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Biomedical subjects

S Dugnani

Publications and source records attributed to S Dugnani.

At least 19 recordsLinked to original sources
PubMed1999

Interpretation of middle ear fluid concentrations of antibiotics: comparison between ceftibuten, cefixime and azithromycin.

AIMS: The aim of this study was to determine the potential influence of variables such as the cell content in the fluid, and serum levels, on the concentrations of ceftibuten, cefixime and azithromycin in the middle ear fluid of patients suffering from acute otitis media. METHODS: This randomized, open study compared the penetration of ceftibuten (9 mg kg(-1) 18 patients), cefixime (8 mg kg(-1), 16 patients) and azithromycin (10 mg kg(-1) 16 patients) into the intracellular and extracellular compartments of middle ear fluid of 50 paediatric patients (aged 8-14 years) with acute otitis media. Middle ear fluid was extracted by tympanocentesis 4, 12 and 24 h after dosing and divided into two fractions: with cells (as collected) (C+) and cell-free (C-). Antibiotics were assayed in C+ and C- samples by h.p.l.c. RESULTS: Ceftibuten achieved greater penetration into middle ear fluid than cefixime and azithromycin. Higher concentrations of ceftibuten (CTB) and cefixime (CFX) were found in the C- fraction (CTB: 4h 13.3+/-1.86; 12h 4.7+/-1.18; 24h 0.5+/-0.2. CFX: 4h 3.2+/-1.4; 12h 1.5+/-0.5; 24h>(0.1 mgl(-1)) than in the C+ fraction (CTB:4 h 8.4+/-4.3; 12 h 2.88+/-1.19; 24 h 0.3+/-0.27. CFX: 4 h 1.2+/-0.6; 12 h 0.8+/-0.2; 24 h>0.1 mg l(-1)) at the each time point, while the opposite was true for azithromycin (C-: 4 h 0.11+/-0.04; 12 h 0.12+/-0.08; 24 h 0.23+/-0.12. C+: 4 h 0.38+/-0.24; 12 h 0.9+/-0.03; 24 h 1.05+/-0.3 mg l(-1)). CONCLUSIONS: This study demonstrates that the penetration of antibiotics into the middle ear fluid is influenced by its serum concentrations as well as by the cell content in the fluid. Ceftibuten achieved higher middle ear fluid concentrations than cefixime in C+ and C- fractions at all time points. Both ceftibuten and cefixime concentrations are negatively influenced by the cell content in the fluid. In contrast the concentration of azithromycin to the middle ear fluid is positively influenced by the cell content in the fluid.

Acute Disease↗
PubMed1999

Morphological variation analysis of the repeatability of soccer offensive schemes.

A landmark-based statistical method, morphological variation analysis, for the quantification of the repeatability in the arrangement of body segments during the execution of sport actions has recently been developed. A two-dimensional shape is produced and its morphology is studied. The method was used to measure the within-team variability of the relative positions of players during the execution of offensive schemes in soccer. Two junior soccer teams of different technical abilities (semi-professional vs. amateur), each playing two standardized offensive schemes of different difficulty (easier: throw-in; more difficult: wing attack) were filmed. Each scheme was repeated 25 (semi-professionals) or 10 (amateurs) times. For each repetition, the position of the players in a single significant frame was analysed using morphological variation analysis. The reproducibility of both schemes was higher among the semi-professionals than among the amateurs (two-way analysis of variance, P<0.005). The repeatability of the players' relative positions was related to the difficulty of the scheme and the technical level of the team. Among the amateurs, the throw-in was more reproducible than the wing attack (Student's t-test, P<0.005). The method not only allows the quantification of collective (team) coordination, but also the separation of the influence of individual players.

Adolescent↗
PubMed1998

Influence of protein binding on the pharmacodynamics of ceftazidime or ceftriaxone against gram-positive and gram-negative bacteria in an in vitro infection model.

