Skip to main content
Log in

Technical aspects and clinical correlations of the serum bactericidal test

  • Reviews
  • Published:
European Journal of Clinical Microbiology Aims and scope Submit manuscript

Abstract

A review of the studies using 50 % human serum as a diluent for the serum bactericidal test has shown correlations with patient outcome. Human serum used as diluent of the patient's serum appears to be essential because of high protein binding of some antibiotics. An inoculum of 10 5–106 bacteria/ml and a bactericidal criteria of 99.9 % killing are technical aspects that have gained popularity. Careful timing of serum collection for the assay is important. Neither the macrotube nor microtiter techniques are entirely satisfactory. The latter method, however, has the advantage of being more reproducible than the macrotube method, less cumbersome and requiring less serum. Preliminary guidelines for performing and interpreting the test are provided. Future research should be directed toward making the microtiter technique more sensitive for identifying antibiotic tolerance, developing effective methods to eliminate the need for human serum as a diluent and obtaining more clinical correlations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Pien, F. D., Vosti, K. L.: Variation in performance of the serum bactericidal test. Antimicrobial Agents and Chemotherapy 1974, 6: 330–333.

    PubMed  Google Scholar 

  2. Coleman, D. L., Horwitz, R. I., Andriole, V. T.: Association between serum inhibitory and bactericidal concentrations and therapeutic outcome in bacterial endocarditis. American Journal of Medicine 1982, 73: 260–267.

    PubMed  Google Scholar 

  3. Wolfson, J. S., Swartz, M. N.: Serum bactericidal activity as a monitor of antibiotic therapy. New England Journal of Medicine 1985, 312: 968–975.

    PubMed  Google Scholar 

  4. Stratton, C. W., Reller, L. B.: Serum dilution test for bactericidal activity. I. Selection of a physiologic diluent. Journal of Infectious Diseases 1977, 136: 187–195.

    PubMed  Google Scholar 

  5. Reller, L. B., Stratton, C. W.: Serum dilution test for bactericidal activity. II. Standardization and correlation with antimicrobial assays and susceptibility tests. Journal of Infectious Diseases 1977, 136: 196–203.

    PubMed  Google Scholar 

  6. Standiford, H. C., Drusano, G. L., McNamee, W. B., Tatem, B., Ryan, P. A., Schimpff, S. C.: Comparative pharmacokinetics of moxalactam, cefoperazone, and cefotaxime in normal volunteers. Reviews of Infectious Diseases 1982, Supplement 4: S585–594.

    Google Scholar 

  7. Drusano, G. L., Standiford, H. C., Fitzpatrick, B., Leslie, J., Tangtatsawasdi, P., Ryan, P., Tatem, B., Moody, M. R., Schimpff, S. C.: Comparison of the pharmacokinetics of ceftazidime and moxalactam and their microbiological correlates in volunteers. Antimicrobial Agents and Chemotherapy 1984, 26: 388–393.

    PubMed  Google Scholar 

  8. Weinstein, M. P., Stratton, C. W., Ackley, A., Hawley, H. B., Robinson, P. A., Fisher, B. D., Alcid, D. V., Stevens, D. S., Reller, L. B.: Multicenter collaborative evaluation of a standardized serum bactericidal test as a prognostic indicator in infective endocarditis. American Journal of Medicine 1985, 78: 262–269.

    PubMed  Google Scholar 

  9. Sculier, J. P., Klastersky, J.: Significance of serum bactericidal activity in gram-negative bacillary bacteremia in patients with and without granulocytopenia. American Journal of Medicine 1984, 76: 429–435.

    PubMed  Google Scholar 

  10. Platt, R., Ehrlich, S. L., Afarian, J., O'Brien, T. F., Pennington, J. E., Kass, E. H.: Moxalactam therapy of infections caused by cephalothin resistant bacteria: influence of serum inhibitory activity on clinical response and acquisition of antibiotic resistance during therapy. Antimicrobial Agents and Chemotherapy 1981, 20: 351–355.

    PubMed  Google Scholar 

  11. Parker, R. H., Fossieck, B. E.: Intravenous followed by oral antimicrobial therapy for staphylococcal endocarditis. Annals of Internal Medicine 1980, 93: 832–834.

    PubMed  Google Scholar 

  12. Prober, C. G., Yeager, A. S.: Use of the serum bactericidal titer to assess the adequacy of oral antibiotic therapy in the treatment of acute hematogenous osteomyelitis. Pediatrics 1979, 95: 131–135.

