Skip to main content
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1991 Aug;35(8):1626–1634. doi: 10.1128/aac.35.8.1626

Bacteremia caused by hemolytic, high-level gentamicin-resistant Enterococcus faecalis.

M M Huycke 1, C A Spiegel 1, M S Gilmore 1
PMCID: PMC245231  PMID: 1929336

Abstract

Between 1 January 1984 and 31 December 1987, 206 enterococcal blood isolates at the University of Wisconsin Hospital and Clinics were analyzed for high-level aminoglycoside resistance (hereafter high-level aminoglycoside resistance is simply referred to as "resistance") and hemolysin production. Of 190 Enterococcus faecalis isolates, 68 (35.8%) were resistant to gentamicin. Of these 68 strains, 67 (98.5%) contained a gene coding for the bifunctional aminoglycoside-modifying 6'-aminoglycoside acetyltransferase-2"-aminoglycoside phosphotransferase [AAC(6')-APH(2")] enzyme. Of 190 isolates, 85 (44.7%) were hemolytic and contained a gene coding for component A of the enterococcal hemolysin. Sixty-two of 68 (91.2%) gentamicin-resistant isolates but only 23 of 122 (18.8%) gentamicin-susceptible isolates were hemolytic (P less than 0.001). Twelve of the hemolytic, gentamicin-resistant E. faecalis blood isolates, but only 2 of 9 nonhemolytic or gentamicin-susceptible isolates, had identical chromosomal DNA restriction endonuclease digestion patterns, suggesting a common derivation for these strains. A historical cohort study from 1 July 1985 to 31 March 1987 identified by regression analysis postsurgical intensive care unit status (odds ratio [OR], 5.0; 95% confidence interval [CI], 1.1 to 22.8) and prior treatment with an expanded- or broad-spectrum cephalosporin (OR, 3.0; 95% CI, 0.9 to 10.1) as risk factors for gentamicin-resistant E. faecalis bacteremia. Patients with hemolytic, gentamicin-resistant E. faecalis bacteremia had a fivefold-increased risk for death within 3 weeks of their bacteremia compared with patients with nonhemolytic, gentamicin-susceptible strains (95% CI, 1.0 to 25.4).

