Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1991 Mar;35(3):524–528. doi: 10.1128/aac.35.3.524

Acquired resistance of Nocardia brasiliensis to clavulanic acid related to a change in beta-lactamase following therapy with amoxicillin-clavulanic acid.

V A Steingrube 1, R J Wallace Jr 1, B A Brown 1, Y Pang 1, B Zeluff 1, L C Steele 1, Y Zhang 1
PMCID: PMC245043  PMID: 2039203

Abstract

Previous studies have demonstrated that Nocardia brasiliensis is susceptible to amoxicillin-clavulanic acid and that its beta-lactamases are inhibited in vitro by clavulanic acid. A cardiac transplant patient with disseminated infection caused by N. brasiliensis was treated with this drug combination with good response, but relapsed while still on therapy. The relapse isolate was found to be identical to the initial isolate by using genomic DNA restriction fragment patterns obtained by pulsed field gel electrophoresis, but it was resistant to amoxicillin-clavulanic acid. On isoelectric focusing, the beta-lactamase from the relapse isolate exhibited a shift in the isoelectric point (pI) of its major band from 5.10 to 5.04 compared with the enzyme from the pretreatment isolate. As determined by using values of the amount of beta-lactamase inhibitor necessary to give 50 +/- 5% inhibition of beta-lactamase-mediated hydrolysis of 50 microM nitrocefin, the beta-lactamase of the relapse isolate was also 200-fold more resistant than the enzyme from the pretreatment isolate to clavulanic acid and was more resistant to sulbactam, tazobactam, cloxacillin, and imipenem. The beta-lactamase of the relapse isolate exhibited a 10-fold decrease in hydrolytic activity for cephaloridine and other hydrolyzable cephalosporins compared with that for nitrocefin. Acquired resistance to amoxicillin-clavulanic acid in this isolate of N. brasiliensis appears to have resulted from a mutational change affecting the inhibitor and active site(s) in the beta-lactamase.

