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Biomedical subjects

R Guerciolini

Publications and source records attributed to R Guerciolini.

34 records · Page 2Linked to original sources

Treatment of infections by staphylococci and other gram-positive bacteria with teicoplanin: an open study.

Teicoplanin, 200-400 mg (3-6 mg/kg) daily iv or im, was used to treat 71 episodes of infection. The average duration of treatment was 22 days. The 64 evaluable episodes comprised 24 skin/soft tissue, 20 osteoarticular, ten urinary tract and one ventriculo-atrial shunt infections; one case of primary bacteraemia, three of endocarditis, two of pneumonia and three of pleural empyema. Fifty-five episodes were treated with teicoplanin monotherapy and nine with teicoplanin in association to other antibiotics. Overall 61% (39/64) of the evaluable infections were cured, 25% (16/64) improved and 14% (9/64) failed. Staphylococcus aureus was the most frequent pathogen, with 46 isolates. Infections by both methicillin-sensitive and resistant Staph. aureus strains showed favourable clinical and microbiological responses to teicoplanin. Side effects were observed in eight of the 64 episodes (12.5%). Bronchospasm was observed in two other cases at the beginning of therapy and the antibiotic administration was discontinued. Teicoplanin is an effective and well tolerated antibiotic for infections by Gram-positive bacteria, and it is effective against methicillin-resistant staphylococci.

Adolescent↗

Effects of the new glycopeptide antibiotic teicoplanin on platelet function and blood coagulation.

Teicoplanin, a new glycopeptide antibiotic, is structurally related to ristocetin, an antibiotic known to induce human platelet agglutination and, thus, thrombocytopenia and thromboembolic side effects. The aim of this study was to evaluate the effects of teicoplanin on platelet function in vitro and ex vivo and on blood coagulation ex vivo. In the in vitro studies, spontaneous platelet aggregation; platelet aggregation induced by ADP, collagen, and ristocetin; and the release of beta-thromboglobulin from platelets were assessed. Platelets from healthy subjects were incubated with teicoplanin at final concentrations of 100, 1,500, 5,000, and 10,000 micrograms/ml. The maximal achievable concentration with therapeutic doses is 100 micrograms/ml. When compared with saline, teicoplanin at concentrations of 100 and 1,500 micrograms/ml had no effect on platelet function, but at concentrations of 5,000 and 10,000 micrograms/ml, it induced greater spontaneous platelet aggregation (P less than 0.01) and inhibited platelet aggregation induced by ADP, collagen, and ristocetin (P less than 0.01). Teicoplanin at concentrations of 100, 1,500, and 5,000 micrograms/ml did not induce the release of beta-thromboglobulin, in contrast to teicoplanin at a concentration of 10,000 micrograms/ml and ristocetin at a concentration of 1.5 mg/ml (P less than 0.01). In the ex vivo studies, platelet count, bleeding time, plasma beta-thromboglobulin, platelet aggregation induced by ADP, ristocetin, and epinephrine, activated partial thromboplastin time, prothrombin time, thrombin clotting time, and serum fibrinogen degradation products were evaluated at days 0, 3, and 6 and at 72 h after the end of therapy. All subjects completed the study without evidence of side effects. When compared with the pretreatment values, none of the values from these assays showed a significant change at any time during and after treatment. We concluded that platelet function and blood coagulation are not affected by therapeutic concentrations of teicoplanin and that in vitro platelet function is affected only by concentrations of teicoplanin far in excess of those that are clinically achievable.

Adult↗

Prospective randomized clinical trial of teicoplanin for empiric combined antibiotic therapy in febrile, granulocytopenic acute leukemia patients.