Full text

PDF
1626

Images in this article

Selected References

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

  1. Alouf J. E., Raynaud M. Purification and some properties of streptolysin O. Biochimie. 1973;55(10):1187–1193. doi: 10.1016/s0300-9084(74)80322-6. [DOI] [PubMed] [Google Scholar]
  2. Axelrod P., Talbot G. H. Risk factors for acquisition of gentamicin-resistant enterococci. A multivariate analysis. Arch Intern Med. 1989 Jun;149(6):1397–1401. [PubMed] [Google Scholar]
  3. Barrall D. T., Kenney P. R., Slotman G. J., Burchard K. W. Enterococcal bacteremia in surgical patients. Arch Surg. 1985 Jan;120(1):57–63. doi: 10.1001/archsurg.1985.01390250049008. [DOI] [PubMed] [Google Scholar]
  4. Basinger S. F., Jackson R. W. Bacteriocin (hemolysin) of Streptococcus zymogenes. J Bacteriol. 1968 Dec;96(6):1895–1902. doi: 10.1128/jb.96.6.1895-1902.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Berry A. M., Yother J., Briles D. E., Hansman D., Paton J. C. Reduced virulence of a defined pneumolysin-negative mutant of Streptococcus pneumoniae. Infect Immun. 1989 Jul;57(7):2037–2042. doi: 10.1128/iai.57.7.2037-2042.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Birnboim H. C., Doly J. A rapid alkaline extraction procedure for screening recombinant plasmid DNA. Nucleic Acids Res. 1979 Nov 24;7(6):1513–1523. doi: 10.1093/nar/7.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bryan C. S., Reynolds K. L., Brown J. J. Mortality associated with enterococcal bacteremia. Surg Gynecol Obstet. 1985 Jun;160(6):557–561. [PubMed] [Google Scholar]
  8. Chen H. Y., Williams J. D. Transferable resistance and aminoglycoside-modifying enzymes in enterococci. J Med Microbiol. 1985 Oct;20(2):187–196. doi: 10.1099/00222615-20-2-187. [DOI] [PubMed] [Google Scholar]
  9. Courvalin P., Carlier C., Collatz E. Plasmid-mediated resistance to aminocyclitol antibiotics in group D streptococci. J Bacteriol. 1980 Aug;143(2):541–551. doi: 10.1128/jb.143.2.541-551.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dougherty S. H., Flohr A. B., Simmons R. L. 'Breakthrough' enterococcal septicemia in surgical patients. 19 cases and a review of the literature. Arch Surg. 1983 Feb;118(2):232–238. doi: 10.1001/archsurg.1983.01390020076013. [DOI] [PubMed] [Google Scholar]
  11. Facklam R. R. Recognition of group D streptococcal species of human origin by biochemical and physiological tests. Appl Microbiol. 1972 Jun;23(6):1131–1139. doi: 10.1128/am.23.6.1131-1139.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ferretti J. J., Gilmore K. S., Courvalin P. Nucleotide sequence analysis of the gene specifying the bifunctional 6'-aminoglycoside acetyltransferase 2"-aminoglycoside phosphotransferase enzyme in Streptococcus faecalis and identification and cloning of gene regions specifying the two activities. J Bacteriol. 1986 Aug;167(2):631–638. doi: 10.1128/jb.167.2.631-638.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Garrison R. N., Fry D. E., Berberich S., Polk H. C., Jr Enterococcal bacteremia: clinical implications and determinants of death. Ann Surg. 1982 Jul;196(1):43–47. doi: 10.1097/00000658-198207000-00010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gatell J. M., Trilla A., Latorre X., Almela M., Mensa J., Moreno A., Miro J. M., Martinez J. A., Jimenez de Anta M. T., Soriano E. Nosocomial bacteremia in a large Spanish teaching hospital: analysis of factors influencing prognosis. Rev Infect Dis. 1988 Jan-Feb;10(1):203–210. doi: 10.1093/clinids/10.1.203. [DOI] [PubMed] [Google Scholar]
