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JAC Advance Access published online on January 14, 2003
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkg095
© 2003 by The British Society for Antimicrobial Chemotherapy
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© 2003 The British Society for Antimicrobial Chemotherapy

Original article

Enzymic degradation of a {beta}-lactam antibiotic, ampicillin, in the gut: a novel treatment modality

Jaana Harmoinen 1*, Kirsi Vaali 2, Pertti Koski 3, Kaisa Syrjänen 3, Outi Laitinen 1, Kai Lindevall 3, Elias Westermarck 1

1 Faculty of Veterinary Medicine, Department of Clinical Veterinary Sciences, PO Box 57, Helsinki
2 Institute of Biomedicine/Pharmacology, PO Box 63, University of Helsinki, FIN-00014 Helsinki
3 Ipsat Therapies Ltd, Sinimäentie 10B, FIN-02630 Espoo, Finland

* Corresponding author. E-mail: jaana.harmoinen{at}helsinki.fi.

Received 8 August 2002 ; revised 29 October 2002 ; accepted 20 November 2002

Abstract

Antibiotics can cause severe alterations in the gut microflora and promote diarrhoea and overgrowth of pathogenic bacteria. The present study investigated the potency of targeted recombinant {beta}-lactamase (TRBL) to degrade a {beta}-lactam antibiotic in the jejunum of fistula-operated beagles. We used different peroral doses of purified {beta}-lactamase (PenP) of Bacillus licheniformis in enteric-coated pellets together with intravenous ampicillin. Serum and jejunal samples were collected for ampicillin and {beta}-lactamase analysis. A dose-response effect of TRBL on ampicillin concentrations in the jejunal samples could be observed. The highest doses applied decreased the jejunal ampicillin concentrations to undetectable levels. In the serum samples, the ampicillin concentrations were not affected by the {beta}-lactamase dose used. Our results indicate that it may be possible to evolve a targeted treatment to degrade {beta}-lactam antibiotics intestinally and, thus, decrease antibiotic-induced adverse effects on the gut microflora.

Keywords: {beta}-lactamase, {beta}-lactams, jejunum, microflora
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