Full text

PDF
526

Images in this article

527Image
on p.527
527Image
on p.527

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bhaduri S., Demchick P. H. Simple and rapid method for disruption of bacteria for protein studies. Appl Environ Microbiol. 1983 Oct;46(4):941–943. doi: 10.1128/aem.46.4.941-943.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bush K. Classification of beta-lactamases: groups 1, 2a, 2b, and 2b'. Antimicrob Agents Chemother. 1989 Mar;33(3):264–270. doi: 10.1128/aac.33.3.264. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bush K. Excitement in the beta-lactamase arena. J Antimicrob Chemother. 1989 Dec;24(6):831–836. doi: 10.1093/jac/24.6.831. [DOI] [PubMed] [Google Scholar]
  4. Chanal C. M., Sirot D. L., Petit A., Labia R., Morand A., Sirot J. L., Cluzel R. A. Multiplicity of TEM-derived beta-lactamases from Klebsiella pneumoniae strains isolated at the same hospital and relationships between the responsible plasmids. Antimicrob Agents Chemother. 1989 Nov;33(11):1915–1920. doi: 10.1128/aac.33.11.1915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chanal C., Sirot D., Labia R., Sirot J. Identification of two novel TEM-derivative ceftazidimases, CAZ-6 and CAZ-7, from Klebsiella pneumoniae isolates. J Antimicrob Chemother. 1989 Jul;24(1):86–87. doi: 10.1093/jac/24.1.86. [DOI] [PubMed] [Google Scholar]
  6. Lévy-Frébault V. V., Thorel M. F., Varnerot A., Gicquel B. DNA polymorphism in Mycobacterium paratuberculosis, "wood pigeon mycobacteria," and related mycobacteria analyzed by field inversion gel electrophoresis. J Clin Microbiol. 1989 Dec;27(12):2823–2826. doi: 10.1128/jcm.27.12.2823-2826.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Martinez J. L., Cercenado E., Rodriguez-Creixems M., Vincente-Perez M. F., Delgado-Iribarren A., Baquero F. Resistance to beta-lactam/clavulanate. Lancet. 1987 Dec 19;2(8573):1473–1473. doi: 10.1016/s0140-6736(87)91180-9. [DOI] [PubMed] [Google Scholar]
  8. Martinez J. L., Vicente M. F., Delgado-Iribarren A., Perez-Diaz J. C., Baquero F. Small plasmids are involved in amoxicillin-clavulanate resistance in Escherichia coli. Antimicrob Agents Chemother. 1989 Apr;33(4):595–595. doi: 10.1128/aac.33.4.595-a. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Masterton R. G., Garner P. J., Harrison N. A., Rainford D. J. Timentin resistance. Lancet. 1987 Oct 24;2(8565):975–976. doi: 10.1016/s0140-6736(87)91464-4. [DOI] [PubMed] [Google Scholar]
  10. Page J. W., Farmer T. H., Elson S. W. Hyperproduction of TEM-1 beta-lactamase by Escherichia coli strains. J Antimicrob Chemother. 1989 Jan;23(1):160–161. doi: 10.1093/jac/23.1.160. [DOI] [PubMed] [Google Scholar]
  11. Paul G. C., Gerbaud G., Bure A., Philippon A. M., Pangon B., Courvalin P. TEM-4, a new plasmid-mediated beta-lactamase that hydrolyzes broad-spectrum cephalosporins in a clinical isolate of Escherichia coli. Antimicrob Agents Chemother. 1989 Nov;33(11):1958–1963. doi: 10.1128/aac.33.11.1958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Philippon A., Labia R., Jacoby G. Extended-spectrum beta-lactamases. Antimicrob Agents Chemother. 1989 Aug;33(8):1131–1136. doi: 10.1128/aac.33.8.1131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Péduzzi J., Barthélémy M., Tiwari K., Mattioni D., Labia R. Structural features related to hydrolytic activity against ceftazidime of plasmid-mediated SHV-type CAZ-5 beta-lactamase. Antimicrob Agents Chemother. 1989 Dec;33(12):2160–2163. doi: 10.1128/aac.33.12.2160. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Quinn J. P., Miyashiro D., Sahm D., Flamm R., Bush K. Novel plasmid-mediated beta-lactamase (TEM-10) conferring selective resistance to ceftazidime and aztreonam in clinical isolates of Klebsiella pneumoniae. Antimicrob Agents Chemother. 1989 Sep;33(9):1451–1456. doi: 10.1128/aac.33.9.1451. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Roy C., Segura C., Torrellas A., Reig R., Teruel D., Hermida M. Activity of amoxycillin/clavulanate against beta-lactamase-producing Escherichia coli and Klebsiella spp. J Antimicrob Chemother. 1989 Nov;24 (Suppl B):41–47. doi: 10.1093/jac/24.suppl_b.41. [DOI] [PubMed] [Google Scholar]
  16. Sanders C. C., Iaconis J. P., Bodey G. P., Samonis G. Resistance to ticarcillin-potassium clavulanate among clinical isolates of the family Enterobacteriaceae: role of PSE-1 beta-lactamase and high levels of TEM-1 and SHV-1 and problems with false susceptibility in disk diffusion tests. Antimicrob Agents Chemother. 1988 Sep;32(9):1365–1369. doi: 10.1128/aac.32.9.1365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Smith P. K., Krohn R. I., Hermanson G. T., Mallia A. K., Gartner F. H., Provenzano M. D., Fujimoto E. K., Goeke N. M., Olson B. J., Klenk D. C. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985 Oct;150(1):76–85. doi: 10.1016/0003-2697(85)90442-7. [DOI] [PubMed] [Google Scholar]
  18. Sougakoff W., Goussard S., Gerbaud G., Courvalin P. Plasmid-mediated resistance to third-generation cephalosporins caused by point mutations in TEM-type penicillinase genes. Rev Infect Dis. 1988 Jul-Aug;10(4):879–884. doi: 10.1093/clinids/10.4.879. [DOI] [PubMed] [Google Scholar]
  19. Wallace R. J., Jr, Nash D. R., Johnson W. K., Steele L. C., Steingrube V. A. Beta-lactam resistance in Nocardia brasiliensis is mediated by beta-lactamase and reversed in the presence of clavulanic acid. J Infect Dis. 1987 Dec;156(6):959–966. doi: 10.1093/infdis/156.6.959. [DOI] [PubMed] [Google Scholar]
  20. Wallace R. J., Jr, Steele L. C. Susceptibility testing of Nocardia species for the clinical laboratory. Diagn Microbiol Infect Dis. 1988 Mar;9(3):155–166. doi: 10.1016/0732-8893(88)90025-9. [DOI] [PubMed] [Google Scholar]
  21. Williams H., King A., Shannon K., Phillips I. Amoxycillin/clavulanate resistant Escherichia coli. Lancet. 1988 Feb 6;1(8580):304–305. doi: 10.1016/s0140-6736(88)90391-1. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES