[Show abstract][Hide abstract] ABSTRACT: Multidrug-resistant (MDR) tuberculosis (TB) is a form of TB that is resistant to some of the first-line drugs used for the treatment of the disease. It is associated both with a higher incidence of treatment failures and of disease recurrence, as well as with higher mortality than forms of TB sensitive to first-line drugs. Levofloxacin (LFX) represents one of the few second-line drugs recently introduced in the therapeutic regimens for MDR TB. We report our experience concerning in vitro activity and clinical safety of LFX in long term second-line regimens for MDR TB. IN VITRO ACTIVITY ON MYCOBACTERIA: The in vitro activity of ciprofloxacin, ofloxacin and LFX was studied on 28 strains belonging to different species of Mycobacteria. In Dubos medium, LFX inhibited the growth of both library and MDR clinical Mycobacteria strains in a range of 0.25-1 mcg/ml. In International Union Tuberculosis Medium (IUTM) the minimum inhibitory concentrations (MIC) were slightly higher, but LFX activity was not affected by the higher complexity of the medium. CLINICAL EXPERIENCE: Four patients with MDR TB were treated with a second-line regimen comprising oral LFX 500 mg twice daily, for at least 9 months. Two isolates obtained from the patients reported here showed multi resistance to isoniazid and rifampin, one to rifampin and streptomycin and one to isoniazid and ethambutol. During therapy, no significant alteration of either liver function tests, blood tests or any other described side effect of the fluoroquinolone class was observed. The 3 patients with pulmonary MDR TB showed radiologic and clinical improvement. CONCLUSION: We confirm the higher in vitro activity of LFX compared to older fluoroquinolones. Furthermore, in a limited number of MDR TB patients, second-line regimens comprising LFX 500 mg b.i.d. administered in a range of 9-24 months were well tolerated and safe.
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo 03/2002; 57(1):39-43.
[Show abstract][Hide abstract] ABSTRACT: In a prospective multicentre open trial, hospitalised adult patients with acute lower respiratory tract infections, mainly pneumonia or bronchitis, were randomised to receive either isepamicin 8 or 15 mg/kg once daily depending on the severity of the infection or amikacin 7.5 mg/kg twice daily. Patients with infections known to be caused by Pseudomonas aeruginosa were to be given concomitant treatment with ceftazidime. In the intent-to-treat population, i.e. patients who received at least one dose randomised treatment, a clinical cure or improvement at the end of treatment was seen in 112/125 (90%) isepamicin patients and 55/60 (92%) amikacin patients. The corresponding rates for patients with a primary diagnosis of pneumonia were 45/52 (87%) and 25/28 (89%). Cure/improvement rates for patients with P. aeruginosa as the causative pathogen (34 of whom also received ceftazidime) were 28/30 (93%) and 16/18 (89%), respectively. In the efficacy population (patients who had a valid pretreatment culture and who met other evaluability criteria), total elimination (documented or presumed if infection had resolved) of target pathogens occurred in 54/63 (86%) of isepamicin patients and 25/30 (83%) of amikacin patients. P. aeruginosa, Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus were commonly isolated pathogens. Treatment-related adverse were mainly mild or moderate in severity and occurred in 10% of isepamicin patients and 13% of amikacin patients. Four patients (3 isepamicin and 1 amikacin) discontinued treatment because of severe adverse events and a further isepamicin patient withdrew because of a mild adverse event. Nephrotoxicity and ototoxicity occurred infrequently.
[Show abstract][Hide abstract] ABSTRACT: The study aim was to evaluate the activity of aztreonam on phagocytosis and intracellular killing of Staphylococcus aureus ATCC6538 by human alveolar macrophages. Drug concentrations of 1, 10, 25, 100 micrograms/ml were assayed in culture medium. Aztreonam induces dose-dependent phagocytosis up to 25 micrograms/ml concentrations; with a phagocytosis index (PIa) of 1.18 +/- 0.2 at 1 microgram/ml; of 1.27 +/- 0.2 at 10 micrograms/ml; of 1.42 +/- 0.3 at 25 micrograms/ml. No phagocytosis increase or inhibition, with unchanged cell viability compared to controls, is shown at 100 micrograms/ml aztreonam (PI 1.03 +/- 0.3). Intracellular killing acts in a similar way: the killing index (KIa) is 1.27 +/- 0.3 at 1 microgram/ml concentrations; 1.38 +/- 0.3 at 10 micrograms/ml; 1.61 +/- 0.4 at 25 micrograms/ml whereas at 100 micrograms/ml the KIa is 1.03 +/- 0.3. This study shows aztreonam's ability to stimulate macrophages' functional activity against a microorganism (S. aureus) which is not susceptible to its antibacterial activity.
[Show abstract][Hide abstract] ABSTRACT: The bronchoalveolar compartment can be easily investigated with BAL (bronchoalveolar lavage) before and after antiblastic therapy. We studied 50 patients affected by primary lung cancer, of whom 31 served as a control group and 19 were submitted to BAL after chemo- and/or radiotherapy. Data from BAL performed in an unaffected lung area show that antiblastic therapy can produce alterations in the terminal airways without clinical evidence. Chemotherapy causes a significant impairment of the alveolo-capillary barrier. Radiotherapy is able to affect lymphocytes, with a CD4/CD8 reduction. The concomitance of both therapies produces synergistic effects. Immunomodulant therapy with thymostimulin in otherwise untreated lung cancer patients seems able to modify alveolar lymphocyte number and subsets, but these are preliminary data which need further substantiation.