The increasing prevalence of bacteremia caused by gram-positive bacteria in granulocytopenic acute leukemia patients prompted us to evaluate, in a prospective randomized trial, the role of teicoplanin, a new glycopeptide antibiotic, when it was added to amikacin plus ceftazidime, as an empiric therapy of fever in these patients. Of 47 evaluable episodes, 22 were treated with the teicoplanin regimen and 25 were treated with the combination of amikacin and ceftazidime. The overall response to therapy of patients treated with teicoplanin was slightly better (82% improvement) than that obtained with amikacin plus ceftazidime (52%). The response rate of patients with gram-positive bacteremias was 80% (4 of 5) to the regimen that included teicoplanin; 25% (1 of 4) of the patients treated with amikacin plus ceftazidime responded to treatment; and for patients with gram-negative bacteremias, the response rates were, respectively, 100% (4 of 4) and 70% (7 of 10). The better results obtained with amikacin-ceftazidime-teicoplanin treatment were most evident in patients with profound (less than 100/mm3) and persistent neutropenia (83 versus 30% improvement). Furthermore, a good response rate of patients with gram-positive bacteremias (seven of eight; 87% improvement) was achieved in a small group of bone marrow transplant patients who were all treated with amikacin-ceftazidime-teicoplanin. No severe side effects were documented in any patient. Teicoplanin, as a drug administered as a single daily dose, seems to be a safe and useful anti-gram-positive agent when used in combination with amikacin-ceftazidime as an empiric therapy of febrile episodes in granulocytopenic acute leukemia patients.

Acute Disease↗

Effects of the monobactam antibiotic aztreonam on platelet function and blood coagulation.

The effects of the new monobactam antibiotic aztreonam on platelet function and blood coagulation were evaluated both in vitro and ex vivo. In the in vitro studies carried out on platelets from 6 healthy volunteers, therapeutic concentrations of aztreonam had no effect on platelet function. Aztreonam inhibited platelet aggregation only at concentrations far in excess of those clinically achievable. In the ex vivo studies carried out in 11 patients with aztreonam-sensitive infections, aztreonam, 1 g t.i.d. intravenously, did not produce any effect on platelet function and blood coagulation. We conclude that therapeutic doses of aztreonam appear not to affect haemostasis.

Adenosine Diphosphate↗

[Immuno-allergic reactions to cotrimoxazole in a hospital population].

By a study of 87 oncologic hospitalized patients, affected by serious infectious complications and treated with high-dose antibiotic therapy including co-trimoxazole, the authors evaluate the allergic and immunologic reactions to the drug on clinical and serological basis and try to outline the pathogenic implicated mechanisms.

Anti-Infective Agents↗

Cephalosporin-induced hypoprothrombinemia: is the N-methylthiotetrazole side chain the culprit?

The reported high incidence of vitamin-K-reversible hypoprothrombinemia associated with the new beta-lactamase-stable cephalosporins prompted us to evaluate the effect on hemostasis of three cephalosporins (cefamandole, ceftriaxone, and ceftazidime) in 30 patients with serious infections. Cefamandole and ceftriaxone, both containing a sulfhydryl group, induced a significant and similar prolongation of prothrombin time and decrease in factor VII activity. Ceftazidime, in contrast, had no effect on these two parameters.

Azoles↗

Immunological studies in patients with alcoholic liver disease: evidence for the in vivo activation of helper T cells and of the monocyte-macrophage system.

Immunologic parameters were evaluated in 22 patients with alcoholic liver disease (ALD). Patients with ALD had increased levels of circulating immune complexes (CIC) and serum immunoglobulins, particularly IgA. The classical complement pathway was preferentially activated in CIC-positive patients. There was no increase in total lymphocyte or total T lymphocyte counts, but a significant rise in both the helper/inducer population (OKT4) and helper/suppressor cell ratio (T4/T8) was noted. The presence of interleukin-2 receptors and HLA-DC/DS and HLA-DR antigens suggested in vivo activation of ALD patients' T cells. The rate of differentiation of B cells to plasma cells was high in both pokeweed mitogen-stimulated and unstimulated cultures of ALD patients' B cells, whereas plasma cell generation doubled when patient T lymphocytes were added to enriched normal B cells. The above data support a role for activated helper (T4+) T cells in the immune response initiated by alcoholic hepatitis. Serum angiotensin-converting enzyme levels and lysozyme levels were increased in ALD patients, and cultured adherent mononuclear cells from ALD patients secreted more lysozyme in vitro than normal cells, suggesting the presence of an activated monocyte-macrophage system in ALD.

Adult↗

Norfloxacin versus pipemidic acid in complicated urinary tract infections due to susceptible pathogens: a comparative clinical trial.

