The tropism of erythromycin for the respiratory system.
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Biomedical subjects
Publications and source records attributed to F Scaglione.
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A study was carried out to establish whether erythromycin stearate was bacteriostatic or bactericidal at the concentrations reached in the bronchial secretion. Twenty-two patients suffering from an acute attack of chronic bronchitis, sustained by streptococci, diplococci, staphylococci or H. influenzae sensitive to erythromycin, were treated with 1500 mg erythromycin per day until symptoms regressed, usually within 3 to 5 days. The results showed that after treatment there was a dramatic reduction in the number of bacterial colonies cultured from the bronchial secretion and marked changes in bacterial morphology were seen using electron microscopy. Further evidence of bactericidal activity was provided by the rapid clinical response of the patients.
Antibacterial kinetics of modified-release clarithromycin (CLA) and azithromycin (AZI) against respiratory tract pathogens were compared in relation to their pharmacokinetic profile. The study was carried out in three strains of Streptococcus pneumoniae, group A beta-hemolytic Streptococcus pyogenes, Moraxella catarrhalis and Haemophilus influenzae, respectively, exposed to concentration gradients of CLA and AZI simulating human serum pharmacokinetics after administration of 500 mg p.o. in a single dose. Bactericidal kinetics were assessed by counting the number of survivors before each change in concentration over a period of 36 h. The minimal inhibitory concentrations (MICs) of CLA and AZI were evaluated at time 0 and after 36 h of exposure to antibiotics in the surviving organisms. The results showed that CLA and AZI, in the experimental conditions adopted, had different antibacterial kinetics. Moreover, the addition of the 14-OH metabolite of CLA at the same concentrations reached in human serum exerted a bactericidal effect against two strains of H. influenzae resistant to CLA and AZI. An increase in MICs was observed against S. pyogenes and H. influenzae, with higher values for AZI.
The most studied endocrine product of the pineal gland, melatonin, has been reported to be involved in the feedback between neuroendocrine and immune functions and to exert oncostatic action, at least in certain experimental conditions. Melatonin seems to be an integral part of the immune system, by exerting direct and/or indirect stimulatory effects on both cellular and humoral immunity. Likewise, an antitumor activity of melatonin has been shown in several experimental models in vivo and in vitro. The means by which melatonin exerts its effects on immunity and neoplastic growth have not been elucidated. The different putative mechanisms of action of melatonin investigated so far are here briefly discussed.
An in vitro infection model was created using a suspension of macrophages, polymorphonuclear leukocytes, lymphocytes, fibroblasts, and human serum to which pathogen and antibiotic were added. Separate intracellular and extracellular antibiotic concentrations and activity against Staphylococcus aureus and Legionella pneumophila were assessed for three antimicrobial agents: amoxicillin, azithromycin and clarithromycin. Amoxicillin was found almost exclusively in extracellular fluid, where it was active; intracellularly, it was ineffective. Azithromycin, in contrast, was primarily concentrated and active intracellularly, with little activity in extracellular fluid. Clarithromycin was present in both compartments and possessed significant activity both intracellularly and extracellularly.
Microbial adherence to epithelial cell surfaces has been implicated as the first step in the initiation of several infectious diseases. The ability of antibiotics to affect the properties of bacterial adherence to cell surfaces may be a criterion in selecting antibiotics for therapy. This study was performed in order to investigate the activity of amoxicillin, chloramphenicol, and clarithromycin in modifying the adhering activity of Bordetella pertussis to human epithelial cells. The actions of antibiotics, alone or combined with aprotinin, were compared with that of trypsin, aprotinin and trypsin+aprotinin, to investigate the chemical nature of the ligand where antibiotics could act. The adhering activity was evaluated on human epithelial cells, collected from the oral mucosa, challenged with B. pertussis A2963 previously incubated in the presence of the tested substances for 1 h at 37 degrees C in a shaker incubator. After staining, the percentage of mucosal cells with more than 50 adhering bacteria was evaluated. Under the described experimental conditions, trypsin significantly reduced the adherence of B. pertussis. Aprotinin had no effect but was able to counteract the inhibitory action of trypsin. Both clarithromycin and chloramphenicol markedly reduced adhering activity and their actions were not counteracted by aprotinin. Amoxicillin was without effect. It was hypothesized that chloramphenicol and clarithromycin, exerting their antimicrobial action by inhibiting bacterial protein synthesis, affected bacterial adhesion through an unknown mechanism without proteolytic effect.
Ceftibuten is a broad-spectrum oral cephalosporin exhibiting antimicrobial activity against a wide range of gram-negative and some gram-positive pathogens. Pharmacokinetic studies have shown that the molecule has an oral bioavailability higher than 90% of the administered dose (reaching peak serum concentrations of 5-19 mg/l after a single dose of 200 and 400 mg). Moreover, ceftibuten has been shown to be useful in the treatment of acute lower respiratory tract infections. This study was performed to determine the distribution of ceftibuten in bronchial secretions from patients affected by the exacerbation of chronic bronchitis. Patients were treated with a single 400-mg oral dose of ceftibuten. Blood and bronchial-secretion samples were obtained just before, and at 0.5, 1, 2, 4, 8, 12, 16 and 24 h after dosing. Cells were separated from bronchial secretions by centrifugation. Ceftibuten in duplicate samples of both serum and bronchial secretion was quantified by HPLC. Ceftibuten reached peak levels 2 and 4 h after oral administration in serum and in bronchial secretions, respectively (18.12 +/- 2.13 and 9.19 +/- 3.1 mg/l, respectively). Falling curves after the peaks showed a monoexponential decay. The absorption was very rapid both in serum and bronchial secretions, but elimination was slower in bronchial secretions than in serum.
The in vitro efficacy of ceftriaxone plus amikacin combination against gram-positive and gram-negative bacteria, clinically isolated from patients affected by pneumonia in intensive care units, was compared to that of the 2 drugs used alone. The study was performed using a dynamic model in which the human kinetics of the drugs after intramuscular administration was simulated. The antibacterial activity was tested by determining the bacterial cell count (CFU/ml). Killing curves came out from plotting the log CFU/ml versus time. In the same way, ceftriaxone and amikacin concentrations were assayed by HPLC and fluorescence polarization immunoassay, respectively. The results show that ceftriaxone plus amikacin combination exert a high killing activity against all tested strains. The two antibiotics alone initially have a good killing activity but this is followed by bacterial regrowth for all tested isolates. This data supports the results of several clinical studies which have shown a good therapeutic efficacy of ceftriaxone plus amikacin combination in the treatment of severe infections caused by organisms intermediately sensitive to these drugs.
The clinical efficacies of 50 mg/kg.day miocamycin and 60 mg/kg.day amoxycillin were studied in 23 patients aged 3-11.5 years with presumed bacterial infection of the lower respiratory tract (bronchopneumonia and acute bronchitis). During the therapy, which continued for 10 days, non-specific immune function, represented by natural killer cell activity, was monitored by measurement of the rate of lysis induced on target K-562 51Cr-labelled tumour cells. The results confirmed the therapeutical efficacy of miocamycin and amoxycillin in the oral therapy of bronchopneumonia and acute bronchitis in paediatric patients. The natural killer cell activity of patients treated with miocamycin was increased on days 7 and 10 of therapy compared with baseline. This finding did not occur in patients treated with amoxycillin.
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