TABLE 2

Overview of proposed confidence levels for grading mutations associated with phenotypic resistance

SymbolLR+ and OR
p-valuevalue
High (Hi) confidence for association with resistance
Strong association of the mutation with phenotypic drug
 resistance; sufficient evidence that the mutation confers or is
 strongly associated with drug resistance
#•<0.05>10
Moderate (Mo) confidence for association with resistance
Moderate association of the mutation with phenotypic drug resistance;
 additional data desirable for improved evidence that the mutation
 confers or is strongly associated with drug resistance
#•<0.055< … ≤10
Minimal (Mi) confidence for association with resistance
Weak association of the mutation with phenotypic drug resistance;
 inconclusive evidence that the mutation confers or is strongly
 associated with drug resistance. Substantial additional data required
#•<0.051< … ≤5
No association with resistance
No evidence of association between the mutation and drug resistance
#•<0.05<1
Indeterminate
No statistically significant threshold reached; additional data required
Indeter≥0.05

The table shows the thresholds applied to likelihood ratios (LR) and odds ratios (OR) to grade the association of mutations with phenotypic drug resistance. LR+: positive likelihood ratio. “Additional data” is defined as a requirement for 1) more phenotypically drug resistant and susceptible isolates tested with the mutation in question; and/or 2) better understanding of the mechanism of drug resistance (e.g. to investigate epistasis, or the interactions between drug-resistance conferring mutations, lineage-specific genetic factors and compensatory mutations [23, 24] or synergistic factors when more than one mutation is required to confer resistance [25]).