Advances in Food Mycology

Mixtures of Natural and Synthetic Antifungal Agents 267
efficacy of the combined agents compared to the sum of the individual
results. Synergism is an increase or enhancement of overall antimicrobial
activity when two agents are combined compared to the sum of
individual results (López-Malo et al., 2005b).
A conclusion that synergism occurs must be approached with
caution since it implies that a reduction of overall antimicrobial concentration
might be achieved in a food system without a reduction in
efficacy. Gardner (1977) stated that true synergism is quite rare in
relation to combined antibiotics. Other concerns about the misuse of
the term “synergism” in relation to antimicrobials have been cited
(Garrett, 1958; Davidson and Parish, 1989). Most commonly, additive
interactions are misidentified as synergistic. A case in which an
increase in antimicrobial activity is observed upon the addition of a
second compound to a food system does not necessarily constitute
synergy. A conclusion of synergism requires that the overall efficacy of
the combination be significantly greater than the sum of the efficacies
of the individual compounds.
Additive, synergistic, or antagonistic interactions can be interpreted
with an MIC isobologram. Isobologram construction can be simplified
using fractional inhibitory concentrations (FIC), which are MICs
normalized to unity. The FIC is the concentration of a compound
needed to inhibit growth (expressed as a fraction of its MIC) when
combined with a known amount of a second antimicrobial compound.
It is calculated as the ratio of the MIC of a compound when
combined with a second compound divided by the MIC of the first
compound alone. The FIC of two compounds in an inhibitory
combination may be added to give a total FIC Index . An FIC Index near 1
indicates additivity, whereas an FIC Index less than 1 indicates synergy
and an FIC Index greater than 1 indicates antagonism. The degree to which
a result must be less than or greater than 1, to indicate synergism or
antagonism is a matter of interpretation. Squires and Cleeland (1985)
proposed that for antibiotic testing FIC Index indicates additive results
between 0.5 and 2.0. Synergism and antagonism are indicated by
results FIC Index < 0.5 and FIC Index > 2.0, respectively. Research is
needed to provide a database for proper interpretation of FIC and
FIC Index in relation to food antimicrobial systems. Data interpretation
must be conducted conditionally and will depend upon a number of
variables, such as specific test conditions, microbial strain, and target
food system (López-Malo et al., 2005b). It should be noted that
interpretations might also vary depending upon the specific concentrations
of each antimicrobial used in combination. Parish and
Carroll (1988) observed additivity between SO 2 and either sorbate or