  15. Geoffroy C., Gaillard J. L., Alouf J. E., Berche P. Purification, characterization, and toxicity of the sulfhydryl-activated hemolysin listeriolysin O from Listeria monocytogenes. Infect Immun. 1987 Jul;55(7):1641–1646. doi: 10.1128/iai.55.7.1641-1646.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Granato P. A., Jackson R. W. Characterization of the A component of Streptococcus zymogenes lysin. J Bacteriol. 1971 Aug;107(2):551–556. doi: 10.1128/jb.107.2.551-556.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Granato P. A., Jackson R. W. Purification and characterization of the L component of Streptococcus zymogenes lysin. J Bacteriol. 1971 Nov;108(2):804–808. doi: 10.1128/jb.108.2.804-808.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gullberg R. M., Homann S. R., Phair J. P. Enterococcal bacteremia: analysis of 75 episodes. Rev Infect Dis. 1989 Jan-Feb;11(1):74–85. doi: 10.1093/clinids/11.1.74. [DOI] [PubMed] [Google Scholar]
  19. Hoffmann S. A., Moellering R. C., Jr The enterococcus: "putting the bug in our ears". Ann Intern Med. 1987 May;106(5):757–761. doi: 10.7326/0003-4819-106-5-757. [DOI] [PubMed] [Google Scholar]
  20. Horodniceanu T., Bougueleret L., El-Solh N., Bieth G., Delbos F. High-level, plasmid-borne resistance to gentamicin in Streptococcus faecalis subsp. zymogenes. Antimicrob Agents Chemother. 1979 Nov;16(5):686–689. doi: 10.1128/aac.16.5.686. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Ike Y., Clewell D. B., Segarra R. A., Gilmore M. S. Genetic analysis of the pAD1 hemolysin/bacteriocin determinant in Enterococcus faecalis: Tn917 insertional mutagenesis and cloning. J Bacteriol. 1990 Jan;172(1):155–163. doi: 10.1128/jb.172.1.155-163.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ike Y., Hashimoto H., Clewell D. B. Hemolysin of Streptococcus faecalis subspecies zymogenes contributes to virulence in mice. Infect Immun. 1984 Aug;45(2):528–530. doi: 10.1128/iai.45.2.528-530.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ike Y., Hashimoto H., Clewell D. B. High incidence of hemolysin production by Enterococcus (Streptococcus) faecalis strains associated with human parenteral infections. J Clin Microbiol. 1987 Aug;25(8):1524–1528. doi: 10.1128/jcm.25.8.1524-1528.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ikeda D. P., Barry A. L., Andersen S. G. Emergence of Streptococcus faecalis isolates with high-level resistance to multiple aminocyclitol aminoglycosides. Diagn Microbiol Infect Dis. 1984 Jun;2(3):171–177. doi: 10.1016/0732-8893(84)90027-0. [DOI] [PubMed] [Google Scholar]
  25. Jackson R. W. Bacteriolysis and inhibition of gram-positive bacteria by components of Streptococcus zymogenes lysin. J Bacteriol. 1971 Jan;105(1):156–159. doi: 10.1128/jb.105.1.156-159.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Johnson J. R., Moseley S. L., Roberts P. L., Stamm W. E. Aerobactin and other virulence factor genes among strains of Escherichia coli causing urosepsis: association with patient characteristics. Infect Immun. 1988 Feb;56(2):405–412. doi: 10.1128/iai.56.2.405-412.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Jones R. N. Gram-positive superinfections following beta-lactam chemotherapy: the significance of the enterococcus. Infection. 1985;13 (Suppl 1):S81–S88. doi: 10.1007/BF01644225. [DOI] [PubMed] [Google Scholar]
  28. Jones W. G., Barie P. S., Yurt R. W., Goodwin C. W. Enterococcal burn sepsis. A highly lethal complication in severely burned patients. Arch Surg. 1986 Jun;121(6):649–653. doi: 10.1001/archsurg.1986.01400060043004. [DOI] [PubMed] [Google Scholar]
  29. Kreger B. E., Craven D. E., McCabe W. R. Gram-negative bacteremia. IV. Re-evaluation of clinical features and treatment in 612 patients. Am J Med. 1980 Mar;68(3):344–355. doi: 10.1016/0002-9343(80)90102-3. [DOI] [PubMed] [Google Scholar]
  30. Landry S. L., Kaiser D. L., Wenzel R. P. Hospital stay and mortality attributed to nosocomial enterococcal bacteremia: a controlled study. Am J Infect Control. 1989 Dec;17(6):323–329. doi: 10.1016/0196-6553(89)90001-1. [DOI] [PubMed] [Google Scholar]
  31. Maki D. G., Agger W. A. Enterococcal bacteremia: clinical features, the risk of endocarditis, and management. Medicine (Baltimore) 1988 Jul;67(4):248–269. [PubMed] [Google Scholar]