Norfloxacin (NOR) was compared to pipemidic acid (PA) in complicated urinary tract infections (UTIs) caused by pathogens susceptible to both agents to evaluate the antibacterial activity of the new 4-quinolone derivative. Sixty-five patients were randomly allocated to receive NOR or PA, 400 mg bid for 7 days, and the results evaluated for treatment efficacy at 5 weeks after completion of therapy. Overall microbiological cure was significantly greater in NOR-treated patients, as 19 of 26 were cured (73%), compared to only 16 of 39 (41%) in the PA group (p less than 0.05). Failures and relapses, considered together, were significantly (p less than 0.05) less frequent in patients treated with NOR (4/26) than in those receiving PA (18/39). Clinical response was strictly related to microbiological outcome: NOR had a broader antibacterial spectrum than PA and in this study seemed to be more efficacious in the treatment of complicated UTIs caused only by bacteria susceptible to both agents. This may be related to greater antibacterial activity and/or tissue penetration by NOR, which is thus to be preferred, according to the results of our study, in the treatment of complicated UTIs.

Clinical Trials as Topic↗

Anaemia and agranulocytosis associated with ticlopidine therapy.

Although ticlopidine has proven anti-aggregant properties, complications due to side-effects, particularly to the haemopoietic system, have been noted since it was recently launched on the market. We here report a case of bicytopenia (anaemia and granulocytopenia) associated with ticlopidine treatment.

Agranulocytosis↗

Empiric antimicrobial therapy in febrile granulocytopenic patients. Randomized prospective comparison of amikacin plus piperacillin with or without parenteral trimethoprim/sulphamethoxazole.

In a prospective randomized trial parenteral trimethoprim/sulphamethoxazole was added to amikacin plus piperacillin in order to compare triple-drug antibiotic combination with a standard regimen as empiric therapy of fever in patients with granulocytopenia. One hundred and sixty-one episodes were evaluated; 74 episodes with amikacin plus piperacillin and 87 episodes with amikacin plus piperacillin plus trimethoprim/sulphamethoxazole. The overall response to therapy (63% vs. 84%) as well as the response of microbiologically documented infections (60% vs. 82%) was significantly better in patients treated with the triple-drug combination (p less than 0.05). However, no statistically significant differences in response to antibiotics at different infection sites or with regard to any single pathogen was found between the two groups. Trimethoprim/sulphamethoxazole seemed to be responsible for additional toxicity (nausea and vomiting) when added to amikacin plus piperacillin, but these side-effects were clearly related to the rate of infusion of trimethoprim/sulphamethoxazole. The findings of this study support the use of a three-drug versus a two-drug combination as empiric antibiotic regimen in febrile granulocytopenic patients.

Adolescent↗

The interaction of the lipase inhibitor orlistat with ethanol in healthy volunteers.

OBJECTIVES: The primary objective was to investigate the possible interference of ethanol on the orlistat effect on inhibition of dietary fat absorption and the possible interference of orlistat on the pharmacokinetics of ethanol. Secondary objectives were to assess the tolerability during concomitant dosing of orlistat and ethanol and to determine the ethanol effect on plasma levels of orlistat. METHODS: This was a double-blind, placebo-controlled, parallel, randomized study performed in 30 (three parallel groups of ten subjects each) healthy normal weight male subjects between the ages of 20 and 30 years. A 5-day run-in period to accustom subjects to a standardized diet of 2500 kcal/day (30% fat) and to establish baseline fecal fat excretion was followed by a 6-day treatment period. Subjects were randomly assigned to one of three treatment groups (A = orlistat 120 mg t.i.d. and ethanol placebo, B = orlistat 120 mg t.i.d. and 40 g ethanol qd on days -1 and 6, and 40 g bid on days 1-5, and C = orlistat placebo tid and 40 g ethanol qd on days -1 and 6, and 40 g b.i.d. on days 1 5). Serial blood samples were collected for determination of ethanol serum concentrations at specified times over 5 h after each dose of ethanol on days -1 and 6, and for determination of orlistat plasma concentrations on days 1, 3, 5, and 6. Feces were collected quantitatively on days -5 through 8 for analysis of fecal fat. RESULTS: The means of baseline-corrected fecal fat excretion values were comparable: 23.7 g for group A (orlistat) and 22.7 g for group B (orlistat and ethanol). No significant difference was found regarding ethanol pharmacokinetic parameters between treatments with orlistat and placebo. No apparent differences existed between the number of plasma samples with measurable orlistat concentrations in groups A and B. CONCLUSION: Concomitant ingestion of social amounts of ethanol did not alter the inhibitory effect of orlistat on dietary fat absorption during short-term treatment (6 days) with orlistat. Short-term treatment with orlistat had no significant influence on ethanol pharmacokinetics.

Adult↗