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Effect of subinhibitory concentrations of antibiotics on extracellular shiga-like toxin I

Wirkung von Antibiotika in subinhibitorischen Konzentrationen auf extrazelluläres Shiga-like-Toxin

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Summary

Patients with diarrhea due to strains of enterohemorrhagicEscherichia coli (EHEC) (e. g. O157:H7) might be at a higher risk of developing hemolytic uremic syndrome when treated with antimicrobial agents. It has been suggested that this might be due to an increase of release or production of vero or shiga-like toxin from such organisms, possibly as a stress response to antimicrobial agents. The aim of this study was to detect such increases in extracellular toxinin vitro with a newly developed method that exposed EHEC to high sublethal concentrations followed by a recovery phase at progressively lower concentrations. Five strains of EHEC were exposed to continuously changing concentrations of ciprofloxacin, co-trimoxazole, cefixime and tetracycline. The amount of free shiga-like toxin I (SLT-I) released was compared to the amount released from inocula that were not exposed to antibiotics. There were significant differences between the five EHEC strains in the amount of toxin detected after exposure to antimicrobial agents (p<0.001). Equally important was the type of antibiotic (p<0.001), with ciprofloxacin inducing the largest increase ranging from 169 to 436%, followed by co-trimoxazole, cefixime and tetracycline. In addition, the increases in free toxin correlated with the concentration of the antibiotics (p<0.001). The association between antibiotic-induced increases in SLT-I produced by strains of EHEC and certain classes of antibiotics might influence the analysis of future epidemiological studies on risk factors for HUS.

Zusammenfassung

Die orale antimikrobielle Behandlung von Patienten mit Durchfällen, die durch enterohämorrhagische Stäme vonEscherichia coli (EHEC), zum Beispiel O157:H7, verursacht werden, ist ein möglicher Risikofaktor für die Entwicklung eines hämalytisch-urämischen Syndroms. Es wird vermutet, daß der Grund hierfür in einer gesteigerten Produktion oder Sekretion von Vero- oder Shiga-like-Toxinen liegt, als Teil einer durch die Antibiotika hervorgerufenen Streßreaktion der Bakterien. Das Ziel dieserIn-vitro-Studie war es, Erhöhungen von extrazellulären Toxinkonzentrationen zu messen nachdem EHEC mit einer Diffusionsmethode wechselnden Konzentrationen von Antibiotika ausgesetzt worden waren. Die Antibiotikakonzentrationen wurden mit der jeweils höchstmöglichen subletalen Konzentration begonnen, die dann stetig abnahm und den Bakterien eine Erholungsphase gestattete. Fünf EHEC- Stämme wurden auf diese Weise Ciprofloxacin, Co-trimoxazol, Cefixim und Tetracyclin ausgesetzt. Zwischen den verschiedenen Stämmen und Antibiotika fanden sich signifikante Unterschiede in den durch die Antibiotika hervorgerufenen Erhöhungen extrazellulärer Toxinkonzentrationen mit p<0,001 für beide Parameter. Ciprofloxacin verursachte die größten Steigerungen von 169 bis 436%, gefolgt von Co-trimoxazol, Cefixim und Tetracyclin. Diese Assoziation von erhöhten Konzentrationen von Vero- und Shiga-like-Toxinen und der Einwirkung von Antibiotika auf verschiedene Keime muß in Zukunft in Studien über die Risikofaktoren, die zur Entwicklung des hämolytischurämischen Syndroms beitragen, berücksichtigt werden.

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Authors and Affiliations

  1. Pediatric Infectious Diseases, University of Texas Medical School, 6431 Fannin, Room JFB 1.739, 77030, Houston, TX, USA

    J. N. Walterspiel M.D., Ardythe L. Morrow Ph.D., M. Sc. & T. G. Cleary M.D.

  2. Dept. of Pediatrics, Beilinson Medical Center, 49100, Petah Tikva, Israel

    S. Ashkenazi M. D.

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  1. J. N. Walterspiel M.D.
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Walterspiel, J.N., Morrow, A.L., Cleary, T.G. et al. Effect of subinhibitory concentrations of antibiotics on extracellular shiga-like toxin I. Infection 20, 25–29 (1992). https://doi.org/10.1007/BF01704889

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  • DOI: https://doi.org/10.1007/BF01704889

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