  32. Malone D. A., Wagner R. A., Myers J. P., Watanakunakorn C. Enterococcal bacteremia in two large community teaching hospitals. Am J Med. 1986 Oct;81(4):601–606. doi: 10.1016/0002-9343(86)90544-9. [DOI] [PubMed] [Google Scholar]
  33. Mandell G. L., Kaye D., Levison M. E., Hook E. W. Enterococcal endocarditis. An analysis of 38 patients observed at the New York Hospital-Cornell Medical Center. Arch Intern Med. 1970 Feb;125(2):258–264. doi: 10.1001/archinte.125.2.258. [DOI] [PubMed] [Google Scholar]
  34. McGowan J. E., Jr, Barnes M. W., Finland M. Bacteremia at Boston City Hospital: Occurrence and mortality during 12 selected years (1935-1972), with special reference to hospital-acquired cases. J Infect Dis. 1975 Sep;132(3):316–335. doi: 10.1093/infdis/132.3.316. [DOI] [PubMed] [Google Scholar]
  35. Mederski-Samoraj B. D., Murray B. E. High-level resistance to gentamicin in clinical isolates of enterococci. J Infect Dis. 1983 Apr;147(4):751–757. doi: 10.1093/infdis/147.4.751. [DOI] [PubMed] [Google Scholar]
  36. Moellering R. C., Jr Enterococcal infections in patients treated with moxalactam. Rev Infect Dis. 1982 Nov-Dec;4 (Suppl):S708–S711. doi: 10.1093/clinids/4.supplement_3.s708. [DOI] [PubMed] [Google Scholar]
  37. Moellering R. C., Jr, Wennersten C., Medrek T., Weinberg A. N. Prevalence of high-level resistance to aminoglycosides in clinical isolates of enterococci. Antimicrob Agents Chemother (Bethesda) 1970;10:335–340. [PubMed] [Google Scholar]
  38. Mullis K. B., Faloona F. A. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Methods Enzymol. 1987;155:335–350. doi: 10.1016/0076-6879(87)55023-6. [DOI] [PubMed] [Google Scholar]
  39. Murray B. E., Mederski-Samaroj B. Transferable beta-lactamase. A new mechanism for in vitro penicillin resistance in Streptococcus faecalis. J Clin Invest. 1983 Sep;72(3):1168–1171. doi: 10.1172/JCI111042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Murray B. E., Singh K. V., Heath J. D., Sharma B. R., Weinstock G. M. Comparison of genomic DNAs of different enterococcal isolates using restriction endonucleases with infrequent recognition sites. J Clin Microbiol. 1990 Sep;28(9):2059–2063. doi: 10.1128/jcm.28.9.2059-2063.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Murray B. E., Tsao J., Panida J. Enterococci from Bangkok, Thailand, with high-level resistance to currently available aminoglycosides. Antimicrob Agents Chemother. 1983 Jun;23(6):799–802. doi: 10.1128/aac.23.6.799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Nachamkin I., Axelrod P., Talbot G. H., Fischer S. H., Wennersten C. B., Moellering R. C., Jr, MacGregor R. R. Multiply high-level-aminoglycoside-resistant enterococci isolated from patients in a university hospital. J Clin Microbiol. 1988 Jul;26(7):1287–1291. doi: 10.1128/jcm.26.7.1287-1291.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Rimailho A., Lampl E., Riou B., Richard C., Rottman E., Auzepy P. Enterococcal bacteremia in a medical intensive care unit. Crit Care Med. 1988 Feb;16(2):126–129. doi: 10.1097/00003246-198802000-00006. [DOI] [PubMed] [Google Scholar]
  44. Segarra R. A., Booth M. C., Morales D. A., Huycke M. M., Gilmore M. S. Molecular characterization of the Enterococcus faecalis cytolysin activator. Infect Immun. 1991 Apr;59(4):1239–1246. doi: 10.1128/iai.59.4.1239-1246.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Shlaes D. M., Levy J., Wolinsky E. Enterococcal bacteremia without endocarditis. Arch Intern Med. 1981 Apr;141(5):578–581. [PubMed] [Google Scholar]
  46. Spengler R. F., Greenough 3d W. B., Stolley P. D. A descriptive study of nosocomial bacteremias at The Johns Hopkins Hospital, 1968--1974. Johns Hopkins Med J. 1978 Mar;142(3):77–84. [PubMed] [Google Scholar]
  47. Spiegel C. A., Huycke M. Endocarditis due to streptomycin-susceptible Enterococcus faecalis with high-level gentamicin resistance. Arch Intern Med. 1989 Aug;149(8):1873–1875. [PubMed] [Google Scholar]