    PubMed  Google Scholar 

  13. Bundtzen, R. W., Gerber, A. U., Cohn, D. L., Craig, W. A.: Post-antibiotic suppression of bacterial growth. Reviews of Infectious Diseases 1981, 3: 28–37.

    PubMed  Google Scholar 

  14. Bustamante, C. T., Drusano, G. L., Tatem, B. A., Standiford, H. C.: Post-antibiotic effect of imipenem againstPseudomonas aeruginosa. Antimicrobial Agents and Chemotherapy 1984, 26: 678–682.

    PubMed  Google Scholar 

  15. Standiford, J., Joshi, J., Wade, J., DeJongh, C., Johnson, D., Drusano, D., Schimpff, S.: Correlation of serum bactericidal activity and response in profoundly granulocytopenic cancer patients with gram-negative bacteremia. 24th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington, DC, 1984, Abstract 390.

  16. Drusano, G. L., Standiford, H. C., Bustamante, C., Forrest, A., Rivera, G., Leslie, J., Tatem, B., Delaportas, D., MacGregor, R. R., Schimpff, S. C.: Multiple-dose pharmacokinetics of imipenem-cilastatin. Antimicrobial Agents and Chemotherapy 1984, 26: 715–721.

    PubMed  Google Scholar 

  17. Levy, J., Klastersky, J.: Serum bactericidal test: A review with emphasis on its role in the evaluation of antibiotic combinations. In: Klastersky, J., Staquet, M. (ed.): Combination antibiotic therapy in the compromised host. New York, Raven Press, 1982, p. 43.

    Google Scholar 

  18. Viollier, A. F., Standiford, H. C., Drusano, G. L., Tatem, B. A., Moody, M., Schimpff, S. C.: Comparative pharmacokinetic and serum bactericidal activity of mezlocillin, ticarcillin, piperacillin with and without gentamicin. Journal of Antimicrobial Chemotherapy 1985, 15: 597–606.

    PubMed  Google Scholar 

  19. Pien, F. D., Williams, R. D., Vosti, K. L.: Comparison of broth and human serum as the diluent in the serum bactericidal test. Antimicrobial Agents and Chemotherapy 1975, 7: 113–114.

    PubMed  Google Scholar 

  20. Tolinson, G. N., Sutherland, R.: The binding of antimicrobials to serum proteins. British Journal of Pharmacology 1965, 25: 638–650.

    PubMed  Google Scholar 

  21. Hirsh, J. G.: Comparative bactericidal activities of blood serum and plasma serum. Journal of Experimental Medicine 1960, 112: 15–22.

    PubMed  Google Scholar 

  22. Ericsson, H. M., Sherris, J. C.: Antibiotic sensitivity testing: report of an International Collaborative Study. Acta Pathologica et Microbiologica Scandinavica (B) 1971, Supplement 217: 1–90.

    Google Scholar 

  23. National Committee for Clinical Laboratory Standards: Tentative standard for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. NCCLS, Villanova, PA, 1983.

    Google Scholar 

  24. Thornsberry, C., McDougal, L. K.: Successful use of broth microdilution in susceptibility test for methicillin-resistant (heteroresistant) staphylococci. Journal of Clinical Microbiology 1983, 18: 1084–1091.

    PubMed  Google Scholar 

  25. Klastersky, J., Daneau, D., Swings, G., Weerts, D.: Antimicrobial activity in serum and urine as a therapeutic guide in bacterial infections. Journal of Infectious Diseases 1974, 129: 187–193.

    PubMed  Google Scholar 

  26. Anhalt, J. P., Sabath, L. D., Barry, A. L.: Special tests: bactericidal activity, activity of antibiotics in combination and detection of B-lactamase production. In:Lennette, E. H., Balows, A., Hausler, W. J., Truant, J. P. (ed.): Manual of clinical microbiology. American Society for Microbiology, Washington, DC, 1980, p. 479.

    Google Scholar 

  27. Washington, J. A.: The role of the microbiology laboratory in the diagnosis and antimicrobial treatment of infective endocarditis. Mayo Clinic Proceedings 1982, 57: 22–32.

    PubMed  Google Scholar 

  28. Pearsons, R. D., Steigbigel, R. T., Davis, H. T., Chapman, S. W.: Method for reliable determination of minimal lethal antibiotic concentrations. Antimicrobial Agents and Chemotherapy 1980, 18: 699–708.

