Use of Synergy vs High Potency

We are assisting implementers in mapping their antibotics to LOINC and have received feedback on the synonymous use of High Potency and Synergy in LOINC. Their feeling is that the two terms are not the same. Research on the internet tells me that ‘Gentamicin synergy and streptomycin synergy are used to predict synergy between ampicillin, penicillin or vancomycin and an aminoglycoside with enterococci.’ Synergy creates a high potency effect, but high potency can also mean one drug alone, not in a synergistic relationship with another drug.

This is what Clinical and Laboratory Standards Institute (formerly NCCLS) says

‘Unusual concentrations may be tested for special purposes (e.g., high concentrations of gentamicin and streptomycin may be tested to indicate a synergistic effect with a penicillin or glycopeptide against enterococci).

High-level resistance to gentamicin and/or streptomycin indicates that an enterococcal isolate will not be killed by the synergistic action of a penicillin or glycopeptide combined with that aminoglycoside.17 Agar or broth high-concentration gentamicin (500 μg/mL) and streptomycin (1000 μg/mL with broth microdilution; 2000 μg/mL with agar) tests can be used to screen for this type of resistance. Other aminoglycosides need not be tested, because their activities against enterococci are not superior to gentamicin or streptomycin.’

It seems “High Level Resistance”, the term used by CLSI, the Manual for Clinical Microbiology, and the Clinical Microbiology Procedures Handbook (Isenberg), the three main references in microbiology, may be a clearer term than High Potency and be more synonymous with Syngergy. Have other implementers come across this challenge? If so, how has it been handled? I appreciate any thoughts on the opinions that are coming forward to Canada Health Infoway. We are considering the need to develop and request new codes that reflect this terminology.

Lorie Carey

Laboratory Terminology SME

Canada Health Infoway

We asked John Stelling from Brigham and Women’s Hospital and WHO to review this questions.

This is John’s response:

  1. True synergy testing: Done on a strain or set of strains of interest using two antibiotics to see whether the two drugs when used together give better (synergy), worse (antagonism), or the same (neutral/additive) killing as you would expect than if the drugs were used separately. There are many examples of such synergism and antagonism.

    The synergy involving enterococcus and aminoglycoside plus either beta-lactam or vancomycin is particularly well known as discussed. There is no need for labs do this test for enterococcus because the synergy has already been well documented for decades.

  2. “Synergy test” as applied to enterococcus is an informal, imprecise, but commonly used term. If the strain is susceptible to BOTH an aminoglycoside and a beta-lactam, then these two drugs can be used synergistically. Or if the strain is susceptible to BOTH an aminoglycoside and vancomycin, then these two drugs can be used synergistically. So in this case, the “synergy test” with high-potency gentamicin is just one piece of the puzzle in ascertaining whether the above well-known synergy exists or not. (We use the high-potency disk because enterococcus is always resistant to the normal gentamicin disk used for other bacteria.) The other pieces of the puzzle are the beta-lactam (PEN/AMP) result and the vancomycin result.