About the CDS Test

About the CDS Test

Background

The Calibrated Dichotomous Sensitivity Test is a method for determining the antibiotic susceptibility of micro-organisms using agar disc diffusion and was developed in 1969 by Sydney M. Bell assisted by members of the Department of Microbiology, The Prince of Wales Hospital, Sydney, Australia. It was introduced into laboratory practice in Australia in an effort to correct the unsatisfactory results of antibiotic susceptibility testing in Australia that were obtained from surveys conducted by The Royal College of Pathologists of Australasia in the late 60’s and early 70’s.

Subsequent Microbiology Surveys demonstrated that errors in susceptibility testing could be eliminated almost entirely with the adoption of the CDS test as a uniform method of susceptibility testing in practice. In the initial stages of the development of the method, it was recognised that there was a need for a method of susceptibility testing that would be applied by laboratories of all sizes and by staff with a wide range of experience and skills in microbiological techniques. Emphasis was given in the CDS test to simplicity of technique and ease of interpretation. It relied heavily on the theoretical principles established by Humphrey and Lightbown in 19521 and each process was rigorously tested in the laboratory for accuracy, ease of performance and reproducibility of results. What evolved was a high potency disc diffusion technique with several unique features that distinguishes it from other disc methods.

Similar to many other laboratory procedures, precision of the CDS method in practice relies heavily on a strict adherence to the details of the technique. It was recognised soon after the introduction of the CDS test that the best way of ensuring this and preventing “unauthorised” modification was by communication between the developers and the users of the test. This CDS web site is the latest addition to the various means we have used in maintaining this highly valuable two-way communication.

Materials, Methods and Interpretations Unique to the CDS Test

In the course of the development of the CDS method, materials were selected on the basis of demonstrable superiority or ready availability. The techniques were designed to be simple yet yield highly reproducible results. The unique method of interpretation of the CDS test into only 2 categories of susceptibility, which is discussed below, evolved from the recognition of the limitations of antibiotic disc testing generally and the need to provide a safe and intelligible result to the clinician.

 

The medium

The base medium originally selected was Sensitest (Oxoid) and was chosen because of its reliability of supply, superior performance (particularly with Gram-negative organisms and sulphonamides) and uniform quality.   Although the quality of other media such as Mueller-Hinton has improved over time, we have not been convinced that it is necessary to change the medium in the CDS test.

 

The inoculum

The inoculum of 107 cfu/ml used in the CDS method is unique and, although the preparation of the inoculum is simple, it is reproducible.   Another advantage of the CDS inoculum of 107 cfu/ml, which is generally higher than that used in other disc methods, is its resultant confluent and uniform lawn of growth.   This facilitates the recognition of various mechanisms of resistance, particularly those mediated by inactivating enzymes or high level mutation.

 

The Disc potencies

In the development of the CDS test, the potencies of antibiotics discs were carefully selected to ensure two results.   The first was that there was a uniform cut-off zone size between resistant and susceptible strains. Secondly, that the cut-off point should lie on the optimal part of the diffusion curve for separation.    With most antibiotics, this lies at a point 6 mm from the edge of the antibiotic disc, so that an annular radius of 6 mm (18 mm diameter) was selected as the uniform cut-off point.   The advantages of a uniform cut-off point for the majority of antibiotics are obvious in that it obviates the need for interpretative charts. More importantly, the selection of a disc potency that yields inhibitory zones in the range achieved by the CDS test enhances the ability of the method to separate resistant and susceptible strains. This was first demonstrated with Staphylococcus aureus and penicillin early in the development of the method and later with the third generation cephalosporins where 5 mg discs were shown to yield far superior results to those achieved with the 30 mg discs used by other methods.