    PubMed  Google Scholar 

  29. Prober, C. G., Dougherty, S. S., Vosti, K. L., Yeager, A. S.: Comparison of a micromethod for the performance of the serum bactericidal test with the standard tube dilution method. Antimicrobial Agents and Chemotherapy 1979, 16: 46–48.

    PubMed  Google Scholar 

  30. Standiford, H. C., Drusano, G. L., Fitzpatrick, B., Tatem, B., Schimpff, S. C.: Bactericidal activity of ceftazidime in serum compared with that of ticarcillin combined with amikacin. Antimicrobial Agents and Chemotherapy 1984, 26: 339–342.

    PubMed  Google Scholar 

  31. Drusano, G., Standiford, H., Ryan, P., McNamee, W., Tatem, B., Schimpff, S.: Correlation of predicted serum bactericidal activities and values measured in volunteers. European Journal of Clinical Microbiology 1986, 5: 88–92.

    PubMed  Google Scholar 

  32. Stratton, C. W., Weinstein, M. P., Reller, L. B.: Correlation of serum bactericidal activity with antimicrobial agent level and minimal bactericidal concentration. Journal of Infectious Diseases 1982, 145: 160–168.

    PubMed  Google Scholar 

  33. McNamee, W., Drusano, G. L., Tatem, B. A., Standiford, H. C.: The serum bactericidal activity of latamoxef (moxalactam), cefoperazone and cefotaxime. Journal of Antimicrobial Chemotherapy 1984, 14: 491–497.

    PubMed  Google Scholar 

  34. Shanholtzer, C. J., Peterson, L. R., Mohn, M. L., Moody, J. A., Gerding, D. N.: MBCs forStaphylococcus aureus as determined by macrodilution and microdilution techniques. Antimicrobial Agents and Chemotherapy 1984, 26: 214–219.

    PubMed  Google Scholar 

  35. Sabath, L. D., Mokhbat, J. E.: What is the clinical significance of tolerance of B-lactam antibiotics? In: Remington, J. S., Schwartz, M. N. (ed.): Current clinical topics in infectious diseases. McGraw Hill, Inc., New York, 1983, p. 358–377.

    Google Scholar 

  36. Auckenthaler, R., Wilson, W. R., Wright, A. J., Washington, J. A., II, Durack, D. T., Geraci, J. E.: Lack of in vivo and in vitro bactericidal activity of n-formimidoyl thienamycin against enterococci. Antimicrobial Agents and Chemotherapy 1982, 22: 448–452.

    PubMed  Google Scholar 

  37. Eagle, H., Musselman, A. D.: The rate of bacterial action of penicillin in vitro as a function of its concentration, and its paradoxically reduced activity at high concentrations against certain organisms. Journal of Experimental Medicine 1948, 88: 99–131.

    Google Scholar 

  38. Pelletier, L. L., Jr.: Lack of reproducibility of macrodilution MBCs forStaphylococcus aureus. Antimicrobial Agents and Chemotherapy 1984, 26: 815–818.

    PubMed  Google Scholar 

  39. Taylor, P. C., Schoenknecht, F. D., Sherris, J. C., Linner, E. C.: Determination of minimal bactericidal concentrations of oxacillin forStaphylococcus aureus: influence and significance of technical factors. Antimicrobial Agents and Cheomtherapy 1983, 23: 142–150.

    Google Scholar 

  40. Ishida, K., Guze, P. A., Kalmanson, G. M., Albrandt, K., Guze, L. B.: Variables in demonstrating methicillin tolerance inStaphylococcus aureus strains. Antimicrobial Agents and Chemotherapy 1982, 21: 688–690.

    PubMed  Google Scholar 

  41. Sabath, L. D., Wheeler, N., Laverdiere, M.: A new type of penicillin resistance ofStaphylococcus aureus. Lancet 1977, i: 443–447.

    Google Scholar 

  42. Kay, D.: The clinical significance of tolerance ofStaphylococcus aureus. Annals of Internal Medicine 1980, 93: 924.

    PubMed  Google Scholar 

  43. Schlichter, J. G., MacLean, H., Milzer, A.: Effective penicillin therapy in subacute bacterial endocarditis and other chronic infections. American Journal of the Medical Sciences 1947, 217: 600–608.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Standiford, H.C., Tatem, B.A. Technical aspects and clinical correlations of the serum bactericidal test. Eur. J, Clin. Microbiol. 5, 79–87 (1986). https://doi.org/10.1007/BF02013474

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02013474

Keywords

Navigation