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Biomedical subjects

A Marchese

Publications and source records attributed to A Marchese.

99 records · Page 6Linked to original sources

In vitro activity of rifaximin, metronidazole and vancomycin against Clostridium difficile and the rate of selection of spontaneously resistant mutants against representative anaerobic and aerobic bacteria, including ammonia-producing species.

BACKGROUND: Rifaximin is a rifamycin derivative characterized by a wide antibacterial activity. This drug is neither absorbed by the gastrointestinal tract nor inactivated by gastric juices, and exerts its action entirely within the intestinal lumen. METHODS: In this study, the activity of this antibiotic was compared with that of metronidazole and vancomycin against 93 Clostridium difficile isolates. The rate of emergence of bacteria spontaneously resistant to the new compound was also evaluated in relation to representative gram-positive and gram-negative strains. In terms of MIC(50) values, rifaximin showed an intrinsic activity superior to that of the other agents. The emergence of spontaneously resistant strains was assessed with 46 aerobic (staphylococci, enterococci, Proteus spp., Citrobacter freundii, Providencia rettgeri, enteropathogenic, enteroinvasive, enterotoxigenic and entero- hemorrhagic Escherichia coli, and Salmonella enteritidis) and anaerobic (Clostridium spp., Bacteroides spp., Fusobacterium nucleatum and Peptococcus spp.) pathogens, most of them also ammonium producers. Two different methods, broth and agar dilution, were employed. RESULTS: When liquid medium was employed, bacteria capable of sustained growth in 100 microg/ml of rifaximin were obtained after 2-5 transfers with gram-positive aerobic cocci, 2-3 transfers with gram-negative aerobic strains and 2-5 transfers with anaerobic species. At the highest dose used with the agar dilution method (8 x MIC), the frequency of emergence of spontaneously resistant mutants ranged from <1 x 10(-9) to 1.6 x 10(-8) with gram-positive aerobic and anaerobic cocci, while with aerobic and anaerobic gram-negative bacteria, this value ranged from <1 x 10(-9) to 1.7 x 10(-7). C. difficile showed a particularly low incidence of spontaneously resistant mutants (<1 x 10(-9)). The low incidence of resistant subpopulations selected by levels of 8 x MIC of rifaximin suggests that the high levels of the drug which were reached in the gastrointestinal lumen may further prevent the selection of mutants. CONCLUSION: The low toxicity, broad antibacterial activity and very poor absorption from the gastrointestinal tract of rifaximin suggest a potential therapeutic use for this drug in gastrointestinal diseases, as well as in the management of patients with cirrhosis and chronic portal-systemic encephalopathy.

Ammonia↗

Evaluation of spontaneous contamination of ocular medications.

BACKGROUND: In order to evaluate whether single-dose ophthalmic preparations in 0.5-ml containers can safely be used within 24 h after the first opening, eigth different sterile ocular medications containing timolol, jaluronic acid, diclofenac, ketotifen, pilocarpine, formocortal, formocortal-gentamycin, and tetryzoline-feniramine (Farmigea, Italy) were opened and tested for spontaneous bacterial contamination after exposure to air. METHODS: Samples (10 microl) were collected from exposed ophthalmic preparations after 0, 2, 4, 8 and 24 h. RESULTS: No viable microorganisms were detected during and at the end of the evaluation period. In order to assess whether the resident or pathogenic ocular bacterial population due to repeated handling might contaminate the medications, about 10(5) cells of different species (Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus pneumoniae, Streptococcus spp., Corynebacterium spp., Pseudomonas aeruginosa, Neisseria spp., Acinetobacter spp., Haemophilus influenzae, Escherichia coli and Candida albicans) were added to the containers and incubated at 37 degrees C or at room temperature. Samples were collected and the number of viable bacteria was estimated. The antibacterial effect of the ophthalmic compounds varied depending on the species considered. Tetryzoline-feniramine, pilocarpine, ketotifen and formocortal-gentamycin exhibited a frank bactericidal activity (<100 survivors after 18-24 h of exposure) against the great majority of the species tested. CONCLUSION: These results indicate that the risk of spontaneous contamination of ophthalmic preparations after their first opening is low, and that all preparations tested exhibit an aspecific antibacterial activity. As a consequence, the safe usage of these ocular medications could be extended from the recommended 3 h to at least 24 h after the first usage.

Administration, Topical↗

Bactericidal activity, morphological alterations, and synergistic interactions of rufloxacin, a new fluoroquinolone, alone and in combination with its N-desmethylate D derivative (MF 922).

The in vitro activity of rufloxacin, alone and in combination with its metabolite (MF 922) against common respiratory and urinary tract pathogens and anaerobes was assessed. No synergistic interaction between rufloxacin and MF 922 was observed by the checkerboard technique against aerobic bacteria. When the time-kill system was employed, 24 synergistic interactions were noted out of 30 tests performed (80%), of which 14 (100%) were with Enterobacteriaceae isolates, 2 with Moraxella catarrhalis (50%), 4 with Haemophilus influenzae (100%), 2 with Staphylococcus aureus (50%) and 2 with Streptococcus pneumoniae and Streptococcus pyogenes (50%). Synergism was found with all Bacteroides fragilis irrespectively of the method used. Rufloxacin alone or in combination with MF 922, at concentrations achieved in vivo, induced morphological alterations in all the pathogens analyzed with the exception of M. catarrhalis and H. influenzae. Towards S. pyogenes and S. pneumoniae, the same levels of rufloxacin and MF 922 were capable of inducing only bacteriostatic rather than bactericidal effect, followed by reversible morphological modifications. The presence of 50% human serum in the test media did not affect the results.

Anti-Infective Agents↗