 

Measuring the inhibitory zones

In the early days of evolution of the test, satisfactory disc dispensers were not available and a multiple pronged paper disc “Multodisk” (Oxoid) was used. This necessitated the measurement of the annular radius as there was no clear or uninterrupted diameter of the inhibitory zone. With the introduction of satisfactory single disc dispensers, this was no longer applicable but feedback from the CDS users was that they were reluctant to change to measuring diameters. The most common reason advanced was that measurement was easier and more accurate because the sharp edge of the antibiotic disc was a preferable reference point to the edge of bacterial growth.

 

Reporting the result

Since inception, the CDS test has separated susceptibilities into only two categories, susceptible and resistant. It was established early in development that the precision of all disc tests did not permit any finer degree of separation. Attempts to identify categories such as “intermediate” or “moderately resistant” were considered unjustified and unscientific. As the CDS evolved we have attempted to make the approach to it analogous to that with other laboratory tests where recognition is given to the sensitivity and specificity of the test. In the CDS test we have considered the aim of the test is to identify the susceptible category i.e. analogous to the positive result of other tests. Cut-off MIC values were chosen so that we could do this with a greater degree of confidence, in other words we increase the specificity of the test. We accept that in some cases, a few marginally susceptible strains may be defined as resistant and thus we sacrifice some sensitivity but this is unavoidable. For if the test is to be safe it must not define a resistant strain as susceptible ie it must have a high degree of specificity.

[1] Humphrey, J.H. & Lightbown, J.W. (1952). A general theory for plate assay of antibiotics with some practical applications.  J. Gen. Microbiol. 7: 129.

