Clinical and bacteriological experience with cefodizime in acute purulent exacerbations of chronic bronchitis.

1 or 2 g doses of cefodizime i.m. were studied in 287 patients admitted to hospital with acute purulent exacerbations of chronic bronchitis, mostly associated with Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis. Pharmacokinetic studies in serum and sputum on the first treatment day yielded mean peak serum concentrations of 50 to 100 mg/l, with corresponding sputum concentrations of 1.4 and 2.7 mg/l, after the two respective doses. No great differences were found between the clinical and microbiological results in the various dosage groups, and no corresponding improvement was noted with the highest dosages studied. In general, infection was eliminated in 90 to 95% of patients at the end of treatment, and in approximately 70 to 80% after a follow-up week. Some infections associated with beta-lactamase producing M. catarrhalis persisted or relapsed after treatment. Unwanted drug effects were recorded in five patients, leading to discontinuation in two. It is concluded that a single daily intramuscular dose of 1 g cefodizime for seven days produces satisfactory results in most patients.

Neuroendocrine cells in anthracosilicotic lungs.

In normal human lungs, neuroendocrine (NE) cells can be found as solitary NE cells and in corpuscular aggregates, the neuroepithelial bodies. By means of a quantitative morphometric method, we compared the number and distribution of chromogranin-reactive NE cells in anthracosilicotic and control lungs. After death, 14 pairs of control and 12 pairs of anthracosilicotic lungs were sampled. The extents of anthracosilicosis and emphysema were described for the right lung. The left upper lobe was used for quantitative determination of the number and distribution of NE cells, visualized by immunohistochemical staining for chromogranin. In contrast to expectations, we found no statistical difference in the numbers of chromogranin-reactive NE cells per 10 cm of epithelium between control (11.0) and anthracosilicotic (2.4) lungs. In both groups, there was a much greater number of chromogranin-reactive cells in the more peripheral compared to the central airways. Most peripheral NE cells were arranged in neuroepithelial bodies, which were not found in the central airways.

Formoterol in the treatment of nocturnal asthma.

Formoterol fumarate is a new beta 2-adrenergic agonist with a long lasting effect. The bronchospasmolytic effect of 12 micrograms of formoterol was compared with that of 200 micrograms of albuterol (salbutamol) in a single-center, double-blind, randomized within-patient study. The drugs were given as aerosols by MDI to 16 patients with nocturnal asthma in a stable phase. The inhalations were given at 10 PM and the FEV1 values as parameter were measured before and at 1, 2, 6, 8, 10, and 12 hours afterwards. The FEV1 6 hours after administration of formoterol was significantly higher than that after albuterol (ANCOVA: p = 0.008), and this was still the case 12 hours after the test dose at 10 AM the following morning (ANCOVA: p = 0.009). At 4 AM, the FEV1 fell below the basic starting value after albuterol, whereas it remained at least 10 percent above the formoterol inhalation. Five patients required rescue therapy after albuterol and two after formoterol. We conclude that formoterol in a dose of 12 micrograms via MDI confers good protection against nocturnal asthma; this was only insufficient for some patients with severe asthma, and further studies with higher dosages in these patients are clearly indicated.

Temafloxacin in acute purulent exacerbations of chronic bronchitis.

Temafloxacin hydrochloride, a new fluoroquinolone, was given orally in doses of 300 or 600 mg twice daily for ten days to 36 patients, all hospitalized because of severe acute purulent exacerbations of chronic bronchitis. Sputum cultures before, during and after treatment showed that the infection was eliminated in 12/18 evaluable patients given 300 mg and in 13/16 receiving the 600 mg doses. Haemophilus influenzae, Branhamella catarrhalis and Streptococcus pneumoniae were effectively eliminated, but only half the Pseudomonas aeruginosa infections were eradicated. MICs for most pathogens were 1 mg/l or less (including the majority of the pneumococci) but the MICs for Ps. aeruginosa ranged from 0.5 to greater than 16 mg/l, those for 10 of the 22 strains being greater than 2 mg/l. Pharmacokinetic studies on serum and sputum specimens showed serum Cmax values of 3.5 and 6.0 mg/l, the sputum Cmax being 2.35 and 4.17 mg/l after the different doses. No interaction with concomitant theophylline could be found. Two patients complained of moderate nausea or water-brash. Temafloxacin can be considered safe and effective at these dosages, but for Ps. aeruginosa infections higher dosages need to be investigated.

Cefodizime and cefotaxime in acute exacerbations of chronic bronchitis: a randomized double-blind prospective study in 180 patients.

In a double-blind prospective study, 180 patients admitted to hospital with acute purulent exacerbations of chronic bronchitis were treated for seven days with twice daily 1 g intramuscular injections of either cefodizime or cefotaxime. Sputum cultures performed before, during and immediately after treatment showed complete eradication of the infection in 89/90 given cefodizime and 86/90 receiving cefotaxime. Some symptomatic Pseudomonas aeruginosa superinfections occurred with each agent. During the follow-up week, recurrences or reinfections after apparent clearance occurred in 15 patients given cefodizime and in 21 receiving cefotaxime. Pharmacokinetic studies in blood showed mean Cmax values of 50.8 mg/l for cefodizime and 36.5 mg/l for cefotaxime, corresponding values in the sputum being 1.61 and 0.62 mg/l. Mean AUC values in both blood and sputum were 2 1/2- to 3-fold higher for cefodizime. Some features suggested better performance by cefodizime than by cefotaxime, but the clinical results were not statistically significantly different.

Bronchodilator effect of inhaled formoterol vs salbutamol over 12 hours.

The bronchodilator effects were compared in 16 stable asthma patients for 12 hours after either 12 micrograms formoterol or 200 micrograms salbutamol from a metered-dose aerosol in a randomized, double-blind, crossover study. The FEV1 measured before 1, 2, 4, 6, 8, 10 and 12 hours after administration was used as the parameter. From 2 hours onwards after dosage, the bronchodilator effect of formoterol was statistically significantly greater than that of salbutamol. The effect of formoterol lasted longer, and even after 12 hours, the FEV1 was still 20 percent above the baseline value. This is clinically significant and offers new possibilities for treatment of the so-called "morning dip." Both agents were well tolerated.