The antibacterial activity of ceftriaxone and ceftazidime against Gram-positive and Gram-negative bacteria, clinically isolated from patients hospitalized in intensive care unit, was compared in vitro. The study was performed using a dynamic model in which the human kinetics of the drugs after i.m. administration were simulated. The antibacterial activity was tested by determining viable colony forming units (CFU) of bacteria/ml. Kill curves were constructed by plotting the log CFU/ml versus time. Simultaneously with CFU detection, ceftriaxone and ceftazidime concentrations were assayed by HPLC. The results obtained show that ceftriaxone and ceftazidime exert the same killing activity against the highly sensitive strains tested. Against the less sensitive strains, both drugs have initial good killing activity followed by bacterial regrowth using ceftriaxone while no regrowth was observed using ceftazidime. These data indicate that both ceftazidime and ceftriaxone exhibit primarily time-dependent bacterial killing. Moreover, only unbound drug appears to be effective, so only free drug should be considered in the pharmacokinetic-pharmacodynamic interaction.

Ceftazidime↗
PubMed1996

Ceftibuten concentrations in human tonsillar tissue.

In a study designed to determine ceftibuten concentrations in tonsillar tissue, subjects scheduled to undergo tonsillectomy were administered 400 mg of ceftibuten in a single oral dose. Between 2 and 24 h after the dose was given, tonsillar tissue samples were taken during surgery and assayed for ceftibuten. Mean concentrations in tonsillar tissue 4.4 h and 24.6 h after the 400 mg dose were 5.3 +/- 2.7 and 0.3 +/- mg/g, respectively. Concurrent mean serum concentrations were 7.42 +/- 1.66 and 0.15 +/- 0.13 mg/ml, respectively. The apparent half-life of drug in the tissue was 5.3 h. The presence of high ceftibuten concentrations in tonsillar tissue suggests that a once-daily regimen may be effective in treating tonsillitis and pharyngitis.

Adolescent↗
PubMed1995

Once-a-day cephalosporins: reality or myth?

The factors that may influence the pharmacodynamics of antimicrobial agents against microorganisms at the site of infection must be considered before using once-daily antimicrobial chemotherapy in clinical practice. From a pharmacokinetic point of view, we can establish which antibiotic is suitable for once-daily therapy. For aminoglycosides and quinolones, where the bacterial killing is rapid and dose dependent, and there is a post-antibiotic effect (PAE), the pharmacodynamic objective is to maintain the tissue levels way above the minimum inhibitory concentration (MIC) for a short period. This can be achieved by giving single bolus doses at long time intervals. With beta-lactam antibiotics, however, which have a slow time-dependent antibacterial effect and do not display a PAE, the aim is to keep the antibiotic concentration above the MIC for the duration of therapy.

Cephalosporins↗
PubMed1993

Immunostimulation by clarithromycin in healthy volunteers and chronic bronchitis patients.

The immune response to infecting pathogens may be either enhanced or depressed by therapeutic antimicrobial agents. Some macrolides have been shown to enhance aspects of the immune response. This study evaluates the effects of clarithromycin, a new broad-spectrum macrolide antibiotic, on leukocyte function in both healthy volunteers (single 500 mg dose) and chronic bronchitis patients (500 mg b.i.d.) by testing blood samples collected at baseline and at 2, 4, 8 and 12 hours after clarithromycin administration. Clarithromycin did not affect leukocyte chemotaxis but did significantly increase (P < 0.01) phagocytosis (both frequency and index), intracellular killing and natural killer activity, in healthy volunteers. In patients, clarithromycin enhanced phagocytosis frequency, index and intracellular killing. Clarithromycin appears to enhance the human immune response; the mechanism, pharmacodynamics, and clinical significance of this enhancement remain unknown.

Adjuvants, Immunologic↗
PubMed1993

Brodimoprim concentrations in bronchial mucosa, bronchial secretions and middle ear effusions.

