1887

Abstract

The aim of this work was to determine whether diazepam could induce the multiple antibiotic resistance (Mar) phenotype in and strains. The Mar phenotype is characterized by decreased susceptibility to multiple antibiotics due to the loss of porins and/or increased expression of active efflux systems. The effect of subinhibitory concentrations of diazepam on the susceptibility of different antimicrobial agents, outer-membrane protein expression and norfloxacin intracellular accumulation was studied. The results revealed that diazepam concentrations equal or twice adult dosage induced the same Mar phenotype as two well known inducers, sodium salicylate and sodium benzoate. Susceptibility to norfloxacin in a clinical isolate and strain Ag100 decreased due to enhanced active efflux and loss of porin expression. A decreased susceptibility to chloramphenicol, tetracycline, nalidixic acid and β-lactam antibiotics was also observed. In conclusion, like sodium salicylate or sodium benzoate, diazepam may induce the Mar phenotype.

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2004-11-01
2019-11-18
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References

  1. Alekshun, M. N. & Levy, S. B. ( 1997;). Regulation of chromosomally mediated multiple antibiotic resistance: the mar regulon. Antimicrob Agents Chemother 41, 2067–2075.
    [Google Scholar]
  2. Balagué, C. & Vescovi, E. G. ( 2001;). Activation of multiple antibiotic resistance in uropathogenic Escherichia coli strains by aryloxoalcanoic acid compounds. Antimicrob Agents Chemother 45, 1815–1822.[CrossRef]
    [Google Scholar]
  3. Covelli, V., Munno, I., Decandia, P., Altamura, M., Cannuscio, B., Maffione, A. B. & Jirillo, E. ( 1991;). Effects of benzodiazepines on the immune system. Acta Neurol (Napoli) 13, 418–423.
    [Google Scholar]
  4. Doménech-Sánchez, A., Martínez-Martínez, L., Hernández-Allés, S., Conejo, M. C., Pascual, A., Tomás, J. M., Alberti, S. & Benedí, V. J. ( 2003;). Role of Klebsiella pneumoniae OmpK35 porin in antimicrobial resistance. Antimicrob Agents Chemother 47, 3332–3335.[CrossRef]
    [Google Scholar]
  5. Galdiero, F., Bentivoglio, C., Nuzzo, I., Ianniello, R., Capasso, C., Mattera, S., Nazzaro, C., Galdiero, M. & Romano Carratelli, C. ( 1995;). Effects of benzodiazepines on immunodeficiency and resistance in mice. Life Sci 57, 2413–2423.[CrossRef]
    [Google Scholar]
  6. George, A. M., Hall, R. M. & Stokes, H. W. ( 1995;). Multidrug resistance in Klebsiella pneumoniae: a novel gene, ramA, confers a multidrug resistance phenotype in Escherichia coli. Microbiology 141, 1909–1920.[CrossRef]
    [Google Scholar]
  7. Kern, W. V., Oethinger, M., Jellen-Ritter, A. S. & Levy, S. B. ( 2000;). Non-target gene mutations in the development of fluoroquinolone resistance in Escherichia coli. Antimicrob Agents Chemother 44, 814–820.[CrossRef]
    [Google Scholar]
  8. Laschi, A., Descotes, J., Tachon, P. & Evreux, J. C. ( 1983;). Adverse influence of diazepam upon resistance to Klebsiella pneumoniae infection in mice. Toxicol Lett 16, 281–284.[CrossRef]
    [Google Scholar]
  9. Martínez-Martínez, L., García, I., Ballesta, S., Benedí, V. J., Hernández-Allés, S. & Pascual, A. ( 1998;). Energy-dependent accumulation of fluoroquinolones in quinolone-resistant Klebsiella pneumoniae strains. Antimicrob Agents Chemother 42, 1850–1852.
    [Google Scholar]
  10. Martínez-Martínez, L., Pascual, A., Conejo, M. C., García, I., Joyanes, P., Doménech-Sánchez, A. & Benedí, V. J. ( 2002;). Energy-dependent accumulation of norfloxacin and porin expression in clinical isolates of Klebsiella pneumoniae and relationship to extended-spectrum β-lactamase production. Antimicrob Agents Chemother 46, 3926–3932.[CrossRef]
    [Google Scholar]
  11. Mortimer, P. G. & Piddock, L. J. ( 1993;). The accumulation of five antibacterial agents in porin-deficient mutants of Escherichia coli. J Antimicrob Chemother 32, 195–213.
    [Google Scholar]
  12. NCCLS, ( 2003a). Methods for dilution susceptibility for bacteria that grow aerobically; approved standard 6th edn. M07-A6. Wayne, PA: National Committee for Clinical Laboratory Standards.
  13. NCCLS, ( 2003b). Performance standards for antimicrobial disk susceptibility tests; approved standard 8th edn. M02-A8. Wayne, PA: National Committee for Clinical Laboratory Standards.
  14. Oethinger, M., Kern, W. V., Jellen-Ritter, A. S., McMurry, L. M. & Levy, S. B. ( 2000;). Ineffectiveness of topoisomerase mutations in mediating clinically significant fluoroquinolone resistance in Escherichia coli in the absence of the AcrAB efflux pump. Antimicrob Agents Chemother 44, 10–13.[CrossRef]
    [Google Scholar]
  15. Schneiders, T., Amyes, S. G. B. & Levy, S. B. ( 2003;). Role of AcrR and RamA in fluoroquinolone resistance in clinical Klebsiella pneumoniae isolates from Singapore. Antimicrob Agents Chemother 47, 2831–2837.[CrossRef]
    [Google Scholar]
  16. Tavío, M. M., Vila, J., Ruiz, J., Ruiz, J., Martín-Sánchez, A. M. & Jiménez de Anta, M. T. ( 1999;). Mechanisms involved in the development of resistance to fluoroquinolones in Escherichia coli isolates. J Antimicrob Chemother 44, 735–742.[CrossRef]
    [Google Scholar]
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