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Table of Contents
Vol. 46, No. 4, 2000
Issue release date: July–August 2000
Section title: Microbiology
Chemotherapy 2000;46:253–266
(DOI:10.1159/000007297)

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

Marchese A. · Salerno A. · Pesce A. · Debbia E.A. · Schito G.C.
Istituto di Microbiologia ‘C.A. Romanzi’, Università di Genova, Italy

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Article / Publication Details

First-Page Preview
Abstract of Microbiology

Published online: 6/15/2000
Issue release date: July–August 2000

Number of Print Pages: 14
Number of Figures: 0
Number of Tables: 9

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: http://www.karger.com/CHE

Abstract

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 MIC50 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 μg/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 × MIC), the frequency of emergence of spontaneously resistant mutants ranged from <1 × 10–9 to 1.6 × 10–8 with gram-positive aerobic and anaerobic cocci, while with aerobic and anaerobic gram-negative bacteria, this value ranged from <1 × 10–9 to 1.7 × 10–7. C. difficile showed a particularly low incidence of spontaneously resistant mutants (<1 × 10–9). The low incidence of resistant subpopulations selected by levels of 8 × 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.

© 2000 S. Karger AG, Basel


  

Author Contacts

Eugenio A. Debbia
Istituto di Microbiologia ‘C.A. Romanzi’, Università di Genova
Largo Rosanna Benzi 10, I–16132 Genova (Italy)
Tel. +39 010 353 7655, Fax +39 010 504 837
E-Mail eude@unige.it or eugenio.debbia@aleph.it

  

Article Information

Number of Print Pages : 14
Number of Figures : 0, Number of Tables : 9, Number of References : 30

  

Publication Details

Chemotherapy (International Journal of Experimental and Clinical Chemotherapy)
Founded 1959 as ‘Chemotherapia’

Vol. 46, No. 4, Year 2000 (Cover Date: July-August 2000)

Journal Editor: H. Schönfeld, Grenzach-Wyhlen
ISSN: 0009–3157 (print), 1421–9794 (Online)

For additional information:http://www.karger.com/journals/che


Article / Publication Details

First-Page Preview
Abstract of Microbiology

Published online: 6/15/2000
Issue release date: July–August 2000

Number of Print Pages: 14
Number of Figures: 0
Number of Tables: 9

ISSN: 0009-3157 (Print)
eISSN: 1421-9794 (Online)

For additional information: http://www.karger.com/CHE


Copyright / Drug Dosage

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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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