Brodimoprim, a structural analogue of trimethoprim, is a long acting broad spectrum antibacterial agent characterized by a good pharmacokinetic profile, allowing once daily (OD) administration. The aim of this study was to investigate the penetration of brodimoprim into bronchial mucosa, bronchial secretion and middle ear effusion, in order to evaluate the efficacy of the antibiotic in respiratory tract infections. The study was performed in patients affected by chronic bronchitis having to undergo diagnostic bronchoscopy (n = 26), in patients affected by exacerbation of chronic bronchitis with purulent or mucopurulent secretions (n = 10), and in patients affected by otitis media with eardrum perforation (n = 28). Patients were orally treated with 400 mg of brodimoprim (single dose). Samples of serum, bronchial mucosa, bronchial secretion and middle ear effusion were collected in the separate series of patients above mentioned, at different times after drug administration. Brodimoprim determinations were performed by a microbiological method using Bacillus subtilis ATCC 6633 as test microorganism. Brodimoprim reached the highest concentration in serum 4 h after administration and was still detectable at 24th hour. In bronchial mucosa and in bronchial secretion the peaks were reached at 8th hour (9.7 +/- 5.3 mg/kg and 4.57 +/- 1 mg/l respectively) while in middle car effusion were reached at 4th hour (4.8 +/- 2.5 mg/l). The drug was still detectable at antibacterial concentrations, both in infected fluids and in tissue samples, 24 hours after administration (4.3 +/- 1.8 mg/kg in bronchial mucosa; 3.5 +/- 0.66 mg/l in bronchial secretions; 3 +/- 0.6 mg/l in middle ear effusion).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Pharmacokinetics of tenoxicam at different dosage regimes.

Tenoxicam, a non-steroid anti-inflammatory of the oxicam type, has a molecular structure similar to that of piroxicam, but is more active and better tolerated. Several studies demonstrated that tenoxicam is a potent analgesic. It is completely absorbed after oral and intramuscular administration and slowly eliminated, the long half-life in tissues consenting once-daily administration. In the present study the pharmacokinetics of tenoxicam have been investigated during repeated parenteral administration, with or without loading dose, in order to establish the dose regime that produces constant tissue concentrations over time. Thirty-six patients of both sexes, suffering from acute pain due to arthritis of the spine, were enrolled in the study and divided into three equal groups. The first group was given 40 mg tenoxicam per day (single i.m. injection) for 2 days followed by 20 mg (single i.m. injection) for 10 days. The second group received 20 mg i.m. once a day for 12 days. The third group received 20 mg i.m. twice a day for two days followed by single 20 mg i.m. injections on the following days. Blood was sampled at 0, 0.5, 1,2,4,6,8,12,16 and 24 hours and at 3,5,7,9 and 12 days. Tenoxicam levels in the samples were assayed by an HPLC method. The results showed that single 40 mg loading doses for 2 days, followed by once-daily 20 mg maintenance administration, established the requisite steady-state tissue concentrations of tenoxicam after the second administration. Tenoxicam was very well tolerated in all three groups.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1991

The diffusion of clarithromycin and roxithromycin into nasal mucosa, tonsil and lung in humans.

The diffusion of clarithromycin and roxithromycin into respiratory tract tissues was studied in 174 adult patients undergoing surgery. Patients received clarithromycin 250 mg orally (500 mg in the case of lung tissue), or roxithromycin 150 mg orally, both given every 12 h, for three days with the last dose administered at different times before surgery. Clarithromycin reached peak tissue levels 4 h after administration and achieved mean peak concentrations of 8.32 mg/kg +/- 2.57 in nasal mucosa, 6.47 mg/kg +/- 2.8 in tonsil, and 17.47 mg/kg +/- 3.29 in lung tissue. Roxithromycin reached peak tissue levels between 4 and 6 h after administration, achieving mean peak concentrations of 1.78 mg/kg +/- 0.73 in nasal mucosa, 2.2 mg/kg +/- 1.21 in tonsil, and 2.14 mg/kg +/- 0.87 in lung tissue. Clarithromycin and roxithromycin demonstrated contrasting pharmacokinetic behaviour. Roxithromycin was characterized by high concentrations in serum and low concentrations in tissues. Clarithromycin on the other hand, is characterized by therapeutic serum concentrations and high tissue concentrations.

Administration, Oral↗
PubMed1990

Pharmacokinetics and tissue distribution of amoxicillin plus clavulanic acid after oral administration in man.