Publications

  1. Bell S. M. (1970).  Microbiology Survey.  Board of Education Report of Surveys.  Royal Coll. Path.   Aust., Sydney.
  2. Bell S. M. (1971).  Microbiology Survey.  Board of Education Report of Surveys.  Royal Coll. Path.   Aust., Sydney.
  3. Bell S. M. (1972).  Microbiology Survey.  Board of Education Report of Surveys.  Royal Coll. Path.   Aust., Sydney.
  4. Bell S. M. (1973).  Microbiology Survey. Board of Education Report of Surveys.  Royal Coll. Path.   Aust., Sydney.
  5. Bell S. M. (1975).  The Calibrated Dichotomous Sensitivity (CDS) disc method of antibiotic sensitivity testing.  Pathology 7 (Supplement); 1-48.
  6. Bell S. M. (1984).  Antibiotic sensitivity testing by the CDS method. Clinical Microbiology Update Program, Editor:  Nerissa Hartwig.
  7. Bell S. M. (1988).  Additions and modifications to the range of antibiotics tested by the CDS method of antibiotic sensitivity testing. Pathology 20.  303-304.
  8. Bell, S.M., Gatus, B.J., Pham, J.N. & Jimenez, A.S. (1990). CDS Users Group Newsletter No 1. The Prince of Wales Hospital, Sydney.
  9. Bell, S.M., Gatus, B.J., Pham, J.N. & Jimenez, A.S. (1991). CDS Users Group Newsletter No 2. The Prince of Wales Hospital, Sydney.
  10. Bell, S.M., Gatus, B.J., Pham, J.N., Jimenez, A.S. & Hardie, M.J (1991). CDS Users Group Newsletter No 3. The Prince of Wales Hospital, Sydney.
  11. Bell, S.M., Gatus, B.J., Pham, J.N., Jimenez, A.S. & Hardie, M.J. (1992). CDS Users Group Newsletter No 4. The Prince of Wales Hospital, Sydney.
  12. Bell, S.M., Gatus, B.J., Pham, J.N., Jimenez, A.S. & Hardie, M.J. (1993). CDS Users Group Newsletter No 5. The Prince of Wales Hospital, Sydney.
  13. Bell, S.M., Gatus, B.J., Pham, J.N., Jimenez, A.S. & Hardie, M.J. (1993). CDS Users Group Newsletter No 6. The Prince of Wales Hospital, Sydney.
  14. Bell, S.M., Gatus, B.J., Pham, J.N., Jimenez, A.S. & Hardie, M.J. (1996). CDS Users Group Newsletter No 7. The Prince of Wales Hospital, Sydney.
  15. Bell, S.M., Gatus, B.J., Pham, J.N. & Jupp, J. (1996).  Detecting Antibiotic Resistance.  Today’s Life Science. Vol. 8, No. 5.
  16. Bell, S.M., Gatus, B.J. & Pham, J.N. (1997). CDS Users Group Newsletter No 8. The Prince of Wales Hospital, Sydney.
  17. Bell, S.M., Gatus, B.J. & Pham, J.N. (1998). CDS Users Group Newsletter No 9. The Prince of Wales Hospital, Sydney.
  18. Bell, S.M., Gatus, B.J. & Pham, J.N. (1999). Antibiotic susceptibility testing in Australia. Abstract. IXth International Congress of Bacteriology and Applied Microbiology. International   Union of Microbiology Societies. Sydney, Australia.
  19. Bell, S.M., Gatus, B.J. & Pham, J.N. (1999). The calibration of trovafloxacin for the CDS test. Abstract. IXth International Congress of Bacteriology and Applied Microbiology.International Union of Microbiology Societies. Sydney, Australia.
  20. Bell, S.M., Gatus, B.J. & Pham, J.N. (1999). Antibiotic susceptibility testing by the CDS in the year 2000. Abstract.       IXth International Congress of Bacteriology and Applied Microbiology. International Union of Microbiology Societies. Sydney, Australia.
  21. Bell, S.M., Gatus, B.J. & Pham, J.N. (1999). The detection of vancomycin resistant enterococci (VRE) by the CDS method. Abstract. IXth International Congress of Bacteriology and Applied Microbiology. International Union of Microbiology Societies. Sydney, Australia.
  22. Bell, S.M., Gatus, B.J. & Pham, J.N. (1999). Antibiotic susceptibility testing by the CDS method. A concise laboratory manual 1999. Arthur Productions Pty., Ltd. Sydney, Australia.ISBN 0-646-37814-7.
  23. Bell, S.M., Gatus, B.J. & Pham, J.N. (2000). The Calibrated Dichotomous Sensitivity (CDS) test. Microbiology Australia. 21: Vol. 1. 23-24.
  24. Bell, S.M., Gatus, B.J. & Pham, J.N. (2000). CDS Users Group Newsletter No 10. The Prince of Wales Hospital, Sydney.
  25. CDS Users Group Newsletter No 11. December 2001. The Prince of Wales Hospital, Sydney.
  26. CDS Users Group Newsletter No 12. 2003 The Prince of Wales Hospital, Sydney.
  27. CDS Users Group Newsletter No 13. 2004 The Prince of Wales Hospital, Sydney.
  28. CDS Users Group Newsletter No 17. November 2005. The Prince of Wales Hospital, Sydney.
  29. CDS Users Group Newsletter No 19. July 2006. The Prince of Wales Hospital, Sydney.
  30. CDS Users Group Newsletter No 20. November 2007. The Prince of Wales Hospital, Sydney.
  31. CDS Users Group Newsletter No 21. March 2007. The Prince of Wales Hospital, Sydney.
  32. CDS Users Group Newsletter No 22. February 2010. The Prince of Wales Hospital, Sydney.
  33. CDS Users Group Newsletter No 23. July 2010. The Prince of Wales Hospital, Sydney.
  34. CDS Users Group Newsletter No 24. September 2010. The Prince of Wales Hospital, Sydney.
  35. Bell, S.M., Pham, J.N. & Fisher G.T. (2009). Antibiotic susceptibility testing by the CDS method.A manual for Medical and Veterinary Laboratories 2009 Fifth Edition.ISBN 978-0-646-51681-3
  36. Bell, S.M., Pham, J.N. & Fisher G.T. (2009). Antibiotic susceptibility testing by the CDS method. A manual for Medical and Veterinary Laboratories 2009 Modified Fifth Edition – August 2010.