[Influenza infection and antibiotic therapy].
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Biomedical subjects
Publications and source records attributed to T Schaberg.
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This review analyzes the pharmacokinetics of new oral cephalosporins, including esters, non-esters, and the carbacephem loracarbef, in healthy volunteers, as described in the literature and evaluated in several studies of our own. Single-dose studies have demonstrated considerable pharmacokinetic differences among these compounds. Cefixime, cefpodoxime proxetil, and cefetamet pivoxil are characterized by a low peak concentration and a prolonged half-life, while the other new agents have higher peak levels and shorter half-lives. Except for cefixime, the new oral cephalosporins are eliminated mainly by the kidneys. Pharmacokinetic studies in the elderly and in children indicate that the bioavailability of these agents is not influenced by age. Food increases the bioavailability of the ester cephalosporins but does not affect the absorption kinetics of the other new drugs.
The main problems of diagnosis in lower respiratory tract infection are the differentiation of infection from colonization or contamination, and the isolation of a reliable and true pathogen. The clinical findings and differentiation of patients into those with pneumonia or infective exacerbations of chronic bronchitis should provide a definitive early diagnosis. Expectorated sputum may be unreliable in pneumonia, because of contamination by oropharyngeal flora. Although blood cultures may be negative, they provide a precise diagnosis and should be obtained in all pneumonias admitted to hospital. Other more invasive procedures are transtracheal needle aspiration, fibrebronchoscopic techniques including protected specimen brush and bronchoalveolar lavage with quantitative culturing and cytological analysis, transthoracic needle aspiration, thoracoscopy--guided biopsy and open lung biopsy. Any invasive procedure in a severely ill patient should be carefully directed weighing the risks as well as the benefits, whilst taking the underlying disease and expected survival into consideration.
This study was designed to investigate the expression and functional properties of leukocyte adhesion molecules (LeuCAM; CD11/CD18 family) on human alveolar macrophages (AM) from patients with sarcoidosis and idiopathic pulmonary fibrosis. Cells were obtained by bronchoalveolar lavage (BAL) from 17 patients with sarcoidosis (SA), 15 with idiopathic pulmonary fibrosis (IPF), and 14 nonsmokers (NS). Expression of LeuCAM on freshly isolated cells was studied using the peroxidase-antiperoxidase method with monoclonal antibodies (MoAb) detecting CD11a, CD11b, CD11c, and CD18. The functional properties of the adhesion molecules were studied by measuring superoxide anion production (O2-) of SA and IPF AM after blocking the CD18 molecule by an MoAb. Compared with nonsmokers, the samples from SA and IPF patients contained an increased number of AM expressing CD11a, CD11b, CD11c, and CD18 (all p < 0.008), which was correlated to the number of AM/ml BAL (p < 0.008). Spontaneous O2- secretion of AM was higher in SA (6.4 +/- 1.2 nMO2-/10(6) AM/120 min) and IPF (12.0 +/- 1.1 nMO2-/10(6) AM/120 min) compared with NS (2.5 +/- 0.2 nMO2-/10(6) AM/120 min) (both p < 0.008). Incubation of the AM with the MoAb anti-CD18 reduced the spontaneous O2- release from SA AM by 52 +/- 8% and from IPF AM by 49 +/- 3% but did not influence O2- release from NS AM (92 +/- 4%). Our data indicate that the increased expression of LeuCAM on AM in subjects with SA and IPF seems to be involved in the increased O2- production of these cells in both diseases.
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Nosocomial pneumonias, especially in ventilated patients, are a continuing problem in modern medicine. Pathogens most commonly involved with these pneumonias are Enterobacteriaceae, Ps. aeruginosa and S. aureus. Several prevention measures for nosocomial pneumonia are possible such as parenteral and topical antibiotics--a very controversial issue. Several studies with parenteral antibiotics, starting as early as 1954, could not prove any benefit of parenteral antibiotics in pneumonia prevention. Topical antibiotics, starting with polymyxin or gentamicin via the endotracheal tube in the 70s, gave controversial results. In a prospective, randomized, double-blind placebo controlled study with gentamicin via the endotracheal tube in ventilated ICU patients we found no significant reduction of pneumonia rate and mortality. However, the combined approach (SDD) of oropharyngeal, gastrointestinal and parenteral use of certain antibiotics appears to give promising results in specific patient subgroups such as ventilated polytrauma patients in ICU.