Augmentin (875 amoxicillin and 125 mg potassium clavulanate) was administered orally to patients with chronic bronchitis. Concentrations of amoxicillin and clavulanic acid were measured in serum, sputum and urine. Peak serum levels for amoxicillin of 11.23 +/- 2.61 micrograms/ml were observed at 2 hours and for clavulanic acid of 2.55 +/- 0.54 micrograms/ml at 1 hour. After 9 hours, 50% of the amoxicillin and 39% of the clavulanic acid had been renally excreted. The peak sputum concentration of amoxicillin was 1.31 +/- 0.42 micrograms/ml at 4 hours and of clavulanate was 0.79 +/- 0.23 micrograms/ml at 2 hours. Patients awaiting surgery received an oral dose of augmentin as above. Samples of lung, tonsil, middle ear mucosa and prostate were obtained and tissue concentrations of both compounds measured. Peak levels of amoxicillin ranged from 0.87 micrograms/g (tonsil) to 2.56 micrograms/g (lung) and of clavulanic acid from 0.20 micrograms/g (prostate) to 0.56 micrograms/g (lung) between 3 and 4 hours after dosing.

Administration, Oral↗
PubMed1990

Immunomodulatory effects of two extracts of Panax ginseng C.A. Meyer.

The effect of Panax ginseng extracts on cell-mediated immune functions in man has been investigated. Three groups, each consisting of twenty healthy volunteers, were treated under conditions of double blindness with capsules containing lactose (Control Group B), with capsules containing 100 mg of aqueous extract of the drug (Group A), and with capsules containing 100 mg of standardized extract of the drug (Group C). All the patients took one capsule every 12 h for 8 weeks. Blood samples were withdrawn before beginning the treatment, at the fourth week and at the eighth week. The immune parameters examined were the following: chemotaxis of PMNs, phagocytosis index (PHI), phagocytosis fraction (PHF), intracellular killing, total lymphocytes (T3), T helper (T4) subset, suppressor cells (T8) subset, blastogenesis of circulating lymphocytes, natural killer-cell activity (NK). Chemotaxis proved to be enhanced (p less than 0.05) already at the fourth week in Group A as well as in Group C; the increase became even more marked (p less than 0.001) at the eight week in subjects belonging to Group C. PHI and PHF proved to be enhanced (p less than 0.05) at the eighth week in subjects of Group A; these increases were found to be higher in subjects of Group C (p less than 0.001) already starting at the fourth week. Intracellular killing was shown to be significantly increased (p less than 0.05) already at the fourth week in Groups A and C; the increase becomes highly significant in both groups (p less than 0.001) at the eighth week; however, a significant increase (p less than 0.05) at the eighth week was also noticed in the placebo group (Group B).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Miokamycin and leukocyte activity in man.

The effects of miokamycin on the immune system were studied in healthy volunteers by means of the following assays: phagocytosis, intracellular killing and natural killer activity. The tests were performed before, 2 and 6 h after oral administration of 600 mg of miokamycin. The findings suggest that miokamycin stimulates phagocytosis and intracellular killing. These effects could be clearly shown 2 h after drug intake and disappeared at the 6th hour. On the contrary, the natural killer activity was not significantly stimulated by miokamycin.

Adult↗
PubMed1987

Effects of lincomycin on the immune system.

The effects of lincomycin on the immune system were studied on patients suffering from chronic bronchitis by means of phagocytosis, chemotaxis and natural-killer tests. The tests were performed before and 2, 4, 8, 12 and 24 h after administration of 600 mg lincomycin i.m. in a single dose. The results indicate that lincomycin stimulates phagocytosis, expressed as enhanced superoxide production (O2-), chemotaxis and the activity of natural killer cells, measured on the basis of their ability to perform a lysis on the K562 tumoral target labelled with 51Cr. The stimulating effects on chemotaxis appear already 2 h after the administration of the drug, while the same effect on phagocytosis and natural-killer activity occurs after 4 h. The maximal stimulating activity on all three parameters can be shown at 8 h and disappears at 24 h.

Adult↗
PubMedDate not supplied

In vitro comparative dynamics of modified-release clarithromycin and of azithromycin.

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.

Anti-Bacterial Agents↗
PubMedDate not supplied

A new model examining intracellular and extracellular activity of amoxicillin, azithromycin, and clarithromycin in infected cells.

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.

Amoxicillin↗
PubMedDate not supplied

Effect of antibiotics on Bordetella pertussis adhering activity: hypothesis regarding mechanism of action.

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.

Amoxicillin↗