  48. Spiegel C. A. Laboratory detection of high-level aminoglycoside-aminocyclitol resistance in Enterococcus spp. J Clin Microbiol. 1988 Nov;26(11):2270–2274. doi: 10.1128/jcm.26.11.2270-2274.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Stevens D. L., Mitten J., Henry C. Effects of alpha and theta toxins from Clostridium perfringens on human polymorphonuclear leukocytes. J Infect Dis. 1987 Aug;156(2):324–333. doi: 10.1093/infdis/156.2.324. [DOI] [PubMed] [Google Scholar]
  50. Thornsberry C. Review of in vitro activity of third-generation cephalosporins and other newer beta-lactam antibiotics against clinically important bacteria. Am J Med. 1985 Aug 9;79(2A):14–20. doi: 10.1016/0002-9343(85)90255-4. [DOI] [PubMed] [Google Scholar]
  51. Weems J. J., Jr, Lowrance J. H., Baddour L. M., Simpson W. A. Molecular epidemiology of nosocomial, multiply aminoglycoside resistant Enterococcus faecalis. J Antimicrob Chemother. 1989 Aug;24(2):121–130. doi: 10.1093/jac/24.2.121. [DOI] [PubMed] [Google Scholar]
  52. Weinstein A. J., Lentnek A. L. Cephalosporin-aminoglycoside synergism in experimental enterococcal endocarditis. Antimicrob Agents Chemother. 1976 Jun;9(6):983–987. doi: 10.1128/aac.9.6.983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Weinstein M. P., Reller L. B., Murphy J. R., Lichtenstein K. A. The clinical significance of positive blood cultures: a comprehensive analysis of 500 episodes of bacteremia and fungemia in adults. I. Laboratory and epidemiologic observations. Rev Infect Dis. 1983 Jan-Feb;5(1):35–53. doi: 10.1093/clinids/5.1.35. [DOI] [PubMed] [Google Scholar]
  54. Wenzel R. P., Osterman C. A., Hunting K. J., Gwaltney J. M., Jr Hospital-acquired infections. I. Surveillance in a university hospital. Am J Epidemiol. 1976 Mar;103(3):251–260. doi: 10.1093/oxfordjournals.aje.a112223. [DOI] [PubMed] [Google Scholar]
  55. Whiteside M., Moore J., Ratzan K. An investigation of enterococcal bacteremia. Am J Infect Control. 1983 Aug;11(4):125–129. doi: 10.1016/0196-6553(83)90028-7. [DOI] [PubMed] [Google Scholar]
  56. Wilson W. R., Wilkowske C. J., Wright A. J., Sande M. A., Geraci J. E. Treatment of streptomycin-susceptible and streptomycin-resistant enterococcal endocarditis. Ann Intern Med. 1984 Jun;100(6):816–823. doi: 10.7326/0003-4819-100-6-816. [DOI] [PubMed] [Google Scholar]
  57. Zervos M. J., Dembinski S., Mikesell T., Schaberg D. R. High-level resistance to gentamicin in Streptococcus faecalis: risk factors and evidence for exogenous acquisition of infection. J Infect Dis. 1986 Jun;153(6):1075–1083. doi: 10.1093/infdis/153.6.1075. [DOI] [PubMed] [Google Scholar]
  58. Zervos M. J., Kauffman C. A., Therasse P. M., Bergman A. G., Mikesell T. S., Schaberg D. R. Nosocomial infection by gentamicin-resistant Streptococcus faecalis. An epidemiologic study. Ann Intern Med. 1987 May;106(5):687–691. doi: 10.7326/0003-4819-106-5-687. [DOI] [PubMed] [Google Scholar]
  59. Zervos M. J., Mikesell T. S., Schaberg D. R. Heterogeneity of plasmids determining high-level resistance to gentamicin in clinical isolates of Streptococcus faecalis. Antimicrob Agents Chemother. 1986 Jul;30(1):78–81. doi: 10.1128/aac.30.1.78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Zervos M. J., Patterson J. E., Edberg S., Pierson C., Kauffman C. A., Mikesell T. S., Schaberg D. R. Single-concentration broth microdilution test for detection of high-level aminoglycoside resistance in enterococci. J Clin Microbiol. 1987 Dec;25(12):2443–2444. doi: 10.1128/jcm.25.12.2443-2444.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Zervos M. J., Terpenning M. S., Schaberg D. R., Therasse P. M., Medendorp S. V., Kauffman C. A. High-level aminoglycoside-resistant enterococci. Colonization of nursing home and acute care hospital patients. Arch Intern Med. 1987 Sep;147(9):1591–1594. doi: 10.1001/archinte.147.9.1591. [DOI] [PubMed] [Google Scholar]

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

RESOURCES