This study was designed to investigate whether the expression and functional properties of leukocyte adhesion molecules (LeuCAM; CD11/CD18) are altered in human alveolar macrophages (AM) from smokers. Cells were obtained from 38 smokers (S) and 27 nonsmokers (NS) by bronchoalveolar lavage (BAL). Expression of LeuCAM on freshly isolated cells was studied using a sensitive peroxidase-antiperoxidase method with monoclonal antibodies (mAB) against CD11a, CD11b, CD11c, and CD18. The functional properties of the adhesion molecules were studied by measuring in vitro the binding of AM to the intracellular adhesion molecule-1 (ICAM-1) on human umbilical-vein endothelial cells (HUVEC). The influence of LeuCAM on the increased superoxide anion production (O2-) of smoker AM was quantified after blocking the CD18 molecule by a mAB. Compared with nonsmoker AM, significantly more AM from smokers expressed CD11b (p < 0.001), CD11c (p < 0.001), CD18 (p < 0.001), and CD11a (p < 0.004), whereas there was no difference in the expression of other common epitopes of human macrophages such as CD68, CD71, CD45, HLA-DQ, and HLA-DR. The number of AM expressing CD11a, CD11c, and CD18 showed a correlation to the total number of AM obtained by BAL (p < 0.001). Adherence of AM to HUVEC was higher for smoker than for nonsmoker AM (p < 0.05). The increased binding of smoker AM to endothelial cells could be inhibited by treating the HUVEC with a mAB against ICAM-1. The mAB anti-CD18 reduced O2- release from smoker AM by 42 +/- 5% after 120 min.(ABSTRACT TRUNCATED AT 250 WORDS)
This study was designed to investigate the effects of the platelet-activating factor (PAF) on the superoxide anion production (O2.) of human alveolar macrophages (AM) from nonsmoking (n = 18) and smoking (n = 30) subjects. Freshly isolated cells were stimulated with (PAF) or with a phorbol ester (phorbol 12-myristate 13 acetate (PMA)). Stimulation with PAF led to a dose-dependent increase of O2. production by AM in both groups. The median effective dose (EC50) for PAF action on O2. production of smoker AM was 0.5 x 10(-8) M, compared to nonsmoker AM with an EC50 of 1.0 x 10(-7) M. This effect of PAF was blockable by the PAF-antagonist WEB 2086 in a dose-dependent manner. Comparison of the relative increase of O2. production after PAF-stimulation showed that smoker cells were significantly more sensitive to PAF than nonsmoker cells (p less than 0.01). In contrast to the findings with PAF, the relative increase of O2. production after PMA-stimulation showed no differences between smoker and nonsmoker AM. Our data suggest that AM from smoking subjects are more sensitive to PAF than AM from nonsmokers.
Azithromycin is a new azalide antimicrobial agent which has a broad spectrum of activity against common lower respiratory tract pathogens including pneumococci, staphylococci, Legionella species, Mycoplasma and Chlamydia species. In particular, it is more active against Haemophilus influenzae than other macrolides. In comparison to other new macrolides, azithromycin achieves higher tissue and intracellular concentrations and these concentrations are sustained for several days after dosing due to a long elimination half-life. The efficacy of azithromycin against lower respiratory tract infections has been proven in several clinical studies. Once-daily dosing with azithromycin, over a 3- or 5- day period was as effective as a 10-day course of other commonly used antibiotics such as amoxycillin/clavulanic acid, erythromycin or cefaclor in lower respiratory tract infections. Azithromycin short-course therapy may offer an advantage in terms of patient compliance and the duration of treatment.
Atypical pneumonias are caused by mycoplasma, chlamydia and legionella species. From a clinical point of view the disease is comparable to influenza-like infections. Macrolide antibiotics covered the species which are most important. Especially new macrolides displayed better pharmacokinetic properties, allowing dose reduction and reduced frequency of intake. For legionella infections also therapy with modern quinolones is possible.
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