Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1983 Jul;24(1):48–53. doi: 10.1128/aac.24.1.48

Influence of clindamycin on derepression of beta-lactamases in Enterobacter spp. and Pseudomonas aeruginosa.

C C Sanders, W E Sanders Jr, R V Goering
PMCID: PMC185103  PMID: 6414365

Abstract

Previous studies in this and other laboratories have shown that derepression of beta-lactamases in strains of Enterobacter and Pseudomonas spp. is responsible for the rapid development of resistance to a variety of beta-lactam antibiotics. The purpose of the current study was to evaluate the effects of clindamycin on derepression of beta-lactamases in these two genera. In tests with four strains of each genus, clindamycin diminished derepression in one isolate of each genus and completely prevented derepression in a second Enterobacter isolate (strain 55). Additional tests with strain 55 revealed that other inhibitors of macromolecular synthesis did not completely prevent derepression of beta-lactamase when tested at concentrations that did not inhibit replication. However, clindamycin did not affect synthesis of beta-lactamase that was constitutively produced in a mutant of this strain (55M). It also did not inhibit derepression of beta-galactosidase in either strain 55 or 55M. Clindamycin did not diminish the bactericidal effects of beta-lactam antibiotics against Enterobacter or Pseudomonas spp. However, it enhanced the bactericidal activity of cefamandole against strain 55. These in vitro effects of clindamycin on strain 55 that were related to prevention of derepression of beta-lactamase were confirmed in vivo with an animal model of infection. These results indicate that in some strains, clindamycin can specifically prevent derepression of beta-lactamases without inhibiting growth. Such a selective effect may provide a new approach for the enhancement of the antibacterial activity of certain beta-lactam antibiotics.

Full text

PDF
48

Selected References

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

  1. Ahonkhai V. I., Cherubin C. E., Shulman M. A., Jhagroo M., Bancroft U. In vitro activity of U-57930E, a new clindamycin analog, against aerobic gram-positive bacteria. Antimicrob Agents Chemother. 1982 Jun;21(6):902–905. doi: 10.1128/aac.21.6.902. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bauer A. W., Kirby W. M., Sherris J. C., Turck M. Antibiotic susceptibility testing by a standardized single disk method. Am J Clin Pathol. 1966 Apr;45(4):493–496. [PubMed] [Google Scholar]
  3. Beckwith D. G., Jahre J. A. Role of a cefoxitin-inducible beta-lactamase in a case of breakthrough bacteremia. J Clin Microbiol. 1980 Oct;12(4):517–520. doi: 10.1128/jcm.12.4.517-520.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cole M. 'Beta-lactams' as beta-lactamase inhibitors. Philos Trans R Soc Lond B Biol Sci. 1980 May 16;289(1036):207–223. doi: 10.1098/rstb.1980.0039. [DOI] [PubMed] [Google Scholar]
  5. Gemmell C. G., Peterson P. K., Schmeling D., Kim Y., Mathews J., Wannamaker L., Quie P. G. Potentiation of opsonization and phagocytosis of Streptococcus pyogenes following growth in the presence of clindamycin. J Clin Invest. 1981 May;67(5):1249–1256. doi: 10.1172/JCI110152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goering R. V., Sanders C. C., Sanders W., Jr Comparison of BL-S786 with cephalothin, cefamandole and cefoxitin in vitro and in treatment of experimental infections in mice. J Antibiot (Tokyo) 1978 Apr;31(4):363–372. doi: 10.7164/antibiotics.31.363. [DOI] [PubMed] [Google Scholar]
  7. Gootz T. D., Sanders C. C. Characterization of beta-lactamase induction in Enterobacter cloacae. Antimicrob Agents Chemother. 1983 Jan;23(1):91–97. doi: 10.1128/aac.23.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Gootz T. D., Sanders C. C., Goering R. V. Resistance to cefamandole: derepression of beta-lactamases by cefoxitin and mutation in Enterobacter cloacae. J Infect Dis. 1982 Jul;146(1):34–42. doi: 10.1093/infdis/146.1.34. [DOI] [PubMed] [Google Scholar]
  9. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  10. Lampe M. F., Allan B. J., Minshew B. H., Sherris J. C. Mutational enzymatic resistance of Enterobacter species to beta-lactam antibiotics. Antimicrob Agents Chemother. 1982 Apr;21(4):655–660. doi: 10.1128/aac.21.4.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Michel J., Bornstein H., Luboshitzky R., Sacks T. Mechanis of chlorampenicol-cephalordine synergism on Enerobacteiaeae. Antimicrob Agents Chemother. 1975 Jun;7(6):845–849. doi: 10.1128/aac.7.6.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Michel J., Stessman P., Stessman J. Effects of subminimal inhibitory concentrations of Erythromycin, Clindamycin, and Pristinamycin on the penicillinase production of Staphlyococcus aureus. Antimicrob Agents Chemother. 1980 Jan;17(1):13–15. doi: 10.1128/aac.17.1.13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Preheim L. C., Penn R. G., Sanders C. C., Goering R. V., Giger D. K. Emergence of resistance to beta-lactam and aminoglycoside antibiotics during moxalactam therapy of Pseudomonas aeruginosa infections. Antimicrob Agents Chemother. 1982 Dec;22(6):1037–1041. doi: 10.1128/aac.22.6.1037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. SYPHERD P. S., DEMOSS J. A. THE STIMULATION BY CHLORAMPHENICOL OF "REPRESSOR" FORMATION IN ESCHERICHIA COLI. Biochim Biophys Acta. 1963 Dec 20;76:589–599. [PubMed] [Google Scholar]
  15. Sacks T., Michel J., Durst A., Stessman J. Inhibition of beta-lactamase: synergistic bactericidal effect of combination of chloramphenicolcephaloridine. J Antimicrob Chemother. 1977 Sep;3(5):525–527. doi: 10.1093/jac/3.5.525. [DOI] [PubMed] [Google Scholar]
  16. Sanders C. C., Moellering R. C., Jr, Martin R. R., Perkins R. L., Strike D. G., Gootz T. D., Sanders W. E., Jr Resistance to cefamandole: a collaborative study of emerging clinical problems. J Infect Dis. 1982 Jan;145(1):118–125. doi: 10.1093/infdis/145.1.118. [DOI] [PubMed] [Google Scholar]
  17. Sanders C. C. Novel resistance selected by the new expanded-spectrum cephalosporins: a concern. J Infect Dis. 1983 Mar;147(3):585–589. doi: 10.1093/infdis/147.3.585. [DOI] [PubMed] [Google Scholar]
  18. Sanders C. C., Sanders W. E., Jr Emergence of resistance to cefamandole: possible role of cefoxitin-inducible beta-lactamases. Antimicrob Agents Chemother. 1979 Jun;15(6):792–797. doi: 10.1128/aac.15.6.792. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Sanders C. C., Sanders W. E., Jr, Goering R. V. In vitro antagonism of beta-lactam antibiotics by cefoxitin. Antimicrob Agents Chemother. 1982 Jun;21(6):968–975. doi: 10.1128/aac.21.6.968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Shibl A. M., Al-Sowaygh I. A. Differential inhibition of bacterial growth and hemolysin production by lincosamide antibiotics. J Bacteriol. 1979 Feb;137(2):1022–1023. doi: 10.1128/jb.137.2.1022-1023.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Waterworth P. M., Emmerson A. M. Dissociated resistance among cephalosporins. Antimicrob Agents Chemother. 1979 Apr;15(4):497–503. doi: 10.1128/aac.15.4.497. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES