A multinational, multicentre, non-blinded, randomized study of moxifloxacin oral tablets compared with co-amoxiclav oral tablets in the treatment of acute exacerbation of chronic bronchitis.

The aim of this study was to compare the efficacy and safety of once daily dosing with moxifloxacin (BAY 12-8039) with that of coamoxiclav given three times daily for the treatment of acute exacerbation of chronic bronchitis (AECB). Moxifloxacin (one 400 mg tablet daily) was administered orally for 5 days and co-amoxiclav (three 625 mg tablets daily) was given orally for 7 days. The study was randomized, non-blinded, multinational (12 countries) and multicentre (68 centres). A total of 575 patients, all with clear signs of AECB, were treated, 292 with moxifloxacin and 283 with co-amoxiclav. Of these, 512 patients were evaluable for efficacy (261 in the moxifloxacin group and 251 in the co-amoxiclav group). The primary efficacy parameter was clinical response at 14 days in the evaluable population. A clinical success was classified as resolution or improvement of symptoms. Variables used to assess clinical response included wheeze, cough, dyspnoea, sputum volume, rales and rhonchi. The success rate for moxifloxacin in the evaluable patients was 96.2% and that for co-amoxiclav was 91.6%. The 95% confidence intervals for this difference (0.4%; 8.7%) indicate equivalence in the treatments. Sputum samples were taken from patients and 140 of these contained a pathogen, Haemophilus influenzae being the most frequently isolated. Moraxella catarrhalis and Streptococcus pneumoniae were also commonly isolated pathogens. The eradication rate at 14 days in the evaluable patients was 87.7% in the moxifloxacin group and 89.6% in the coamoxiclav group. Both drugs were well tolerated with no significant differences in the numbers of drug-related adverse events or the numbers of patients withdrawing because of an adverse event. These results and the broad spectrum of antibacterial activity make moxifloxacin a promising and safe alternative to conventional therapy for the empirical treatment of AECB.

Sparfloxacin for the treatment of community-acquired pneumonia: a pooled data analysis of two studies.

A pooled data analysis of two double-blind studies encompassing 1137 episodes of community-acquired pneumonia in hospitalised adults, of which 560 were treated with sparfloxacin and 577 were randomised to comparator antibacterial agents (amoxycillin/clavulanic acid, erythromycin or amoxycillin administered at reference dosages), was performed. The global efficacy rate at the end of treatment in evaluable patients treated with sparfloxacin was 88.3% compared with 84.1% in those who received comparator antibacterial agents. This analysis verified the efficacy of this new aminofluoroquinolone, given orally once daily, in the treatment of community acquired pneumonia. The overall outcome favoured sparfloxacin for use in the empirical treatment of community-acquired pneumonia.

Influence of Pneumocystis carinii pneumonia on serum and tissue concentrations of pentamidine administered to rats by tracheal injections.

Pentamidine isethionate was administered by the tracheal route to control rats and immunodepressed rats with Pneumocystis carinii pneumonia (PCP). The serum concentration of pentamidine base 20 min after the administration was higher in the PCP rats (309 +/- 165 ng/ml) than in the control animals (71 +/- 36 mg/ml; p less than 0.001); 90 min after the injection the proportion of the pentamidine administered was lower in the right lung of the PCP rats (29 +/- 15%) than in the control rats (57 +/- 23%; p = 0.038); the proportion of pentamidine in the left kidney was higher in the PCP rats (14 +/- 4%) than in the control animals (4 +/- 2%; p less than 0.001). Respiratory clearance of 99mTc-DTPA, an index of the permeability of the respiratory epithelium, was higher in the PCP rats (1.84 +/- 0.42 %/min) than in the controls (0.44 +/- 0.11 %/min; p less than 0.001). We conclude that the more rapid diffusion of pentamidine from the alveolar lumen to the pulmonary circulation is explained by the increased alveolocapillary permeability as a result of pneumocystosis.

Methods for clinical assessment of expectorants: a critical review.

The purpose of the paper is to discuss some aspects of the methods that are most appropriate for the clinical assessment of new expectorants. Expectorants are drugs devised to help in the removal of bronchial secretions. The evaluation of these drugs is aimed at demonstrating, in controlled trials, their efficacy, safety and, if possible, mechanism of action. Unfortunately, there is no universally accepted assessment technique available. Evaluation of symptoms with the use of self-reported measures is imprecise. Studies of quality of life can assist as a means of assessing the usefulness of this class of drug for patients. Lung function tests evaluate only the possible indirect effects of expectorants; the changes observed are often minor and they do not correlate with other methods of evaluation. Mucociliary clearance studies evaluate bronchial drainage by mucociliary transport and cough. They are a useful pharmacological approach but they cannot replace therapeutic trials. In vitro and ex vivo studies of bronchial secretion, while improving knowledge of the mechanisms of bronchial secretion, fail to predict the modifications of bronchial drainage produced in vivo by cough or mucociliary transport. To be considered efficient, expectorants should not only ease the removal of bronchial secretions, but also improve the patient's condition for the duration of treatment.

[Paraneoplastic hypercalcemia in primary bronchial cancer]. / L'Hypercalcémie paranéoplasique du cancer bronchique primitif

Paraneoplastic hypercalcemia is frequently observed in squamous cell carcinoma of the bronchus. Clinically, apart from the general symptoms which are always very marked, neurological signs are the most common. This hypercalcemia, accompanied by hypophosphatemia, is of sudden onset and immediately very high. Metabolic alkalosis, with hypokalemia and hypochloremia, differentiates it from true hyperparathyroidism. Symptomatic treatment is only transiently effective. However, the obvious effect of mitramycin may be useful before surgical operation, which alone produces a lasting normalisation of serum calcium. Inappropriate secretion of a parathormone substance by the tumour may be demonstrated by radio-immunoassay, and this explains a large number of cases of hypercalcemia but this does not exclude other possible factors in the etiology. Finally, hypercalcemia originally attributed to bony lysis, may be explained in some cases by a paraneoplastic process.