[Show abstract][Hide abstract] ABSTRACT: Twenty-three patients suffering from lower respiratory tract infections caused by Gram-negative germs were treated with aztreonam (AZT) administered according to two different regimens: 17 subjects (Group A) with 2 g i.v. every 12 h and 6 patients (Group B) with 4 g in 100 ml of saline every 24 hours. Group A included 8 cases of superinfected bronchiectasis, 8 purulent bronchitis and 1 gangrene caused by Gram-negative and anaerobic agents. Group B comprised 6 patients with severe bronchiectasis infection. Pseudomonas aeruginosa was isolated from the sputum in 10/23 cases. The treatment was performed for 10 days on the average. The local and systemic tolerability was good. Group B, with higher antibiotic sputum concentrations for at least 12 hours, attained a better response than Group A: with clinical cure in 100% vs 76% cured plus 18% improved patients; therapy lasted 9.5 days for Group B vs 10.8 days for Group A. Moreover, in 14 subjects affected by pulmonary interstitial diseases who underwent diagnostic broncho-alveolar lavage, we dosed AZT in lavage fluids about 1 hour after the injection of a 2 g dose (Group C: 8 cases) or a 4 g dose (Group D: 6 cases). In group D antibiotic concentrations were significantly higher (P less than 0.005) than group C, while all the parameters that usually define the intensity of the alveolar alterations were not significantly different. Therefore, aztreonam administration in a daily monodose seems able to assure higher and longer lasting concentrations at the site of infection.
[Show abstract][Hide abstract] ABSTRACT: We report the levels of concentration of ampicillin, dicloxacillin, and carbenicillin reached in the blood and in the expectoration following the administration of these drugs by rapid venous infusion, once every 24 h. The concentration of ampicillin in the blood serum varied from 150 to 180 micrograms/ml at the end of the infusion and from 30 to 3 micrograms/ml 4 afterwards and the dicloxacillin concentration from 150 to 120 micrograms/ml, and from 24 to 6 micrograms/ml. The concentration of ampicillin in purulent expectoration was 5-7 micrograms/ml and that of dicloxacillin 2.5-4 micrograms/ml. The concentration of carbenicillin in the plasma varied from 1,040 to 130 micrograms/ml, and in the expectoration it was around 15 micrograms/ml. Several cases of acute and chronic lung and bronchial diseases caused by bacteria have been treated by means of venous infusion once every 24 h and results were excellent.
[Show abstract][Hide abstract] ABSTRACT: We report the levels of concentration of ampicillin, dicloxacillin and carbenicillin reached in the blood and in the expectoration following the administration of these drugs by rapid venous infusion, once every 24 h. The concentration of ampicillin in the blood serum varied from 150 to 180μg/ml at the end of the infusion and from 30 to 3 μg/ml 4 afterwards and the dicloxacillin concentration from 150 to 120 μg/ml, and from 24 to 6 μg/ml. The concentration of ampicillin in purulent expectoration was 5–7 μg/ml and that of dicloxacillin 2.5–4 μg/ml. The concentration of carbenicillin in the plasma varied from 1,040 to 130 μg/ml, and in the expectoration it was around 15 μg/ml. Several cases of acute and chronic lung and bronchial diseases caused by bacteria have been treated by means of venous infusion once every 24 h and results were excellent.
[Show abstract][Hide abstract] ABSTRACT: Compelling evidence suggests that co-trimoxazole prophylaxis reduces mortality in HIV-infected patients, although it is unclear whether these effects are directly related to antimicrobial activities. We evaluated in vitro phagocytosis and killing of Staphylococcus aureus in alveolar macrophages (AM) obtained from AIDS patients who smoke, treated (n=19) or not treated (n=13) with co-trimoxazole, as compared to non-HIV-infected healthy smokers (n=15). Phagocytosis and killing of Staphylococcus aureus by AM obtained from non-co-trimoxazole treated AIDS patients were significantly lower compared to non-HIV-infected healthy smokers. In contrast, AIDS patients treated with co-trimoxazole prophylaxis showed phagocytosis and killing levels similar to those of healthy controls. These results might help to clarify the observed positive effect of co-trimoxazole on survival in HIV-infected patients.
Journal of biological regulators and homeostatic agents 25(3):461-4. · 5.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: At present the increased incidence of infections with mycobacteria other than tuberculosis and leprae bacilli seems to be correlated with several causes: improved diagnostic techniques, prolonged life expectancy, immunodepression. Rational chemotherapy depends upon the identification of the etiologic mycobacterium and the determination of its drug susceptibility. Besides the "classic" treatment with 3 or 4 antituberculous and, sometimes, nonantituberculous chemotherapics, clinical trials are in progress to assess the effectiveness of new molecules: rifamycin derivatives, fluorinated quinolones, anti-lepromatous drugs, and the latest macrolides. Yet at present, national and international data do not permit to define a standard treatment for every mycobacteriosis; in fact, the drug resistance is high and varies not only between different strains but also within the same strain; moreover, there are discrepancies between in vitro and in vivo results. When possible, appropriated surgery for circumscribed disease is recommended.
[Show abstract][Hide abstract] ABSTRACT: Tuberculosis appears to be a diagnostic challenge and an important therapeutical problem in industrialized and in developing countries, where most infections occur. Besides several rifamycin derivatives, new molecules (fluorinated quinolones, macrolides, beta-lactam antibiotics) are being explored in the face of increasing bacterial-resistance with the aim of improving the efficacy and safety of anti-tuberculous drugs, shortening the period of treatment or allowing intermittent regimens. At present, in severe forms of the disease three or more of the available anti-tuberculous agents must be administered simultaneously for at least 3-4 months and two for the following 6-7 months. Nevertheless, a variety of highly effective 6 months regimens are currently used for the treatment of less severe tuberculosis.