of felodipine with a beta-blocker allow a simplified regimen for hypertensive patients who were previously taking three or more drugs for satisfactory blood pressure control.

Can a new beta 2-agonist reduce the mortality of asthma?

Tulobuterol is a synthetic beta-adrenergic agonist which, when administered orally, is a potent, long-acting bronchodilator. The safety and efficacy of 2 mg tulobuterol tablets taken twice daily was compared to that of 4 mg salbutamol tablets taken three times daily for a period of 12 weeks in outpatients with stable chronic asthma in a randomized, double-blind, multi-center study conducted in Australia. Strict entry criteria were employed; only those patients whose baseline FEV1 value was between 40-70% of the predicted normal value and increased at least 20% after two inhalations of a metered dose (250 micrograms per dose) of terbutaline aerosol at a screening visit were included. Treatment with active study drug was preceded by a 2 week single-blind, placebo lead-in period. The onset and duration of the bronchodilating effect was studied on the first day of the placebo lead-in period and on the first and last days of the 12 week parallel design treatment period. Of 140 patients enrolled, 73 had tulobuterol and 67 had salbutamol. Of these, 61 tulobuterol and 59 salbutamol treated patients could be evaluated for efficacy. Of the 140 patients, 129 completed the study. All patients were issued a mini peak flow meter and diary cards to record daily PEFRs and symptoms of airways obstruction throughout the study. The demographics of the patients in both treatment groups were similar in all modalities: they were comparable in age, duration of asthma, mean FEV1 (expressed as percent of predicted normal), and reversibility (as demonstrated by an increase in FEV1 after administration of a beta 2-agonist aerosol).(ABSTRACT TRUNCATED AT 250 WORDS)

Activity of erythromycin against Haemophilus influenzae from respiratory tract infections.

Ampicillin and amoxycillin are very frequently used for treating respiratory infections due to Haemophilis influenzae, but the emergence of beta-lactamase producing strains of this organism may limit their use. Erythromycin would be a suitable alternative but to date variable absorptions and reported minimal inhibitory concentrations (MICs) outside the range of achievable blood levels of erythromycin have prevented its use. The purpose of this study was to determine the MICs of erythromycin for strains of H. influenzae isolated from patients with lower respiratory tract infection and the frequency of beta-lactamase production in these strains. Eighty-five of 100 strains were sensitive to erythromycin (MIC much less than 2.00 mg/L). Eleven strains were resistant to ampicillin and 10 of these produced beta-lactamase. Nine beta-lactamase producing strains had MICs to erythromycin of 2.0 mg/L or less. With the blood levels of erythromycin obtainable with new formulations, this antibiotic should prove of use in the treatment of respiratory infections due to H. influenzae.

Isophorone diisocyanate induced respiratory disease (IPDI).

A 50-year-old male spray painter developed severe asthma soon after the introduction of a new paint containing isophorone diisocyanate (IPDI). His asthma was associated with an abnormal chest X-ray, blood eosinophilia, normal IgE level, negative skin prick tests and no precipitins to A. fumigatus. A bronchial challenge test, performed when he was well, with the paint containing the additive gave a positive response. It was considered that IPDI was the cause of his illness. He is now well on maintenance therapy and he no longer works in the industry.

The nature of asthma in Brisbane.

Clinical details and skin prick test reactions are described for 183 asthmatic patients who attended an asthma clinic at the Royal Brisbane Hospital in 1976. These features were compared with similar studies reported from London, Sydney, Tristan da Cunha and New Guinea. Asthma in Brisbane was shown to be similar in many ways to asthma in those centres; however, a higher frequency of positive immediate skin test reactions to antigens of A. fumigatus, a larger percentage of skin test-negative patients developing symptoms before the age of 10 years, and a lack of association between the age of onset of symptoms and number of positive skin tests was noted. A difference in mean weal diameter (in mm) on skin testing with house dust mite antigens was not found between patients giving a history of sensitivity to these antigens and those that did not. A seasonal increase in symptoms was only described by 27% of patients.