1887

Abstract

Fourteen apparently carbapenem-susceptible clinical isolates that exhibited colonies within the inhibition zone around carbapenem discs were analysed. MICs of carbapenems were determined and the isolates were genotyped by PFGE. Population analysis, one-step selection of carbapenem-resistant mutants and growth curves of progenitors and carbapenem-resistant subpopulations were performed. Agar dilution MICs of imipenem and meropenem ranged from 0.5 to 4 mg l and from 0.25 to 2 mg l, respectively. Population analysis confirmed subpopulations that grew in concentrations of up to 18 mg l and 12 mg l of imipenem and meropenem, respectively, at frequencies ranging from 6.9×10 to 1.1×10, suggesting that they might not be detected by standard agar dilution MIC testing. The minority subpopulations exhibited MICs for imipenem ranging from 10 to 20 mg l and for meropenem from 4 to 14 mg l. The one-step 8 mg l selection of imipenem-resistant mutants test showed growth in all isolates at frequencies ranging from 3.8×10 to 5.1×10. Growth curves revealed a prolonged lag phase and a short exponential phase for the heterogeneous subpopulations compared with their respective native subpopulations. These findings may be indicative that the use of carbapenems can lead to selection of resistant subpopulations that subsequently cause infections and result in treatment failure.

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2007-01-01
2019-11-12
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References

  1. Alam, M. R., Donabedian, S., Brown, W., Gordon, J., Chow, J. W., Zervos, M. J. & Hershberger, E. ( 2001; ). Heteroresistance to vancomycin in Enterococcus faecium. J Clin Microbiol 39, 3379–3381.[CrossRef]
    [Google Scholar]
  2. Clinical and Laboratory Standards Institute ( 2003; ). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow Aerobically, 6th edn, approved standard M7-A6. Wayne, PA: Clinical and Laboratory Standards Institute.
  3. Clinical and Laboratory Standards Institute ( 2005; ). Performance Standards for Antimicrobial Susceptibility Testing; 15th informational supplement, CLSI/NCCLS M100-S15. Wayne, PA: Clinical and Laboratory Standards Institute.
  4. Gales, A. C., Jones, R. N. & Sader, H. S. ( 2006; ). Global assessment of the antimicrobial activity of polymyxin B against 54 731 clinical isolates of Gram-negative bacilli: report from the SENTRY antimicrobial surveillance programme (2001–2004). Clin Microbiol Infect 12, 315–321.[CrossRef]
    [Google Scholar]
  5. Hiramatsu, K., Aritaka, N., Hanaki, H., Kawasaki, S., Hosoda, Y., Hori, S., Fukuchi, Y. & Kobayashi, I. ( 1997; ). Dissemination in Japanese hospitals of strains of Staphylococcus aureus heterogeneously resistant to vancomycin. Lancet 350, 1670–1673.[CrossRef]
    [Google Scholar]
  6. Kayser, F. H., Morenzoni, G., Strassle, A. & Hadorn, K. ( 1989; ). Activity of meropenem, against Gram-positive bacteria. J Antimicrob Chemother 24 Suppl. A, 101–112.
    [Google Scholar]
  7. Kohler, T., Michea-Hamzehpour, M., Epp, S. F. & Pechere, J. C. ( 1999; ). Carbapenem activities against Pseudomonas aeruginosa: respective contributions of OprD and efflux systems. Antimicrob Agents Chemother 43, 424–427.
    [Google Scholar]
  8. Livermore, D. M. ( 2002; ). The impact of carbapenemases on antimicrobial development and therapy. Curr Opin Investig Drugs 3, 218–224.
    [Google Scholar]
  9. Plipat, N., Livni, G., Bertram, H. & Thomson, R. B., Jr ( 2005; ). Unstable vancomycin heteroresistance is common among clinical isolates of methicillin-resistant Staphylococcus aureus. J Clin Microbiol 43, 2494–2496.[CrossRef]
    [Google Scholar]
  10. Pournaras, S., Maniati, M., Petinaki, E., Tzouvelekis, L. S., Tsakris, A., Legakis, N. J. & Maniatis, A. N. ( 2003; ). Hospital outbreak of multiple clones of Pseudomonas aeruginosa carrying the unrelated metallo-β-lactamase gene variants bla VIM-2 and bla VIM-4. J Antimicrob Chemother 51, 1409–1414.[CrossRef]
    [Google Scholar]
  11. Pournaras, S., Ikonomidis, A., Markogiannakis, A., Maniatis, A. N. & Tsakris, A. ( 2005a; ). Heteroresistance to carbapenems in Acinetobacter baumannii. J Antimicrob Chemother 55, 1055–1056.[CrossRef]
    [Google Scholar]
  12. Pournaras, S., Maniati, M., Spanakis, N., Ikonomidis, A., Tassios, P. T., Tsakris, A., Legakis, N. J. & Maniatis, A. N. ( 2005b; ). Spread of efflux pump-overexpressing, non-metallo-β-lactamase-producing, meropenem-resistant but ceftazidime-susceptible Pseudomonas aeruginosa in a region with bla VIM endemicity. J Antimicrob Chemother 56, 761–764.[CrossRef]
    [Google Scholar]
  13. Rinder, H. ( 2001; ). Hetero-resistance: an under-recognised confounder in diagnosis and therapy? J Med Microbiol 50, 1018–1020.
    [Google Scholar]
  14. Tam, V. H., Schilling, A. N., Neshat, S., Poole, K., Melnick, D. A. & Coyle, E. A. ( 2005; ). Optimization of meropenem minimum concentration/MIC ratio to suppress in vitro resistance of Pseudomonas aeruginosa. Antimicrob Agents Chemother 49, 4920–4927.[CrossRef]
    [Google Scholar]
  15. Tenover, F. C., Arbeit, R. D., Goering, R. V., Mickelsen, P. A., Murray, B. E., Persing, D. H. & Swaminathan, B. ( 1995; ). Interpreting chromosomal DNA restriction patterns produced by pulsed-field gel electrophoresis: criteria for bacterial strain typing. J Clin Microbiol 33, 2233–2239.
    [Google Scholar]
  16. Tomasz, A., Nachman, S. & Leaf, H. ( 1991; ). Stable classes of phenotypic expression in methicillin-resistant clinical isolates of staphylococci. Antimicrob Agents Chemother 35, 124–129.[CrossRef]
    [Google Scholar]
  17. Yamazumi, T., Pfaller, M. A., Messer, S. A., Houston, A. K., Boyken, L., Hollis, R. J., Furuta, I. & Jones, R. N. ( 2003; ). Characterization of heteroresistance to fluconazole among clinical isolates of Cryptococcus neoformans. J Clin Microbiol 41, 267–272.[CrossRef]
    [Google Scholar]
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