Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1989 Apr;33(4):498–502. doi: 10.1128/aac.33.4.498

Activity of cefepime against ceftazidime- and cefotaxime-resistant gram-negative bacteria and its relationship to beta-lactamase levels.

J Fung-Tomc 1, T J Dougherty 1, F J DeOrio 1, V Simich-Jacobson 1, R E Kessler 1
PMCID: PMC172467  PMID: 2499250

Abstract

One hundred clinical isolates resistant to ceftazidime and/or cefotaxime were examined for susceptibility to cefepime. The most frequently encountered ceftazidime-cefotaxime-resistant strains belonged to the genera Enterobacter, Pseudomonas, and Citrobacter. Among these strains, 92% were resistant to cefoperazone, 91% were resistant to cefotaxime, 84% were resistant to ceftazidime, and 6% were resistant to cefepime. Of the members of the family Enterobacteriaceae, 57% were resistant to ceftriaxone. The six strains resistant to cefepime were all Pseudomonas aeruginosa and were resistant to both cefotaxime and ceftazidime. Cefepime-resistant P. aeruginosa strains had exceptionally high levels of beta-lactamase activity, higher than the levels found in strains resistant to ceftazidime but susceptible to cefepime. The beta-lactamases from the cefepime-resistant strains were type I (Richmond-Sykes), were constitutively produced, and did not have increased affinity or hydrolytic activity for cefepime. Thus, cefepime was active against most gram-negative bacteria which have developed resistance to the broad-spectrum cephalosporins, and resistance to cefepime in P. aeruginosa appears to be associated with higher beta-lactamase levels than in cefepime-susceptible strains.

