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Antibiotic treatment of bacterial exacerbation of chronic obstructive pulmonary disease (COPD) shows some immediate clinical benefits and may also minimise the frequency of further recurrences.Patients (n=511) were enrolled into a randomised double-blind multicentric study comparing the exacerbation-free interval (EFI), efficacy and safety of 7-day levofloxacin versus 10-day clarithromycin in patients with COPD exacerbation. Patients were monitored over a 1-yr period. A total of 434 patients (per protocol population) received the medication for o5 days.The median EFI in the per protocol population was 300 days for levofloxacin and 350 days for clarithromycin. For patients with a new documented exacerbation during follow-up (n=223), the median EFI was 100.5 days in the levofloxacin group and 95 days for clarithromycin. No significant differences in EFI between groups could be observed when stratifying the study population according to microbial aetiology and severity of bronchial obstruction. Levofloxacin and clarithromycin showed similar clinical success rates. The bacteriological success rate was significantly higher in the levofloxacin group. Both antibiotics were well tolerated.In summary, levofloxacin was associated with a significantly higher bacteriological eradication rate but similar exacerbation-free interval in patients with chronic obstructive pulmonary disease exacerbation compared to clarithromycin. Eur Respir J 2004; 24: 947-953.

The pharmacokinetics and serum bactericidal activities (SBAs) of imipenem and meropenem were investigated in a randomized crossover study. Twelve healthy male volunteers received a constant 30-min infusion of either 1 g of imipenem plus 1 g of cilastatin or 1 g of meropenem. The concentrations of the drugs in serum and urine were determined by bioassay and high-pressure liquid chromatography. Pharmacokinetic parameters were based on an open two-compartment model and a noncompartmental technique. At the end of infusion, the mean concentrations of imipenem and meropenem measured in serum were 61.2 +/- 9.8 and 51.6 +/- 6.5 mg/liter, respectively; urinary recoveries were 48.6% +/- 8.2% and 60.0% +/- 6.5% of the dose in 12 h, respectively; and the areas under the concentration-time curve from time zero to infinity were 96.1 +/- 14.4 and 70.5 +/- 10.3 mg.h/liter, respectively (P < or = 0.02). Imipenem had a mean half-life of 66.7 +/- 10.4 min; that of meropenem was 64.4 +/- 6.9 min. The volumes of distribution at steady state of imipenem and meropenem were 15.3 +/- 3.3 and 18.6 +/- 3.0 liters/70 kg, respectively, and the mean renal clearances per 1.73 m2 were 85.6 +/- 17.6 and 144.6 +/- 26.0 ml/min, respectively. Both antibiotics were well tolerated in this single-dose administration study. The SBAs were measured by the microdilution method of Reller and Stratton (L. B. Reller and C. W. Stratton, J. Infect. Dis. 136:196-204, 1977) against 40 clinically isolated strains. Mean reciprocal bactericidal titers were measured 1 and 6 h after administration. After 1 and 6 h the median SBAs for imipenem and meropenem, were 409 and 34.9 and 97.9 and 5.8, respectively, against Staphylococcus aureus, 19.9 and 4.4 and 19.4 and 4.8, respectively, against Pseudomonas aeruginosa, 34.3 and 2.2 and 232 and 15.5, respectively, against Enterobacter cloacae, and 13.4 and 2.25 and 90.7 and 7.9, respectively, against Proteus mirabilis. Both drugs had rather short biological elimination half-lives and a predominantly renal route of elimination. Both carbapenems revealed high SBAs against clinically important pathogens at 1 h; meropenem had a higher SBA against E. cloacae and P. mirabilis, and the SBA of imipenem against S. aureus was greater than the SBA of meropenem.

We were previously able to show that the number of alveolar macrophages (AM) expressing CD11/CD18 molecules is increased in smokers compared with nonsmokers and related to the superoxide anion (O2-) production of these cells. Since it has been demonstrated that AM are a heterogeneous cell population that can be separated by density, we performed this study to investigate the expression of CD11/CD18 molecules and O2- production in relation to cell density of AM from smokers and nonsmokers. AM were obtained by bronchoalveolar lavage (BAL) from smokers (n = 32) and nonsmokers (n = 20). Subpopulations were isolated using discontinuous Percoll density-gradient centrifugation with four densities (fraction 1: 1.030; fraction 2: 1.040; fraction 3: 1.050; and fraction 4: 1.070 g/ml). Expression of CD11/CD18 on freshly isolated cells and on AM before and after density centrifugation was studied using peroxidase-antiperoxidase staining. The contribution of AM subpopulations to O2- production in smokers was determined by monitoring the reduction of ferricytochrome C to ferrocytochrome C. We obtained 0.92 +/- 0.1 x 10(5) AM/ml BAL in nonsmokers and 2.4 +/- 0.3 x 10(5) AM/ml in smokers. Recovery after density centrifugation was > or = 72%. The absolute number of AM in smokers was significantly increased in fractions 3 and 4 (median 4.37 x 10(6) and 2.05 x 10(6), respectively) compared with nonsmokers (median 1.26 x 10(6) and 0.7 x 10(6), respectively) (p < 0.05). In both smokers and nonsmokers, fractions 3 and 4 showed a comparable increase in the percentage of CD11/CD18-positive AM compared with fractions 1 and 2.(ABSTRACT TRUNCATED AT 250 WORDS)