Full text

PDF
499

Selected References

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

  1. Benn R. A., Kemp R. J. Effect of antibiotic use on the incidence of cephalosporin resistance in two Australian hospitals. J Antimicrob Chemother. 1984 Sep;14 (Suppl B):71–76. doi: 10.1093/jac/14.suppl_b.71. [DOI] [PubMed] [Google Scholar]
  2. Dworzack D. L., Pugsley M. P., Sanders C. C., Horowitz E. A. Emergence of resistance in gram-negative bacteria during therapy with expanded-spectrum cephalosporins. Eur J Clin Microbiol. 1987 Aug;6(4):456–459. doi: 10.1007/BF02013110. [DOI] [PubMed] [Google Scholar]
  3. Follath F., Costa E., Thommen A., Frei R., Burdeska A., Meyer J. Clinical consequences of development of resistance to third generation cephalosporins. Eur J Clin Microbiol. 1987 Aug;6(4):446–450. doi: 10.1007/BF02013108. [DOI] [PubMed] [Google Scholar]
  4. Fung-Tomc J., Huczko E., Pearce M., Kessler R. E. Frequency of in vitro resistance of Pseudomonas aeruginosa to cefepime, ceftazidime, and cefotaxime. Antimicrob Agents Chemother. 1988 Sep;32(9):1443–1445. doi: 10.1128/aac.32.9.1443. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hiraoka M., Masuyoshi S., Mitsuhashi S., Tomatsu K., Inoue M. Cephalosporinase interactions and antimicrobial activity of BMY-28142, ceftazidime and cefotaxime. J Antibiot (Tokyo) 1988 Jan;41(1):86–93. doi: 10.7164/antibiotics.41.86. [DOI] [PubMed] [Google Scholar]
  6. Kessler R. E., Bies M., Buck R. E., Chisholm D. R., Pursiano T. A., Tsai Y. H., Misiek M., Price K. E., Leitner F. Comparison of a new cephalosporin, BMY 28142, with other broad-spectrum beta-lactam antibiotics. Antimicrob Agents Chemother. 1985 Feb;27(2):207–216. doi: 10.1128/aac.27.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. King A., Shannon K., Eykyn S., Phillips I. Reduced sensitivity to beta-lactam antibiotics arising during ceftazidime treatment of Pseudomonas aeruginosa infections. J Antimicrob Chemother. 1983 Oct;12(4):363–370. doi: 10.1093/jac/12.4.363. [DOI] [PubMed] [Google Scholar]
  8. Medeiros A. A., O'Brien T. F., Rosenberg E. Y., Nikaido H. Loss of OmpC porin in a strain of Salmonella typhimurium causes increased resistance to cephalosporins during therapy. J Infect Dis. 1987 Nov;156(5):751–757. doi: 10.1093/infdis/156.5.751. [DOI] [PubMed] [Google Scholar]
  9. Nikaido H. Role of permeability barriers in resistance to beta-lactam antibiotics. Pharmacol Ther. 1985;27(2):197–231. doi: 10.1016/0163-7258(85)90069-5. [DOI] [PubMed] [Google Scholar]
  10. O'Callaghan C. H., Morris A., Kirby S. M., Shingler A. H. Novel method for detection of beta-lactamases by using a chromogenic cephalosporin substrate. Antimicrob Agents Chemother. 1972 Apr;1(4):283–288. doi: 10.1128/aac.1.4.283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Phelps D. J., Carlton D. D., Farrell C. A., Kessler R. E. Affinity of cephalosporins for beta-lactamases as a factor in antibacterial efficacy. Antimicrob Agents Chemother. 1986 May;29(5):845–848. doi: 10.1128/aac.29.5.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Quinn J. P., DiVincenzo C. A., Foster J. Emergence of resistance to ceftazidime during therapy for Enterobacter cloacae infections. J Infect Dis. 1987 May;155(5):942–947. doi: 10.1093/infdis/155.5.942. [DOI] [PubMed] [Google Scholar]
  13. Richmond M. H., Sykes R. B. The beta-lactamases of gram-negative bacteria and their possible physiological role. Adv Microb Physiol. 1973;9:31–88. doi: 10.1016/s0065-2911(08)60376-8. [DOI] [PubMed] [Google Scholar]
  14. Samuni A. A direct spectrophotometric assay and determination of Michaelis constants for the beta-lactamase reaction. Anal Biochem. 1975 Jan;63(1):17–26. doi: 10.1016/0003-2697(75)90185-2. [DOI] [PubMed] [Google Scholar]
  15. Sanders C. C., Sanders W. E., Jr Clinical importance of inducible beta-lactamases in gram-negative bacteria. Eur J Clin Microbiol. 1987 Aug;6(4):435–438. doi: 10.1007/BF02013106. [DOI] [PubMed] [Google Scholar]
  16. Sanders C. C., Sanders W. E., Jr Emergence of resistance during therapy with the newer beta-lactam antibiotics: role of inducible beta-lactamases and implications for the future. Rev Infect Dis. 1983 Jul-Aug;5(4):639–648. doi: 10.1093/clinids/5.4.639. [DOI] [PubMed] [Google Scholar]
  17. Sanders C. C., Sanders W. E., Jr Type I beta-lactamases of gram-negative bacteria: interactions with beta-lactam antibiotics. J Infect Dis. 1986 Nov;154(5):792–800. doi: 10.1093/infdis/154.5.792. [DOI] [PubMed] [Google Scholar]
  18. Then R. L., Angehrn P. Trapping of nonhydrolyzable cephalosporins by cephalosporinases in Enterobacter cloacae and Pseudomonas aeruginosa as a possible resistance mechanism. Antimicrob Agents Chemother. 1982 May;21(5):711–717. doi: 10.1128/aac.21.5.711. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Vu H., Nikaido H. Role of beta-lactam hydrolysis in the mechanism of resistance of a beta-lactamase-constitutive Enterobacter cloacae strain to expanded-spectrum beta-lactams. Antimicrob Agents Chemother. 1985 Mar;27(3):393–398. doi: 10.1128/aac.27.3.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Waley S. G. A spectrophotometric assay of beta-lactamase action on penicillins. Biochem J. 1974 Jun;139(3):789–790. doi: 10.1042/bj1390789. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES